levetiracetam and Seizures

To evaluate the safety and effectiveness of levetiracetam and phenytoin by evaluating the events of seizure termination and recurrence in children.. We used the internet databases PubMed, Embase, and Google Scholar to conduct a literature search for the appropriate studies. A meta-analysis was performed to calculate the odds ratio using fixed and random-effects models.. We identified 15 studies that were eligible for the meta-analysis. The incidence of seizure termination within 24 h was 76.9% for levetiracetam and 70.5% for phenytoin. Levetiracetam had a higher number of seizure termination events than phenytoin (P = 0.005, I. The efficacy and safety of levetiracetam are superior to that of phenytoin in children with status epilepticus. Large Randomized Controlled Trial studies are needed to confirm the result in children.

Topics: Anticonvulsants; Child; Humans; Levetiracetam; Phenytoin; Seizures; Status Epilepticus

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

Topics: Aged; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Quality of Life; Seizures

Cortical network hyperexcitability related to synaptic dysfunction in Alzheimer's disease (AD) is a potential target for therapeutic intervention. In recent years, there has been increased interest in the prevalence of silent seizures and interictal epileptiform discharges (IEDs, or seizure tendency), with both entities collectively termed "subclinical epileptiform activity" (SEA), on neurophysiologic studies in AD patients. SEA has been demonstrated to be common in AD, with prevalence estimates ranging between 22-54%. Converging lines of basic and clinical evidence imply that modifying a hyperexcitable state results in an improvement in cognition. In particular, though these results require further confirmation, post-hoc findings from a recent phase II clinical trial suggest a therapeutic effect with levetiracetam administration in patients with AD and IEDs. Here, we review key unanswered questions as well as potential clinical trial avenues. Specifically, we discuss postulated mechanisms and treatment of hyperexcitability in patients with AD, which are of interest in designing future disease-modifying therapies. Criteria to prompt screening and optimal screening methodology for hyperexcitability have yet to be defined, as does timing and personalization of therapeutic intervention.

Topics: Alzheimer Disease; Causality; Clinical Relevance; Electroencephalography; Humans; Levetiracetam; Seizures

We aim to assess the effect of anti-epileptic drug (AED) prophylaxis for early or late posttraumatic seizures, targeting the pediatric population with traumatic brain injury (TBI). We systematically searched for studies reporting the incidence of posttraumatic seizures in pediatric patients who suffered from TBI and received AEDs prophylactically following their TBI incident. Studies that included adult patients, adult and pediatric patients but did not report results for the pediatric population separately, and patients who did not suffer from a TBI were excluded. Studies that did not indicate the use of antiepileptic drugs prophylactically following TBI were excluded. A total of 10 studies were included involving 4621 posttraumatic brain injury patients of the pediatric age population (<18). Five studies assessed the effect of prophylaxis on early seizures, four on late seizures and one on any seizure. The mean incidence of posttraumatic seizures with AED prophylaxis was 8% for early seizures and 7.1% for late seizures. Moreover, one study revealed no benefit of AED prophylaxis for early posttraumatic seizures. Meta-analysis revealed a significant difference in the incidence of early posttraumatic seizures with antiepileptic prophylaxis. However, no significant difference for late posttraumatic seizures has been shown. In conclusion, AED prophylaxis seems to be effective against early posttraumatic seizures for the pediatric population, with levetiracetam possibly being more effective. Also, there is no observed benefit for late posttraumatic seizures.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Child; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a "U-shaped" dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.

Topics: Anticonvulsants; Carbamazepine; Diazepam; Epilepsy; Epilepsy, Generalized; Fructose; Gabapentin; Humans; Levetiracetam; Seizures; Triazines

This review aimed to summarize the available data and offer a practical recommendation regarding the optimal regimen of levetiracetam (LEV) for the prevention of busulfan-induced seizure (BIS) in patients undergoing hematopoietic stem cell transplantation (HSCT).. Published articles by searching databases (PubMed, Google Scholar, Cochrane Library, ScienceDirect) were reviewed. All types of original studies performed in pediatric and adult populations have been investigated and required data was extracted.. Eleven articles were eligible to be included in this review. A loading dose was not used in any of the studies. LEV had been started from 6 to 48 h before busulfan (Bu) initiation and continued up to 24 to 48 h after its termination. The dose range of LEV was 10 to 20 mg/kg/day divided every 12 h in pediatrics and 500 to 1000 mg twice daily in adults. Both oral and intravenous (IV) routes of administration were used. Except for three studies, no seizure had occurred in patients who had received LEV.. Considering the available evidence, LEV with the dose range from 500 to 1000 mg twice daily in adults and 10 mg/kg twice daily (20 mg/kg/day in 2 divided doses) in children orally or IV started from 6 to 24 h before Bu initiation up to 24 to 48 h after the last dose of Bu seems to prevent BIS appropriately. More prospective clinical trials with a larger population are needed to validate the optimal dosing of LEV for BIS prophylaxis in patients undergoing HSCT.

Topics: Adult; Busulfan; Child; Hematopoietic Stem Cell Transplantation; Humans; Levetiracetam; Prospective Studies; Seizures; Transplantation Conditioning

Medical treatment is the primary therapy option for patients with epilepsy. Recently, the International League Against Epilepsy (ILAE) proposed that the current medications used to treat epilepsy should be referred to as 'antiseizure medications' (ASMs) due to the symptomatic effect exerted against seizures. The present article reviews the recent clinical practice guidelines (Clinical Practice Guidelines for Epilepsy 2018, in Japan, and the NICE guideline, published in April 2022) and expert opinions (USA, South Korea, and Spain) based on which the selection of ASMs has been discussed. The classification of seizure types and epilepsies should be examined before selecting the ASMs for each patient with epilepsy. For focal epilepsy, lamotrigine, levetiracetam, and lacosamide would be the first-line ASM, whereas, for generalized epilepsy, valproic acid, lamotrigine, and levetiracetam would be the first-line ASM. However, valproic acid is not to be prescribed to women of childbearing potential.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Seizures; Valproic Acid

The late onset myoclonic epilepsy in Down Syndrome (LOMEDS) is a peculiar epilepsy type characterized by cortical myoclonus and generalized tonic-clonic seizures (GTCS), in people suffering from cognitive decline in Down syndrome (DS). In this review, we analyzed available data on the diagnostic and therapeutic management of individuals with LOMEDS.. We performed a systematic search of the literature to identify the diagnostic and therapeutic management of patients with LOMEDS. The following databases were used: PubMed, Google Scholar, EMBASE, CrossRef. The protocol was registered on PROSPERO (registration code: CRD42023390748).. Data from 46 patients were included. DS was diagnosed according to the patient's clinical and genetic characteristics. Diagnosis of Alzheimer's dementia (AD) preceded the onset of epilepsy in all cases. Both myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were reported, the latter preceding the onset of MS in 28 cases. EEG was performed in 45 patients, showing diffuse theta/delta slowing with superimposed generalized spike-and-wave or polyspike-and-wave. A diffuse cortical atrophy was detected in 34 patients on neuroimaging. Twenty-seven patients were treated with antiseizure medication (ASM) monotherapy, with reduced seizure frequency in 17 patients. Levetiracetam and valproic acid were the most used ASMs. Up to 41% of patients were unresponsive to first-line treatment and needed adjunctive therapy for seizure control.. AD-related pathological changes in the brain may play a role in LOMEDS onset, although the mechanism underlying this phenomenon is still unknown. EEG remains the most relevant investigation to be performed. A significant percentage of patients developed a first-line ASM refractory epilepsy. ASMs which modulate the glutamatergic system may represent a good therapeutic option.

Topics: Alzheimer Disease; Anticonvulsants; Down Syndrome; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Epilepsy, Generalized; Humans; Levetiracetam; Seizures

To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.. Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).. Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).. All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.

Topics: Anticonvulsants; Child; Epilepsy, Generalized; Ethosuximide; Humans; Levetiracetam; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Topiramate; Valproic Acid

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizure

Topics: Anticonvulsants; Consensus; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenytoin; Seizures

Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.. 1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.. We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.. We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.. Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.. We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizure. Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.

Topics: Adolescent; Adult; Child; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Phenobarbital; Phenytoin; Seizures

To evaluate and synthesize the evidence and knowledge gaps on primary prevention and treatment of post-stroke acute symptomatic seizures (ASSs) using antiseizure medications (ASMs).. We systematically searched of EMBASE, MEDLINE (accessed from PubMed), and the Cochrane Central Register of Controlled Trials (CENTRAL) to include randomized, double- or single-blinded trials (RCTs) on primary prophylaxis and treatment of post-stroke ASSs with ASMs. The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.. Two placebo-controlled RCTs (totaling 114 participants) evaluating valproate or levetiracetam as primary prophylaxis of ASSs due to hemorrhagic stroke were included. In one RCT, post-stroke ASS occurred in 1/36 patients (2.7%) on valproate and in 4/36 patients (7%) on placebo (p = 0.4). In the other RCT, ASSs were only electrographic and occurred in 3/19 (16%) with levetiracetam and in 10/23 (43%) with placebo (p = 0.043). We found no RCTs on the treatment of post-stroke ASSs or discontinuation of ASMs administered for the treatment of post-stroke ASSs.. Evidence to support primary prophylaxis of ASSs is sparse and of very low quality and is insufficient to recommend it routinely. Secondary prevention of post-stroke ASSs is usually not recommended except in selected cases (the most relevant being acute symptomatic status epilepticus, which carries a high risk of subsequent poststroke seizures (PSE)). The choice of which ASM to administer and for how long is not based on solid RCT evidence. Management of post-stroke PSE should be done according to an evidence-based framework, considering the individuality of the patient and the pharmacological properties of the drugs.

Topics: Anticonvulsants; Humans; Levetiracetam; Primary Prevention; Seizures; Systematic Reviews as Topic; Valproic Acid

We systematically compared the effects of prophylactic anticonvulsant drug use in patients with traumatic brain injury. We searched four electronic databases from their inception until July 13, 2021. Two researchers independently screened, appraised, and extracted the included studies. Network meta-analysis using multivariate random effects and a frequentist framework was adopted for data analysis. The risk of bias of each study was assessed using the Cochrane risk of bias tool, and confidence in evidence was assessed through confidence in network meta-analysis (CINeMA). A total of 11 randomized controlled trials involving 2,450 participants and six different treatments (i.e., placebo, carbamazepine, phenytoin, levetiracetam, valproate, and magnesium sulfate) were included. We found that anticonvulsant drugs as a whole significantly reduced early posttraumatic seizures (PTS) but not late PTS compared with placebo (odd ratios [ORs] = 0.42 and 0.82, 95% confidence intervals [CIs] = 0.21-0.82 and 0.47-1.43). For the findings of network meta-analysis, we observed that phenytoin (ORs = 0.43 and 0.71; 95% CIs = 0.18-1.01 and 0.23-2.20), levetiracetam (ORs = 0.56 and 1.58; 95% CIs = 0.12-2.55 and 0.03-84.42), and carbamazepine (ORs = 0.29 and 0.64; 95% CIs = 0.07-1.18 and 0.08-5.28) were more likely to reduce early and late PTS compared with placebo; however, the treatment effects were not significant. Sensitivity analysis, after excluding a study enrolling only children, revealed that phenytoin had a significant effect in preventing early PTS (OR = 0.33; 95% CI = 0.14-0.78). Our findings indicate that no antiepileptic drug had an effect on early or late PTS superior to that of another; however, the sensitivity analysis revealed that phenytoin might prevent early PTS. Additional studies with large sample sizes and a rigorous design are required to obtain high-quality evidence on prophylactic anticonvulsant drug use in patients with traumatic brain injury.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Carbamazepine; Child; Humans; Levetiracetam; Network Meta-Analysis; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures

Epileptic myoclonus or myoclonic seizures can occur in idiopathic generalized epilepsy (IGE) and progressive myoclonus epilepsy (PME). However, symptomatic myoclonus which is stimulus-sensitive and provoked by movement is typically seen in PME and Lance-Adams syndrome. Symptomatic myoclonus is not always associated with epileptiform discharges on the electroencephalogram. Therapeutic interventions such as anti-seizure medications (ASMs), the ketogenic diet and vagus nerve stimulation are not always effective. There is emerging evidence that perampanel (PER), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, may be effective for the treatment of myoclonic seizures and symptomatic myoclonus. We performed a systematic review of the literature to assess the efficacy of PER as treatment for myoclonic seizures and symptomatic myoclonus. Twenty-seven studies with a total sample size of 260 patients were included. The efficacy of PER was analysed separately for myoclonic seizures and symptomatic myoclonus. In the group with myoclonic seizures, 50% responder, 75% responder and seizure freedom rates were reported as 74.3% (101/ 136), 60.3% (82/136) and 57.4% (78/136), respectively, with a follow-up duration of 6-12 months. However, in one post-hoc analysis of data from patients with IGE, the efficacy of PER as treatment for myoclonic seizures during the double-blind phase showed no significant difference compared to placebo. The efficacy of PER for symptomatic myoclonus was reported in a total of 119 patients. Four studies (n=88 patients) reported the efficacy of PER as a decrease in myoclonus score/scale. In the remaining 31 patients, symptomatic myoclonus resolved in three patients, decreased in 21 patients and seven patients showed no improvement. We also analysed the number of patients who were already on levetiracetam (LEV) or valproic acid (VPA) at the time of PER initiation; these data were available for 153 patients. Of these, 56.8% were on LEV and 75.1% were on VPA when PER was initiated. This systematic review suggests that PER maybe effective as treatment for drug-resistant myoclonic seizures and symptomatic myoclonus. It may also be effective in patients who have already failed to respond to LEV and VPA. These findings are preliminary yet encouraging. This study has several limitations, particularly given the scarcity of high-quality randomized controlled trials and marked heterogeneity regarding the type and results of

Topics: Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Immunoglobulin E; Levetiracetam; Myoclonic Epilepsies, Progressive; Myoclonus; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome; Valproic Acid

A concise review of recent findings in brain tumor-related epilepsy (BTRE), with focus on the effect of antitumor treatment on seizure control and the management of antiepileptic drugs (AEDs).. Isocitrate dehydrogenase mutation and its active metabolite d -2-hydroxyglutarate seem important contributing factors to epileptogenesis in BTRE. A beneficial effect of antitumor treatment (i.e. surgery, radiotherapy, and chemotherapy) on seizure control has mainly been demonstrated in low-grade glioma. AED prophylaxis in seizure-naïve BTRE patients is not recommended, but AED treatment should be initiated after a first seizure has occurred. Comparative efficacy randomized controlled trials (RCTs) are currently lacking, but second-generation AED levetiracetam seems the preferred choice in BTRE. Levetiracetam lacks significant drug-drug interactions, has shown favorable efficacy compared to valproic acid in BTRE, generally causes no hematological or neurocognitive functioning adverse effects, but caution should be exercised with regard to psychiatric adverse effects. Potential add-on AEDs in case of uncontrolled seizures include lacosamide, perampanel, and valproic acid. Ultimately, in the end-of-life phase when oral intake of medication is hampered, benzodiazepines via nonoral administration routes are potential alternatives.. Management of seizures in BTRE is complex and with currently available evidence levetiracetam seems the preferred choice. Comparative efficacy RCTs in BTRE are warranted.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Epilepsy; Humans; Isocitrate Dehydrogenase; Lacosamide; Levetiracetam; Seizures; Valproic Acid

Many clinical interventions are trialled to manage medical complications following Traumatic Brain Injury (TBI). However, published evidence for the effects of those clinical interventions is limited. This article is an overview of common complications and their management from published systematic reviews in TBI.. A health science electronic database search for published systematic reviews for management of common complications in TBI was conducted in the last decade till 31st January 2021. Methodological quality and evidence were critically appraised using the Grading of Recommendations, Assessment, Development and Evaluations and Revised-Assessment of Multiple Systematic review tools. Overall, only six systematic reviews complied with search criteria, these evaluated fatigue, spasticity and post traumatic seizures (29 RCTs, 13 cohort studies, n = 5639 participants). No systematic reviews for other common TBI-related complications met criteria for this review. The included reviews varied from 'moderate to high' in methodological quality. The findings suggest beneficial treatment effect of anti-epileptic drugs (phenytoin/levetiracetam) compared with placebo in reducing early seizure incidence, but no significant benefit of phenytoin over levetiracetam, valproate, or neuroprotective agent for early or late posttraumatic seizures. There was 'limited' evidence for spasticity-related interventions, and 'insufficient' evidence of cardiorespiratory training on fatigue levels.. Despite the high prevalence and associated functional impact of TBI-related complications, there is limited evidence to guide treating clinicians for management of common TBI complications. More robust studies are needed to build evidence in this population.

Topics: Brain Injuries, Traumatic; Fatigue; Humans; Levetiracetam; Phenytoin; Seizures; Systematic Reviews as Topic

Among autonomic seizures apnea still represent a challenge for physicians, and it might constitute the only isolated sign of neurological disorder. The aim of this review is to describe ictal apnea (IA) and its treatment options.. MeSH and keywords were combined: "neonatal seizures", "ictal neonatal apnea", "apneic seizures". All identified papers were screened for neonatal seizures titles and abstracts; case reports describing patients with IA as an isolated manifestation of neonatal seizures were included.. Eight studies including a total of 13 patients were identified. Among 13 patients, 9 were full-term and 4 were preterm neonates. All patients developed IA within twenty-one days from birth. Etiologies of seizures included: temporal lobe hemorrhage (3 pt), occipital stroke (1 pt), hypoxic-ischemic encephalopathy (HIE) (1 pt), parasagittal injury (1 pt), 18 trisomy (2 pt). Five patients showed no structural CNS alterations. Ten patients had the ictal focus localized in the temporal lobe; the occipital lobe was the second most involved site. Phenobarbital was administered in 76 % of cases with IA (10 pt), and showed efficacy in 74 % of them; 2 required a second anti-epileptic drug (AED) to reach seizure control. Levetiracetam was given to 11 % (2 pt) successfully. Only one was treated with midazolam and one did not require any anticonvulsant.. Not homogeneous data and paucity of isolated IA currently reported in literature limits agreement about definition, management and treatment of entity, however an ever-growing attention is needed, and EEG/aEEG, despite their possible controversies in the diagnosis, should be performed to investigate unexplained forms of apnea.

Topics: Apnea; Electroencephalography; Humans; Infant, Newborn; Levetiracetam; Midazolam; Seizures

Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.. All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.. Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.. Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.

Topics: Adult; Anticonvulsants; Benzodiazepines; Child; Drug Resistance; Humans; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus; Treatment Outcome; Valproic Acid

Status epilepticus is defined as the situation resulting from the failure of the mechanisms responsible for terminating an epileptic seizure. In 2015, an operational concept was adopted internationally in which two times are identified: a first time, at which treatment must begin (five minutes for convulsive status, 10-15 minutes for focal and non-convulsive status); and a second time, after which there is considered to be a high risk of subsequent sequelae (30 minutes in the case of the convulsive). It occurs in 3-42/100,000 children per year, who are refractory or super-refractory in 10-40% of cases.. This article will review the different therapeutic options for status, from early treatment at home to the different first-line (benzodiazepines), second-line (phenobarbital, valproic acid, phenytoin, levetiracetam and lacosamide) or third-line treatments, which include both pharmacological (anaesthetics, propofol, ketamine, lidocaine, topiramate, brivaracetam or perampanel) and non-pharmacological (ketogenic diet, immunomodulatory treatments or epilepsy surgery) therapies.. Early identification and treatment of a prolonged crisis are essential to prevent progression to status. Although with fewer sequelae than in adults, status epilepticus in children represents a cause of mortality of up to 3-5%, while 25% of them will develop subsequent epilepsy, as well as a considerable percentage of neurological sequelae.. Estado epiléptico pediátrico.. Introducción. El estado epiléptico se define como la situación resultante del fallo de los mecanismos responsables de finalizar una crisis epiléptica. En 2015, se adoptó internacionalmente un concepto operativo en el que se identifican dos tiempos: un primer momento, en el que hay que comenzar un tratamiento (cinco minutos para los estados convulsivos, 10-15 minutos para los estados focales y no convulsivos); y un segundo tiempo, a partir del cual se considera que hay un riesgo elevado de secuelas posteriores (30 minutos en los convulsivos). Ocurre en 3-42/100.000 niños al año, y son refractarios o superrefractarios en el 10-40% de las ocasiones. Desarrollo. En este artículo se revisarán las diferentes opciones terapéuticas del estado, desde el tratamiento precoz domiciliario hasta los diferentes tratamientos de primera línea (benzodiacepinas), segunda línea (fenobarbital, ácido valproico, fenitoína, levetiracetam y lacosamida) o tercera línea, que incluyen tanto terapias farmacológicas (anestésicos, propofol, cetamina, lidocaína, topiramato, brivaracetam o perampanel) como no farmacológicas (dieta cetógena, tratamientos inmunomoduladores o cirugía de epilepsia). Conclusiones. Son fundamentales la identificación y el tratamiento precoz de una crisis prolongada para evitar la evolución a estado. Aunque con menores secuelas que en los adultos, el estado epiléptico en niños representa una causa de mortalidad hasta del 3-5%, al mismo tiempo que un 25% de ellos desarrollará una epilepsia posterior, así como un porcentaje considerable de secuelas neurológicas.

Topics: Adult; Anesthetics; Anticonvulsants; Benzodiazepines; Child; Epilepsy; Humans; Ketamine; Lacosamide; Levetiracetam; Lidocaine; Phenobarbital; Phenytoin; Propofol; Seizures; Status Epilepticus; Topiramate; Valproic Acid

Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures.. To evaluate the efficacy of Levetiracetam in the management of neonatal seizures.. The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences.. Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB.. Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.

Topics: Adult; Anticonvulsants; Child; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear.. A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged < 18 years), preclinical, reviews, case reports, and articles that included patients with a preexisting seizure condition or epilepsy were excluded. The coprimary meta-analyses examined first seizure events in (1) levetiracetam versus no antiseizure medication and (2) levetiracetam versus other antiseizure medications in all ICH, TBI, SAH, and supratentorial neurosurgery populations. Secondary meta-analyses evaluated the same comparator groups in individual disease populations. Risk of bias in non-randomised studies - of interventions (ROBINS-I) and risk-of-bias tool for randomized trials (RoB-2) tools were used to assess risk of bias.. A total of 30 studies (n = 6 randomized trials, n = 9 prospective studies, and n = 15 retrospective studies), including 7609 patients (n = 4737 with TBI, n = 701 with SAH, n = 261 with ICH, and n = 1910 with neurosurgical diseases) were included in analyses. Twenty-seven of 30 (90%) studies demonstrated moderate to severe risk of bias, and 11 of 30 (37%) studies used low-dosage levetiracetam (250-500 mg twice daily). In the primary meta-analyses, there were no differences in seizure events for levetiracetam prophylaxis (n = 906) versus no antiseizure medication (n = 2728; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.53-1.16, P = 0.23, fixed-effect, I. Based on the current moderately to seriously biased heterogeneous data, which frequently used low and possibly subtherapeutic doses of levetiracetam, our meta-analyses did not demonstrate significant reductions in seizure incidence and neither supports nor refutes the use of levetiracetam prophylaxis in TBI, SAH, or ICH. Levetiracetam may be preferred post supratentorial neurosurgery. More high-quality randomized trials of prophylactic levetiracetam are warranted.

Topics: Adolescent; Anticonvulsants; Child; Humans; Levetiracetam; Prospective Studies; Retrospective Studies; Seizures

Topics: Anticonvulsants; Death; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures

Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the American Stroke Association, but practice variation still exists due to inconclusive data. We performed a meta-analysis to assess the current relevant literature to determine the efficacy of seizure prophylaxis following ICH.. We performed searches of PubMed, Scopus, and Embase up to September 15, 2020. We included observational and randomized controlled studies reporting seizure prophylaxis and occurrence in adults with ICH. Outcomes were seizures, as defined by the authors, within 14 days of ICH and at the longest point of follow-up. We used random-effects models to estimate the odds ratios (ORs) for seizure prophylaxis and outcomes. The PROSPERO registration was CRD42019140493.. We included 8 studies (2852 patients) in our analysis. The mean (± standard deviation) age of the pooled patients was 65 (±4) years; 39 % (± 5%) were female. Seizure prophylaxis did not prevent seizures at the longest follow-up time (OR 0.708, 95 % CI 0.438-1.143, p = 0.158, I2 = 34 %). This result was confirmed in subgroup analyses using categorical variables and in meta-regressions using continuous variables. Additionally, seizure prophylaxis was not associated with preventing early seizures, defined as < 14 days of ICH (OR 0.66, 95 % CI 0.21-2.08, p = 0.48, I2 = 35 %).. Seizure prophylaxis following ICH was not associated with seizure prevention in adults. Most included studies were observational. Further randomized controlled trials examining the efficacy of seizure prophylaxis in high-risk patients and different types of antiepileptic drugs are needed.

Topics: Aged; Anticonvulsants; Cerebral Hemorrhage; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures

Frequency of clinical seizures may be as high as 16% in patients with spontaneous intracerebral hemorrhage (ICH). Current guidelines recommend against antiepileptic drug (AED) prophylaxis, but this recommendation is based on older trials, and the effect of newer AEDs is uncertain. The aim of this review was to study effects of AEDs on seizure occurrence and outcome in patients with spontaneous ICH.. We searched key databases using combinations of the following terms: "levetiracetam," "prophylaxis," "ICH," "intracerebral hemorrhage," "intraparenchymal hemorrhage." Selected studies were reviewed for level of evidence and overall quality of data using Grading of Recommendations, Assessment, Development and Evaluations criteria. A meta-analysis was performed to evaluate seizure prevention, functional outcome, and mortality in patients with seizure prophylaxis compared with no prophylaxis following spontaneous ICH.. Seven articles met inclusion criteria and were graded level III studies. Administration of AEDs was not associated with reduced seizure risk (odds ratio 1.14, 95% confidence interval 0.47-2.77, P = 0.77). There was an association between AED prophylaxis and poor functional outcome (odds ratio 1.65, 95% confidence interval 1.17-2.31, P = 0.004) but not mortality (odds ratio 1.04, 95% confidence interval 0.62-1.72, P = 0.89). The overall quality of evidence using Grading of Recommendations, Assessment, Development and Evaluations criteria was low.. This systematic review and meta-analysis including recent studies focusing on newer AEDs supports the 2015 guidelines regarding AED use in spontaneous ICH. There are some important caveats, including a possible confounding association between AED use and higher ICH score and the overall poor quality of the available data. A randomized clinical trial may be helpful.

Topics: Anticonvulsants; Cerebral Hemorrhage; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

There is no definite proven or accepted strategy in the management of patients with focal epilepsy uncontrolled by the first anti-seizure medication (ASM). Clinical studies failed to find a significant difference in efficacy or tolerability between alternative monotherapy and/or adjunctive therapy in these patients. A second ASM is often added, the efficacy of the combination is assessed, and the dose of the first drug can be gradually reduced and withdrawn. If seizures recur, the effective combination therapy can be reinstated. In this review, we discussed experimental and clinical data about the efficacy and tolerability of the most frequently used combinations of ASMs. Animal studies suggested that the most favorable combinations are those between ASMs with different or multiple mechanisms of action, whereas combining drugs with similar pharmacodynamic properties is often associated with additive or infra-additive efficacy and additive or synergistic toxicity. Clinical studies have shown that levetiracetam (LEV) can be favorably combined with the sodium channel blockers (SCBs) lacosamide (LCM) and lamotrigine (LTG). Lamotrigine is particularly effective when associated with valproate (VPA) and possibly with LEV and topiramate (TPM). Carbamazepine (CBZ) has negative pharmacokinetic interactions with several ASMs and should not be combined with other SCBs; it could be effectively and safely combined with gabapentin (GBP) and LEV. Valproic acid has enzyme inhibiting properties and can be cautiously used with SCBs; its combination with TPM or zonisamide (ZNS) may be associated with higher toxicity.

Topics: Animals; Anticonvulsants; Epilepsy; Humans; Lamotrigine; Levetiracetam; Seizures

To assess the effectiveness and safety of levetiracetam when used as first-line treatment of neonatal seizures.. Four electronic databases, Medline, Embase, Web of Science, and ClinicalTrials.gov were systematically searched from inception until 20th November 2020. Randomized controlled trials (RCTs) and observational studies that included neonates born preterm and term were eligible for inclusion. The primary outcome measure was levetiracetam effectiveness, defined as seizure cessation within 24 hours of starting treatment. Secondary outcomes included short-term adverse events, mortality before discharge, and long-term neurodevelopmental outcomes.. Fourteen studies assessing 1188 neonates were included: four RCTs, three observational trials with phenobarbital as the control arm, and seven observational studies of levetiracetam with no control arm. Pooled efficacy of levetiracetam from observational studies was 45% (95% confidence interval [CI] 34-57%) (GRADE - very low). Meta-analysis of RCTs evaluating levetiracetam versus phenobarbital showed that both were equally effective (risk ratio [95% CI] 0.6 [0.30-1.20]) (GRADE - very low). Levetiracetam resulted in a lower risk of short-term adverse events compared to phenobarbital (risk ratio [95% CI] 0.24 [0.06-0.92]) (GRADE - moderate).. Very low certainty of evidence suggests levetiracetam might not be more effective than phenobarbital. Moderate certainty of evidence indicates levetiracetam is associated with a lower risk of adverse events. Future trials on neonatal antiseizure medication therapy should include continuous electroencephalogram (EEG) monitoring as standard of care and enrol a homogenous population with similar seizure aetiology. What this paper adds Levetiracetam is effective in 45% of neonatal seizures. Levetiracetam might not be more effective than phenobarbital. Levetiracetam is likely to be safer than phenobarbital. Evidence available is limited and of very low certainty.

Topics: Anticonvulsants; Humans; Infant, Newborn; Levetiracetam; Seizures

Topics: Adolescent; Adult; Anticonvulsants; Diagnosis, Differential; Electroencephalography; Epilepsy; Ethanol; Female; Humans; Lamotrigine; Levetiracetam; Practice Guidelines as Topic; Seizures; Valproic Acid

Patients with primary brain tumors may present with neuropsychiatric symptoms such as behavioral and personality changes at any point during the disease course. Symptoms may be due to tumor treatment, the disease itself, or due to therapy for symptoms such as seizures. Levetiracetam is an attractive choice of antiepileptic medication because of relatively fewer drug interactions and may be administered through the subcutaneous route. Aggressive behavior in advanced brain tumors can have a profound negative impact on patients and their families and carers, particularly when deteriorating toward death. We report a case of neuropsychiatric symptoms in progressive glioblastoma multiforme while on stable levetiracetam doses, which improved with reduction and cessation of the drug. We review the existing literature on seizures in primary brain tumors, their antiepileptic drug management, and the risk of consequent neuropsychiatric adverse events.

Topics: Anticonvulsants; Death; Humans; Levetiracetam; Piracetam; Seizures

This is an updated version of the Cochrane Review previously published in 2018. The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs).. To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective.. For the latest update we searched the following databases on 29 September 2019: Cochrane Epilepsy Group Specialized Register, CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions.. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group.. Three review authors (JW, JG, YD) independently selected trials for inclusion, extracted data and assessed risk of bias. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots.. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One, three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Only five trials reported incidences of death. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low certainty for all reported outcomes due to methodological issues and variability of comparisons made in the trials.. There is limited, low-certainly evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Topics: Anticonvulsants; Carbamazepine; Craniotomy; Humans; Isoxazoles; Levetiracetam; Phenobarbital; Phenytoin; Piracetam; Postoperative Complications; Randomized Controlled Trials as Topic; Seizures; Valproic Acid; Zonisamide

To date, there has not been a single randomized controlled trial (RCT) conducted to directly compare the efficacy and safety of perampanel to brivaracetam in the adjunctive treatment of focal-onset seizures. This study makes these comparisons through the use of indirect treatment comparison (ITC) methods.. A systematic review was conducted to identify RCTs that evaluated either one of perampanel or brivaracetam in the treatment of patients with focal-onset seizures. The Bucher ITC method was then used to compare efficacy and safety outcomes between perampanel and brivaracetam. Additional subgroup analyses, by levetiracetam usage (prior or concomitant), were conducted.. Eight RCTs (four comparing perampanel to placebo, four comparing brivaracetam to placebo) were included in the ITC. For patients taking concomitant levetiracetam, perampanel showed a significantly better responder rate compared to brivaracetam [relative risk (RR) and 95 % confidence interval (CI): 2.62 (1.15, 5.99)]. For patients who had previously, or never, taken levetiracetam, there was no difference in the responder rate. In the overall population, both perampanel and brivaracetam were more effective than placebo in terms of responder rate, seizure freedom, and secondarily generalized tonic-clonic seizure responder rate; however, for these outcomes, no evidence of a difference between perampanel and brivaracetam was found. Patients taking brivaracetam showed significantly less dizziness compared to patients taking perampanel. No differences for any other safety outcome were found.. Perampanel and brivaracetam are effective for the adjunctive treatment of focal-onset seizures and display similar adverse event profiles. Perampanel demonstrated an improved focal-onset seizure responder rate compared to brivaracetam in patients taking concomitant levetiracetam. This may be due to the similarity in the mechanism of action between brivaracetam and levetiracetam.

Topics: Anticonvulsants; Drug Therapy, Combination; Humans; Levetiracetam; Nitriles; Pyridones; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

The objective of the study was to perform a systematic review and meta-analysis to evaluate the efficacy and safety of levetiracetam (LEV) or phenytoin (PHT) as second-line treatment for status epilepticus (SE).. PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Sciences Literature (LILACS), Scopus, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Google Scholar were assessed for prospective randomized trials comparing LEV with PHT as second-line treatment of SE published from inception until December 18th, 2019. The primary outcome was seizure cessation. Data were analyzed using a random-effects model. Quality analysis was performed using version 2 of the Cochrane risk-of-bias tool (RoB 2). The study protocol was registered on PROSPERO (CRD42020136417).. Nine studies with a total of 1732 patients were included. Overall, seizure cessation occurred in 657 of 887 (74%) of patients in the LEV group and 600 of 845 (71%) in the PHT group. Treatment success did not differ significantly between groups, and the relative risk (RR) was 1.05 (95% confidence interval (CI): 0.98-1.12; I. The use of LEV or PHT as second-line agents after benzodiazepine (BZD) for the treatment of SE was not associated with a difference in seizure cessation. Because there are minimal differences in efficacy at this time, clinicians should consider alternative factors when deciding on an antiepileptic drug (AED).

Topics: Anticonvulsants; Benzodiazepines; Drug Therapy, Combination; Humans; Levetiracetam; Phenytoin; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus; Treatment Outcome

Status epilepticus (SE) is a neurologic emergency with high morbidity and mortality. After many advances in the field, several unanswered questions remain for optimal treatment after the early stage of SE. This narrative review describes some of the important drug trials for SE treatment that have shaped the understanding of the treatment of SE. The authors also propose possible clinical trial designs for the later stages of SE that may allow assessment of currently available and new treatment options. Status epilepticus can be divided into four stages for treatment purposes: early, established, refractory, and superrefractory. Ongoing convulsive seizures for more than 5 minutes or nonconvulsive seizure activity for more than 10 to 30 minutes is considered early SE. Failure to control the seizure with first-line treatment (usually benzodiazepines) is defined as established SE. If SE continues despite treatment with an antiseizure medicine, it is considered refractory SE, which is usually treated with additional antiseizure medicines or intravenous anesthetic agents. Continued seizures for more than 24 hours despite use of intravenous anesthetic agents is termed superrefractory SE. Evidence-based treatment recommendations from high-quality clinical trials are available for only the early stages of SE. Among the challenges for designing a treatment trial for the later stages SE is the heterogeneity of semiology, etiology, age groups, and EEG correlates. In many instances, SE is nonconvulsive in later stages and diagnosis is possible only with EEG. EEG patterns can be challenging to interpret and only recently have consensus criteria for EEG diagnosis of SE emerged. Despite having these EEG criteria, interrater agreement in EEG interpretation can be challenging. Defining successful treatment can also be difficult. Finally, the ethics of randomizing treatment and possibly using a placebo in critically ill patients must also be considered. Despite these challenges, clinical trials can be designed that navigate these issues and provide useful answers for how best to treat SE at various stages.

Topics: Anticonvulsants; Benzodiazepines; Clinical Trials as Topic; Clonazepam; Consensus; Critical Illness; Drug Therapy, Combination; Evidence-Based Medicine; Forecasting; Humans; Levetiracetam; Seizures; Status Epilepticus

BACKGROUND Levetiracetam (LEV) is an anticonvulsant commonly used for treatment of generalized and partial seizure disorder. Some of the common side effects associated with levetiracetam include somnolence, dizziness, headaches, and mood changes. Rhabdomyolysis and increase in creatine kinase (CK) levels is one of the rarely reported effects of LEV. CASE REPORT We report a case of a 22-year-old man admitted for evaluation of new-onset generalized tonic-clonic seizures. The patient was started on levetiracetam 500 mg twice a day, after which his CK levels started to increase, with maximum level of 21 936 IU/L noted on day 5. No improvement in CK levels was observed even with aggressive intravenous hydration. In the absence of any other obvious cause, the persistent elevation in patient's CK levels was suspected to be due to LEV. Our suspicion was supported by significant decrease in CK levels (from 21 936 IU/L to 11 337 IU/L) after about 30 h of discontinuation of LEV. We reviewed cases of LEV-induced rhabdomyolysis reported in the literature over the last decade and found 13 cases with almost similar correlation between initiation of LEV and increase in CK levels. CONCLUSIONS Our case report stresses the importance of close monitoring of CK levels and kidney functions after initiation of LEV, and to consider changing the anticonvulsant medication if CK levels are noted to be significantly high to avoid kidney injury.

Topics: Adult; Anticonvulsants; Headache; Humans; Levetiracetam; Male; Rhabdomyolysis; Seizures; Young Adult

Neurocutaneous melanosis (NCM) is a rare disorder characterised by giant or multiple melanocytic nevi and meningeal melanosis or melanoma. Onset of neurological symptoms is typically in children younger than 2 years and can be rapidly fatal. We present the case of a 13-year-old adopted girl presenting with numerous congenital melanocytic nevi and a seizure. She had no significant previous neurological history. Electroencephalogram showed epileptiform discharges over the right frontal region. MRI of the brain showed T1 hyperintensity in the bilateral amygdala and anterior temporal lobes with corresponding hyperintensity on T2 and fluid attenuated inversion recovery. There was no hydrocephalus. Along with the history of nevi, these imaging findings were concerning for NCM. The patient is being managed with levetiracetam and trametinib and shows no further neurological decline at 1-year follow-up, providing prognostic hope in this case of NCM.

Topics: Adolescent; Amygdala; Anticonvulsants; Electroencephalography; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Melanosis; Mitogen-Activated Protein Kinase Kinases; Neurocutaneous Syndromes; Nevus, Pigmented; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Seizures; Temporal Lobe

Among the most common autonomic signs visible in preterm neonates, apnea can represent the first sign of several neurologic and non-neurologic disorders, and seizure is a relatively infrequent cause. Herein authors present a case of neonatal autonomic apnea, discussing the polygraphic video-EEG features of this pathological entity and the differential diagnosis with central apnea and autonomic apnea.. A female preterm Caucasian infant (29 + 4 weeks' gestational age (GA)), first twin of a twin pregnancy, at birth was intubated and surfactant administration was performed. She was ventilated via invasive ventilation for three days, with subsequent weaning with non-invasive ventilation for other two days, when she stopped requiring any ventilator support. After one week the ventilation weaning, the child presented episodes of cyanosis associated with sudden oxygen desaturation, skin pallor, apnea, and bradycardia. Therefore, the child underwent a continuous video-eeg recording with polygraphic study. The exam showed the presence of apneic episodes with an abrupt and clear start, associated with oxygen desaturation at 70%, with minimal thoracic effort at onset, and then evolving into central apnea. Central apnea lasted about 16 s and presented clear start- and end-points. These episodes were also associated with suppression of the EEG trace in frequency and amplitude, and after about 10 s of central apnea an abrupt decrease of the child's heart rate (more than 50% variation, from 160 bpm to 65 bpm) was recorded. In the suspect of epileptic apneas of autonomic origin, a therapy with oral Levetiracetam, at a starting dose of 10 mg/Kg/day, then increased up to 40 mg/Kg/day, was initiated, and after about 48 h the first administration of the anticonvulsant therapy, no new episodes of cyanosis or electrical apneas were recorded.. Herein the authors suggest to consider the diagnosis of autonomic seizures in those neonates with apneic events associated with EEG suppression. Considering that apnea events are not only present in preterm infants but also in term neonates, it is mandatory to diagnose in this context neonatal seizures for a correct diagnosis and a proper therapeutic choice.

Topics: Anticonvulsants; Apnea; Autonomic Nervous System Diseases; Bradycardia; Cyanosis; Diagnosis, Differential; Diseases in Twins; Electroencephalography; Female; Gestational Age; Humans; Hypoxia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Levetiracetam; Seizures; Sleep Apnea, Central; Video Recording

OBJECTIVEDe novo seizure following craniotomy (DSC) for nontraumatic pathology may adversely affect medical and neurological outcomes in patients with no history of seizures who have undergone craniotomies. Antiepileptic drugs (AEDs) are commonly used prophylactically in patients undergoing craniotomy; however, evidence supporting this practice is limited and mixed. The authors aimed to collate the available evidence on the efficacy and tolerability of levetiracetam monotherapy and compare it with that of the classic AED, phenytoin, for DSC.METHODSPubMed, Embase, Web of Science, and the Cochrane Library were searched for studies that compared levetiracetam with phenytoin for DSC prevention. Inclusion criteria were adult patients with no history of epilepsy who underwent craniotomy with prophylactic usage of phenytoin, a comparator group with levetiracetam treatment as the main treatment difference between the two groups, and availability of data on the numbers of patients and seizures for each group. Patients with brain injury and previous seizure history were excluded. DSC occurrence and adverse drug reaction (ADR) were evaluated. Seizure occurrence was calculated using the Peto odds ratio (POR), which is the relative effect estimation method of choice for binary data with rare events.RESULTSData from 7 studies involving 803 patients were included. The DSC occurrence rate was 1.26% (4/318) in the levetiracetam cohort and 6.60% (32/485) in the phenytoin cohort. Meta-analysis showed that levetiracetam is significantly superior to phenytoin for DSC prevention (POR 0.233, 95% confidence interval [CI] 0.117-0.462, p < 0.001). Subgroup analysis demonstrated that levetiracetam is superior to phenytoin for DSC due to all brain diseases (POR 0.129, 95% CI 0.039-0.423, p = 0.001) and tumor (POR 0.282, 95% CI 0.117-0.678, p = 0.005). ADRs in the levetiracetam group were cognitive disturbance, thrombophlebitis, irritability, lethargy, tiredness, and asthenia, whereas rash, anaphylaxis, arrhythmia, and hyponatremia were more common in the phenytoin group. The overall occurrence of ADR in the phenytoin (34/466) and levetiracetam (26/432) groups (p = 0.44) demonstrated no statistically significant difference in ADR occurrence. However, the discontinuation rate of AEDs due to ADR was 53/297 in the phenytoin group and 6/196 in the levetiracetam group (POR 0.266, 95% CI 0.137-0.518, p < 0.001).CONCLUSIONSLevetiracetam is superior to phenytoin for DSC prevention for nontra

Topics: Anticonvulsants; Craniotomy; Humans; Levetiracetam; Phenytoin; Postoperative Complications; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

The aim of the current study was to systematically review the literature to compare the efficacy of levetiracetam (LEV) with that of carbamazepine (CBZ) to control seizures and reduce the burden of interictal epileptiform discharges in children with rolandic epilepsy (RE) and also to compare their tolerability.. We searched the electronic database PubMed on January 9, 2019 for original articles that included the following English-language search terms in the title: "Rolandic epilepsy" OR "benign childhood epilepsy with centrotemporal spikes" since 2000. We concentrated our review on three main areas: 1. Neuropsychological impairments in children with RE; 2. Influence of epileptic activity on cognitive performance in RE; 3. Effects of antiepileptic drug (AED) therapies in RE.. The primary search yielded 308 papers. We reviewed the results and removed duplicate articles and all nonoriginal, non-English papers. Finally, after carefully reviewing the full texts, we included 44 original articles to achieve the aims of this review.. Physicians taking care of children with RE should be aware of the risks for cognitive dysfunctions in these patients and screen their patients for any subtle dysfunction that may affect their academic performance and achievement. If and when the physician decides to prescribe an AED for their patients with RE, LEV is probably a better option compared with CBZ to prescribe for these children.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Child; Electroencephalography; Epilepsy, Rolandic; Humans; Levetiracetam; Seizures

Epilepsy is a common neurological disease that affects approximately 1% of the UK population. Approximately one-third of these people continue to have seizures despite drug treatment. Pregabalin is one of the newer antiepileptic drugs which have been developed to improve outcomes.This is an updated version of the Cochrane Review published in Issue 3, 2014, and includes three new studies.. To assess the efficacy and tolerability of pregabalin when used as an add-on treatment for drug-resistant focal epilepsy.. For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), on 5 July 2018, MEDLINE (Ovid, 1946 to 5 July 2018), ClinicalTrials.gov (5 July 2018), and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 5 July 2018), and contacted Pfizer Ltd, manufacturer of pregabalin, to identify published, unpublished, and ongoing trials.. We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug as an add-on for people of any age with drug-resistant focal epilepsy. Double-blind and single-blind trials were eligible for inclusion. The primary outcome was 50% or greater reduction in seizure frequency; secondary outcomes were seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse effects, and proportion of individuals experiencing adverse effects.. Two review authors independently selected and assessed trials for eligibility and extracted data. Analyses were by intention-to-treat. We presented results as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CIs). Two review authors assessed the included studies for risk of bias using the Cochrane 'Risk of bias' tool.. We included nine industry-sponsored randomised controlled trials (3327 participants) in the review. Seven trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42, 7 trials, 2193 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65, 7 trials, 2193 participants, moderate-certainty evidence) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74, 7 trials, 2193 participants, moderate-certainty evidence).Three trials compared pregabalin to three active-control drugs: lamotrigine, levetiracetam, and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12, 1 trial, 293 participants) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11, 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12, 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We found no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin versus lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; versus levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; versus gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue were significantly associated with pregabalin.We rated the overall risk of bias in the included studies as low or unclear due to the possibility of. Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, is significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, however issues with tolerability were noted at higher doses. The trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision making.

Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Gabapentin; Humans; Lamotrigine; Levetiracetam; Pregabalin; Randomized Controlled Trials as Topic; Seizures

Very little has been written on seizure management in palliative care (PC). Given this situation, and considering the forthcoming setting up of the Palliative Care Unit at our neurorehabilitation centre, the Clínica San Vicente, we decided to establish a series of guidelines on the use of antiepileptic drugs (AEDs) for handling seizures in PC.. We conducted a literature search in PubMed to identify articles, recent manuals, and clinical practice guidelines on seizure management in PC published by the most relevant scientific societies.. Clinical practice guidelines are essential to identify patients eligible for PC, manage seizures adequately, and avoid unnecessary distress to these patients and their families. Given the profile of these patients, we recommend choosing AEDs with a low interaction potential and which can be administered by the parenteral route, preferably intravenously. Diazepam and midazolam appear to be the most suitable AEDs during the acute phase whereas levetiracetam, valproic acid, and lacosamide are recommended for refractory cases and long-term treatment.. These guidelines provide general recommendations that must be adapted to each particular clinical case. Nevertheless, we will require further well-designed randomised controlled clinical trials including large samples of patients eligible for PC to draft a consensus document recommending adequate, rational, and effective use of AEDs, based on a high level of evidence, in this highly complex area of medical care.

Topics: Anticonvulsants; Carbamazepine; Guidelines as Topic; Humans; Levetiracetam; Palliative Care; Seizures; Valproic Acid

To report the results of a combined case series analysis of subcutaneous levetiracetam (Keppra) for the management of seizures in palliative care patients.. A comprehensive literature review on the use of subcutaneous levetiracetam was performed, and these data were combined with a prospective observational audit of its use in terminal care undertaken in a regional palliative care network.. 7 papers were identified from the literature review-four case reports and three observational case series-reporting on a total of 53 cases where subcutaneous levetiracetam was administered.We report 20 further cases of subcutaneous levetiracetam administration from a prospective observational audit. Doses ranged from 250mg to 4000 mg daily. Oral to subcutaneous conversion ratios where stated were 1:1. Levetiracetam was reported as the sole administered antiepileptic drug (AED) in eight cases, and no seizures were reported until death in five cases. Five were switched back to enteral levetiracetam. In seven cases, levetiracetam was combined with AEDs to provide seizure control at the end of life. There was one report of a sterile abscess after 25 days of continuous subcutaneous administration.. Combined analysis of 73 reported cases of subcutaneous levetiracetam suggests this treatment may have a role in the management of seizures at the end of life. However, randomised controlled trials are urgently needed to establish the efficacy and tolerability of subcutaneous levetiracetam administration. If proven to be safe and effective, subcutaneous levetiracetam offers the potential to prevent and treat seizures without causing unnecessary sedation at the end of life.

Topics: Anticonvulsants; Disease Management; Humans; Infusions, Subcutaneous; Levetiracetam; Palliative Care; Piracetam; Seizures; Terminal Care; Treatment Outcome

Seizures occur commonly in cats and can be classified as idiopathic epilepsy, structural epilepsy, or reactive seizures. Pursuit of a diagnosis may include a complete blood count, serum biochemistry, brain MRI, and cerebrospinal fluid analysis as indicated. Antiepileptic drugs should be considered if a cat is having frequent seizures, or any 1 seizure longer than 5 minutes. Phenobarbital is often the drug of choice; however, levetiracetam may be more useful for certain types of epilepsy in cats. Long-term prognosis depends on the underlying diagnosis and response to therapy.

Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Epilepsy; Levetiracetam; Phenobarbital; Piracetam; Prognosis; Risk Factors; Seizures

Seizures are the most common neurological complication in neonatal intensive care units. Phenobarbital (PB) remains the first-line antiepileptic drug (AED) for neonatal seizures despite known neurotoxicity. Levetiracetam (LEV) is a newer AED not approved for neonates. Retrospective and pilot studies have investigated the use of LEV in neonatal seizures. Our objective was to compare the efficacy of LEV to PB in neonatal seizures based upon published data.. We searched PubMed to perform a systematic review. We found no studies of LEV with comparison or control groups; therefore, we utilized data from two randomized controlled trials of PB as our comparison group.. Five studies of LEV met all inclusion/exclusion criteria. The pooled sample size for LEV was 102 (48 received primary LEV, 54 received secondary LEV). The pooled sample size for primary PB was 52. Complete or near-complete seizure cessation was achieved as follows: primary LEV 37/48 (77%), secondary LEV 34/54 (63%), and primary PB 24/52 (46%).. Our findings suggest that LEV may be at least as or more effective for neonatal seizures as PB. Our review, though limited, is the first to examine LEV efficacy compared with PB in neonates.

Topics: Anticonvulsants; Humans; Infant, Newborn; Levetiracetam; Piracetam; PubMed; Seizures

A generalized tonic-clonic seizure (GTCS) is the most severe form of common epileptic seizure and carries the greatest risk of harm. The aim of this review is to provide an evidence-based guide for the selection of antiepileptic drugs (AEDs) for patients with GTCSs. Eight AEDs are approved in Europe and the USA for the treatment of both primarily GTCSs (PGTCSs) and secondarily GTCSs (SGTCSs) and are considered in this paper.. Each AED is evaluated using five criteria: (1) efficacy, by seizure type (a: PGTCSs and b: SGTCSs); (2) adverse effects; (3) interactions; (4) adherence and dosing; and (5) mechanism of action (MOA). To ensure the inclusions of robust data, only efficacy data accepted by regulatory authorities were considered, and data related to adverse effects, interactions, adherence, and MOA were all extracted from UK Summaries of Product Characteristics (SPCs).. (1a) There is class 1 evidence of the efficacy of only four AEDs in controlling PGTCSs (lamotrigine, levetiracetam, perampanel, and topiramate). (1b) There is no class 1 evidence of the efficacy of any AED in SGTCSs although some evidence from pooled/subgroup analyses or meta-analyses supports the use of the four AEDs (levetiracetam, perampanel, topiramate, and with less robust data for lamotrigine). (2) AEDs are associated with different, but to some extent overlapping, common adverse effect profiles but have differing idiosyncratic adverse effects. (3) Pharmacokinetic interactions are seen with most, but not all, AEDs and are most common with carbamazepine and phenytoin. (4) Good adherence is important for seizure control and is influenced by frequency of dosing, among other factors. (5) Mechanism of action is also a consideration in rationalising AED selection when switching or combining AEDs.. Ultimately, the choice of AED depends on all these factors but particularly on efficacy and adverse effects. Different patients will weigh the various factors differently, and the role of the treating physician is to provide accurate information to allow patients to make informed choices.

Topics: Anticonvulsants; Benzodiazepines; Carbamazepine; Drug and Narcotic Control; Drug-Related Side Effects and Adverse Reactions; Humans; Lamotrigine; Levetiracetam; Nitriles; Phenytoin; Pyridones; Seizures; Topiramate; Treatment Outcome

This is an updated version of the Cochrane Review previously published in Issue 3, 2015.The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be between 15% to 20%; however, the risk of experiencing a seizure appears to vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials (RCTs).. To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective.. For the latest update we searched the following databases on 26 June 2017: Cochrane Epilepsy Group Specialized Register, the CENTRAL, MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We did not apply any language restrictions.. We included RCTs of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons. We included trials with adequate randomisation methods and concealment; these could either be blinded or unblinded parallel trials. We did not stipulate a minimum treatment period, and we included trials using active drugs or placebo as a control group.. Three review authors (JW, JG, YD) independently selected trials for inclusion and performed data extraction and risk of bias assessments. We resolved any disagreements through discussion. Outcomes investigated included the number of participants experiencing seizures (early (occurring within first week following craniotomy), and late (occurring after first week following craniotomy)), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, we did not combine data from the included trials in a meta-analysis; we presented the findings of the review in narrative format. Visual comparisons of outcomes are presented in forest plots.. We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence.Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability.We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials.. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Topics: Anticonvulsants; Carbamazepine; Craniotomy; Humans; Isoxazoles; Levetiracetam; Phenobarbital; Phenytoin; Piracetam; Postoperative Complications; Randomized Controlled Trials as Topic; Seizures; Valproic Acid; Zonisamide

Early and/or late onset in patients with brain injury (BI) is associated with a poorer prognosis, and phenytoin (PHT) is standard of care to prevent seizures. Levetiracetam (LEV), an alternative antiepileptic drug, is associated with less cognitive disruption. The purpose of this study was to evaluate the safety and efficacy of LEV in the prevention of brain traumatic seizures with the standard drug PHT.. Search the publications on comparison the safety and efficacy of LEV against the standard agent PHT in prevention of traumatic seizures in BI to January 2018. After rigorous reviewing on quality, the data were extracted from eligible trials. All trials analyzed the summary hazard ratios of the endpoints of interest.. LEV was found not more effective than PHT in terms of overall seizure (odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.51-1.05; P = .09), and late seizure (OR = 0.64; 95% CI = 0.34-1.19; P = .16) occurrence. However, there is significant difference in terms of early seizure (OR = 0.63; 95% CI = 0.40-0.99; P = .04). Moreover, there were no significant differences in terms of mortality (OR = 0.67; 95% CI = 0.43-1.05; P = .08), or side effects (OR = 1.31; 95% CI = 0.80-2.15; P = .29) between groups.. The meta-analysis showed that LEV prevention of seizures was associated with early seizure rates that were lower than the PHT-prolonged course of treatment. There is no statistically significant difference in the efficacy and safety profile of PHT and LEV in cases of traumatic BI.

Topics: Anticonvulsants; Brain Injuries; Humans; Levetiracetam; Phenytoin; Seizures

A 55-year-old man with no mental retardation had presented a history of frequent transient clumsiness of his right upper and lower extremities for about 20 years. He was admitted to a general hospital with weakness of right side of the body, and first-ever generalized seizure attack occurred the next day. Brain CT showed calcification in the left cerebral cortices. So he was referred to our hospital. On neurological examination, he had mild clumsiness of his right upper limb and right pyramidal tract sign. He had neither facial port-wine stain nor glaucoma. The blood test and cerebrospinal fluid analysis were unremarkable. Electroencephalogram showed slowing and reduction of activity at the left frontal and parietal areas with no epileptic activities. Brain CT showed "tram-track calcification" and lobar atrophy in the left fronto-parietal cortices. Susceptibility weighted imaging (SWI) on MRI revealed enlarged transmedullary veins in the left periventricular white matter and low intensity lesions along the cortical gyri. Post gadolinium fluid-attenuated inversion recovery imaging (FLAIR-Gd) showed leptomeningeal enhancement in the left fronto-parietal lobes more extensively than those by post gadolinium T

Topics: Administration, Oral; Brain; Humans; Late Onset Disorders; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Seizures; Sturge-Weber Syndrome; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Neonatal seizures are the most common clinical manifestation of Central Nervous System (CNS) dysfunction and are associated with various neurological sequelae. There are currently no evidence-based guidelines for the management of neonatal seizures and currently used drugs such as phenobarbital, and phenytoin have limited efficacy and potential toxicities. Newer second line anticonvulsant, levetiracetam, has been used in refractory neonatal seizures despite limited data and off-label use.. In this review, we will discuss various pharmacological properties of levetiracetam when used in neonatal population.. A PubMed search for MEDLINE was undertaken to look for studies using the terms "Levetiracetam", AND "Neonates" as key words from year 1995 to January 2017. Relevant articles were selected and information was extracted about pharmacokinetics, pharmacodynamics and clinical uses of levetiracetam in neonates.. Levetiracetam is an active, water-soluble S-enantiomer of racemic pyrrolidine acetamide which exerts its antiepileptic action by binding to the synaptic vesicle protein within the brain. Metabolism of levetiracetam does not include the CYP P450 system and it is mainly eliminated through kidneys after rapid absorption. Also, no significant interactions with other drugs have been identified. Unlike other commonly used antiepileptic drugs, levetiracetam is not bound to plasma proteins, thereby, reducing the chances of toxicity and severe, life threatening side effects have not been reported. In fact, it has been shown to prevent neuro-degeneration after hypoxia/ischemia in rodent models of epilepsy.. Levetiracetam has been emerging as a potential therapeutic option for refractory neonatal convulsions owing to its non-hepatic elimination, linear pharmacokinetics, low protein binding and better safety profile.

Topics: Animals; Anticonvulsants; Humans; Infant, Newborn; Levetiracetam; Piracetam; Seizures

Background The onset of early and/or late seizures in brain injured patients is associated with worse outcome. So far, phenytoin is the most commonly used antiepileptic drug to prevent seizures in this group of patients. Objective In the current metaanalysis, we aimed to compare the efficacy and safety of phenytoin versus levetiracetam for seizure prophylaxis in brain injured patients. Methods A systematic search was conducted in PubMed and Cochrane Library Database by 2 investigators. Four randomized controlled trials (RCTs) were included (295 patients). Data were extracted and the quality of each RCT was assessed. Results Levetiracetam was found to be more effective than phenytoin in seizure prophylaxis (OR = 0.23; CI 95% [0.09-0.56]; Q test p value = 0.18 and I

Topics: Anticonvulsants; Brain Injuries; Humans; Levetiracetam; Phenytoin; Piracetam; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Seizures

Seizures are important complications following a subarachnoid hemorrhage (SAH). The evidence for the use of antiepileptic drugs (AEDs) in treatment and prevention of those seizures is conflicting. The purpose of this review is to provide an up-to-date evidence summary of the incidence and outcomes of seizures following an SAH as well as the use of different AEDs post-SAH in order to evaluate the need for seizure prophylaxis, the choice of AEDs, and their dosing considerations in SAH patients. A literature search of PubMed, Medline, Embase, and the Cochrane Library was performed. A total of 37 studies were reviewed, mostly observational. Definitions of seizures in temporal relation to initial hemorrhage were variable. Similarly, the rates of seizures varied in the literature, ranging from 0 to 31%. Given the reported adverse outcomes associated with AED usage, seizure prophylaxis is not warranted. Levetiracetam appears to be better tolerated than phenytoin in SAH patients, though further research is needed. Higher initial dosing of levetiracetam might be required due to its enhanced clearance in SAH patients. In conclusion, there is a lack of quality evidence to definitively recommend the use of one AED over another. Further prospective research comparing the use of different AEDs in patients with an SAH is needed.

Topics: Anticonvulsants; Carbamazepine; Humans; Incidence; Levetiracetam; Phenytoin; Seizures; Subarachnoid Hemorrhage

Epilepsy is significantly more frequent in AD patients than in age-matched controls, even though the true extent of the phenomenon is not clear yet. Areas covered: In this review, we describe in detail the available data on the pharmacological treatment of epilepsy in patients with AD. We also briefly describe general principles of AEDs use in elderly, as well as the potential cognitive profile of AEDs and safety of concomitant psychotropic drugs in patients with epilepsy and AD. Expert commentary: As some preclinical data suggest a role of epileptiform discharges in cognitive decline in AD, a prompt diagnosis and treatment of seizures in these patients should be pursued. The few data on the use of AEDs in AD patients suggest that newer AEDs (in particular lamotrigine and levetiracetam) might be good choices. Experimental data even support a potential role of some AEDs in modifying the disease course of AD.

Topics: Alzheimer Disease; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures

Neonatal crises are a common problem in the first month, where phenobarbital and phenytoin are still the most frequently used medication in treatment. Whereas, Levetiracetam (LEV) is an antiepileptic drug (AED) with an innovative action. Our present review is updated on the current literature regarding the use of LEV in neonatal seizures treatment. The available data is analyzed to assess LEV pharmacokinetics, efficacy and tolerability in neonatal crises treatment. Several clinical trials, prospective and retrospective, comparative and pharmacokinetic studies were evaluated in LEV pharmacokinetics, efficacy, dosage, route of administration and side effects. Many cases were reported on neonatal seizures control in using LEV in certain clinical conditions. In spite of the limitations in current studies available, which have evaluated LEV efficacy and safety in neonatal crises treatment, the authors still believe that LEV seems to be a promising and useful AED in the treatment for neonatal seizures, but likewise further studies are required to better define LEV efficacy and tolerability in term and preterm neonates.

Topics: Anticonvulsants; Humans; Infant, Newborn; Levetiracetam; Piracetam; Seizures; Treatment Outcome

In neurological malignancies, antiepileptic drugs (AEDs) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics (PK) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid (VPA) and carbamazepine have histone deacetylase (HDAC) inhibitory activities, and levetiracetam and VPA reduce the activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA-repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AEDs for purposes other than seizure prophylaxis and their selection based on non-PK properties present a potential paradigm shift in the field of neuro-oncology.

Topics: Animals; Anticonvulsants; Brain Neoplasms; Carbamazepine; Humans; Levetiracetam; Piracetam; Seizures; Valproic Acid

Status epilepticus (SE) requires rapid identification of its cause and urgent pharmacological treatment. Despite an estimated incidence of up to 61 per 100,000 per year, evidence from high-class clinical trials is only available for the early stages of SE.. Following a four-stage approach of SE (early, established, refractory and super-refractory), we present pharmacological treatment options and their clinical utility.. Intravenous lorazepam and intramuscular midazolam appear as most effective treatments for early SE. In children, buccal midazolam has emerged as first-line non-intravenous drug with similar efficacy and safety to other intravenous or rectal benzodiazepines. In established SE intravenous antiepileptic drugs are in use. There are no double-blind, but six randomized open studies with valproate and two with levetiracetam. A meta-analysis found higher rates of seizure cessation with valproate 75.7% (95% CI 63.7-84.8) and phenobarbital 73.6%, (95% CI 58.3-84.8) than with levetiracetam (68.5%, 95% CI 56.2-78.7) or phenytoin (50.2%, 95% CI 34.2-66.1). Based on the favourable tolerability profile of levetiracetam and valproate, the authors prefer these drugs in established SE over phenytoin. Treatment options in refractory SE are intravenous anaesthetics. In super-refractory SE ketamine, magnesium, steroids and other drugs have been used with variable outcomes. At this stage therapeutic decisions are based on doctors' preferences, patient factors such as age and comorbidity, and cause of SE, if identified.

Topics: Anticonvulsants; Benzodiazepines; Humans; Ketamine; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Seizures; Status Epilepticus; Treatment Failure; Valproic Acid

Treatment of epilepsy starts with antiepileptic drug (AED) monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual AEDs is essential for optimal treatment for epilepsy. This article addresses AEDs individually, focusing on key pharmacokinetic characteristics, indications, and modes of use.. Older-generation AEDs are effective but have tolerability and pharmacokinetic disadvantages. Several newer-generation AEDs have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older AEDs as first-line therapy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, and, more recently, zonisamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy. Other newer-generation AEDs with a variety of mechanisms of action are suitable for adjunctive therapy. Rational AED combinations should avoid AEDs with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action.. Knowledge of AED pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate AED therapy for patients with epilepsy.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenytoin; Piracetam; Pregabalin; Seizures; Triazines

The aim of this study was to perform an up-to-date systematic review and meta-analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients.. A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects.. The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta-analysis. The combined results from the meta-analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03-0.42]: χ(2) = 1.76: I(2) = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14-2.99]: χ(2) = 8.79: I(2) = 77%).. The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.

Topics: Anticonvulsants; Craniotomy; Humans; Levetiracetam; Perioperative Care; Phenytoin; Piracetam; Seizures; Supratentorial Neoplasms; Valproic Acid

Topics: Adult; Anticonvulsants; Exanthema; Female; Humans; Levetiracetam; Male; Piracetam; Seizures; Young Adult

Seizures are common complications for patients with brain tumors. No clear evidence exists regarding the use of antiepileptic agents for prophylactic use yet newer agents are being favoured in many clinical settings. The objective of this systematic review was to determine the efficacy of levetiracetam for preventing seizures in patients with brain tumors. A literature search was completed using the databases PubMed (1948 to December 2015), EMBASE (1980 to December 2015), Cochrane Database of Systematic Reviews, and Google Scholar. Studies were included if they reported seizure frequency data pertaining to levetiracetam use in patients with brain tumors as either monotherapy or as an add on agent. The literature search produced 21 articles (3 randomized controlled trials, seven prospective observational studies, and 11 retrospective observational studies). All studies were found to be at high risk of bias. Overall, studies show levetiracetam decreased seizure frequency in brain tumor patients with or without craniotomy. Safety outcomes were also favourable. As such, levetiracetam appears effective for reducing seizures in patients with brain tumors and may be considered a first-line agent. However, there is an urgent need for more high quality prospective data assessing levetiracetam and other antiepileptic drugs in this population.

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Observational Studies as Topic; Piracetam; Prospective Studies; Randomized Controlled Trials as Topic; Reproducibility of Results; Retrospective Studies; Seizures; Treatment Outcome

Pediatric post-traumatic epilepsy incidence varies depending on reporting mechanism and injury severity; anti-epileptic drug (AEDs) use also varies with lack of quality evidence-based data. Adverse AED effects are not negligible; some may negatively affect functional outcome. This review focuses on clarifying available data.. This review discusses seizures associated with traumatic brain injury in children, including seizure incidence, relationship to severity of injury, potential detrimental effects of seizures, potential benefits of AED, adverse effects of AED, new developments in preventing epileptogenesis, and suggested recommendations for patient management. English language papers were identified from PubMed using search terms including but not excluding the following: adverse drug effects, anti-epileptic drugs, children, electroencephalogram, epilepsy, epileptogenesis, head injury, levetiracetam, pediatrics, phenytoin, post-traumatic epilepsy, prevention, prophylaxis, seizures, and traumatic brain injury. Expert commentary: Identification of high-risk patients for post-traumatic seizures is a key goal. Levetiracetam may prevent epileptogenesis, as may other developments.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Child; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

The standard for early traumatic brain injury (TBI) seizure prophylaxis is phenytoin (PHT). Levetiracetam (LEV) has been proposed as an alternative to PHT. The aim of this study was to evaluate the safety and efficacy of LEV on TBI seizure when compared with PHT.. A search was carried out based on the databases from Pubmed, Embase and the Cochrane database up to May 2015. The relative risk (RR) and the relevant 95% confidence intervals (CI) were determined.. Eight observational studies and one randomized controlled trial involving 2035 cases were included. The results indicated that no significant differences in terms of overall seizure (RR = 0.90; 95% CI = 0.51-1.53; p = 0.68), early seizure (RR = 1.06; 95% CI = 0.37-3.07; p = 0.92) and late seizure (RR = 1.10; 95% CI = 0.43-2.79; p = 0.85) occurrence. However, LEV was associated with a lower adverse drug reaction rate (RR = 0.43; 95% CI = 0.23-0.81; p = 0.01). Moreover, there were no significant differences in terms of mortality, length of ICU or hospital stay between groups.. The meta-analysis suggests that LEV appears to have a similar efficacy to PHT on TBI. A better safety profile of LEV is supported by this analysis.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

Seizure following traumatic brain injury (TBI) constitutes a common complication that requires effective prevention to improve the outcome of TBI. Phenytoin has been the only recommended antiepileptic drug (AED) for seizure prophylaxis; however, several shortcomings have affected its use. Intravenous levetiracetam has been available since 2006 and has been increasingly accepted as a seizure prophylaxis for brain injury, mainly due to its favorable pharmacokinetic features and minimal adverse events profile. However, the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI are not well clarified.. The aim of this study was to assess the efficacy and safety of levetiracetam versus phenytoin for seizure prophylaxis following TBI.. We conducted a search of the MEDLINE, EMBASE, and Cochrane library databases to March 2016, and screened original research that included patients with TBI who received levetiracetam. We included randomized controlled trials (RCTs) or controlled observational cohort studies that compared levetiracetam and phenytoin, as well as uncontrolled case series regarding prophylactic levetiracetam following TBI. The outcomes included early or late seizure prophylaxis and safety. The estimates of seizure prophylaxis were pooled using a meta-analysis, and the estimates for the case series were pooled using descriptive statistics.. A total of 1614 patients from 11 studies were included in this review, of whom 1285 patients from eight controlled studies (one RCT and seven cohort studies) were included in the meta-analysis. Levetiracetam was not superior to phenytoin with regard to early seizure prophylaxis (risk ratio [RR] 1.10, 95 % confidence interval [CI] 0.64-1.88); the estimate of early seizure incidence was 0.05 (95 % CI 0.02-0.08). Three studies that assessed late seizure did not indicate the superiority of levetiracetam to phenytoin. There were no differences in mortality during hospitalization or after 6 months, or in the number of patients with adverse reactions between levetiracetam and phenytoin.. Levetiracetam does not appear to be superior to phenytoin in efficacy or safety with regard to early or late seizure prophylaxis following TBI; however, no class I evidence was identified. Additional evidence from high-quality studies is required.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Cohort Studies; Humans; Levetiracetam; Observational Studies as Topic; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures

The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT).. With the assistance of an experienced medical librarian specialized in pharmacy and toxicology, we searched MEDLINE, EMBASE, CINAHL, Web of Science, WorldCat, and Scopus through May 2016.. Four hundred three articles were screened for inclusion, of which 130 were identified as potentially relevant. Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known.. Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations. Known pharmacokinetic parameters should guide dosing, and recommendations are provided where possible.. Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents.

Topics: Acetamides; Acute Kidney Injury; Amines; Anticonvulsants; Carbamates; Critical Illness; Cyclohexanecarboxylic Acids; Dibenzazepines; Dose-Response Relationship, Drug; Ethosuximide; Felbamate; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lacosamide; Lamotrigine; Levetiracetam; Phenobarbital; Phenylcarbamates; Phenylenediamines; Phenytoin; Piracetam; Propylene Glycols; Renal Dialysis; Renal Replacement Therapy; Seizures; Topiramate; Triazines; Valproic Acid; Zonisamide

Topics: Adult; Anticonvulsants; Female; Humans; Levetiracetam; Male; Piracetam; Pyrrolidinones; Seizures

Posttraumatic seizure (PTS) is a significant complication of traumatic brain injury (TBI).. To perform a systematic review and meta-analysis to compare levetiracetam with phenytoin for seizure prophylaxis in patients diagnosed with severe TBI.. An inclusive search of several electronic databases and bibliographies was conducted to identify scientific studies that compared the effect of levetiracetam and phenytoin on PTS. Independent reviewers obtained data and classified the quality of each article that met inclusion criteria. A random effects meta-analysis was then completed.. During June and July 2015, a systematic literature search was performed that identified 6097 articles. Of these, 7 met inclusion criteria. A random-effects meta-analysis was performed. A total of 1186 patients were included. The rate of seizure was 35 of 654 (5.4%) in the levetiracetam cohort and 18 of 532 (3.4%) in the phenytoin cohort. Our meta-analysis revealed no change in the rate of early PTS with levetiracetam compared with phenytoin (relative risk, 1.02; 95% confidence interval, 0.53-1.95; P = .96).. The lack of evidence on which antiepileptic drug to use in PTS is surprising given the number of patients prescribed an antiepileptic drug therapy for TBI. On the basis of currently available Level III evidence, patients treated with either levetiracetam or phenytoin have similar incidences of early seizures after TBI.. ADE, adverse drug eventAED, antiepileptic drugCI, confidence intervalOR, odds ratioPTS, posttraumatic seizureTBI, traumatic brain injury.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

Topics: Anticonvulsants; Brain Injuries; Humans; Levetiracetam; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures

This review provides management recommendations for medical and neurologic problems in patients with brain tumors, including vasogenic edema, infections, seizures, prophylaxis and treatment of venous thromboembolism, drug interactions, cognitive and emotional problems, palliative symptom management, and long-term sequelae of brain tumors and their therapy.. Non-enzyme-inducing antiepileptic drugs are the preferred category of seizure medication for patients with brain tumors, and levetiracetam is emerging as the drug of choice. Select groups of patients, such as those with cortically based hemorrhagic melanoma metastases, may benefit from prophylactic antiepileptic drug use. Antiangiogenic agents can reduce the steroid requirement of patients with vasogenic edema. Patients with brain tumors remain at risk for infections from the perioperative period through many months after treatment, and steroids may mask signs of infection. Few studies have been done on management of common cognitive issues such as short-term memory deficits and fatigue, but memantine may help delay cognitive deficits in patients receiving whole-brain radiation therapy. Palliative care conversations should begin early in the course of treatment.. Meticulous medical management begins at diagnosis of brain tumors and continues through the active treatment course and into either palliative care strategies or management of long-term sequelae of treatment. During the active treatment phase, problems such as vasogenic edema, seizures, and venous thromboembolism predominate, whereas late complications include the continuing risk of infections; sequelae of radiation such as vascular disease, cavernous angiomas, and cognitive decline; and secondary tumors. Attention to symptom palliation is an important part of the neurologist's role throughout the course of a brain tumor patient's illness.

Topics: Angiogenesis Inhibitors; Anticonvulsants; Brain Edema; Brain Neoplasms; Cognition Disorders; Dopamine Agents; Humans; Levetiracetam; Memantine; Palliative Care; Piracetam; Seizures

Seizures, transient disruptions of normal brain electrical activity, are common for patients with low-grade glioma (LGG) and significantly affect quality of life. Up to 75% of patients with a LGG will have seizures in the course of their disease (compared with 1%-2% of the general population). Depending on the type of abnormal electrical activity, the functional implications of seizure can impact any domain, including mental status, sensation or strength. In most cases, either the seizure or the medications used to treat the seizure may contribute to cognitive and psychosocial difficulties of various degrees of severity. Hence, effective management of seizures is a major priority for patients with LGG. Evidence-based guidelines suggest that levetiracetam is the best first-line agent for treatment of seizures in this population due to both its efficacy and tolerability. An important consideration in the field of neuro-oncology is that levetiracetam has very few drug interactions. Unfortunately, approximately one-third of patients with LGG have refractory epilepsy where additional agents such as valproic acid, or lacosamide, lamotrigine and nonpharmacologic therapies such as diet-based interventions, epilepsy surgery, and devices are considered.

Topics: Anticonvulsants; Brain Neoplasms; Glioma; Humans; Lamotrigine; Levetiracetam; Piracetam; Seizures; Triazines

Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term 'epilepsy' which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level "A") as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient's compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.

Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Drug Administration Schedule; Drug Approval; Drug Prescriptions; Electroencephalography; Encephalitis; Epilepsies, Partial; Humans; Hungary; Isoxazoles; Levetiracetam; Magnetic Resonance Imaging; Medication Adherence; Obesity; Phenytoin; Piracetam; Risk Assessment; Risk Factors; Seizures; Stroke; Weight Loss; Young Adult; Zonisamide

This meta-analysis aimed to systematically collect and synthesize the current evidence regarding the efficacy and tolerability of levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types. We selected randomized-controlled trials (RCT) of LEV as an adjunctive therapy in epilepsy according to predefined criteria. Outcome measures included a > or =50% reduction in seizure frequency, seizure freedom, and adverse events. Thirteen RCT were analyzed. Results showed that the efficacy of adjunctive LEV was superior to placebo both in achieving > or =50% reduction in seizure frequency (pooled odds ratio [OR] 3.36, 95% confidence interval [CI] 2.78-4.07, Z=12.46; p<0.00001) and seizure freedom (pooled OR 4.72, 95% CI 2.96-7.54, Z=6.50; p<0.00001). The heterogeneity was mild (chi-squared=12.28, I2=2% in > or =50% reduction in seizure frequency, and chi-squared=0.49, I2=0% in seizure freedom). Subgroup analysis suggested similar effects across different dosages in adults. The incidence of adverse reactions was not significantly different between the LEV group and the placebo group. The adverse events of relatively high incidence in the LEV group included somnolence, agitation, dizziness, asthenia, and infection. Incidence of serious adverse reaction such as rash and white blood cells and platelets decreasing was quite low. Adjunctive therapy with LEV was superior to placebo in reducing the frequency of seizures in patients with partial and idiopathic generalized epilepsy with effect in both adults and children, and demonstrated good tolerance in patients with epilepsy.

Topics: Adult; Anticonvulsants; Child; Drug Therapy, Combination; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

Occurrence of generalized tonic-clonic seizures (GTCS) is one of the most important risk factors of seizure-related complications and comorbidities in patients with epilepsy. Their prevention is therefore an important aspect of therapeutic management both in idiopathic generalized epilepsies and in focal epilepsies.. It has been shown that the efficacy of antiepileptic drugs (AEDs) varies across epilepsy syndromes, with some AEDs efficacious against focal seizures with secondary GTCS (sGTCS) but aggravating primary GTCS (pGTCS). In patients with pGTCS, evidence-based data support the preferential use of valproic acid, lamotrigine, levetiracetam and topiramate. In patients with sGTCS, all AEDs approved in the treatment of focal epilepsies might be used.. Both in pGTCS and sGTCS, additional data are required, specifically to inform about the relative efficacy of AEDs in relation to each other. Although valproic acid might be the most efficacious drug in idiopathic generalized epilepsies, it should be avoided in women of childbearing age due to its safety profile. In patients with sGTCS, AEDs for which the impact on this seizure type has been formally evaluated and which have demonstrated greater efficacy than placebo might preferentially be used, such as lacosamide, perampanel and topiramate.

Topics: Acetamides; Anticonvulsants; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Fructose; Humans; Lacosamide; Lamotrigine; Levetiracetam; Piracetam; Risk Factors; Seizures; Topiramate; Treatment Failure; Triazines; Valproic Acid

During the establishment of a research branch, all relevant matters encountered will be of interest to study. After having acquired a body of basal knowledge, it becomes possible to derive ideas or hypotheses for further elaboration of information. The purpose of the present study was to show that therapies for nerve agent poisoning based on specific neuropharmacological approaches can have greater probability for being successful than treatment regimens based on fragmental research or serendipitous discoveries. By following the guidelines for research in experimental epilepsy, neuronal target areas for nerve agents have been identified through lesion studies, and critical receptors for pharmacological treatment have been specified through microinfusion studies of rats. Subsequent experimentations have shown that the results achieved from microinfusion studies are transferable to systemic administration. It is demonstrated that a treatment regimen developed through the novel approach is more efficacious than regimens derived from conventional research on countermeasures. A therapy consisting of HI-6, levetiracetam, and procyclidine that has been worked out along the new lines, exerts powerful anticonvulsant capacity and appears to have universal utility as a stand-alone therapy against soman intoxication in rats. It would be of great interest to examine whether the latter findings can be expanded to other animal species than rats and other classical nerve agents than soman.

Topics: Animals; Anticonvulsants; Antidotes; Brain; Cholinergic Agents; Humans; Levetiracetam; Organophosphate Poisoning; Oximes; Piracetam; Procyclidine; Pyridinium Compounds; Rats; Seizures

Diagnostic work-up and treatment of patients who have developed epilepsy after the age of 65 can both be difficult. Epilepsy is one of the most common neurological conditions in the elderly, and the incidence of de novo geriatric epilepsy is rising. The aim of this review is to provide guidance on the management of epilepsy in this patient group.. The review is based on a discretionary selection of original articles and reviews found in PubMed using the search term combination 'epilepsy' and 'elderly', and the authors' personal experience.. The seizures, which are most commonly of the focal type, are not infrequently overlooked or misdiagnosed. Cerebrovascular disease is the underlying cause of about half of the cases. When selecting an anticonvulsant, it is important to take age-related physiological changes and comorbidities into consideration. Because elderly patients have a narrower therapeutic window than younger persons and greater susceptibility to cognitive and other side effects, a low starting dose and slower dose titration are particularly important.. The results of studies of young epilepsy patients cannot be extrapolated to apply to elderly patients. More studies directly targeting this patient population are therefore needed. As a general rule, we do not recommend starting on enzyme-inducing drugs such as phenytoin, phenobarbital and carbamazepine, partly because of their high interaction potential.

Topics: Age Factors; Aged; Aging; Anticonvulsants; Dose-Response Relationship, Drug; Epilepsy; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Piracetam; Quality of Life; Seizures; Triazines; Zonisamide

The treatment of neonatal seizures has not changed significantly over the last 50 years despite advances in antiepileptic drug (AED) development for older children and adults. Recently new drugs have emerged some of which address age-specific challenges or mechanisms and will be discussed in this review. The loop diuretic bumetanide blocks the neuronal NKCC1 co-transporter and is thought specifically to supress seizures in the immature brain. Levetiracetam has been used in children and infants with good efficacy, an excellent safety profile, and near-ideal pharmacokinetic characteristics. Randomised controlled trials are now underway to test the efficacy of some newer AEDs for neonatal seizures. Topiramate has been shown to have neuroprotective properties in addition to its antiepileptic action and trials in babies with hypoxic-ischaemic encephalopathy are now planned. There is an urgent need to develop age-specific AEDs for preterm and term babies. These drugs must be evaluated with multicentre, collaborative trials using innovative methods and high ethical standards to overcome age-specific challenges with the ultimate aim of improving the outcome for neonates with seizures.

Topics: Animals; Anticonvulsants; Brain; Bumetanide; Child Development; Epilepsy; Fructose; Humans; Infant, Newborn; Levetiracetam; Neurogenesis; Neurons; Neuroprotective Agents; Piracetam; Seizures; Sodium Potassium Chloride Symporter Inhibitors; Topiramate

Acute seizure and status epilepticus constitute one of the major medical emergencies in children. Among children, the incidence ranges from 4-38/100,000 children per year respectively. The incidence in developing countries is somewhat higher because of infections. Although, the definition of status epilepticus is based on duration of seizures, the operational definition is to treat any child who is brought seizing to the emergency room, as status epilepticus. An urgent time bound approach is of paramount importance when managing a child in status epilepticus. Benzodiazepines remain the first line antiepileptic drugs in the emergency room; a long acting drug (Lorazepam) is preferred when available. This is followed by Phenytoin (20 mg/kg) loading. In patients refractory to above drugs, valproate (30 mg/kg) loading is commonly used and if effective, followed by an infusion (5 mg/kg/h) for seizure free period of 6 h. In non-responders, a trial of Levetiracetam (40 mg/kg infused at 5 mg/kg/min) can be used before starting benzodiazepine or thiopental coma (3-4 mg/kg loading dose, followed by 2 mg/kg/min infusion). When pharmacological coma is initiated, the child needs to be shifted to pediatric intensive care unit for proper monitoring and titration of medications.

Topics: Anesthesia, Intravenous; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Combined Modality Therapy; Cross-Sectional Studies; Developing Countries; Dose-Response Relationship, Drug; Emergency Service, Hospital; Epilepsy; Humans; India; Infant; Infusions, Intravenous; Intensive Care Units, Pediatric; Levetiracetam; Lorazepam; Phenytoin; Piracetam; Seizures; Status Epilepticus; Thiopental; Valproic Acid

Current standard therapy for seizure prophylaxis in Neuro-surgical patients involves the use of Phenytoin (PHY). However, a new drug Levetiracetam (LEV) is emerging as an alternate treatment choice. We aimed to conduct a meta-analysis to compare these two drugs in patients with brain injury.. An electronic search was performed in using Pubmed, Embase, and CENTRAL. We included studies that compared the use of LEV vs. PHY for seizure prophylaxis for brain injured patients (Traumatic brain injury, intracranial hemorrhage, intracranial neoplasms, and craniotomy). Data of all eligible studies was extracted on to a standardized abstraction sheet. Data about baseline population characteristics, type of intervention, study design and outcome was extracted. Our primary outcome was seizures.. The literature search identified 2489 unduplicated papers. Of these 2456 papers were excluded by reading the abstracts and titles. Another 25 papers were excluded after reading their complete text. We selected 8 papers which comprised of 2 RCTs and 6 observational studies. The pooled estimate's Odds Ratio 1.12 (95% CI = 0.34, 3.64) demonstrated no superiority of either drug at preventing the occurrence of early seizures. In a subset analysis of studies in which follow up for seizures lasted either 3 or 7 days, the effect estimate remained insignificant with an odds ratio of 0.96 (95% CI = 0.34, 2.76). Similarly, 2 trials reporting seizure incidence at 6 months also had insignificant pooled results while comparing drug efficacy. The pooled odds ratio was 0.96 (95% CI = 0.24, 3.79).. Levetiracetam and Phenytoin demonstrate equal efficacy in seizure prevention after brain injury. However, very few randomized controlled trials (RCTs) on the subject were found. Further evidence through a high quality RCT is highly recommended.

Topics: Adult; Aged; Brain Injuries; Causality; Comorbidity; Convulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Prevalence; Risk Factors; Seizures; Treatment Outcome

Topics: Acute Disease; Allosteric Regulation; Animals; Anticonvulsants; Calcium; Calcium Channel Blockers; Calcium Channels, N-Type; Disease Models, Animal; Epilepsy; Humans; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Randomized Controlled Trials as Topic; Seizures

Seizures are a common symptom of brain tumours. The mainstay of treatment for seizures is medical therapy with antiepileptic drugs.. To evaluate the relative effectiveness and tolerability of antiepileptic drugs commonly used to treat seizures in adults with brain tumours.. We searched CENTRAL (Issue 2 of 4, The Cochrane Library 2011), MEDLINE (1948 to May week 3, 2011) and EMBASE (1980 to 31 May 2011) databases. In addition, we handsearched articles published since 2000 in the following journals selected by the authors: Epilepsia; The Lancet Neurology and Neuro-Oncology.. Controlled clinical trials with random allocation of the use of antiepileptic drugs to treat seizures in adults with brain tumours.. Both review authors screened the search results and reviewed the abstracts of potentially relevant articles before retrieving the full text of eligible articles.. Only one trial met the inclusion criteria for this review which was a small, open-label, unblinded, randomised trial of the safety and feasibility of switching from phenytoin to levetiracetam monotherapy or continuing phenytoin for glioma-related seizure control following craniotomy (Lim 2009). Levetiracetam (a non enzyme-inducing antiepileptic drug) appears to have been at least as well tolerated and as effective as phenytoin (an enzyme-inducing antiepileptic drug) for the treatment of seizures in people with brain tumours. Eighty-seven per cent of participants treated with levetiracetam were free of seizures at six months compared with 75% of participants treated with phenytoin. There is one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours. No data from this study were available at the time of preparing this review.. There is a lack of robust, randomised, controlled evidence to support the choice of antiepileptic drug for the treatment of seizures in adults with brain tumours. While some authors support the use of non enzyme-inducing antiepileptic drugs, reliable, comparative evidence to provide clinical justification for this is limited. There is a need for further large, randomised, controlled trials in this area.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Drug Substitution; Humans; Levetiracetam; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures

Levetiracetam (Keppra®, E Keppra®) is an established second-generation antiepileptic drug (AED). Worldwide, levetiracetam is most commonly approved as adjunctive treatment of partial-onset seizures with or without secondary generalization; other approved indications include monotherapy treatment of partial-onset seizures with or without secondary generalization, and adjunctive treatment of myoclonic seizures associated with juvenile myoclonic epilepsy and primary generalized tonic-clonic (GTC) seizures associated with idiopathic generalized epilepsy. Levetiracetam has a novel structure and unique mechanisms of action. Unlike other AEDs, the mechanisms of action of levetiracetam appear to involve neuronal binding to synaptic vesicle protein 2A, inhibiting calcium release from intraneuronal stores, opposing the activity of negative modulators of GABA- and glycin-gated currents and inhibiting excessive synchronized activity between neurons. In addition, levetiracetam inhibits N-type calcium channels. Levetiracetam is associated with rapid and complete absorption, high oral bioavailability, minimal metabolism that consists of hydrolysis of the acetamide group and primarily renal elimination. It lacks cytochrome P450 isoenzyme-inducing potential and is not associated with clinically significant pharmacokinetic interactions with other drugs, including other AEDs. The efficacy of oral immediate-release levetiracetam in controlling seizures has been established in numerous randomized, double-blind, controlled, multicentre trials in patients with epilepsy. Adjunctive levetiracetam reduced the frequency of seizures in paediatric and adult patients with refractory partial-onset seizures to a significantly greater extent than placebo. Monotherapy with levetiracetam was noninferior to that with carbamazepine controlled release in controlling seizures in patients with newly diagnosed partial-onset seizures. Levetiracetam also provided seizure control relative to placebo as adjunctive therapy in patients with idiopathic generalized epilepsy with myoclonic seizures or GTC seizures. In addition, patients receiving oral levetiracetam showed improvements in measures of health-related quality of life relative to those receiving placebo. Although treatment-emergent adverse events were commonly reported in the clinical trials of levetiracetam, the overall proportion of patients who experienced at least one treatment-emergent adverse event was broadly similar in the levetiracet

Topics: Anticonvulsants; Carbamazepine; Chemotherapy, Adjuvant; Epilepsy; Humans; Levetiracetam; Piracetam; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome

Multiple new anticonvulsants have been introduced recently and they are supplanting the older medications. Whereas the older drugs have well-recognized side effects, both in typical therapeutic doses and in overdosage, the properties of the newer ones are unique and largely unknown to all but sub-specialists.. This article gives a concise overview of the potential complications of these new medications in both therapeutic use and overdose.. Clinically significant side effects of the new anticonvulsants, such as metabolic acidosis from topiramate, autoimmune reactions from lamotrigine, hyponatremia from oxcarbazepine, or psychosis from levitiracetam can cause serious morbidity and mortality if unrecognized. The effects of these medications in overdose are also largely unknown to most emergency physicians.. This article reviews the major potential side effects of the new seizure medications and the treatment of their overdoses for the practicing emergency physician.

Topics: Acidosis; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Overdose; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Psychoses, Substance-Induced; Seizures; Tiagabine; Topiramate; Triazines

Epileptic seizures are a common clinical problem in children with brain tumors. The conventional antiepileptic drugs (AEDs) permit a good seizure control in most of these children. An emerging problem is the possible interactions between AEDs and chemotherapeutic drugs, because many of these drugs are metabolized by the cytochrome P450. The aim of this article is to propose a novel therapeutic approach for new-onset epilepsy in children with brain tumors. Among the new AEDs not metabolized by the P450 system, levetiracetam seems to be a promising AED owing to its pharmacokinetic features, efficacy, and safety.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Child; Child, Preschool; Drug Interactions; Drug Therapy, Combination; Humans; Levetiracetam; Piracetam; Seizures

To determine the safety and tolerability of IV and oral levetiracetam monotherapy for seizures in brain tumor patients following resection. Brain tumor patients undergoing neurosurgery with >or=1 seizure within the preceding month prior to surgery were enrolled to receive intravenous levetiracetam for a minimum of 48 h, transitioned to oral levetiracetam at the same dose, and followed for 1-month after discharge. Patients were assessed daily in the hospital, provided with a seizure diary, and supplied with 30 days of levetiracetam upon discharge. Study patients were telephoned weekly to assess their cognitive status and seizure frequency. Of the 17 patients enrolled, the baseline seizure types were tonic clonic, partial, and complex partial with secondary generalization. The most common type of tumor was glioblastoma multiforme. Levetiracetam was well tolerated with no medication discontinuation during the study period. Adverse effects reported were somnolence, nausea/vomiting, headache, and insomnia. Eleven patients were evaluable for TICS scores (64.7%) with an average score of 33.3. Two patients were deemed to be cognitively impaired (18.2%). Eleven of twelve patients (91.7%) that completed the study period achieved a >or=50% reduction in their number of seizures. A total of 92 drug interactions were avoided (P = 0.0016) with dexamethasone, acetaminophen, and fentanyl being the most common. Levetiracetam monotherapy was found to be safe and tolerable in this patient population. Nearly all patients achieved a >or=50% reduction in seizure frequency post-op with levetiracetam monotherapy. Levetiracetam also has the potential for less drug interactions compared to phenytoin in these patients.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Brain Neoplasms; Dose-Response Relationship, Drug; Drug Interactions; Female; Follow-Up Studies; Glioma; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures; Survival Rate; Treatment Outcome

High-dose busulfan is frequently used in a variety of conditioning regimens for hematopoietic cell transplantation. In this setting, busulfan has marked neurotoxicity, specifically causing seizures that generally are tonic-clonic in character. Phenytoin has been the preferred drug to treat busulfan-induced seizures, but this practice should be reexamined in light of newer antiepileptic drugs being preferentially used by neurologists. Characteristics of ideal seizure prophylaxis include lack of overlapping toxicity with the conditioning regimen, lack of interference with engraftment of donor cells, and minimal potential for pharmacokinetic drug interactions. Based on these criteria, phenytoin is suboptimal due to possible toxicities and is especially ill suited because of its ability to induce busulfan metabolism. It is postulated that this induction adversely affects efforts to update methods for targeting busulfan doses to individual patients, based on recent developments in the understanding of the pharmacogenomics of busulfan metabolism. The existing clinical data support the use of benzodiazepines, most notably clonazepam and lorazepam, to prevent busulfan-induced seizures. The second-generation antiepileptic drug levetiracetam possesses the characteristics of optimal prophylaxis for busulfan-induced seizures, and early data of its efficacy are promising, although further study is needed.

Topics: Alkylating Agents; Animals; Anticonvulsants; Benzodiazepines; Busulfan; Dose-Response Relationship, Drug; Humans; Levetiracetam; Piracetam; Seizures

Seizures may occur during or soon after rupture of an intracranial aneurysm. The use of antiepileptic drugs (AEDs) is a controversial issue. The overall conclusions from 2 recent studies in aneurysmal subarachnoid hemorrhage are that 1) many patients receive AEDs but should not; 2) long-term use is associated with worse outcome; and 3) short-term use is safer. Phenytoin may not be the first choice for seizure prophylaxis; newer AEDs such as levetiracetam might be more helpful in prevention and treatment of seizures.

Topics: Animals; Anticonvulsants; Electroencephalography; Head Injuries, Closed; Humans; Levetiracetam; Neurons; Neuroprotective Agents; Phenytoin; Piracetam; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Both seizures and antiepileptic drugs may induce disturbances in hormonal system. Regarding endocrine effects of anticonvulsants, an interaction of these drugs with gonadal, thyroid, and adrenal axis deserves attention. Since majority of antiepileptic drugs block voltage dependent sodium and calcium channels, enhance GABAergic transmission and/or antagonize glutamate receptors, one may expect that similar neurochemical mechanisms are engaged in the interaction of these drugs with synthesis of hypothalamic neurohormones such as gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH). Moreover some antiepileptic drugs may affect hormone metabolism via inhibiting or stimulating cytochrome P-450 iso-enzymes. An influence of antiepileptic drugs on hypothalamic-pituitary-gonadal axis appears to be sex-dependent. In males, valproate decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but elevated dehydroepiandrosterone sulfate (DHEAS) concentrations. Carbamazepine decreased testosterone/sex-hormone binding globulin (SHBG) ratio, whereas its active metabolite--oxcarbazepine--had no effect on androgens. In females, valproate decreased FSH-stimulated estradiol release and enhanced testosterone level. On the other hand, carbamazepine decreased testosterone level but enhanced SHBG concentration. It has been reported that carbamazepine, oxcarbazepine or joined administration of carbamazepine and valproate decrease thyroxine (T4) level in patients with no effect on thyrotropin (TSH). While valproate itself has no effect on T4, phenytoin, phenobarbital and primidone, as metabolic enzyme inducers, can decrease the level of free and bound thyroxine. On the other hand, new antiepileptics such as levetiracetam, tiagabine, vigabatrine or lamotrigine had no effect on thyroid hormones. With respect to hormonal regulation of metabolic processes, valproate was reported to enhance leptin and insulin blood level and increased body weight, whereas topiramate showed an opposite effect. In contrast to thyroid and gonadal hormones, only a few data concern antiepileptic drug action in HPA axis. To this end, no effect of antiepileptic drugs on adrenocorticotropic hormone (ACTH)/cortisol circadian rhytmicity was found. Valproate decreased CRH release in rats, whereas lamotrigine stabilized ACTH/cortisol secretion. Moreover, felbamate was found to inhibit stress-indu

Topics: Anticonvulsants; Carbamazepine; Endocrine System Diseases; Estradiol; Female; Hormones; Humans; Levetiracetam; Male; Oxcarbazepine; Piracetam; Seizures; Testosterone; Thyroid Hormones; Valproic Acid

In this post hoc analysis, individual seizure counts from four double-blind trials of adjunctive treatment with levetiracetam were analyzed by non-linear mixed-effects modeling (NONMEM). First, a model was fitted to the individual count data assuming a Poisson distribution, in order to classify the patients as either improving or deteriorating from baseline. In the second stage, the dose-response relationship in improving patients was determined by fitting the data to an E(max) model including a placebo effect. The percentage of improvers was 59% on placebo and 73%, 74%, 77% and 73% on levetiracetam 1, 2, 3 and 4g/day, respectively. The ED(50) of 1408mg/day was close to the current WHO Defined Daily Dose of levetiracetam (1500mg). The maximum recommended dose of 3000mg/day was predicted to reduce seizures by >or=90% in 10% of improving patients. Age, gender, body weight, race, and number of concomitant antiepileptic drugs neither affected the percentage of responders nor the extent of change in seizure frequency from baseline.

Topics: Anticonvulsants; Clinical Trials, Phase III as Topic; Computer Simulation; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Nonlinear Dynamics; Piracetam; Seizures

To assess the advantages and disadvantages of six methodologies used in calculating seizure freedom rates in placebo-controlled, adjunctive therapy trials of new antiepileptic drugs (AEDs) in partial epilepsy, and two methodologies for long-term follow-up studies.. Data from levetiracetam trials were used to illustrate the impact of different methodologies on seizure freedom rates. Seizure-freedom data for several new AEDs were identified from the published medical literature using MEDLINE and from a recent comprehensive textbook.. Most randomized, placebo-controlled add-on clinical trials of new AEDs contain little or no information about seizure freedom. Importantly, the methodology used can profoundly affect results when calculating seizure-free rates. Seizure freedom data should be reported as well as the methodology used. The minimum duration for assessing seizure freedom should be the entire stable dose period in short-term trials and at least six months for long-term follow-up studies. It is proposed that the seizure freedom rates be calculated and reported with at least two different methodologies, one that considers patients withdrawing from treatment without having had a seizure as successes, and one that considers the same patients as failures. For an effective and well-tolerated AED, seizure freedom rates will be consistent across the two methodologies.. Seizure freedom is the ultimate goal of AED therapy and should be reported for all clinical trials. Methodological differences among the few clinical studies reporting seizure freedom rates make it difficult to compare results across trials. Improved reporting of methodologies and seizure-free rates is warranted.

Topics: Adult; Anticonvulsants; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Remission Induction; Research Design; Seizures

The mechanism of epilepsy in brain tumor patients is probably multifactorial, and its incidence depends on tumor type and location. Refractory epilepsy is common in patients with a structural brain lesion, and a role for multidrug resistance proteins has been suggested. Until now, the medical treatment of epilepsy in brain tumor patients has only been studied retrospectively. Therefore, the optimal seizure management by antiepileptic drugs (AEDs) in this patient category is essentially unsure. Choices depend on the outcome of retrospective studies, a few nonrandomized series, extrapolation from other studies in symptomatic epilepsy, and anticipated interactions, most notably between AEDs and anticancer agents. The newly developed AEDs levetiracetam and gabapentin are recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents. The use of prophylactic AEDs in brain tumor patients is disputable and generally not advised.

Topics: Amines; Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Cyclohexanecarboxylic Acids; Drug Interactions; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures

There has been a growing interest in the use of antiepileptic drugs (AEDs) for neuroprotection, and in the possible role of AEDs in disease modification (i.e., antiepileptogenesis). Increased understanding of the mechanisms underlying brain injury has led to advances in the study of neuroprotection. However, defining the clinical paradigm and selecting appropriate outcomes to detect neuroprotective effects present challenges to clinicians studying the neuroprotective properties of drugs. Established AEDs, such as phenytoin, phenobarbital, and carbamazepine, have shown neuroprotective activity in an ischemic/hypoxic model of neuronal injury. Animal model studies also have suggested that newer AEDs, such as levetiracetam, topiramate, and zonisamide, may have neuroprotective or antiepileptogenic properties. However, the prevention of epileptogenesis by an AED has yet to be demonstrated in clinical trials. The future of neuroprotection may involve established and newer AEDs, as well as other compounds, such as immunophilins, caspase inhibitors, endocannabinoids, and antioxidants.

Topics: Animals; Anticonvulsants; Brain; Epilepsy; Fructose; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Neuroprotective Agents; Piracetam; Seizures; Topiramate; Triazines; Zonisamide

Although short-term clinical trials provide important data regard-ing efficacy and tolerability, long-term studies are needed to address important aspects of clinical practice, such as long-term efficacy and safety. Long-term studies and post-marketing data show that the efficacy of levetiracetam is sustained over the long term and that this antiepileptic drug continues to be well tolerated, with low withdrawal rates and high retention rates. Patients continue to achieve significant reductions in seizure frequency and may achieve seizure freedom. Levetiracetam may allow patients to decrease the number of concomi-tant antiepileptic medications or withdraw to monotherapy. Add-on therapy with levetiracetam should be considered when additional control of seizures is needed.

Topics: Anticonvulsants; Drug Evaluation; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Longitudinal Studies; Piracetam; Product Surveillance, Postmarketing; Quality of Life; Seizures

Levetiracetam is a novel antiepileptic drug (AED) with proven efficacy against partial seizures, but there is limited information about its effectiveness against generalized seizures. In animal models, levetiracetam protects against seizures in audiogenic susceptible rodents, and it is effective in the Genetic Absence Epilepsy Rat from Strasbourg, a model of absence seizures. In these models, levetiracetam has a therapeutic index that is higher than those of other AEDs. A number of small open-label studies suggest that levetiracetam reduces seizure frequency in patients with generalized seizures, including primarily generalized seizures and myoclonic seizures. Case reports provide additional information regarding the potential efficacy of levetiracetam in postanoxic, post-encephalitic and progressive myoclonus. Although random-ized controlled studies of patients with generalized seizures have not yet been conducted, on the basis of available information, levetiracetam may be prom-ising in the treatment of generalized seizures.

Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Electroencephalography; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Piracetam; Product Surveillance, Postmarketing; Prospective Studies; Seizures

Treatment of seizures in pediatric patients is complicated by the fact that the etiology of the disorder and the pharmacokinetics, efficacy, and safety of antiepileptic drugs (AEDs) may differ from that in adults. With few controlled clinical trials of AEDs in children, the selection of agents to treat pediatric patients must be made on the basis of information from small uncontrolled studies or the extrapolation of clinical trial results in adults. Data from a large number of children with a wide range of seizure disorders who were treated in small-scale prospective studies, or whose records were retrospectively evaluated, indicate that levetiracetam reduces the frequency of seizures in pediatric patients. Available data also indicate that levetiracetam is well tolerated in pediatric patients, with a safety profile similar to that in adults, a low potential for behavioral disturbances, and no reported idiosyncratic adverse reactions. As with other AEDs, children metabolize and clear levetiracetam more rapidly than adults, and somewhat higher doses (based on body weight) are needed to achieve desired plasma concentrations. Several ongoing studies will provide further information on the pharmacokinetics, efficacy, and safety of levetiracetam in this patient population.

Topics: Anticonvulsants; Child; Drug Administration Schedule; Epilepsy; Humans; Levetiracetam; Piracetam; Prospective Studies; Seizures

The standard of care for prescribing antiepileptic drugs (AEDs) has come to favor the use of monotherapy when possible; i.e., when compa-rable efficacy can be achieved with fewer risks of adverse events and drug interactions. Most patients with epilepsy are started on one of the classic AEDs and, if it proves ineffective, another drug is tried, usually as monotherapy. While most of the newer AEDs that have come into clinical use in recent years are initially used as add-on therapy, their success at improving seizure control in combination treatments has led to their cautious use as monotherapy even before they have been approved for this indication. As a first study to determine the potential efficacy of levetiracetam in monotherapy, a withdrawal trial model was used. Patients who achieved adequate seizure control with levetiracetam as add-on therapy in a double-blind, placebo-controlled study entered a monotherapy phase of the trial in which the baseline AED was gradually withdrawn. Also, long-term data of 505 patients who received levetiracetam for refractory partial seizures were reviewed and found to include 49 patients still treated with levetiracetam monotherapy at the end of the study for a duration between 3 months and 5.5 years. Data from patients in the two trials lend supportive evidence that levetiracetam monotherapy is safe and effective for partial seizures.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures; Time Factors

A good balance between safety and tolerability is necessary for an antiepileptic drug (AED) to be successful in the management of patients with epilepsy. Levetiracetam is one of the new generation of AEDs licensed as an add-on therapy for the treatment of patients with partial-onset seizures. Leveti-racetam's mechanisms of action are not fully understood. Controlled clinical trials, open-label studies, and postmarketing surveillance indicate that leveti-racetam has a favorable safety profile characterized by little effect on vital signs or clinical laboratory values, reported adverse events that are mild to moderate, and no known drug-drug interactions. The tolerability of levetiracetam may extend to both pediatric and elderly patients based on analyses of small numbers of patients. Tolerability is maintained over the long term. Levetirac-etam does not appear to have a different safety profile in learning-disabled patients. Levetiracetam appears to have a good balance between tolerability and efficacy in the treatment of a wide variety of patients with partial epilepsy.

Topics: Age Factors; Anticonvulsants; Drug Interactions; Epilepsy; Humans; Levetiracetam; Persons with Mental Disabilities; Piracetam; Renal Insufficiency; Seizures

Physicians treating patients with epilepsy have a host of thera-peutic options. Drug choice is dictated first by the seizure(s) and/or epilepsy syndrome. Age is also a factor. Special considerations apply to women, particu-larly during their childbearing years, and to patients who are learning-disabled. Drug selection is further influenced by such characteristics as spectrum of activity, rapid response, low potential for drug-drug interactions, and ease of use. In addition to clinical trial data, postmarketing assessments of the new antiepileptic drugs provide useful clinical information on efficacy and safety. Levetiracetam has specific characteristics that make it an optimal choice for many patient populations.

Topics: Adult; Age Factors; Aged; Anticonvulsants; Drug Resistance; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Persons with Mental Disabilities; Piracetam; Prospective Studies; Seizures

We examined the effect of adjunctive levetiracetam (LEV; 1,000 to 3,000 mg/day) on the number of seizure-free days gained per quarter in adult patients with refractory partial-onset epilepsy.. The treatment effect was studied in a meta-analysis using individual patient data of a subpopulation of patients (n = 846) emerging from the three randomized, double-blind, placebo-controlled, phase III trials (n = 904).. Adding LEV effectively increased the number of days without seizures by 5.19 days per quarter [95% confidence interval (CI), 3.63-6.76; p = 0.0001; titration and stable dose periods].. LEV adjunctive treatment shows a clear benefit in terms of seizure-free days gained for patients with refractory epilepsy. This gain is significant for the pooled and for each LEV dose compared with placebo.

Topics: Adult; Confidence Intervals; Dose-Response Relationship, Drug; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Randomized Controlled Trials as Topic; Seizures

Levetiracetam is a new antiepileptic drug (AED) devoid of anticonvulsant activity in the two classic screening models for AEDs, the maximal electroshock and pentylenetetrazol seizure tests in both mice and rats. This contrasts a potent seizure suppression in genetic and kindled mice and rats and against chemoconvulsants inducing partial seizures in rats. The highly selective action in "epileptic" animals distinguishes levetiracetam from classic and other new AEDs that have nearly equipotent effects in normal and "epileptic" animals. Levetiracetam induces minor behavioral alterations in normal and in kindled mice and rats. This results in an unusually high safety margin in animal models reflecting both partial and primary generalized epilepsy. Furthermore, experiments in the kindling model suggest that levetiracetam may possess antiepileptogenic properties due to a potent ability to prevent the development of kindling in mice and rats at doses devoid of adverse effects. Electrophysiologic recordings from different experimental models suggest that levetiracetam exerts a selective action against abnormal patterns of neuronal activity, which probably explains its selective protection in epileptic animals and its unique tolerability. This effect appears to derive from one or more novel mechanisms of action that do not involve a conventional interaction with traditional drug targets implicated in the modulation of inhibitory and excitatory neurotransmission. Instead, ligand-binding assays have disclosed a brain-specific binding site for levetiracetam. These studies reveal a unique preclinical profile of levetiracetam, distinct from that of all known AEDs, suggesting that levetiracetam could represent the first agent in a new class of AEDs.

Topics: Amygdala; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electric Stimulation; Epilepsy; Kindling, Neurologic; Levetiracetam; Mice; Piracetam; Rats; Seizures

Levetiracetam, the S-enantiomer of alpha-ethyl-2-oxo-1-pyrollidine acetamide, is approved for use as adjunctive therapy in adult patients with partial onset seizures. Oral levetiracetam 1000, 2000 and 3000 mg/day administered as adjunctive therapy for up to 18 weeks significantly increased responder rates and reduced seizure frequency compared with placebo in 3 well designed pivotal trials in adults with treatment-refractory partial seizures with or without secondary generalisation. Levetiracetam 3000 mg/day also significantly increased the number of seizure-free patients, but the effects of levetiracetam 1000 and 2000 mg/day on this end-point were unclear. Effects on seizure severity were not assessed in these trials. Although not yet approved as monotherapy or for use in paediatric patients, efficacy was observed with levetiracetam 3000 mg/day as monotherapy in adult patients with refractory partial seizures with or without secondary generalisation and with the 10 to 40 mg/kg/day dosage as adjunctive therapy in children with refractory partial seizures. However, these data are limited. Oral levetiracetam 1000, 2000 and 3000 mg/day as adjunctive therapy is generally well tolerated with an overall incidence of adverse events similar to that observed with placebo. The most commonly reported events in individual clinical trials were CNS-related and included somnolence, asthenia, headache and dizziness. Levetiracetam administered as adjunctive therapy does not appear to interact with other anticonvulsant drugs, and no clinically relevant interactions were observed between levetiracetam and digoxin, warfarin or probenecid; oral contraceptive protective efficacy was also not affected by levetiracetam.. Levetiracetam is a new anticonvulsant agent with a favourable tolerability profile and a low potential for drug interactions. It has shown efficacy as adjunctive therapy in patients with treatment-refractory partial onset seizures with or without secondary generalisation in clinical trials. Direct comparative trials with other anticonvulsant agents are not yet available, but placebo-controlled clinical evidence to date suggests that levetiracetam (1000, 2000 and 3000 mg/day) is a useful option as adjunctive therapy in patients with this subtype of epilepsy.

Topics: Administration, Oral; Adult; Animals; Anticonvulsants; Child; Cognition; Dose-Response Relationship, Drug; Drug Interactions; Drug Tolerance; Humans; Intestinal Absorption; Kidney; Levetiracetam; Models, Biological; Piracetam; Quality of Life; Seizures; Tissue Distribution

Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors.. To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression.. Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence.. A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period.. The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Prospective Studies; Seizures

Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE.. We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug.. A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061).. The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT.. jRCTs031190160.

Topics: Adult; Anticonvulsants; Diazepam; Humans; Levetiracetam; Phenytoin; Seizures; Status Epilepticus; Treatment Outcome

Via measures of efficacy, tolerability, and safety, this open-label, single-center study assessed the overall effectiveness of Brivaracetam (BRV) for the treatment of epilepsy in the context of 'real-world' clinical practice.. Unselected consecutive patients were recruited and stratified into 3 cohorts with either fully prospective, fully retrospective or mixed data collection, dependent on whether their BRV prescriptions were historical, current, or pending. Prospective data were obtained at baseline, 3 and 6 months, and at 6-month intervals thereafter, from patient interviews and seizure diaries, and retrospective data from medical records. Efficacy variables were derived from seizure-related changes, and tolerability and safety variables from reported treatment-emergent adverse events (TEAEs), BRV withdrawal, and changes to questionnaire scores. Additionally, we investigated treatment outcomes for those with previous levetiracetam (LEV) use, a history of psychiatric comorbidity, a learning disability, and of older age.. One hundred and nine patients (58.7% female, mean age 42 years, range: 18 to 72) were included, 59 with prospective follow-up for a minimum of 6 (47 patients, excluding those who withdrew) and a maximum of 24 months (2 patients). Of the full cohort, 87.2% had drug-resistant epilepsy. Retention: At the study end, the median treatment duration was 384 days (range: 6 to 1514 days), and BRV retention was 68.8%. Kaplan-Meier survival functions predicted retention rates of 74.0% and 70.0% at 6 and 12 months respectively.. At the last follow-up, there was a ≥ 50% responder rate of 30.8%, with 12.1% seizure-free. Seizure frequency categories improved in 31.4% of patients, remained the same in 44.2%, and worsened in 24.4%. Monthly tonic-clonic seizure frequency had significantly decreased, and of those reporting these seizures, 58.3% showed reductions and 25.0% showed complete tonic-clonic seizure freedom.. 91.7% of patients reported at least 1 TEAE, with fatigue (30.3%), irritability (29.4%), and depression/low mood (28.4%) as the most common. Only 58.4% of all TEAEs were persistent. Brivaracetam discontinuation due to side effects occurred in 27.5% of the cohort. Depression and anxiety scores remained stable over time, and quality-of-life scores improved. Subgroups: Measures of BRV efficacy and tolerability did not differ according to previous LEV exposure. Tolerability profiles of those with learning disabilities, histories of psychiatric comorbidities, and older age did not greatly differ from the rest of the cohort. Of note, specific history of depression predicted the reporting of suicidal ideation.. The BRIVEST study provides real-world evidence of the effectiveness of BRV, suggesting that neither drug-resistant epilepsy nor previous LEV failure should preclude its use. Furthermore, BRV appears to be well-tolerated, even among those from vulnerable patient populations.

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Prospective Studies; Pyrrolidinones; Retrospective Studies; Seizures; Treatment Outcome

The efficacy and tolerability of eslicarbazepine acetate (ESL), a once-daily, orally-administered, anti-seizure medication (ASM), have primarily been established in treatment-resistant epilepsy patients, the population most often enrolled in clinical trials of anti-seizure medications. More recently, ESL was also shown to be effective and well-tolerated as first adjunctive therapy in non-treatment-resistant patients in an open-label, non-randomized, Phase IV, 24-week study of ESL using standard efficacy parameters in adults with focal seizures.. To determine the time required to reach baseline seizure count, as an alternative method of assessing the efficacy of adjunctive ESL in patients with relatively low baseline monthly seizure frequencies. This additional analysis was undertaken, as subtle changes and improvements are difficult to analyze using standard efficacy parameters, such as standardized seizure frequency reduction when the baseline frequency of seizures is particularly low.. This was a post-hoc analysis of the Phase IV study data, which investigated time to baseline seizure count in patients aged ≥ 18 years with focal seizures as an alternative measure of anti-seizure efficacy. In the Phase IV trial, patients had been enrolled into 2 groups: Arm 1: ESL as first adjunctive therapy to levetiracetam (LEV) or lamotrigine (LTG), the two most commonly-prescribed ASMs, in patients with inadequate response to treatment; Arm 2: ESL as a later adjunctive therapy, following prior use of 1-2 ASMs in patients who required an additional therapeutic option.. The time to reach individual baseline seizure count was longer in patients with focal seizures receiving ESL as a first (Arm 1) versus later (Arm 2) adjunctive therapy (p = 0.005). Patients who received ESL as a first adjunctive therapy had a longer time to ESL discontinuation than patients who received ESL as a later adjunctive therapy (p = 0.04). In Arm 1, patients receiving concomitant LTG reported treatment-emergent adverse events (TEAEs) significantly earlier than those receiving LEV (p = 0.02). Compared to patients receiving concomitant LTG, a greater number of patients in Arm 1 who were taking concomitant LEV had a modal ESL dose > 1200 mg and completed the full maintenance period. A greater number of patients in Arm 1 who were receiving concomitant LEV and completed the 24-week maintenance period reached a maximum ESL dose of 1600 mg, compared to those taking LTG, who reached a maximum ESL dose of 1200 mg.. This analysis of the Phase IV clinical trial data provides an alternative way of assessing efficacy beyond standardized seizure frequency reduction, in the context of relatively low monthly median seizure frequencies at baseline (SSF 2.0-2.4). These results provide further support for the use of ESL as an earlier or later adjunctive therapy to LEV or LTG.

Topics: Adult; Anticonvulsants; Dibenzazepines; Double-Blind Method; Humans; Lamotrigine; Levetiracetam; Seizures; Treatment Outcome

Topics: Anticonvulsants; Developing Countries; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Pilot Projects; Seizures

Valproate (VPA) and levetiracetam (LEV), the two broad spectrum antiseizure drugs with antiabsence effects were previously tested for their antiepileptogenic effects when administered in the early postnatal period and revealed possible modification of the epileptogenic process though the effect being not persistent. The aim of this study was to investigate the effects of in utero exposure to these drugs on the absence epilepsy seizures of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats on electroencephalogram (EEG) which are characterised by bilateral, symmetrical, and synchronized spike-and-wave discharges (SWDs). Considering LEV was proposed as a safer drug of choice in pregnancy, its effects on the newborn histopathology of GAERS was also investigated. Adult female GAERS were randomly grouped as VPA-(400 mg/kg/day), LEV- (100 mg/kg/day), and saline-treated. The drugs were injected into the animals intraperitoneally starting before pregnancy until parturition. The lungs, kidneys, and brains of the LEV-exposed newborns were evaluated histologically to be compared with unexposed naïve Wistar and GAERS newborns. Rest of the VPA-, LEV-, and saline-exposed offsprings were taken for EEG recordings on postnatal day 90. VPA or LEV did not show significant effect on mean cumulative duration and mean number of SWDs on EEG. The lungs of the LEV-exposed offsprings showed thickened alveolar epithelium in most regions, suggesting incomplete development of the alveoli. The renal examination revealed dilated Bowman's spaces in some renal corpuscles, which may be interpreted as a deleterious effect of LEV on the kidney. In addition, brain examination of LEV- and saline-exposed groups revealed irregularities in cortical thickness compared to Wistar control group. Lack of significant difference on SWD parameters may indicate that the mechanism responsible for the antiepileptogenic effects of VPA and LEV may not be operating in the prenatal period. The detrimental effect of LEV exposure observed in our study on the lungs and the kidneys of the newborns should be investigated by further studies with advanced molecular and biochemical techniques.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroencephalography; Epilepsy, Absence; Female; Levetiracetam; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Seizures; Valproic Acid

This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China.. Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods.. In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups.. OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

Topics: Adult; Anticonvulsants; Epilepsies, Partial; Humans; Levetiracetam; Oxcarbazepine; Quality of Life; Seizures; Treatment Outcome

Neonatal seizures are one of the most challenging problems for experts across the globe. Although there is no consensus on the "ideal" treatment of neonatal seizures, phenobarbitone has been the drug of choice for decades. Unfortunately, although extensively studied in adults and children, levetiracetam lacks rigorous evaluation in the neonatal population, despite its frequent use as an off-label drug. The objective of this open-label, randomized, active-control, single-center, pragmatic trial was to compare the effectiveness of levetiracetam with phenobarbitone for term asphyxiated infants as a first-line drug.. The participants included in this study were inborn term asphyxiated infants with seizures in the first 48 hours of life. Infants satisfying the inclusion criteria were randomized to receive levetiracetam (20 mg/kg) or phenobarbitone (20 mg/kg). Clinical seizure control was noted. Infants who failed to respond to the primary drug were given the other group drug.. Of 103 eligible infants, 82 were randomly assigned (44 levetiracetam group, 38 phenobarbitone group). Clinical seizure control with the primary drug and maintenance of the same for 24 hours was observed in 29 infants (65.9%) in the levetiracetam group and 13 infants (34.2%) in the phenobarbitone group (P < .05, relative risk 0.52, 95% confidence interval 0.32-0.84). Of the infants in the phenobarbitone group who did not respond to the primary drug, 57.8% were controlled after adding levetiracetam.. Levetiracetam can be used with effectiveness as a first- and second-line drug in asphyxiated term infants. A more extensive study on pharmacokinetics and optimal regimen is required.

Topics: Adult; Anticonvulsants; Child; Epilepsy; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Off-Label Use; Phenobarbital; Seizures

We describe a subset of patients with toxin-related precipitants of seizures/status epilepticus enrolled in the Established Status Epilepticus Treatment Trial (ESETT).. The ESETT was a prospective, double-blinded, adaptive trial evaluating levetiracetam, valproate, and fosphenytoin as second-line agents in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was the absence of seizures and improvement in the level of consciousness 1 hour after study drug administration. In this post hoc analysis, the safety and efficacy of second-line agents in a subset of patients with toxin-related seizures are described.. A total of 249 adults and 229 children were enrolled in the ESETT. Toxin-related seizures occurred in 29 (11.6%) adults and 1 child (0.4%). In adults, men were more likely to have toxin-related seizures than women (25 of 145, 17.2% versus 4 of 104, 3.9%). The most common toxin-related precipitants were alcohol withdrawal and cocaine, 11(37%) of 30 patients each. Cocaine was used with other substances by most patients 10 (91%) of 11, most commonly with an opioid 7 (64%) of 11. For alcohol withdrawal-related seizures, treatment successes with levetiracetam, valproate, and fosphenytoin were 3 (100%) of 3, 3 (50%) of 6, and 1 (50%) of 2, respectively. For cocaine-related seizures, treatment success was 1 (14%) of 7 for levetiracetam, 0 (0%) of 1 for valproate, and 1 (33%) of 3 for fosphenytoin. One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension.. In the ESETT, approximately 1 in 10 adult patients with status epilepticus presented with a toxin-related seizure. Alcohol withdrawal and cocaine/opioid use were the most common toxin-related precipitants. Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients.

Topics: Adult; Alcoholism; Analgesics, Opioid; Anticonvulsants; Benzodiazepines; Child; Cocaine; Female; Humans; Levetiracetam; Male; Phenytoin; Prospective Studies; Seizures; Status Epilepticus; Substance Withdrawal Syndrome; Valproic Acid

The incidence of early seizures (occurring within 7 days of stroke onset) after intracerebral haemorrhage reaches 30% when subclinical seizures are diagnosed by continuous EEG. Early seizures might be associated with haematoma expansion and worse neurological outcomes. Current guidelines do not recommend prophylactic antiseizure treatment in this setting. We aimed to assess whether prophylactic levetiracetam would reduce the risk of acute seizures in patients with intracerebral haemorrhage.. The double-blind, randomised, placebo-controlled, phase 3 PEACH trial was conducted at three stroke units in France. Patients (aged 18 years or older) who presented with a non-traumatic intracerebral haemorrhage within 24 h after onset were randomly assigned (1:1) to levetiracetam (intravenous 500 mg every 12 h) or matching placebo. Randomisation was done with a web-based system and stratified by centre and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Treatment was continued for 6 weeks. Continuous EEG was started within 24 h after inclusion and recorded over 48 h. The primary endpoint was the occurrence of at least one clinical seizure within 72 h of inclusion or at least one electrographic seizure recorded on continuous EEG, analysed in the modified intention-to-treat population, which comprised all patients who were randomly assigned to treatment and who had a continuous EEG performed. This trial was registered at ClinicalTrials.gov, NCT02631759, and is now closed. Recruitment was prematurely stopped after 48% of the recruitment target was reached due to a low recruitment rate and cessation of funding.. Between June 1, 2017, and April 14, 2020, 50 patients with mild-to-moderate severity intracerebral haemorrhage were included: 24 were assigned to levetiracetam and 26 to placebo. During the first 72 h, a clinical or electrographic seizure was observed in three (16%) of 19 patients in the levetiracetam group versus ten (43%) of 23 patients in the placebo group (odds ratio 0·16, 95% CI 0·03-0·94, p=0·043). All seizures in the first 72 h were electrographic seizures only. No difference in depression or anxiety reporting was observed between the groups at 1 month or 3 months. Depression was recorded in three (13%) patients who received levetiracetam versus four (15%) patients who received placebo, and anxiety was reported for two (8%) patients versus one (4%) patient. The most common treatment-emergent adverse events in the levetiracetam group versus the placebo group were headache (nine [39%] vs six [24%]), pain (three [13%] vs ten [40%]), and falls (seven [30%] vs four [16%]). The most frequent serious adverse events were neurological deterioration due to the intracerebral haemorrhage (one [4%] vs four [16%]) and severe pneumonia (two [9%] vs two [8%]). No treatment-related death was reported in either group.. Levetiracetam might be effective in preventing acute seizures in intracerebral haemorrhage. Larger studies are needed to determine whether seizure prophylaxis improves functional outcome in patients with intracerebral haemorrhage.. French Ministry of Health.

Topics: Cerebral Hemorrhage; Epilepsy; Humans; Levetiracetam; Seizures; Stroke; Treatment Outcome; United States

This study was undertaken to compare the efficacy of modified Atkins diet (MAD) among children with non-surgical drug-resistant epilepsy (DRE) to levetiracetam, when added to on-going anti-seizure medications.. An open-label, randomized controlled trial among children aged 2-12 years with non-surgical DRE was conducted. Eligible children were randomized in a 1:1 ratio to receive add-on MAD or levetiracetam. Baseline and post-intervention seizure frequency at 12 weeks was determined from seizure logs maintained by parents. The primary outcome was the proportion of responders, i.e., patients who achieved > 50% seizure reduction from baseline. Adverse events were compared. Analysis was intention-to-treat. (NCT04172311) RESULTS: One hundred and one children were enrolled (MAD-51, levetiracetam-50). The majority of the enrolled children had generalized seizures of mixed types secondary to structural brain lesions and Lennox-Gastaut syndrome was the most common electroclinical syndrome (46%). The proportion of children with >50% seizure reduction at 12 weeks was significantly higher in the MAD arm compared to the levetiracetam arm (27/51(52.9%) vs 11/50(22%); p < 0.001). At 12-weeks post-intervention, the change in mean seizure frequency compared to baseline was -47.33 ± 39.57% in the MAD arm and -31.15 ± 32.18% in the levetiracetam arm (p = 0.03). Constipation (41.1%) was the most frequent adverse effect with MAD. Sedation/lethargy (18%) and anxiety and irritability (14%) were the most frequent adverse effects in the levetiracetam group.. Addition of MAD was found to be superior to levetiracetam among children with non-surgical DRE with predominant generalized seizures in achieving seizure reduction at 12 weeks. Both treatments were well tolerated. Adverse effects, although higher with MAD, were expected side effects.

Topics: Child; Diet, High-Protein Low-Carbohydrate; Diet, Ketogenic; Drug Resistant Epilepsy; Drug-Related Side Effects and Adverse Reactions; Humans; Levetiracetam; Seizures; Treatment Outcome

It is unknown how often and how early EEG is obtained in patients presenting with status epilepticus. The Established Status Epilepticus Treatment Trial enrolled patients with benzodiazepine-refractory seizures and randomized participants to fosphenytoin, levetiracetam, or valproate. The use of early EEG, including frequency of electrographic seizures, was determined in Established Status Epilepticus Treatment Trial participants.. Secondary analysis of 475 enrollments at 58 hospitals to determine the frequency of EEG performed within 24 hours of presentation. The EEG type, the prevalence of electrographic seizures, and characteristics associated with obtaining early EEG were recorded. Chi-square and Wilcoxon rank-sum tests were calculated as appropriate for univariate and bivariate comparisons. Odds ratios are reported with 95% confidence intervals.. A total of 278 of 475 patients (58%) in the Established Status Epilepticus Treatment Trial cohort underwent EEG within 24 hours (median time to EEG: 5 hours [interquartile range: 3-10]). Electrographic seizure prevalence was 14% (95% confidence interval, 10%-19%; 39/278) in the entire cohort and 13% (95% confidence interval, 7%-21%) in the subgroup of patients meeting the primary outcome of the Established Status Epilepticus Treatment Trial (clinical treatment success within 60 minutes of randomization). Among subjects diagnosed with electrographic seizures (39), 15 (38%; 95% confidence interval, 25%-54%) had no clinical correlate on the video EEG recording.. Electrographic seizures may occur in patients who stop seizing clinically after treatment of convulsive status epilepticus. Clinical correlates might not be present during electrographic seizures. These findings support early initiation of EEG recordings in patients suffering from convulsive status epilepticus, including those with clinical evidence of treatment success.

Topics: Electroencephalography; Emergency Service, Hospital; Humans; Levetiracetam; Seizures; Status Epilepticus

Network hyperexcitability may contribute to cognitive dysfunction in patients with Alzheimer disease (AD).. To determine the ability of the antiseizure drug levetiracetam to improve cognition in persons with AD.. The Levetiracetam for Alzheimer's Disease-Associated Network Hyperexcitability (LEV-AD) study was a phase 2a randomized double-blinded placebo-controlled crossover clinical trial of 34 adults with AD that was conducted at the University of California, San Francisco, and the University of Minnesota, Twin Cities, between October 16, 2014, and July 21, 2020. Participants were adults 80 years and younger who had a Mini-Mental State Examination score of 18 points or higher and/or a Clinical Dementia Rating score of less than 2 points. Screening included overnight video electroencephalography and a 1-hour resting magnetoencephalography examination.. Group A received placebo twice daily for 4 weeks followed by a 4-week washout period, then oral levetiracetam, 125 mg, twice daily for 4 weeks. Group B received treatment using the reverse sequence.. The primary outcome was the ability of levetiracetam treatment to improve executive function (measured by the National Institutes of Health Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research [NIH-EXAMINER] composite score). Secondary outcomes were cognition (measured by the Stroop Color and Word Test [Stroop] interference naming subscale and the Alzheimer's Disease Assessment Scale-Cognitive Subscale) and disability. Exploratory outcomes included performance on a virtual route learning test and scores on cognitive and functional tests among participants with epileptiform activity.. Of 54 adults assessed for eligibility, 11 did not meet study criteria, and 9 declined to participate. A total of 34 adults (21 women [61.8%]; mean [SD] age, 62.3 [7.7] years) with AD were enrolled and randomized (17 participants to group A and 17 participants to group B). Thirteen participants (38.2%) were categorized as having epileptiform activity. In total, 28 participants (82.4%) completed the study, 10 of whom (35.7%) had epileptiform activity. Overall, treatment with levetiracetam did not change NIH-EXAMINER composite scores (mean difference vs placebo, 0.07 points; 95% CI, -0.18 to 0.32 points; P = .55) or secondary measures. However, among participants with epileptiform activity, levetiracetam treatment improved performance on the Stroop interference naming subscale (net improvement vs placebo, 7.4 points; 95% CI, 0.2-14.7 points; P = .046) and the virtual route learning test (t = 2.36; Cohen f2 = 0.11; P = .02). There were no treatment discontinuations because of adverse events.. In this randomized clinical trial, levetiracetam was well tolerated and, although it did not improve the primary outcome, in prespecified analysis, levetiracetam improved performance on spatial memory and executive function tasks in patients with AD and epileptiform activity. These exploratory findings warrant further assessment of antiseizure approaches in AD.. ClinicalTrials.gov Identifier: NCT02002819.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anticonvulsants; Cognition; Cross-Over Studies; Double-Blind Method; Executive Function; Female; Humans; Levetiracetam; Male; Middle Aged; Seizures

We report outcomes from an open-label, non-randomized, 24-week study of eslicarbazepine acetate (ESL) in adults at earlier and later stages of their treatment history for focal seizures, conducted in a real-world clinical setting.. ESL was taken as the first adjunctive therapy to levetiracetam (LEV) or lamotrigine (LTG) monotherapy (Arm 1), or as a later adjunctive therapy in treatment-resistant patients (Arm 2). The primary objective was to evaluate the effectiveness of ESL (by retention rates). Secondary objectives were to evaluate efficacy (seizure frequency), safety, tolerability, behavioral changes, mood, and health-related quality of life (HRQoL) associated with ESL treatment.. The modified intent-to-treat population included 96 patients (Arm 1: n = 41; Arm 2: n = 55) and the safety population included 102 patients (Arm 1: n = 44; Arm 2: n = 58). Overall, 81.8 % of patients in Arm 1 and 63.8 % of patients in Arm 2 completed the 24-week maintenance period. Median reductions in standardized seizure frequency (SSF) were markedly higher in Arm 1 (72.8 %) than Arm 2 (22.8 %), as were responder rates (≥50 % reduction in SSF; Arm 1: 62.5 %; Arm 2: 38.5 %) and rates of seizure freedom (Arm 1: 25.0 %; Arm 2: 9.6 %). Efficacy outcomes were generally more favorable in patients taking ESL in combination with LEV versus other anti-seizure medications (ASMs). Treatment-emergent adverse events (TEAEs; 81 % vs 73 %) and TEAEs leading to discontinuation (16 % vs 2 %) were reported more frequently in Arm 2 than Arm 1, respectively. Serious adverse events were reported infrequently (Arm 1: 0; Arm 2: 7 %). The most common TEAEs were dizziness, nausea, headache, somnolence, fatigue, nasopharyngitis, vomiting, and anxiety. There were no notable changes in depressive symptoms, mood status, or aggression throughout the study. Health and HRQoL scores were generally high at baseline and did not change throughout the study. However, on average, both clinicians and patients perceived improvement in illness over the course of the study.. ESL was effective and well tolerated both as the first adjunctive therapy to either of the most prescribed first-line ASMs, LEV or LTG, and as a later adjunctive therapy in treatment-resistant patients.

Topics: Anticonvulsants; Dibenzazepines; Double-Blind Method; Humans; Lamotrigine; Levetiracetam; Quality of Life; Seizures; Treatment Outcome

Recently, a novel trial design has been proposed to overcome challenges with traditional placebo-controlled trials of antiepileptic drugs in infants and young children (≥1 month of age) (Auvin S, et al. Epilepsia Open 2019;4:537-43). The proposed time-to-event trial design involves seizure counting by caregivers and allows adjustment of the duration of the baseline period and duration of exposure to placebo or potentially ineffective treatment based on the patient's seizure burden and response. We performed post hoc analyses to mimic this trial design and evaluate its viability. As these analyses required trials with prolonged baseline and treatment periods and diary data, which is not a typical design of trials in infants and young children (1 month to <4 years of age), data from two trials in pediatric patients (4-16 years of age) were used.. We performed post hoc analyses of two randomized, double-blind, placebo-controlled trials of adjunctive levetiracetam (N159; NCT00615615) and lacosamide (SP0969; NCT01921205) in children and adolescents (4-16 years of age) with focal-onset seizures. In these analyses, patients were followed until they completed the 10-week maintenance period, discontinued during the maintenance period, or reached their "nth" seizure (n = number of seizures patient had during baseline). Efficacy was assessed by determining time to nth seizure.. In the analyses of both trials, patients on levetiracetam or lacosamide had a 34% lower risk of reaching their baseline seizure count during their 10-week maintenance period than patients on placebo. The previously published primary results of these trials also demonstrated efficacy of adjunctive levetiracetam and lacosamide.. Although these were post hoc analyses of trials in older children (4-16 years of age), our results provide supportive evidence for the utility of the novel time-to-event trial design for future trials in infants and young children (1 month to <4 years of age).

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsies, Partial; Epilepsy; Humans; Lacosamide; Levetiracetam; Seizures

Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti-epileptic drug pharmacokinetics (PK). This prospective practice-based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1-hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient-specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12-46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36-73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.

Topics: Academic Medical Centers; Acute Kidney Injury; Administration, Intravenous; Administration, Oral; Aged; Anticonvulsants; Area Under Curve; Continuous Renal Replacement Therapy; Critical Illness; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Humans; Intensive Care Units; Levetiracetam; Male; Middle Aged; Prospective Studies; Renal Elimination; Seizures

There are no US Food and Drug Administration-approved therapies for neonatal seizures. Phenobarbital and phenytoin frequently fail to control seizures. There are concerns about the safety of seizure medications in the developing brain. Levetiracetam has proven efficacy and an excellent safety profile in older patients; therefore, there is great interest in its use in neonates. However, randomized studies have not been performed. Our objectives were to study the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment of neonatal seizures.. The study was a multicenter, randomized, blinded, controlled, phase IIb trial investigating the efficacy and safety of levetiracetam compared with phenobarbital as a first-line treatment for neonatal seizures of any cause. The primary outcome measure was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 neurophysiologists.. In this phase IIb study, phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures. Higher rates of adverse effects were seen with phenobarbital treatment. Higher-dose studies of levetiracetam are warranted, and definitive studies with long-term outcome measures are needed.

Topics: Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsy, Benign Neonatal; Female; Humans; Infant, Newborn; Levetiracetam; Male; Phenobarbital; Seizures

Prophylactic antiepileptic drugs (pAEDs) are often prescribed for seizure prophylaxis in patients undergoing surgical treatment of unruptured intracranial aneurysms (UIAs). We aimed to evaluate the benefit of pAEDs in patients undergoing surgical repair of UIAs.. We randomly assigned eligible patients undergoing surgical repair of UIAs to receive levetiracetam for seven days post-operatively or standard care alone. The primary outcome was the evaluation of seizures in the perioperative period (within 4 weeks). We also evaluated seizure occurrence throughout follow-up and assessed functional outcomes using the modified Rankin scale score (mRS).. 35 patients were randomized to the "no-levetiracetam" group and 41 patients were randomized to receive levetiracetam. The two study groups had similar overall baseline characteristics and the surgical complication rate was similar for both groups (p = 0.8). One patient in the "no-levetiracetam" group had a seizure in the perioperative period versus 2 patients in the group randomized to receive levetiracetam (2.9% vs 4.9%, respectively, p = 1.00). No patients in the "no-levetiracetam" group had any additional late seizures (mean follow-up of 20.4 months), but three patients in the levetiracetam group had late seizures during follow-up (mean follow-up of 19.1 months) (0% vs 7.3%, p = 0.2). mRS score of 0-2 at 90 days and at the latest follow-up were similar between the two groups (p = 1.00).. Perioperative seizure prophylaxis with levetiracetam does not reduce the rate of seizures as compared to controls in patients undergoing surgical repair of UIAs.

Topics: Adult; Aged; Anticonvulsants; Craniotomy; Drug Administration Schedule; Female; Humans; Intracranial Aneurysm; Levetiracetam; Male; Michigan; Microsurgery; Middle Aged; Prospective Studies; Risk Factors; Seizures; Time Factors; Treatment Outcome

Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.. Children 24-83 months old with CM were enrolled in an eLVT dose-finding study starting with standard dose (40 mg/kg load, then 30 mg/kg Q12 hours) titrated upward until seizure freedom was attained in 75% of subjects. The RCT that followed randomized children to eLVT vs. phenobarbital for acute seizures and compared the groups on minutes with seizures based upon continuous electroencephalogram. Due to safety concerns, midway through the study children allocated to phenobarbital received the drug only if they continued to have seizures (either clinically or electrographically) after benzodiazepine treatment. Secondary outcomes were treatment failure requiring cross over, coma duration and neurologic sequelae at discharge. PK and safety assessments were also undertaken.. Among 30 comatose CM children, eLVT was rapidly absorbed and well-tolerated. eLVT clearance was lower in patients with higher admission serum creatinine (SCr), but overall PK parameters were similar to prior pediatric PK studies. Within 4 h of the first dose, 90% reached therapeutic levels (> 20 μg/mL) and all were above 6 μg/mL. 7/7 children achieved seizure freedom on the initial eLVT dose. Comparing 23 eLVT to 21 phenobarbital patients among whom 15/21 received phenobarbital, no differences were seen for minutes with seizure, seizure freedom, coma duration, neurologic sequelae or death, but eLVT was safer (p = 0.019). Phenobarbital was discontinued in 3/15 due to respiratory side effects.. Enteral LVT offers an affordable option for seizure control in pediatric CM and is safer than phenobarbital.. NCT01660672 . NCT01982812 .

Topics: Acute Disease; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Coma; Cross-Over Studies; Electroencephalography; Female; Humans; Levetiracetam; Malaria, Cerebral; Malawi; Male; Phenobarbital; Seizures; Time Factors

Therapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) is an emerging and promising antiepileptic drug (AED). The aim of this phase II trial is to determine the benefits of LEV by applying a strict methodology and to estimate the optimal dose of LEV as a first-line AED to treat seizures in newborns suffering from hypoxic-ischaemic encephalopathy.. LEVNEONAT-1 is an open and sequential LEV dose-finding study. The optimal dose is that which is estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy is defined by a seizure burden reduction of 80% after the loading dose. Four increasing dose regimens will be assessed including one loading dose of 30, 40, 50 or 60 mg/kg followed by eight maintenance doses (ie, a quarter of the loading dose) injected every 8 hours. A two-patient cohort will be necessary at each dose level to consider an upper dose level assignment. The maximal sample size expected is 50 participants with a minimum of 24 patients or fewer in the case of a high rate of toxicity. Patients will be recruited in five neonatal intensive care units beginning in October 2017 and continuing for 2 years. In parallel, the LEV pharmacokinetics will be measured five times (ie, 30 min; 4 and 7 hours after the loading dose; 1-3 hours and 12-18 hours after the last maintenance dose).. Ethics approval has been obtained from the regional ethical committee (2016-R25) and the French Drug Safety Agency (160652A-31). The results will be published in a peer-reviewed journal. The results will also be presented at medical meetings.. NCT02229123; Pre-results.

Topics: Anticonvulsants; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; France; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Levetiracetam; Multicenter Studies as Topic; Seizures; Treatment Outcome

The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea.. In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes.. Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM.. In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures.

Topics: Adult; Anticonvulsants; Dizziness; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Republic of Korea; Seizures; Sleepiness; Topiramate

Treatment options for at-home management of cluster seizures (CS) and status epilepticus (SE) are limited. The pharmacokinetics of levetiracetam (LEV) after rectal administration in both healthy and epileptic dogs has been investigated recently.. To investigate the clinical efficacy of rectally administered LEV in preventing additional seizures in dogs presented for CS and SE. We hypothesized that rectal administration of LEV in addition to a standard treatment protocol would provide better control of seizure activity as compared with the standard treatment protocol alone.. Fifty-seven client-owned dogs with CS or SE.. Prospective open-label clinical trial. Patients included in the study were assigned to receive either a standard treatment protocol comprising IV/rectal diazepam and IV phenobarbital q8h (control group) or a standard treatment protocol in association with a single dose of 40 mg/kg LEV rectally (rectal LEV group). Dogs that experienced no additional seizures were defined as responders, whereas those that showed additional seizure activity were classified as nonresponders.. Twenty-one dogs were assigned to the rectal LEV group, and 36 to control group. Given the small number of cases of SE, statistical analysis was performed only on patients with CS. The response rate was 94% in the rectal LEV group and 48% in the control group (P < .001).. Rectally administered LEV combined with a standard treatment protocol provided good control of seizure activity in patients with CS. The validity of these results should be confirmed in a double-blinded, placebo-controlled clinical trial.

Topics: Administration, Intravenous; Administration, Rectal; Animals; Anticonvulsants; Diazepam; Dog Diseases; Dogs; Levetiracetam; Male; Phenobarbital; Seizures; Status Epilepticus

Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates.. The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures.. This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1).. We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB.. This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age group.

Topics: Anticonvulsants; Female; Humans; Infant, Newborn; Italy; Levetiracetam; Male; Neurodevelopmental Disorders; Phenobarbital; Prospective Studies; Seizures; Treatment Outcome

Seizures occur in 10-20% of patients with subarachnoid hemorrhage (SAH), predominantly in the acute phase. However, anticonvulsant prophylaxis remains controversial, with studies suggesting a brief course may be adequate and longer exposure may be associated with worse outcomes. Nonetheless, in the absence of controlled trials to inform practice, patients continue to receive variable chemoprophylaxis. The objective of this study was to compare brief versus extended seizure prophylaxis after aneurysmal SAH.. We performed a prospective, single-center, randomized, open-label trial of a brief (3-day) course of levetiracetam (LEV) versus extended treatment (until hospital discharge). The primary outcome was in-hospital seizure. Secondary outcomes included drug discontinuation and functional outcome.. Eighty-four SAH patients had been randomized when the trial was terminated due to slow enrollment. In-hospital seizures occurred in three (9%) of 35 in the brief LEV group versus one (2%) of 49 in the extended group (p = 0.2). Ten (20%) of the extended group discontinued LEV prematurely, primarily due to sedation. Four of five seizures (including one pre-randomization) occurred in patients with early brain injury (EBI) on computed tomography (CT) scans (adjusted OR 12.5, 95% CI 1.2-122, p = 0.03). Good functional outcome (mRS 0-2) was more likely in the brief LEV group (83 vs. 61%, p = 0.04).. This study was underpowered to demonstrate superiority of extended LEV for seizure prophylaxis, although a trend to benefit was seen. Seizures primarily occurred in those with radiographic EBI, suggesting targeted prophylaxis may be preferable. Larger trials are required to evaluate optimal chemoprophylaxis in SAH, especially in light of worse outcomes in those receiving extended treatment.

Topics: Adult; Aged; Anticonvulsants; Female; Humans; Intracranial Aneurysm; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Prospective Studies; Seizures; Subarachnoid Hemorrhage

Prediction of brivaracetam effects in children was obtained by scaling an existing adult pharmacokinetic/pharmacodynamic (PK/PD) model for brivaracetam to children, using an existing population PK model for brivaracetam in children. The scaling was supported by estimating the change from adults to children in the concentration-effect relationship parameters for levetiracetam, a compound interacting with the same target protein (synaptic vesicle protein SV2A).. The existing adult PK/PD model for brivaracetam was applied to a combined adult-pediatric dataset of levetiracetam. This model was then used to predict the effective oral twice-daily dose of brivaracetam in children aged ≥4 to <16 years as adjunctive treatment for focal (partial onset) seizures. The existing model described daily seizure counts using a negative binomial distribution, taking previous-day seizure frequencies into account, and using a mixture model to separate 'placebo-like' and 'responder' subpopulations. The model was adapted to describe aggregated monthly seizure counts for adult patients in the levetiracetam studies: daily seizure counts were only available for children in the levetiracetam studies.. The levetiracetam PK/PD model successfully described both the adult and pediatric data using the same drug effect parameters, and using a model structure similar to the existing adult brivaracetam PK/PD model.. Simulation with the adult brivaracetam PK/PD model in combination with an existing pediatric brivaracetam population PK model allowed characterization of the dose-response curve, suggesting maximum response at brivaracetam 4 mg/kg/day dosing (capped at 200 mg/day, the maximum adult dose) in children aged ≥4 years.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Models, Theoretical; Pyrrolidinones; Seizures; Young Adult

Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control.. To determine if, in pregnant women with epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels.. A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken. Stratified block randomisation with a 1 : 1 allocation method was carried out.. Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK.. Pregnant women with epilepsy on one or more of the following AEDs: lamotrigine, carbamazepine, phenytoin or levetiracetam. Women with a ≥ 25% decrease in serum AED level from baseline were randomised to therapeutic drug monitoring or clinical features monitoring strategies.. In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control. In the clinical features monitoring group, AED dosage adjustment was based only on clinical features.. Primary outcome - seizure deterioration, defined as time to first seizure and to all seizures after randomisation per woman until 6 weeks post partum. Secondary outcomes - pregnancy complications in mother and offspring, maternal quality of life, seizure rates in cohorts with stable serum AED level, AED dose exposure and adverse events related to AEDs.. Analysis of time to first and to all seizures after randomisation was performed using a Cox proportional hazards model, and multivariate failure time analysis by the Andersen-Gill model. The effects were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes were reported as mean differences (MDs) or odds ratios.. A total of 130 women were randomised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group; 294 women did not have a reduction in serum AED level. A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group (98% of complete data) were included in the primary analysis. There were no significant differences in the time to first seizure (HR 0.82, 95% CI 0.55 to 1.2) or timing of all seizures after randomisation (HR 1.3, 95% CI 0.7 to 2.5) between both trial groups. In comparison with the group with stable serum AED levels, there were no significant increases in seizures in the clinical features monitoring (odds ratio 0.93, 95% CI 0.56 to 1.5) or therapeutic drug monitoring group (odds ratio 0.93, 95% CI 0.56 to 1.5) associated with a reduction in serum AED levels. Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) in the therapeutic drug monitoring group than in the clinical features monitoring group. There were no differences between the groups on daily AED exposure or quality of life. An increase in exposure to lamotrigine, levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs, but not maternal or fetal complications. Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs.. Fewer women than the original target were recruited.. There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes.. Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both randomised groups is needed. An individualised prediction model will help to identify those women who need close monitoring in pregnancy.. Current Controlled Trials ISRCTN01253916.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in

Topics: Anticonvulsants; Carbamazepine; Double-Blind Method; Drug Monitoring; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Phenytoin; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Quality of Life; Seizures; United Kingdom

Levetiracetam can be used for seizure control alone or in combination with other antiepileptic medications. A previous study achieved the minimum targeted serum drug concentration after rectal administration of levetiracetam in healthy dogs. The purpose of the present study was to determine the pharmacokinetics of rectal LEV in dogs presented for cluster seizures or status epilepticus and potentially in treatment with other anti-epileptic drugs. Furthermore, preliminary information on response to this treatment as add-on to the standard treatment protocol is reported.. Eight client-owned dogs were enrolled. Plasma levetiracetam concentrations (measured at 0, 30, 60, 90, 120, 180, 240, 360, 720, and 1440 min after drug administration) reached the minimum target concentration (5 μg/ml) at 30 min in all but one patient. At T1 (30 min) the mean concentration was 28.2 ± 15.5 μg/ml. Plasma concentrations remained above the targeted minimum concentration in all patients until 240 min and in 7/8 until 360 min. Six out of eight patients experienced no seizures in the 24-h period after hospitalization and were classified as "responders".. Minimum plasma levetiracetam concentration can be reached after rectal administration of 40 mg/kg in dogs affected by cluster seizures and status epilepticus and concurrently receiving other antiepileptic drugs. These preliminary results may encourage the evaluation of rectal levetiracetam as an additional treatment option for cluster seizures and status epilepticus in a larger number of dogs.

Topics: Administration, Rectal; Animals; Anticonvulsants; Dog Diseases; Dogs; Female; Levetiracetam; Male; Pilot Projects; Piracetam; Seizures; Status Epilepticus

Levetiracetam has been introduced for the control of seizures besides phenobarbital as monotherapy in children with epilepsy. This study was aimed to compare the effectiveness of these two drugs for the control of seizures in epilepsy. This randomized controlled trial was done to assess the efficacy and tolerability of levetiracetam compared to phenobarbital in childhood epilepsy and was conducted in Institute of Pediatric Neurodisorder and Autism (IPNA), Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh among children between 1 month to 15 years who were diagnosed as cases of epilepsy (idiopathic focal, generalized, focal with secondary generalization) according to ILAE to assess the effect of Levetiracetam (n=50) and Phenobarbital (n=68) from May 2015 to July 2016. The children were followed up for 12 months at 3 months interval to compare the seizure remission and side effects of Levetiracetam and Phenobarbital. The children in levetiracetam group was about 10 months older along with older age of onset of seizure (p=0.02) than those of phenobarbital group (p=0.03 and 0.02 respectively). GTCS was the most common type of seizure in both groups. During 3 months of intervention 55.8% patients of levetiracetam group achieved 50-75% seizure remission compared to 44.2% in phenobarbital group, at 6 months period 75-100% seizure remission observed among 57.4% patients of levetiracetam group compared to 42.6% of phenobarbital group (p=0.06), which continued to increase at 9 months in levetiracetam (n=33, 55.9%) compared to phenobarbital (n=26, 44.1%) and this value is statistically significant (p=0.05). No further improvement observed at 12 months follow up. Behavioral problem was reported among 4 patients of phenobarbital group without any evidence of cognitive deterioration, only 3 patients of levetiracetam experienced irritability, but no children of both group discontinued treatment due to side effects. Levetiracetam mono-therapy is more effective in controlling seizures in focal, generalized and focal with secondary generalization epilepsy compared to phenobarbital with minimum side effects.

Topics: Adolescent; Anticonvulsants; Bangladesh; Child; Child, Preschool; Cognition; Drug Monitoring; Epilepsy, Generalized; Female; Humans; Infant; Levetiracetam; Male; Phenobarbital; Problem Behavior; Seizures; Treatment Outcome

To study efficacy and safety of prophylactic levetiracetam (LEV) administration in adults undergoing cranioplasty.. We prospectively enrolled and randomly divided 200 adults undergoing cranioplasty into 2 groups: LEV (prophylactic LEV for 24 weeks) and control (no prophylactic antiepileptic drugs). Demographic and clinical characteristics; occurrence of postoperative seizure; changes in IQ, memory quotient, and activities of daily living scores; and postoperative side effects during hospital stay were analyzed at 2-, 24-, and 48-week follow-up visits.. Significant differences were found between groups in both early-stage seizures in the initial 2 weeks and late-stage seizures in the 3-24 weeks after cranioplasty (P < 0.05). Postoperative seizures occurred in 17.0% in the control group and 4.1% in the LEV group 48 weeks after cranioplasty, which was found to be significant (P = 0.0020). Patients with abnormal preoperative or postoperative electroencephalography (EEG) with spikes or sharp waves presented with an increased number of postoperative seizures compared with patients with normal EEG readings at 48 weeks. Significant differences were found between patients with postoperative seizures and patients without postoperative seizures in regard to changes in IQ, memory quotient, activities of daily living, and patient satisfaction scores (P < 0.01). No significant difference was found in side effects between the 2 groups.. Postoperative seizure is a common complication of cranioplasty, especially in patients with preoperative or postoperative abnormal EEG with spikes or sharp waves. Prophylactic LEV administration significantly reduced postcranioplasty seizures during LEV usage and had few side effects.

Topics: Adult; Anticonvulsants; Craniotomy; Electroencephalography; Female; Humans; Intracranial Hypertension; Kaplan-Meier Estimate; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Retrospective Studies; Seizures; Surgery, Plastic; Tomography Scanners, X-Ray Computed

Status Epilepticus (SE) is a common medical emergency carrying a high morbidity and mortality. Levetiracetam (LEV) is a novel anticonvulsant effective against varied seizures. Few prospective studies have addressed its use in SE. We aimed to examine the efficacy of intravenous LEV in controlling SE and cluster attacks of seizures (CS), in comparison with IV phenytoin (DPH), using a prospective, randomized study design.. Adult patients with SE or CS, following an initial dose of IV benzodiazepine to control ongoing seizure, were randomized to receive either medication. Rates of seizure control over 24h, adverse effects and outcomes were compared. A logistic regression model was used to identify outcome predictors.. 52 patients with SE and 63 with CS received either LEV or DPH. In the SE group, LEV was effective in18/22(82%) and DPH in 22/30(73.3%) patients in controlling seizures. Among patients with CS, LEV was effective in 31/38(81.6%) and DPH in 20/25(80%). With the use of LEV, DPH or both, SE and CS were controlled among 92% and 96% of patients respectively. Adverse events included hypotension (in 2 on DPH) and transient agitation (2 on LEV).. IV Levetiracetam controls status epilepticus or cluster seizures with an efficacy comparable to that of phenytoin. Use of these two agents consecutively may control >90% of all such conditions without resort to anaesthetic agents. Further studies should explore its efficacy in larger cohorts of epileptic emergencies.

Topics: Adult; Anticonvulsants; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Prospective Studies; Seizures; Status Epilepticus

Treatment of canine epilepsy is problematic. Few antiepileptic drugs have proven efficacy in dogs and undesirable adverse effects and pharmacoresistance are not uncommon. Consequently, the need for investigation of alternative treatment options is ongoing. The objective of this study was to investigate the efficacy and tolerability of levetiracetam as mono-therapy in dogs with idiopathic epilepsy. The study used a prospective single-blinded parallel group design. Twelve client-owned dogs were included and were randomised to treatment with levetiracetam (30 mg/kg/day or 60 mg/kg/day divided into three daily dosages) or phenobarbital (4 mg/kg/day divided twice daily). Control visits were at days 30, 60 and then every 3 months for up to 1 year. Two or more seizures within 3 months led to an increase in drug dosage (levetiracetam: 10 mg/kg/day, phenobarbital: 1 mg/kg/day). Five of six levetiracetam treated dogs and one of six phenobarbital treated dogs withdrew from the study within 2-5 months due to insufficient seizure control. In the levetiracetam treated dogs there was no significant difference in the monthly number of seizures before and after treatment, whereas in the phenobarbital treated dogs there were significantly (P = 0.013) fewer seizures after treatment. Five phenobarbital treated dogs were classified as true responders (≥50% reduction in seizures/month) whereas none of the levetiracetam treated dogs fulfilled this criterion. Adverse effects were reported in both groups but were more frequent in the phenobarbital group. In this study levetiracetam was well tolerated but was not effective at the given doses as mono-therapy in dogs with idiopathic epilepsy.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Female; Levetiracetam; Male; Phenobarbital; Piracetam; Prospective Studies; Seizures; Single-Blind Method

This was an open-label study (N01281 [NCT00419393]) assessing the long-term safety of extended-release levetiracetam (LEV XR) in patients with partial-onset seizures (POS); the study was a follow-up to a double-blind, randomized, historical controlled, multicenter, conversion to monotherapy study (N01280 [NCT00419094]). Eligible patients initially received LEV XR 2000 mg/day; dose adjustments and the addition of other antiepileptic drugs (AEDs) were permitted. Overall, 190 patients were enrolled, 189 (99.5%) received LEV XR (safety and efficacy populations) and 166 patients (87.4%) completed the study. The study duration in completed patients was 5.5-24.6 months. Mean daily dose of LEV XR was 2131 mg/day. Treatment-emergent adverse events (TEAEs) occurred in 126 patients (66.7%); most were of mild or moderate severity. Five patients (2.6%) had a TEAE that led to treatment discontinuation. Treatment-emergent serious adverse events occurred in 22 patients (11.6%). Twenty-six patients (13.8%) experienced a psychiatric TEAE. The median 7-day normalized POS frequency was: 1.38 at N01280 study baseline; 0.50 at the first visit of N01281 (last visit of N01280); and 0.00-0.36 between all subsequent visits. Overall, 171 patients (90.5%) entered the N01281 study on LEV XR monotherapy; 65.3% (32/49) of patients remained on monotherapy for 12 months and 47.1% (8/17) for 18 months. While remaining on LEV XR monotherapy, 27/139 patients (19.4%) were seizure-free at 6 months and 8/49 (16.3%) at 12 months. In conclusion, LEV XR was well tolerated when administered as long-term monotherapy or in combination with other AEDs in patients with inadequately controlled POS.

Topics: Adult; Anticonvulsants; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Treatment Outcome

To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults.. Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool.. In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The ≥50% responder rate was 34.2% (50 mg/d, p = 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment-emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n = 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in ≥5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%).. Adjunctive BRV was effective and generally well tolerated in adults with POS.. This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Pyrrolidinones; Seizures; Young Adult

To evaluate the efficacy and safety of levetiracetam (LEV) in the management of seizures in neonates.. A prospective non-blind, single arm clinical trial conducted in the Department of Neonatology and Pediatric Intensive Care, Mohamad Kermanshahi, and Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran from May 2014 to December 2014. Fifty out of 60 newborns with gestational age >/=30 weeks with clinically diagnosed seizures were included. Levetiracetam was administered orally with an initial dose of 10 mg/kg twice a day. The patients were observed continuously by Neuro Intensive Care nurses, and visited daily by a neuropediatrician in the first 7 days and then at days 14, 30, and 90 after the start of LEV administration. Clinical examination was performed for every patient, and seizure number, antiepileptic medication, and adverse events were detailed at every visit.. 47 infants were seizure free under LEV at the end of the first week, 47 remained seizure free at 4 weeks, and 46 remained seizure free at 11 weeks. No immediate and long-term side effects were noted in our patients.. This study investigated the efficacy and safety of LEV in neonatal seizure control but confirmation with further randomized controlled trials is required.

Topics: Anticonvulsants; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Iran; Levetiracetam; Male; Phenobarbital; Phenytoin; Piracetam; Seizures; Treatment Outcome

Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients.. This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged ≥ 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age.. Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs.. 0.46 (0.16-1.33); LEV vs.. 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively.. Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged ≥ 60 years with newly diagnosed epilepsy.. ClinicalTrials.gov: NCT00175903 ; September 9, 2005.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Valproic Acid

Phenytoin (PHT) is routinely used for seizure prophylaxis in patients with brain tumours during and after craniotomy, despite incomplete evidence. We performed a prospective, randomised study to investigate the significance of prophylactic use of levetiracetam (LEV), in comparison with PHT, for patients with supratentorial tumours in the perioperative period.. Patients were randomised to receive LEV, 500 mg/body every 12 h until postoperative day 7, or PHT, 15-18 mg/kg fosphenytoin followed by 125 mg PHT every 12 h until postoperative day 7. The primary end point was the occurrence of seizures, and secondary end points included the occurrence of haematological and non-haematological adverse events.. One hundred and forty-six patients were randomised to receive LEV (n=73) or PHT (n=73). The incidence of seizures was significantly less in the LEV group (1.4%) compared with the PHT group (15.1%, p=0.005), suggesting benefit of LEV over PHT. The observed OR for being seizure free in the LEV prophylaxis group relative to the PHT group was 12.77 (95% CI 2.39 to 236.71, p=0.001). In a subgroup analysis of patients who did not have seizures before craniotomy, similar results were demonstrated: the incidence of seizures was 1.9% (LEV) and 13.8% (PHT, p=0.034), and OR was 8.16 (95% CI 1.42 to 154.19, p=0.015). LEV was completed in all cases, although PHT was withdrawn in five patients owing to liver dysfunction (1), skin eruption (2) and atrial fibrillation (2).. Prophylactic use of LEV in the perioperative period is recommended because it is safe and significantly reduces the incidence of seizures in this period.. UMIN13971.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Cohort Studies; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Neurosurgical Procedures; Phenytoin; Piracetam; Postoperative Complications; Prospective Studies; Seizures; Treatment Outcome; Young Adult

To evaluate the efficacy of levetiracetam (LEV) and the usefulness of measurement of its blood levels during the follow-up of patients with focal seizures.. Twenty-four patients (13 cases without impairment of consciousness or awareness and 11 cases with them or evolving to a bilateral, convulsive seizure) treated with LEV had their peak blood levels measured. The blood concentrations were measured at 2 weeks, 1 year and 2 years after reaching the LEV maintenance dosage. The efficacy of LEV was evaluated with repeated blood sampling to determine the seizure reduction rate. The patients were classified as effective cases (seizure reduction rate>50%) and ineffective cases (⩽50%).. In Japanese children treated with LEV, the dosage and blood level showed positive correlations. The blood levels were higher in effective cases than in ineffective cases at all time points (p<0.05). In effective cases, the blood concentration was 23.26±6.88 μg/mL (mean±SD) 2 weeks later, 23.59±8.23 μg/mL 1 year later, and 24.46±7.57 μg/mL 2 years later. However, the blood levels and efficacies showed positive correlations only at 2 weeks and 1 year later. No patients had any side effects.. No precise definition of the therapeutic range was possible because of the incomplete correlation between the blood level and seizure frequency. Instead of a therapeutic range, we recommend an optimal range for LEV of 20-30 μg/mL as a therapeutic target without any side effects.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Piracetam; Prospective Studies; Seizures; Treatment Outcome

To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen.. NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week titration phase (initiation on 150mg/day [50mg three times daily (TID)] with weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a flexible dose evaluation (FDE) phase (optional weekly dose changes of 50-150mg/day, to an optimal daily dosage [300-1200mg/day]). The primary efficacy endpoint was percentage of patients experiencing a ≥50% reduction from baseline in partial seizure frequency (responder rate) during the treatment phase (titration and FDE phases). Safety and tolerability were also assessed.. Patients (N=203) were enrolled and received ≥1 dose of EZG/RTG. The dose of EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC), 32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity.. EZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed.

Topics: Aged; Anticonvulsants; Carbamates; Carbamazepine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Kaplan-Meier Estimate; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenylenediamines; Piracetam; Seizures; Treatment Outcome; Triazines; Valproic Acid

Following the first period of the multicenter, open-label, single-armed N01223 trial, the second period of the N01223 trial was conducted to evaluate long-term safety, along with the efficacy of adjunctive levetiracetam treatment (individualized dose range, 20-60 mg/kg/day or 1,000-3,000 mg/day) in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). Of the 62 children who completed the first period, 55 children [age: 10.4 ± 3.4 years (mean ± standard deviation)] were elected to enter the second period for a maximum of 39 months. Twenty children were withdrawn during this second period. Frequencies of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 98.2% (54/55 cases) and 27.3% (15/55 cases), respectively. The most common TEAEs were nasopharyngitis (76.4%), influenza (36.4%) and pyrexia (25.5%). The only frequent ADR (>2%) was somnolence (3.6%). Although serious TEAEs and death were reported in 8 cases and 1 case (drowning), respectively, a serious ADR was only reported in 1 case (vomiting). The median percentage reduction and 50% response rate for POS were 43.32% and 41.8%, respectively. One child showed a maximum seizure-free period of 163 days. In conclusion, levetiracetam demonstrated long-term safety and good tolerance with beneficial efficacy as an adjunctive therapy in Japanese children with uncontrolled POS. (Received June 30, 2015; Accepted July 14, 2015: Published November 1, 2015).

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Seizures; Time; Treatment Outcome

Electrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep.. A multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response.. After a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects.. Levetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.

Topics: Anticonvulsants; Brain; Child; Child, Preschool; Electroencephalography; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Retrospective Studies; Seizures; Sleep; Status Epilepticus; Time Factors; Treatment Outcome

Brain Trauma Foundation guidelines recommend seizure prophylaxis for preventing early posttraumatic seizure (PTS). Phenytoin (PHE) is commonly used. Despite a paucity of data in traumatic brain injury, levetiracetam (LEV) has been introduced as a potential replacement, which is more costly but does not require serum monitoring. The purpose of this study was to compare the efficacy of PHE with that of LEV for preventing early PTS.. Consecutive blunt traumatic brain injury patients undergoing seizure prophylaxis were prospectively enrolled at two Level 1 trauma centers during a 33-month period. Seizure prophylaxis was administered according to local protocol. Patients were monitored prospectively throughout their hospital stay for clinical evidence of seizure activity. PHE was compared with LEV with clinical early PTS as the primary outcome measure, defined as a seizure diagnosed clinically, occurring within 7 days of admission.. A total of 1,191 patients were screened for enrollment, after excluding 378 (31.7%) who did not meet inclusion criteria; 813 (68.3%) were analyzed (406 LEV and 407 PHE). There were no significant differences between LEV and PHE in age (51.7 [21.3] vs. 53.6 [22.5], p = 0.205), male (73.9% vs. 68.8%, p = 0.108), Injury Severity Score (ISS) (20.0 [10.0] vs. 21.0 [10.6], p = 0.175), Marshall score of 3 or greater (18.5% vs. 14.7%, p = 0.153), or craniectomy (8.4% vs. 11.8%, p = 0.106). There was no difference in seizure rate (1.5% vs.1.5%, p = 0.997), adverse drug reactions (7.9% vs. 10.3%, p = 0.227), or mortality (5.4% vs. 3.7%, p = 0.236).. In this prospective evaluation of early PTS prophylaxis, LEV did not outperform PHE. Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent.. Therapeutic study, level III.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Injuries; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Length of Stay; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Prospective Studies; Seizures; Survival Rate; Trauma Centers; Treatment Outcome; United States; Young Adult

A multicenter, open-label, single-armed study (N01223) was conducted to evaluate efficacy and safety of levetiracetam (LEV) as an add-on therapy in Japanese pediatric patients with uncontrolled partial-onset seizures (POS). A total of 73 children aged 4-15 years (mean±SD=10.1±3.4 years) were enrolled in the study, which consisted of an 8-week baseline period and a 14-week treatment period, including a 4-week titration period. A historical placebo control from a pivotal overseas pediatric study in POS add-on therapy was used. A 16.3% median percent reduction from the baseline in POS was observed in this placebo control. Therefore, in the present study, this value (16.3%) was chosen as the predefined threshold for the lower limit of the 95% confident interval (95% CI) of the median percent reduction from the baseline for LEV. In the present study, the percentage reduction (95% CI) in POS during the treatment period was 43.21% (26.19-52.14%), indicating a beneficial impact of LEV. The incidences of treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were 82.2% (60/73 cases) and 56.2% (41/73 cases), respectively. The most common TEAEs were somnolence, nasopharyngitis, upper respiratory tract infection, and pyrexia. Frequent ADRs (more than 3%) were somnolence and feeling jittery. No serious TEAE or death was reported during the study. Our results suggested that adjunctive therapy with LEV is clinically efficacious and well tolerated in Japanese children with uncontrolled POS.

Topics: Adolescent; Asian People; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Nootropic Agents; Piracetam; Seizures; Treatment Outcome

Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous agents and requirements of special patient groups. This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting.. This prospective, randomized, single-center study with appropriate blinding comprised evaluation pertaining to intravenous use 3 days following craniotomy and at discharge, and to total intravenous-plus-oral AED regimen at 90 days. Primary tolerability end points were discontinuation because of side effect and first side effect. Safety combined end point was major side effect or seizure. Seizure occurrence and side effect profiles were compared as secondary outcomes.. Of 81 patients randomized, 74 (36 LEV, 38 PHT) received parenteral AEDs. No significant difference attributable to intravenous use was found between LEV and PHT in discontinuation because of side effect (LEV 1/36, PHT 2/38, p = 1.00) or number of patients with side effect (LEV 1/36, PHT 4/38, p = 0.36). No significant difference was found between LEV and PHT total intravenous-plus-oral regimen in discontinuation because of side effect (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.21-2.92, p = 0.72) or number of patients with side effect (HR 1.51, 95% CI 0.77-2.98, p = 0.22). More patients assigned PHT reached the undesirable clinical end point for safety of major side effect or seizure (HR 0.09, 95% CI 0.01-0.70, p = 0.002). Seizures occurred only in patients assigned PHT (n = 6, p = 0.01). Although not significant, trends were observed for major side effect in more patients assigned PHT (p = 0.08) and mild side effect in more assigned LEV (p = 0.09).. Both LEV and PHT are well-tolerated perioperatively in parenteral preparation, and in total intravenous-plus-oral prophylactic regimen. Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures

Levetiracetam (LEV) is a newer anticonvulsant with a favorable safety profile. There seem to be no relevant drug interactions, and an intravenous formulation is available. Therefore, LEV might be a suitable drug for the perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosurgery.. In this prospective study (NCT00571155) patients with suspected primary brain tumors and tumor-related seizures were perioperatively treated with oral and intravenous LEV up to 4 weeks before and until 4 weeks after a planned neurosurgical procedure.. Thirty patients with brain tumor-related seizures and intended neurosurgery were included. Three patients did not undergo the scheduled surgery after enrollment, and two patients were lost to follow-up. Therefore, 25 patients were fully evaluable. After initiation of therapy with LEV, 100% of the patients were seizure-free in the pre-surgery phase (3 days up to 4 weeks before surgery), 88% in the 48 h post-surgery phase and 84% in the early follow-up phase (48 h to 4 weeks post surgery). Treatment failure even after dose escalation to 3,000 mg/day occurred in three patients. No serious adverse events related to the treatment with LEV occurred.. Our data show the feasibility and safety of oral and intravenous LEV in the perioperative treatment of tumor-related seizures. Although this was a single arm study, the efficacy of LEV appears promising. Considering the side effects and interactions of other anticonvulsants, LEV seems to be a favorable option in the perioperative treatment of brain tumor-related seizures.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Brain Neoplasms; Chemotherapy, Adjuvant; Electroencephalography; Feasibility Studies; Female; Follow-Up Studies; Glioma; Humans; Infusions, Intravenous; Levetiracetam; Male; Meningioma; Middle Aged; Monitoring, Physiologic; Neurosurgery; Neurosurgical Procedures; Pilot Projects; Piracetam; Prospective Studies; Seizures; Treatment Outcome; Young Adult

To evaluate the long-term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE).. This phase III, open-label, long-term, follow-up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic-clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000-4,000 mg/day; 20-80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention-to-treat (ITT) population, N = 217] and subpopulations with tonic-clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline.. One hundred twenty-five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1-Q3) exposure to LEV was 2.1 (1.5-2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or ≥2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of ≥6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of ≥6 months from tonic-clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment-emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%).. Adjunctive LEV (range 1,000-4,000 mg/day) demonstrated efficacy as a long-term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety; Child; Child, Preschool; Depression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome; Young Adult

Strokes are the leading cause of epileptic seizures in adults and account for 50% of seizures in those over the age of 65 years. The use of antiepileptic drugs to prevent recurrent poststroke seizures is recommended.. One hundred and twenty-eight patients with poststroke seizures were randomly allocated to treatment with either levetiracetam (LEV) or sustained-release carbamazepine (CBZ) in a multicenter randomized open-label study. After a titration study phase (2 weeks), the optimal individual dose of trial medication was determined and treatment was continued for another 52 weeks. The primary endpoint was defined as the proportion of seizure-free patients; the secondary endpoints were: evaluation of time recurrence to the first seizure, EEG tracings, cognitive functions and side effects.. Of 128 patients, 22 discontinued the trial prematurely; thus a total of 106 patients (52 treated with LEV and 54 treated with CBZ) were included in the analysis. The results of the study were as follows: no significant difference in number of seizure-free patients between LEV and CBZ (p = 0.08); time to the first recurrence tended to be longer among patients on LEV; there was no correlation between the therapeutic effect and the EEG findings in either treatment group; LEV caused significantly fewer (p = 0.02) side effects than CBZ; attention deficit, frontal executive functions and functional scales (Activities of Daily Living and Instrumental Activities of Daily Living indices) were significantly worse in the CBZ group.. This trial suggests that LEV may be a valid alternative to CBZ in poststroke seizures, particularly in terms of efficacy and safety. In addition, our results show that LEV has significant advantages over CBZ on cognitive functions. This trial also indicates that LEV in monotherapy is a safe and effective therapeutic option in elderly patients who have suffered epileptic seizures following a stroke.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures; Stroke; Treatment Outcome

To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 μg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study.. Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury.. Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.. Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 μg/ml or greater, 20 μg/ml or greater, and 6-20 μg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 μg/ml, minimum serum concentration 3.1 ± 1.8 μg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 μg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 μg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 μg/ml.. Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 μg/ml.

Topics: Anticonvulsants; Brain Injuries; Critical Care; Female; Hematoma, Subdural; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Monte Carlo Method; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Cognitive impairment and seizures are common in our aging population. Anticonvulsant treatment is problematic due to sedation, cognitive slowing, and behavioral changes. Levetiracetam has favorable pharmacokinetics, good efficacy in elderly individuals, a favorable side effect profile, and lacks major drug interactions. We conducted a prospective, uncontrolled, phase 4, open label, 12-week study of levetiracetam to better profile its efficacy, safety, and impact on cognitive/behavioral status in 24 cognitively impaired, elderly individuals. In total, 69% were seizure free for the duration of the study; the remaining participants had satisfactory seizure control. Fatigue was the most common side effect (5 participants). Significant overall improvements were observed for the Folstein's Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive. No significant changes were seen in behavioral or functional measures. Levetiracetam is an effective antiepileptic drug in elderly individuals with cognitive impairment. At 3 months, participants who remained on levetiracetam showed excellent cognitive tolerability.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Cognition; Cognition Disorders; Disease-Free Survival; Fatigue; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Psychiatric Status Rating Scales; Seizures; Severity of Illness Index; Treatment Outcome

Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury. We performed a study comparing intravenous (IV) levetiracetam (LEV) to IV phenytoin (PHT) for seizure prophylaxis after neurological injury.. In this prospective, single-center, randomized, single-blinded comparative trial of LEV versus PHT (2:1 ratio) in patients with severe traumatic brain injury (sTBI) or subarachnoid hemorrhage (NCT00618436) patients received IV load with either LEV or fosphenytoin followed by standard IV doses of LEV or PHT. Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures. Continuous EEG (cEEG) monitoring was performed for the initial 72 h; outcome data were collected.. A total of 52 patients were randomized (LEV = 34; PHT = 18); 89% with sTBI. When controlling for baseline severity, LEV patients experienced better long-term outcomes than those on PHT; the Disability Rating Scale score was lower at 3 months (P = 0.042) and the Glasgow Outcomes Scale score was higher at 6 months (P = 0.039). There were no differences between groups in seizure occurrence during cEEG (LEV 5/34 vs. PHT 3/18; P = 1.0) or at 6 months (LEV 1/20 vs. PHT 0/14; P = 1.0), mortality (LEV 14/34 vs. PHT 4/18; P = 0.227). There were no differences in side effects between groups (all P > 0.15) except for a lower frequency of worsened neurological status (P = 0.024), and gastrointestinal problems (P = 0.043) in LEV-treated patients.. This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients. LEV appears to be an alternative to PHT for seizure prophylaxis in this setting.

Topics: Adult; Anticonvulsants; Brain Injuries; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Prospective Studies; Seizures; Single-Blind Method; Subarachnoid Hemorrhage

At present, neonatal seizures are usually treated with Phenobarbital (PB) despite the limited efficacy and the potential risk this treatment holds for the developing brain. We report here a prospective pilot feasibility study on the use of Levetiracetam as monotherapy in the treatment of neonatal seizures.. Six newborns (body weight>2000 g, gestational age>30 weeks) presenting with neonatal seizures were enrolled. Patients whose seizures were caused by electrolyte disturbances or hypoglycemia, or whose seizures did respond to pyridoxine were excluded. Patients previously treated with other antiepileptic drugs (AEDs), with the exception of single PB doses before and during titration, were excluded. LEV was administered orally, increasing the dose by 10mg/(kg day) over 3 days. Endpoint was the need of any additional AEDs (or PB) after day 3, or 3 months of LEV treatment. A decision regarding further treatment was made on an individual basis and follow-up was documented up to 8 months of age.. No severe adverse effects were observed. Mild sedation was reported in one infant. All six patients treated with oral LEV became seizure free within 6 days. Five patients remained seizure free after 3 months with ongoing LEV monotherapy. One infant developed pharmacoresistant epilepsy. Seizures relapsed later in the clinical course of two more patients, one of whom was no longer under LEV therapy.. Results from our small patient group indicate that LEV may be an alternative therapeutic option in neonatal seizures.

Topics: Anticonvulsants; Feasibility Studies; Female; Humans; Infant, Newborn; Levetiracetam; Male; Pilot Projects; Piracetam; Seizures; Treatment Outcome

Seizures are common in patients with gliomas, and phenytoin (PHT) is frequently used to control tumor-related seizures. PHT, however, has many undesirable side effects (SEs) and drug interactions with glioma chemotherapy. Levetiracetam (LEV) is a newer antiepileptic drug (AED) with fewer SEs and essentially no drug interactions. We performed a pilot study testing the safety and feasibility of switching patients from PHT to LEV monotherapy for postoperative control of glioma-related seizures. Over a 13-month period, 29 patients were randomized in a 2:1 ratio to initiate LEV therapy within 24 h of surgery or to continue PHT therapy. 6 month follow-up data were available for 15 patients taking LEV and for 8 patients taking PHT. In the LEV group, 13 patients (87%) were seizure-free. In the PHT group, 6 patients (75%) were seizure-free. Reported SEs at 6 months was as follows (%LEV/%PHT group): dizziness (0/14), difficulty with coordination (0/29), depression (7/14) lack of energy or strength (20/43), insomnia (40/43), mood instability (7/0). The pilot data presented here suggest that it is safe to switch patients from PHT to LEV monotherapy following craniotomy for supratentorial glioma. A large-scale, double-blinded, randomized control trial of LEV versus PHT is required to determine seizure control equivalence and better assess differences in SEs.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Craniotomy; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Pilot Projects; Piracetam; Seizures

To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV; Keppra) as an adjunctive therapy for Chinese patients with refractory partial seizures.. This randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period, and concluded with a 4-week medication withdrawal period or entered an open-label study. LEV was compared with placebo.. The 50% responder rate (the proportion of patients with a minimum of 50% reduction in partial seizure frequency) occurred in 46.4% of the LEV group, compared with 39.3% of the placebo group (p = 0.590). The median of the absolute weekly frequency reduction from baseline of partial seizures was 0.66 per week for LEV versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent adverse events, mostly mild to moderate in severity, were somnolence, dizziness and agitation.. In this study, adjunctive therapy with LEV 3,000 mg daily was well tolerated but not as effective as expected in controlling partial seizures in this study population. Considering the lower mean weight of this study population, we suggest the dosage of LEV 3,000 mg daily may contribute to the results.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anticonvulsants; Body Weight; Chemotherapy, Adjuvant; China; Dizziness; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Psychomotor Agitation; Seizures; Sleep Wake Disorders; Treatment Outcome; Young Adult

Intravenous antiepileptic drugs are required in patients needing urgent treatment or unable to take oral medication. The safety of intravenous levetiracetam has been established in prospective studies of adult epilepsy and healthy participants. The authors performed a prospective, single-center study to evaluate the safety of a rapid loading dose of intravenous levetiracetam. Patients were divided into 3 equal dosing groups (N = 15 each): 20, 40, and 60 mg/kg (corresponding to maximum doses of 1, 2, and 3 g). Electrocardiogram and safety assessment were performed during the infusion. Ages were 4 to 32 years. Postinfusion serum levetiracetam concentrations were 14 to 189 microg/mL. There were no significant changes in blood pressure, no local infusion site reactions, and no electrocardiogram abnormalities. The authors concluded that high serum levels of parenteral levetiracetam can be achieved rapidly and safely, in a small infusion volume. This finding has important implications for the treatment of status epilepticus.

Topics: Adolescent; Adult; Anticonvulsants; Blood Pressure; Child; Child, Preschool; Electrocardiography; Epilepsy; Female; Heart; Humans; Injections, Intravenous; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Young Adult

The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G).. Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day.. At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities.. Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Topics: Adolescent; Anticonvulsants; Child; Drug Administration Schedule; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Patient Selection; Pilot Projects; Piracetam; Prospective Studies; Seizures; Treatment Outcome

To evaluate the use and tolerability of intravenous (IV) levetiracetam (LEV) in a pediatric cohort under 14 years of age.. A retrospective analysis of the use of the IV formulation of LEV was performed for the first 9 months that it was available in our institution.. Overall, 118 infusions in 15 patients were performed during the period assessed. No adverse reactions were observed during the infusion phase of the IV formulation. Nine minor adverse reactions were observed during the rest of the hospitalization that were potentially related to the IV formulation. Three of these were decreases in the white cell counts, while the majority of the rest were behavioral adverse effects. The median starting dose in LEV naïve patients was 8.8 mg/kg (range=5.0-50), with a median maintenance dose of 30.4 mg/kg/day for all patients (range=5.0-92). The majority of these infusions (82/118) were in a subgroup of children under 4 years of age where the median maintenance dose was 28 mg/kg/day.. IV LEV was very well tolerated in this cohort of pediatric patients including a subgroup of children under the age of 4 years.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Tolerance; Evaluation Studies as Topic; Female; Humans; Infant; Injections, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures

We investigated the clinical characteristics of children with continuous spike waves during slow-wave sleep syndrome and their treatment response to levetiracetam. Five boys and one girl, diagnosed with epilepsy with continuous spike waves during slow-wave sleep syndrome, were enrolled. Their clinical characteristics, including neuroimaging findings, were reviewed. The signs related to continuous spike waves during slow-wave sleep included increased seizure frequency (6/6), impaired responsiveness (3/6), and psychomotor regression (2/6). Magnetic resonance imaging disclosed lissencephaly in one patient, and porencephaly of the left hemisphere in another. The number of antiepileptic drugs before the use of levetiracetam was 0-4 (mean +/- SD, 2.3 +/- 1.5). Five of 6 children demonstrated a good response to levetiracetam, whereas 2 (40%) underwent a relapse of electrical status epilepticus during sleep pattern on electroencephalograms 4 and 5 months after clinical improvement. Both were 5 years old. The most common presenting sign in children with continuous spike waves during slow-wave sleep syndrome is increasing seizure frequency. Levetiracetam is effective in treating children with continuous spike waves during slow-wave sleep syndrome. However, the relapse rate of continuous spike waves during slow-wave sleep syndrome remains high in young children.

Topics: Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Sleep

To study the efficacy and tolerability of add-on levetiracetam in children and adolescents with refractory epilepsy.. In this prospective multi-centre, open-label, add-on study, 33 children aged 4-16 years (median 8.5 years) with epilepsy refractory to at least two antiepileptic drugs were treated with levetiracetam in addition to their present treatment regimen with a follow-up of 26 weeks. The starting dose of 10 mg/kg/day was increased with 2-week steps of 10 mg/kg/day, if necessary, up to a maximum dose of 60 mg/kg/day.. Retention rate was 69.7% after 26 weeks on a median levetiracetam dosage of 22 mg/kg/day. Four children dropped-out because levetiracetam was ineffective, four because seizure frequency increased and/or seizures became more severe, and two because they developed aggressive behaviour. Compared to their baseline seizure frequency, 13 children (39.4%) had a >50% seizure reduction 12 weeks after initiation of levetiracetam, and 17 children (51.5%) at 26 weeks. At 26 weeks, nine children (27.3%) had been seizure-free for at least the last 4 weeks, terminal remission ranged from 0 to 187 days (mean 46 days). Levetiracetam was effective in both partial and primary generalized seizures, but had most effect in partial seizures. Most reported side effects were hyperactivity (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behaviour (27.3%). Severity of most side effects was mild. Five children had a serious adverse event, which all concerned hospital admissions that were not related to levetiracetam use.. Levetiracetam proved to be an effective and well-tolerated add-on treatment in this group of children with refractory epilepsy.

Topics: Adolescent; Anticonvulsants; Child; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Epilepsies, Partial; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Irritable Mood; Levetiracetam; Male; Piracetam; Prospective Studies; Seizures; Treatment Outcome

Levetiracetam (LEV) is a new generation anti-epileptic drug, which has been approved as add-on therapy for partial epilepsy. The mechanism of LEV is not yet completely understood.. To evaluate the efficacy and tolerability of LEV in adult patients with refractory epilepsy.. We report the results of 49 patients with refractory epilepsy, with partial and generalized seizures, who received LEV as an add-on treatment, in two tertiary medical centers. There were 27 males, mean age 35.4+13 years. The average duration of epilepsy was 21 + 11 years, the average seizure rate was 31 + 30 per month. The patients were treated with a mean of 2.6 AED when LEV was introduced. The patients were treated for 12.6 + 9.7 months with an average dose of 1964 + 743.7 mg LEV per day.. Five (10%) patients became seizure free, 12 (25%) responded with seizure reduction of more than 50% following the introduction of LEV, 8 (16%) responded with seizure reduction of less than 50%, no response to LEV was reported in 20 (41%) and seizure aggravation occurred in 4 (8%). No serious persistent adverse events were reported. The main side effect was drowsiness in 10% of patients.. The results of this study, as well as previous studies, suggest that LEV is a well-tolerated new antiepileptic drug, and as an add-on therapy it may effectively improve seizure control in patients with intractable epilepsy.

Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

Seizures may occur after orthotopic liver transplantation. Antiepileptic drugs (AEDs) are used to treat these seizures, but the immunosuppressant regimen also may be altered. Levetiracetam is an attractive treatment because of its efficacy, lack of hepatic enzyme induction, and its rapid attainment of serum levels. Treatment with levetiracetam is efficacious, and levetiracetam-treated patients require significantly lower doses of immunosuppressant medications to achieve an equivalent antirejection effect.

Topics: Anticonvulsants; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Immunosuppressive Agents; Levetiracetam; Liver; Liver Transplantation; Male; Phenytoin; Piracetam; Postoperative Complications; Retrospective Studies; Seizures; Treatment Outcome

To evaluate the long-term clinical usefulness of levetiracetam (LEV, Keppra((R))(1)) as add-on therapy in patients with refractory epilepsy.. Data for all 1422 patients with refractory epilepsy treated with LEV during the development program were analyzed for changes in seizure frequency per week, seizure freedom, and adverse events.. Median percent reduction from baseline in seizure frequency per week over the whole treatment period was 39.6%, and no decrease over time was observed within each cohort exposed to LEV for durations ranging from 6 to 54 months. The median treatment period was 399 days (range 1-8 years). The proportion of responders during the first 3 months of LEV treatment was 39.2%. This proportion remained stable at 6 months (36.1%). Overall, 38.6 and 20.1% of patients had reductions in seizure frequency of at least 50 and 75%. Sixty-five (4.6%) patients were seizure-free over their entire treatment period, compared with 167 (11.7%) and 126 (8.9%) during their last 6 and 12 months of follow-up. Ninety-seven (19.8%) of 491 patients who received only one other antiepileptic drug (AED) in addition to LEV were seizure-free during their last 6 months. The proportion of patients who reduced their number of concomitant AEDs was 14.4% (205 patients), while 5.5% (79 patients) were treated with LEV only at the end of follow-up. Accidental injury (28.0%), infection (26.6%), headache (25.8%), somnolence (23%), asthenia (22.6%), and dizziness (18.9%) were among the most common adverse events.. LEV offers sustained efficacy in patients with refractory partial seizures, and its long-term tolerability is similar to that seen in the short-term placebo-controlled trials.

Topics: Adolescent; Adult; Anticonvulsants; Behavior; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (n=65) was observed. Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%) and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients >/=65 years of age, including those requiring concomitant medications.

Topics: Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Drug Tolerance; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

The management of epilepsy during pregnancy requires optimal seizure control, avoiding the potential teratogenic effects of antiepileptic drugs.. This study aims to describe the clinical characteristics and perinatal outcomes of pregnant patients with epilepsy; to analyse the factors associated with seizures during pregnancy; to describe the most commonly used antiseizure drugs in these patients; and to analyse changes in treatment regimens in 2 periods, 2000-2010 and 2011-2018.. We conducted a prospective observational study of patients with epilepsy who reported their pregnancy between 2000 and 2018. Patients were evaluated in the first and second trimesters of pregnancy, after delivery, and at one year. Data were collected on demographic variables, epilepsy, and perinatal and obstetric variables.. A total of 101 pregnancies were included. Patients' mean age was 32.6 years; 55.4% had focal epilepsy, 38.6% had generalised epilepsy, and 5.9% had undetermined epilepsy. We recorded 90 live births, 9 miscarriages, and 5 cases of congenital malformations, 4 of which were born to women who received valproate monotherapy. Forty patients (39.6%) presented seizures, with 16 (40%) presenting generalised tonic-clonic seizures. The variables associated with seizures during pregnancy were poor seizure control in the year prior to pregnancy (66.7% vs 15.1%; P < .001), treatment with 2 or more antiseizure drugs (30% vs 14.8%; P < .001), and untreated epilepsy (25% vs 0%; P < .001). Antiseizure medications most widely used in monotherapy were lamotrigine (n = 19; 27.1%), valproate (n = 17; 24.2%), and levetiracetam (n = 12; 17.1%). In the most recent period (2011-2018), we observed a greater proportion of patients receiving monotherapy (81.5%, vs 55.3%), as well as a decrease in the use of carbamazepine (2.3%, vs 23.1%) and valproate (20.5%, vs 30.8%); and a marked increase in the use of levetiracetam (27.3%, vs 0%).. The factors associated with the presence of seizures during pregnancy were previous poor seizure control, treatment with 2 or more antiseizure drugs, and lack of treatment during pregnancy. The most commonly used drugs were lamotrigine, valproate, and levetiracetam, with an increase in levetiracetam use and a decrease in valproate use being observed in the later period (2011-2018).

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Seizures; Valproic Acid

Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI.. This retrospective single-center cohort study included admitted patients ≥ 18 years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000 mg/day, 1500 mg/day, and ≥ 2000 mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding.. Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000 mg/day group, 137 patients in the 1500 mg/day group, and 440 patients in the ≥ 2000 mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000 mg/day group, 8.8% in the 1500 mg/day group, and 9% in the ≥ 2000 mg/day group. The 1500 mg/day and ≥ 2000 mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000 mg/day levetiracetam group, respectively, but these differences were not statistically significant.. In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7 days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000 mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Cohort Studies; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures

Topics: Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Seizures

Pharmacologic treatment of epilepsy in pregnant women is balancing between risks for the mother and fetus. Levetiracetam (LEV) is considered to be safe during pregnancy because of its low teratogenic potential and lack of drug-drug interaction with other antiseizure medications (ASMs). Recent studies have shown decline of ASM concentrations during pregnancy because of physiologically based pharmacokinetic changes. In this study, we established this decrease in LEV concentration during pregnancy. In addition, we aimed at investigating the effect of the low LEV levels during pregnancy and developing a target value for the level during pregnancy.. Pregnant patients using levetiracetam were studied in this retrospective cohort study. Blood samples were monthly collected through venous puncture or the dried blood spot method. ASM serum concentrations were determined at least 6 months before conception and for each month of pregnancy. Seizure frequency and ASM dosages during pregnancy were obtained from patient records. Patients were divided into 2 groups: a seizure-free group and a non-seizure-free group, which contained pregnancies in which the mother had experienced an epileptic seizure more than 12 months and less than 12 months before pregnancy, respectively.. We found decreased concentration/dose ratios in 29 pregnancies throughout all months of pregnancy. In the non-seizure-free group, it was found that low LEV concentrations were associated with seizure increase frequency (. All in all, we recommend therapeutic drug monitoring for all pregnant patients on LEV as the concentrations of LEV significantly decrease throughout most months of pregnancy. However, this decrease in LEV concentration was only significantly correlated with seizure deterioration in patients who had a seizure in the year preceding the pregnancy. Therefore, we suggest more careful monitoring of non-seizure-free patients as they are at higher risk for experiencing an increase of seizure frequency. For this group, we advise physicians to keep LEV concentration above 65% of the preconceptional concentration. For seizure-free patients, we recommend an LEV threshold value of approximately 46% of the preconceptional concentration.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Pregnancy; Pregnant Women; Retrospective Studies; Seizures; Treatment Outcome

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV - V who underwent aneurysmal obliteration within 72 h post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013 - 2015), levetiracetam for patients at high risks of seizures (2016 - 2019), and perampanel for all patients (2020 - 2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging, which was related to less development of DCI. Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modified Rankin Scale 0 - 2). The present study suggests that prophylactic administration of levetiracetam and perampanel was not associated with worse outcomes and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

Topics: Anticonvulsants; Brain Ischemia; Cerebral Infarction; Cohort Studies; Humans; Levetiracetam; Microcirculation; Prospective Studies; Retrospective Studies; Seizures; Subarachnoid Hemorrhage

This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients.. In this nationwide retrospective observational cohort study, Grade 2-4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders.. In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20-2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78-2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89-12.55, p = .001).. In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.

Topics: Anticonvulsants; Epilepsy; Glioma; Humans; Levetiracetam; Retrospective Studies; Seizures

Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol.. We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020.. First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001).. Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses.

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Retrospective Studies; Seizures

Caffeine is the most widely used psychoactive substance in the world. Animal studies indicate that acute caffeine exposure at high doses may induce seizures and diminish the anticonvulsant activity of antiepileptic drugs (AEDs) at much lower doses. The aim of the current study was to assess the effect of caffeine on the anticonvulsant action of levetiracetam (LEV) and vigabatrin (VGB).. The anticonvulsant activity of LEV and VGB was examined in the maximal electroshock seizure threshold test in mice (MEST test). All drugs were administered intraperitoneally by single injections, and caffeine was applied at doses capable of interfering with AEDs. Effects of caffeine exposure on AEDs were also investigated in tests of memory and motor performance.. Caffeine reduced the protective effect of LEV against electroconvulsions. Total brain concentration of LEV was unaffected by caffeine as well as inversely; LEV had no significant impact on the brain caffeine concentration, suggesting a pharmacodynamic nature of the interaction between LEV and caffeine in the MEST test. VGB at applied doses did not affect the convulsive threshold. Administration of VGB, but not LEV, alone or in combination with caffeine, impaired memory retention. In the chimney test, the combined treatment with AEDs and caffeine did not cause motor coordination impairment.. It is suggested that caffeine may negatively affect the anticonvulsant action of LEV in patients with epilepsy.

Topics: Animals; Anticonvulsants; Caffeine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Electroshock; Levetiracetam; Mice; Seizures

The purpose of this study was to compare the electrocardiographic parameters before and at the sixth month of treatment of patients diagnosed with epilepsy and who were started on levetiracetam therapy.. The files of 30 patients diagnosed with epilepsy and on levetiracetam therapy were examined in this study. Clinical findings, electroencephalography (EEG), cranial magnetic resonance imaging (MRI) and electrocardiography (ECG) data before and at the sixth month of treatment were recorded.. The patients' mean age was 10.93 ± 3.74 (4-17) years; 16 (53.33%) patients were boys. In total, 13 (43.3%) were found to experience focal seizures, and 17 (56.7%) generalized epilepsy-type seizures. Comparison of the ECG parameters (PR interval, QTc, QT interval, and QRS duration) revealed a shortening in the PR interval and QTc values at the sixth month of treatment, although the changes were not statistically significant. No significant differences in terms of gender and epilepsy types were observed between the ECG parameters before treatment and at the sixth month (p > 0.05).. In this study, levetiracetam was found to have no effect on ECG parameters.

Topics: Adolescent; Child; Electrocardiography; Epilepsy; Female; Humans; Levetiracetam; Male; Seizures

Levetiracetam is currently being used to treat epilepsy in pregnant women. The plasma concentration of levetiracetam drops sharply during pregnancy, and the inability of pregnant women to maintain therapeutic concentrations can lead to seizures. This study aimed to predict the changes in fetal and maternal plasma exposure to levetiracetam during pregnancy and provide advice on dose adjustment. The physiology-based pharmacokinetics (PBPK) model was developed using PK-Sim and Mobi software, and validated following comparison of the observed plasma concentration and pharmacokinetic parameters. The levetiracetam PBPK model for mother and the fetus at various stages of pregnancy was successfully established and verified. Predictions indicated that the area under the steady-state concentration-time curve for levetiracetam decreased to 83, 62, and 67% of baseline values in the first, second, and third trimesters, respectively. Based on PBPK predictions, the recommended dose of levetiracetam is 1.2, 1.6, and 1.5 times the baseline dose in the first, second, and third trimesters, respectively, not exceeding 4000 mg/day in the third trimester due to fetal safety. The levetiracetam PBPK model for pregnancy was successfully developed and validated, and could provide alternative levetiracetam dosing regimens across the stages of pregnancy.

Topics: Female; Fetus; Humans; Levetiracetam; Models, Biological; Pregnancy; Seizures; Software

The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma.. This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line.. Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates.. More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Freedom; Glioma; Humans; Levetiracetam; Seizures; Treatment Failure; World Health Organization

Seizures are common in palliative care patients and its control is essential in the management of these patients as it helps to reduce suffering at the end of life. Subcutaneous levetiracetam has been used off-license for seizure control in palliative care.. The objective of the study was to describe our experience with subcutaneous levetiracetam in two hospitals in Bogota, Colombia.. We conducted a retrospective review of patients treated with subcutaneous levetiracetam in two hospitals in Colombia during 2019-2021. Data were extracted from medical records, and participants were followed up as outpatients.. Twenty-one patients were included into the study. No severe adverse effects or rise in ictal frequency were documented. Twelve patients died during hospitalization and nine continued treatments as outpatients. The principal diagnosis was structural focal epilepsy. The daily dose of levetiracetam ranged from 1,000 mg to 3,000 mg, and the duration of treatment varied among subjects between 1 and 360 days.. Subcutaneous levetiracetam was well tolerated and effective in controlling seizures in palliative care when oral administration or intravenous access was not an option. Randomized controlled trials are needed to elucidate the efficacy and tolerability of subcutaneous levetiracetam in clinical practice.

Topics: Anticonvulsants; Humans; Levetiracetam; Palliative Care; Piracetam; Seizures; Treatment Outcome

Levetiracetam is used for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis.. This retrospective cohort study included adult patients at an academic tertiary hospital presenting with SAH or TBI who received levetiracetam at a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was combined seizure incidence, including clinical and subclinical seizures.. We identified 139 patients (49.6% male, mean age 53 years) for inclusion. For patients receiving a 1000-mg TDD, the administration was 500 mg twice daily. For patients receiving >1000-mg TDD, 77/78 patients received 1000 mg twice daily and one patient received 750 mg twice daily. Patients receiving 1000-mg TDD had a higher seizure incidence than those receiving >1000-mg TDD (p = 0.01), despite no difference in examined confounders, including history of alcoholism (p = 0.49), benzodiazepine use (p = 0.28), or propofol use (p = 0.17). No difference in adverse effects was observed (anemia, p = 0.44; leukopenia, p = 0.60; thrombocytopenia, p = 0.86).. Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures; Subarachnoid Hemorrhage

It is rare for uremia patients to have epileptic seizures after eating star fruit, only a dozen cases are reported worldwide. Such patients usually have poor prognoses. Few patients had good prognoses, all of them were treated with expensive renal replacement therapy. At present, there is no report on the addition of drug therapy to these patients based on the initial renal replacement therapy.. A 67-year-old male patient with star fruit intoxication who had a history of diabetic nephropathy, hypertension, polycystic kidney, and chronic kidney disease in the uremic phase, and regular hemodialysis 3 times a week for 2 years. Initial clinical manifestations include hiccups, vomiting, speech disturbances, delayed reactions, and dizziness, which gradually progress to hearing and visual impairment, seizures, confusion, and coma.. This patient was diagnosed with seizures caused by star fruit intoxication. The experience of eating star fruit and the electroencephalograms can prove our diagnosis.. We performed intensive renal replacement therapy according to the recommendations in the literature. However, his symptoms did not improve significantly until he received an extra dose of levetiracetam and resumed his previous dialysis schedule.. The patient was discharged after 21 days without neurologic sequelae. Five months after discharge, he was readmitted due to poor seizure control.. To improve the prognosis of these patients and to reduce their financial burden, the use of antiepileptic drugs should be emphasized.

Topics: Aged; Anticonvulsants; Fruit; Humans; Levetiracetam; Male; Renal Dialysis; Seizures

To investigate caregivers' assessments of outcome in dogs with idiopathic epilepsy (IE) administered levetiracetam (LEV), zonisamide (ZNS), or phenobarbital (PB) monotherapy.. 100 dogs with IE administered LEV (n = 34), ZNS (31), or PB (35) monotherapy between January 1, 2003, and February 6, 2019, and survey responses from their caregivers.. Information on duration of therapy, adverse effects (AEs), and outcome was obtained from medical record review and caregiver questionnaire.. A significant improvement in mean quality of life score was reported during monotherapy (7.7; SD, 2.14) compared to before treatment (6.25; SD, 2.63; P < .0001), with no difference identified between monotherapy groups. Compared to ZNS monotherapy, dogs prescribed PB monotherapy had a significantly younger median age at seizure onset (2.6 vs 4.3 years; P = .024). A significant relationship was identified between the occurrence of reported AEs and monotherapy group, with a higher prevalence in the PB group (77% [27/35]) and a lower prevalence in the ZNS group (39% [12/31]; P = .0066). Treatment failure rates for PB, LEV, and ZNS monotherapy were 51%, 35%, and 45%, respectively, with failure attributed most commonly to inadequate seizure control. No significant difference was identified between groups with respect to rate of or time to failure.. Most caregivers reported a favorable outcome with administration of LEV, ZNS, or PB monotherapy to dogs with IE. Phenobarbital is associated with the highest prevalence of AEs but no difference in quality of life score. Prospective controlled studies are needed to further compare the efficacy and safety of these monotherapies in dogs with IE.

Topics: Animals; Anticonvulsants; Caregivers; Dog Diseases; Dogs; Epilepsy; Humans; Levetiracetam; Phenobarbital; Prospective Studies; Quality of Life; Seizures; Zonisamide

We used the lateral fluid percussion injury (LFPI) model of moderate-to-severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post-traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI.. Adult male Sprague-Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post-LFPI, and were continuously video-EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post-LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d-to-7d neuroscore recovery, using machine learning.. Low 2d plasma levels of Thr. Antiseizure medications and early seizures need to be considered in the interpretation of early post-traumatic biomarkers.

Topics: Animals; Biomarkers; Blood Proteins; Brain Injuries, Traumatic; HMGB1 Protein; Levetiracetam; Male; Rats; Rats, Sprague-Dawley; Seizures

Wolf-Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. This article evaluates the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs). Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared with the premedication level. Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5-32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in 10 patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS.

Topics: Anticonvulsants; Epilepsy; Humans; Levetiracetam; Retrospective Studies; Seizures; Status Epilepticus; Wolf-Hirschhorn Syndrome

To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects.. We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors.. In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects.. Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Topics: Anticonvulsants; Drug Resistant Epilepsy; Electroencephalography; Epilepsies, Partial; Epilepsy; Humans; Levetiracetam; Seizures; Treatment Outcome

The aim of this study is to evaluate the effects of clinical and electroencephalographic features on spike reduction with a focus on the first EEG characteristics in self-limited epilepsy with centrotemporal spikes (SeLECTS).. This retrospective study was conducted on SeLECTS patients of with at least five years follow-up and at least two EEG recordings in which spike wave indexes (SWI) were calculated.. 136 patients were enrolled. Median SWI in the first and last EEGs were 39% (7.6-89%) and 0 (0-112%). Gender, seizure onset age, psychiatric diseases, seizure characteristics (semiology, duration, and relationship to sleep), last EEG time, and spike lateralization in the first EEG did not have a statistically significant effect on the SWI change. Multinomial logistic regression analysis revealed that presence of phase reversal, interhemispheric generalization, and SWI percentage had a significant effect on spike reduction. The frequency of seizures was also significantly decreased in patients with a greater decrease in SWI. Both valproate and levetiracetam were statistically superior in suppressing SWI, with no significant difference between them.. Interhemispheric generalization and phase reversal in the first EEG in SeLECTS had negative effects on the spike reduction. The most effective ASMs in reducing spikes were valproate and levetiracetam.

Topics: Electroencephalography; Epilepsy, Rolandic; Humans; Levetiracetam; Retrospective Studies; Seizures; Valproic Acid

Post-traumatic seizure (PTS) prophylaxis is recommended in patients with traumatic brain injury (TBI) at high risk for PTSs, but consensus on the optimal pharmacologic therapy has not yet been established. Levetiracetam is frequently used for seizure prophylaxis in combat-related TBI, but its efficacy and safety in this patient population has not yet been described.. A retrospective cohort of 687 consecutive casualties transferred to the CONUS from October 2010 to December 2015 was analyzed. Seventy-one patients with combat-related injuries and radiographic evidence of skull fractures or intracranial hemorrhage were included. Data collection included demographics and injury characteristics including initial Glasgow Coma Scale, computed tomography findings, interventions, and 6-month Glasgow Outcome Score.. All patients in this cohort were male, with an average age of 25 (median 24; Interquartile range (IQR) 4.5) and an average Injury Severity Score of 28 (median 27; IQR 15). The most common mechanism of injury was explosive blast (76%). Penetrating TBI was common (51%). Most patients (88.7%) were administered seizure prophylaxis. Of these, the majority (61/63) received levetiracetam, and the additional two were administered phenytoin. The remaining 11.3% of patients were deemed not to require seizure prophylaxis. The incidence of seizures while on prophylaxis was low (2.8%) and occurred in patients who suffered transcranial gunshot wounds and ultimately died. No serious adverse effects were attributed to levetiracetam.. Levetiracetam appears to be a safe and effective medication for PTS prophylaxis in combat casualties. The rate of PTSs in combat-related TBI on appropriate prophylaxis is low.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Wounds, Gunshot

To evaluate Epileptic drop attacks (EDAs) treatment options among pediatric neurologists in Saudi Arabia (SA) and to develop a recommendation scheme for the management of EDAs in SA. Epileptic drop attacks are one of the most pharmaco-resistant epileptic seizures. The different approaches to EDA treatment are influenced by a variety of factors, including pharmaceutical availability, costs, side effects, treating physicians' experience and personal preferences.. This cross-sectional study was conducted online. A structured questionnaire that aimed to measure the therapeutic options for patients with EDA was electronically distributed to pediatric neurologists across SA. It contained 21 questions, and the data were collected in Excel sheets and analyzed.. Our study included a cohort of 71 pediatric neurologists from SA, of which male doctors represented 60%. Most of the participating pediatric neurologists had more than 10 years of experience in the field. We found that 77% of the included pediatric neurologists used valproic acid as a first-line drug in patients with EDA. Further, in the different case scenarios provided to participants, levetiracetam, clobazam, topiramate, and rufinamide were included in the initial management protocol for EDA.. The majority of pediatric neurologists in Saudi Arabia chose valproic acid and/or levetiracetam as the first line of treatment for EDA. These results highlight the need for an evidence-based clinical guidelines to treat EDA.

Topics: Anticonvulsants; Child; Cross-Sectional Studies; Humans; Levetiracetam; Male; Neurologists; Saudi Arabia; Seizures; Syncope; Valproic Acid

Patients with epilepsy are significantly burdened by the disease due to long-term health risks, the severe side effect profiles of anti-epileptic drugs, and the strong possibility of pharmacoresistant refractory seizures. New animal models of epilepsy with unique characteristics promise to further research to address these ongoing problems. Here, we characterize a newly developed line of prairie voles (Microtus ochrogaster, UTol:HIC or "Toledo" line) that presents with a hereditary, adult-onset, handling-induced convulsion phenotype. Toledo voles were bred for four generations and tested to determine whether the observed phenotype was consistent with epileptic seizures. Toledo voles maintained a stable 22 % incidence of convulsions across generations, with an average age of onset of 12-16 weeks. Convulsions in Toledo voles were reliably evoked by rodent seizure screens and were phenotypically consistent with murine seizures. At the colony level, Toledo voles had a 7-fold increase in risk for sudden unexpected death from unknown causes, which parallels sudden unexpected death in epilepsy (SUDEP) in human patients. Finally, convulsions in Toledo voles were reduced or prevented by treatment with the anti-epileptic drug levetiracetam. Taken in combination, these results suggest that convulsions in Toledo voles may be epileptic seizures. The Toledo prairie vole strain may serve as a new rodent model of epilepsy in an undomesticated, outbred species.

Topics: Animals; Arvicolinae; Epilepsy; Grassland; Humans; Infant; Levetiracetam; Mice; Seizures

Seizures are a common neurological disorder that affects people of all ages. These sudden, uncontrolled electrical disturbances in the brain can cause a variety of symptoms, including convulsions, loss of consciousness, and abnormal sensations. While seizures have long been recognized as a potential cause of hormonal imbalances, recent research has shed new light on the link between seizures and prolactin. The study involved 30 adult female Wistar rats, which were divided into a control group (treated with normal saline) and four treatment groups: chronic group (treated with 30 mg/kg pentylenetetrazol intraperitoneally three days a week for 10 weeks), chronic + Levetiracetam (50 mg/kg, gavage), chronic + Cabergoline (0.05 mg/kg, gavage), and chronic + Levetiracetam (25 mg/kg) + cabergoline (0.025). The drugs were administered three days a week for 10 weeks. Field action potentials were recorded from the CA1 area of the hippocampus using eLab after anesthetizing the animals with a ketamine-xylazine combination (70 +7 mg/kg). The prolactin levels were measured using the ELISA method after serum preparation. The findings indicate that the use of levetiracetam as an anticonvulsant drug resulted in a significant decrease in the amount of prolactin and spike number of convulsive activities compared to the chronic group. However, the amplitudes of convulsive activities did not show a significant difference between the control and other treatment groups. In conclusion, investigating the possibility of subclinical seizures and utilizing anticonvulsant medications in hyperprolactinemia that is resistant to treatment are crucial in treating infertility.

Topics: Animals; Anticonvulsants; Cabergoline; Female; Hyperprolactinemia; Levetiracetam; Prolactin; Rats; Rats, Wistar; Seizures

In women with epilepsy, antiepileptic drugs with low teratogenic risk should be used at the lowest dose necessary to control seizures. The medication adjustment and folic acid supplementation are started before pregnancy. Valproic acid should be avoided unless indispensable. Levetiracetam and lamotrigine are often used as less teratogenic agents. Moreover, appropriate information on possible changes in seizure frequency with pregnancy and childbirth preparation and breastfeeding should be provided. Generally, women taking antiepileptic drugs for epilepsy treatment may undergo natural delivery and breastfeeding. We should collaborate with obstetricians and other professionals to help ensure a safe environment for pregnancy and childbirth.

Topics: Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Seizures; Valproic Acid

Kappa opioid receptor (KOR) agonists have anticonvulsant effect but their antiepileptogenic effect is unknown. U50488, a selective KOR agonist is used to determine its effect on status epilepticus (SE), spontaneous convulsive seizures (SS) and cognitive impairment in rat lithium-pilocarpine SE model. Effect of an antiepileptic drug levetiracetam is also studied.. Male Wistar rats with SE were divided into three groups namely, LiP, LiP + U50488 (10 mg/kg, i.p.) and LiP + levetiracetam (400 mg/kg, i.p.) group. SE was terminated after 90 min of its onset with diazepam (15 mg/kg, i.p.) and phenobarbitone (25 mg/kg, i.p.). Drug treatment was started after 15 min of onset of SE and repeated once after 4 h. Rats were video monitored 12 h daily (9 AM to 9 PM) to determine severity of SE using modified Racine scale and onset and frequency of SS from day 0 to day 21. Morris water maze (MWM) test was done at baseline i.e. day -1 (before lithium administration) and day 22, to assess cognitive impairment.. As compared to LiP, U50488 decreased the severity of SE (1.98 ± 0.13 vs 2.95 ± 0.12; p-value < 0.0001) but not levetiracetam (2.62 ± 0.09; p-value = 0.3112). Survival increased with both U50488 (90%, n = 10) and levetiracetam (81.8%, n = 11) as compared to NS (56.2%, n = 16). No effect on onset and frequency of SS was found in U50488/levetiracetam group. U50488 improved seizures-induced cognitive impairment. Levetiracetam group showed thigmotactic (wall hugging) behaviour in MWM in 8 out of 9 rats.. Acute treatment with U50488, a kappa opioid receptor agonist has a beneficial effect on SE, SE-related mortality and memory impairment. The dual protective effect of U50488 on seizures and related cognitive impairment is advantageous over currently used antiseizure drugs which are known to cause cognitive impairment.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Anticonvulsants; Disease Models, Animal; Levetiracetam; Lithium; Male; Pilocarpine; Rats; Rats, Wistar; Receptors, Opioid, kappa; Seizures; Status Epilepticus

People with epilepsy (PWE) have a high prevalence of developing depression and anxiety. The objective is to determine the feasibility of brief screening tools to screen for depression and anxiety in epilepsy, and the predictive factors.. This is a cross-sectional study in the neurology clinic in a tertiary teaching hospital in Kuala Lumpur. The screening tools used were the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the General Anxiety Disorder Form (GAD-7).. Five hundred and eighty-five patients were recruited in this study, and 50.8% of them were male, predominantly Chinese (46.7%), with a mean age of seizure onset of 21.8 ± 16.1 years. The majority had focal seizures (75.0%), and 41.9% had seizure remission. There were 15.5% who scored ≥15 in the NDDI-E, and 17.0% had moderate or severe anxiety (scored ≥10 in the GAD-7). In a regression model to predict the NDDI-E score, the age of seizure onset recorded a higher beta value (β = -0.265, p =< 0.001), followed by the duration of epilepsy (β = -0.213, p =< 0.001), use of levetiracetam (LEV) (β = 0.147, p = 0.002), clonazepam (CLZ) (β = 0.127, p = 0.011), and lamotrigine (LTG) (β = 0.125, p = 0.011), number of current antiseizure medications (β = -0.124, p = 0.049), seizure remission for ≥1 year (β = -0.108, p = 0.011), and female (β = 0.082, p = 0.049). For the GAD-7 score, the predictors included current age (β = -0.152, p = 0.001), the use of LEV (β = 0.122, p = 0.011), Indian ethnicity (β = 0.114, p = 0.006), and the use of carbamazepine (β = -0.090, p = 0.043).. Implementation of simple psychological screening using self-administered questionnaires was feasible in a busy tertiary epilepsy clinic.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Cross-Sectional Studies; Depression; Epilepsy; Feasibility Studies; Female; Humans; Levetiracetam; Male; Seizures; Young Adult

Cognitive impairment is a potential drawback of antiseizure medications. This study aimed to evaluate the impact of different levetiracetam drug regimens on cognitive function.. A retrospective analysis identified 221 patients diagnosed with seizures who underwent cognitive screening. Patients were categorized into four groups: no medications, non-levetiracetam medications, high and low dose levetiracetam. Composite scores determined low and high levetiracetam groups whereby one point was added for each increment in dosage, duration since uptake, and concurrent anti-seizure medication. Variables known to affect cognition were recorded and classified as demographic, seizure-related, diagnosis-related, and psychopathology. Logistic regression was used to identify variables associated with cognitive scores below cut-off.. Multivariable analysis found being male, non-active in the community, less than 12 years of education, left temporal lobe epilepsy, high seizure frequency, and depression were associated with poor cognitive performance. In a final regression analysis, the high levetiracetam group exhibited a 4.5-fold higher likelihood of scoring below cut-off than the medication-free group (OR 4.5, CI 1.5-13.6, p<.08). Depression (OR 2.1, CI 1.1-3.9, p<.03), being male (OR 2.2, CI 1.1-4.3, p<.02), and not being active in the community (OR 3.8, 1.6-8.7, p <.003) remained significant contributors to the model. Language (p<.05), attention (p<.05), and delayed recall (p<.001) were the most affected cognitive domains.. When taken in small doses, for brief periods as monotherapy, levetiracetam minimally influences cognition. At higher doses, as part of long-term seizure management, in conjunction with multiple ASMs, LEV is associated with cognitive impairment.

Topics: Anticonvulsants; Cognition; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures

Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated.. This study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations.. The clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared.. Among the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) (P < 0.01).. The findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.

Topics: Anticonvulsants; Child, Preschool; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Membrane Proteins; Nerve Tissue Proteins; Oxcarbazepine; Retrospective Studies; Seizures; Topiramate

Data of large pregnancy registries have improved the recommendations for women with epilepsy before pregnancy. Monotherapy containing antiepileptic drugs with a low malformation rate (lamotrigine or levetiracetam) is recommended as well as preconceptional folic acid supplementation, while valproic acid should be avoided. The practicability of these recommendations remains controversial.. Retrospective case series of 160 women with epilepsy over a period of 5 years who were advised in our outpatient department before and during pregnancy.. Only 18.9% of women presented with valproic acid. Even without valproic acid, complications or emergency admissions rarely occurred under specialist supervision. In our case series, lamotrigine proved to be less effective and less controllable than other drugs during pregnancy. Levetiracetam also has a low malformation rate, but showed a better effect on seizure outcome during pregnancy than lamotrigine. Only 12% of women who wanted to have children took folic acid.. This case series comes from a tertiary center; the referred women were mainly accompanied by neurologists with special expertise in epileptology. In this group valproate could be avoided in most cases. Lamotrigine is probably less effective due to the drop in blood levels during pregnancy. Levetiracetam seems to be a good alternative, working well against focal and generalized seizures. Folic acid may be taken later than recommended.. HINTERGRUND: Die Auswertung großer Schwangerschaftsregister hat die Empfehlungen für Frauen mit Epilepsie und Kinderwunsch in den letzten Jahren verbessert. So werden eine Monotherapie mit einem fehlbildungsarmen Medikament (Lamotrigin oder Levetiracetam) unter Vermeidung von Valproinsäure sowie eine präkonzeptionelle Folsäureprophylaxe empfohlen. Die Praktikabilität dieser Empfehlungen ist umstritten.. Retrospektive Fallserie von 160 Frauen mit Epilepsie über einen Zeitraum von 5 Jahren, die vor und bei Schwangerschaften in unserer Ambulanz beraten wurden.. Nur 18,9 % der Frauen stellten sich noch mit Valproinsäure vor. Auch ohne Valproinsäure kam es unter fachärztlicher Kontrolle selten zu Komplikationen oder Notfalleinweisungen. Lamotrigin erwies sich in unserer Fallserie in der Schwangerschaft als weniger gut wirksam und schlechter steuerbar als andere Medikamente. Levetiracetam ist ebenfalls wenig teratogen, kontrollierte Anfälle in der Schwangerschaft aber besser als Lamotrigin. Nur 12 % der Frauen mit Kinderwunsch nahmen Folsäure ein.. Diese Fallserie stammt aus einem tertiären Zentrum; die zugewiesenen Frauen wurden überwiegend von epileptologisch kompetenten Fachärzten für Neurologie betreut. In dieser Gruppe konnte auf Valproat in den meisten Fällen verzichtet werden. Lamotrigin ist vermutlich wegen des Spiegelabfalls in der Schwangerschaft weniger effektiv. Eine gute Alternative scheint Levetiracetam zu sein, das gut gegen fokale und generalisierte Anfälle wirkt. Folsäure wird möglicherweise später eingenommen als empfohlen.

Topics: Anticonvulsants; Counseling; Epilepsy; Female; Folic Acid; Humans; Lamotrigine; Levetiracetam; Outpatients; Pregnancy; Pregnancy Complications; Retrospective Studies; Seizures; Valproic Acid

We evaluated a 39-year-old pregnant woman with right temporal lobe epilepsy. During the second trimester, seizure deterioration was responsive to an increased daily dose of levetiracetam (LEV). However, immediately after delivery, new non-habitual seizures emerged along with a sharply increased LEV concentration. The frequency of habitual seizures also slightly increased. The non-habitual seizures completely disappeared, and the frequency of the habitual seizures improved to the baseline level after the LEV dosage was reduced. Thus, a paradoxical effect of an increased LEV blood concentration was assumed to be a potential cause of these events. Peripartum pharmacokinetic fluctuations in LEV levels should be monitored carefully.

Topics: Adult; Anticonvulsants; Epilepsy, Temporal Lobe; Female; Humans; Levetiracetam; Piracetam; Postpartum Period; Pregnancy; Seizures; Treatment Outcome

Status Epilepticus is the most common non-traumatic neurologic emergency in childhood. Current algorithms prioritize the use of benzodiazepines as first line treatment followed by Levetiracetam or Valproic Acid, possibly Fosphenytoin and eventually high dose Propofol and intubation.. A 9-month old girl was brought to the emergency department with a continuous seizure involving the right upper and lower extremity for 45 min prior to arrival. Patient received a dose of rectal Diazepam, intramuscular Midazolam, 2 doses of Lorazepam, Levetiracetam, Fosphenytoin and 2 additional doses of Lorazepam. The seizure remained refractory and generalized. In anticipation of intubation, and because of its action on the NMDA receptor, Ketamine (1 mg/kg IV) was administered. The clonic movements and eye deviations stopped. Patient was intubated for airway protection, sedated with Propofol, then admitted to the PICU. EEG showed no evidence of a seizure pattern. Labs (CBC, CMP, COVID) were unremarkable except for WBC 24.5, blood glucose of 346 and CO2 of 17 with normal anion gap. Urinalysis showed a urinary tract infection. Patient was at her baseline on 1 week post-discharge re-evaluation. Ketamine theoretically may abort seizures through blockade of NMDA receptors which are unregulated in status epilepticus. To date, no randomized controlled trials have been reported. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Ketamine may have a role in treating status epilepticus. It may be considered for induction for rapid sequence intubation and possibly as a third or fourth line agent in refractory cases.

Topics: Aftercare; Anticonvulsants; COVID-19; Female; Humans; Infant; Ketamine; Levetiracetam; Lorazepam; Patient Discharge; Propofol; Seizures; Status Epilepticus

Prophylactic antiseizure medications (ASMs) for pediatric traumatic brain injury (TBI) are understudied. We evaluated clinical and radiographic features that inform prescription of ASMs for pediatric TBI. We hypothesized that despite a lack of evidence, levetiracetam is the preferred prophylactic ASM but that prophylaxis is inconsistently prescribed.. This retrospective study assessed children admitted with TBI from January 1, 2017, to December 31, 2019. TBI severity was defined using Glasgow Coma Scale (GCS) scores. Two independent neuroradiologists reviewed initial head computed tomography and brain magnetic resonance imaging. Fisher exact tests and descriptive and regression analyses were conducted.. Among 167 children with TBI, 44 (26%) received ASM prophylaxis. All 44 (100%) received levetiracetam. Prophylaxis was more commonly prescribed for younger children, those with neurosurgical intervention, and abnormal neuroimaging (particularly intraparenchymal hematoma) (odds ratio = 10.3, confidence interval 1.8 to 58.9), or GCS ≤12. Six children (13.6%), all on ASM, developed early posttraumatic seizures (EPTSs). Of children with GCS ≤12, four of 17 (23.5%) on levetiracetam prophylaxis developed EPTSs, higher than the reported rate for phenytoin.. Although some studies suggest it may be inferior to phenytoin, levetiracetam was exclusively used for EPTS prophylaxis. Intraparenchymal hematoma >1 cm was the single neuroimaging feature associated with ASM prophylaxis regardless of the GCS score. Yet these trends are not equivalent to optimal evidence-based management. We still observed important variability in neuroimaging characteristics and TBI severity for children on prophylaxis. Thus, further study of ASM prophylaxis and prevention of pediatric EPTSs is warranted.

Topics: Adolescent; Anticonvulsants; Brain Injuries, Traumatic; Child; Child, Hospitalized; Child, Preschool; Female; Humans; Infant; Levetiracetam; Male; Retrospective Studies; Seizures

Epileptic seizures are increasingly recognized as part of the clinical phenotype of patients with Alzheimer's disease (AD). However, the evidence base on which to make treatment decisions for such patients is slim, there being no clear recommendation based on systematic review of the few existing studies of anti-seizure drugs in AD patients. Here the authors examine the potential implications for the treatment of seizures in AD of the results of the recently published SANAD II pragmatic study, which examined the effectiveness of levetiracetam, zonisamide, or lamotrigine in newly diagnosed focal epilepsy, and of valproate and levetiracetam in generalized and unclassifiable epilepsy.

Topics: Alzheimer Disease; Anticonvulsants; Epilepsy; Humans; Levetiracetam; Seizures

Expression of inhibitory designer receptors exclusively activated by designer drugs (DREADDs) on excitatory hippocampal neurons in the hippocampus represents a potential new therapeutic strategy for drug-resistant epilepsy. To overcome the limitations of the commonly used DREADD agonist clozapine, we investigated the efficacy of the novel DREADD ligand JHU37160 in chemogenetic seizure suppression in the intrahippocampal kainic acid (IHKA) mouse model for temporal lobe epilepsy (TLE). In addition, seizure-suppressing effects of chemogenetics were compared to the commonly used anti-epileptic drug (AED), levetiracetam (LEV). Therefore, an adeno-associated viral vector was injected in the sclerotic hippocampus of IHKA mice to induce expression of a tagged inhibitory DREADD hM4Di or only a tag (control) specifically in excitatory neurons using the CamKIIα promoter. Subsequently, animals were treated with LEV (800 mg/kg), clozapine (0.1 mg/kg), and DREADD ligand JHU37160 (0.1 mg/kg) and the effect on spontaneous seizures was investigated. Clozapine and JHU37160-mediated chemogenetic treatment both suppressed seizures in DREADD-expressing IHKA mice. Clozapine treatment suppressed seizures up to 34 h after treatment, and JHU37160 effects lasted for 26 h after injection. Moreover, both compounds reduced the length of seizures that did occur after treatment up to 28 h and 18 h after clozapine and JHU37160, respectively. No seizure-suppressing effects were found in control animals using these ligands. Chemogenetic seizure treatment suppressed seizures during the first 30 min after injection, and seizures remained suppressed during 8 h following treatment. Chemogenetics thus outperformed effects of levetiracetam (p < 0.001), which suppressed seizure frequency with a maximum of 55 ± 9% for up to 1.5 h (p < 0.05). Only chemogenetic and not levetiracetam treatment affected the length of seizures after treatment (p < 0.001). These results show that the chemogenetic therapeutic strategy with either clozapine or JHU37160 effectively suppresses spontaneous seizures in the IHKA mouse model, confirming JHU37160 as an effective DREADD ligand. Moreover, chemogenetic therapy outperforms the effects of levetiracetam, indicating its potential to suppress drug-resistant seizures.

Topics: Animals; Clozapine; Disease Models, Animal; Kainic Acid; Levetiracetam; Ligands; Mice; Seizures

Topics: Anticonvulsants; Child; Emergency Service, Hospital; Epilepsy, Generalized; Humans; Levetiracetam; Seizures; Status Epilepticus

The aim of the current study was to investigate the seizure outcome and also factors associated with that in patients with epilepsy [i.e., idiopathic generalized epilepsies (IGEs), symptomatic generalized epilepsies (SGEs), and focal epilepsies], who received either lamotrigine (LTG) or levetiracetam (LEV). This was a retrospective longitudinal study. All patients with a diagnosis of IGE, focal epilepsy, or SGE, who received either LTG or LEV, were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran from 2008 until 2020. All patients had to be followed at our center for at least 14 months. Two hundred and thirty-six patients were studied (101 IGE, 98 focal epilepsy, and 37 SGE). At the first visit, LTG was prescribed for 159 patients; 40 people (25.2%) became seizure-free, and LEV was prescribed for 77 people; 23 persons (29.9%) became seizure-free (p = 0.438). Patients who were not taking any drug at the time of their first visit, or were receiving fewer drugs, and those who had received fewer drugs in their drug history were more likely to enjoy a seizure-free state at the follow-up. Among the patients, who received LTG at the first visit, taking any Na-channel blocking drug (e.g., carbamazepine) in the drug history was associated with a poor seizure outcome; this was not the case for LEV. Implementation of appropriate personalized treatment plans in patients with epilepsy is of paramount significance. Rational selection of appropriate drug(s) is the mainstay of this process.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Humans; Immunoglobulin E; Lamotrigine; Levetiracetam; Longitudinal Studies; Retrospective Studies; Seizures; Treatment Outcome; Triazines

High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden <10% following initial treatment with levetiracetam, compared with 5 of 8 (63%) with phenobarbital. Thirteen (76%) patients treated with levetiracetam had sustained seizure burden <20% compared with 6 (75%) treated with phenobarbital. The phenobarbital group showed a larger absolute reduction in average seizure burden in the hour before and after treatment (-24.3  vs -14.2 minutes/h). Six of 17 (35%) patients treated with levetiracetam remained seizure free after initial treatment, compared with 2 of 8 (25%) patients treated with phenobarbital. Initial treatment with levetiracetam was associated with shorter average time to seizure freedom (15 vs 21 hours). None of these results were statistically significant. Cumulative doses of levetiracetam 100 mg/kg were well tolerated and associated with substantial decrease in seizure burden in several cases. Levetiracetam remains a promising first-line treatment for neonatal seizures; additional randomized controlled trials evaluating the effects of high-dose levetiracetam on seizure burden and long-term outcomes are warranted.

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Retrospective Studies; Seizures

To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy.. A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety.. For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (. Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.

Topics: Child; Epilepsy; Humans; Levetiracetam; Prospective Studies; Retrospective Studies; Seizures

In newly diagnosed neurocysticercosis (NCC) with seizures, the choice of anti-seizure medication (ASM) seems to be arbitrary due to a lack of comparative studies. Although oxcarbazepine (OXC) is often considered efficacious for focal seizures in NCC, due to adverse effects, newer ASMs like levetiracetam (LCM) and lacosamide are also being explored.. This study was performed by case record review of children with newly diagnosed solitary viable parenchymal NCC aged 4-18years who received lacosamide and OXC at least for 12 weeks between August 2019 and April 2021, from a prospective registry of a tertiary care teaching hospital in north India. Seizure control, electroencephalographic abnormalities, resolution of inflammatory granulomas and adverse effects were compared between two arms at 12 and 24 weeks.. Total 31 (8.3 ± 4.7 years, 19 boys) and 72 (8.6 ± 4.2 years, 43 boys) completed at least 12 weeks follow-up in LCM and OXC groups, out of which 2 and 51 completed at least 24 weeks follow-up in LCM and OXC groups, respectively. The occurrence of breakthrough seizure was comparable in both arms at 12 and 24 weeks (1/31 and 2/22 in lacosamide group vs. 2/72 and 4/51 in OXC group, p = 0.66 and 0.59, respectively). Patients receiving OXC had more frequent treatment-emergent adverse events (p = 0.0001) and four patients required discontinuation due to severe adverse events (SAEs), while none in the lacosamide group had SAEs.. Lacosamide appears to be efficacious and safe for achieving seizure freedom in patients with solitary viable parenchymal neurocysticercosis.

Topics: Anticonvulsants; Child; Epilepsies, Partial; Female; Humans; Lacosamide; Levetiracetam; Male; Neurocysticercosis; Oxcarbazepine; Seizures; Treatment Outcome

Paediatric status epilepticus (SE) has potential for long-term sequelae. Existing data demonstrate delays to aspects of care. The objective of the present study was to examine the feasibility of collecting data on children with paediatric SE and describe current management strategies in pre-hospital and in-hospital settings.. A pilot, prospective, observational cohort study of children 4 weeks to 16 years of age with SE, in four EDs in Australia. Clinical details including medications administered, duration of seizure and short-term outcomes were collected. Follow up occurred by telephone at 1 month.. We enrolled 167 children with SE. Mean age was 5.4 years (standard deviation [SD] 4.1), and 81 (49%) male. Median seizure duration was 10 min (interquartile range 7-30). Midazolam was the first medication administered in 87/100 (87%) instances, mean dose of 0.21 mg/kg (SD 0.13). The dose of midazolam was adequate in 30 (35%), high (>0.2 mg/kg) in 44 (51%) and low (<0.1 mg/kg) in 13 (15%). For second-line agents, levetiracetam was administered on 33/55 (60%) occasions, whereas phenytoin and phenobarbitone were administered on 11/55 (20%) occasions each. Mean dose of levetiracetam was 26.4 mg/kg (SD 13.5). One hundred and four (62%) patients were admitted to hospital, with 13 (8%) admitted to ICU and seven (4%) intubated.. In children presenting with SE in Australia medical management differed from previous reports, with midazolam as the preferred benzodiazepine, and levetiracetam replacing phenytoin as the preferred second-line agent. This pilot study indicates the feasibility of a paediatric SE registry and its utility to understand and optimise practice.

Topics: Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Cohort Studies; Female; Humans; Levetiracetam; Male; Midazolam; Phenobarbital; Phenytoin; Pilot Projects; Prospective Studies; Registries; Seizures; Status Epilepticus

Phenytoin is one of the most used antiepileptic drugs (AEDs), but it has serious potential side effects and drug interactions. Although studies have shown levetiracetam to have a much lower side-effect profile, its efficacy when compared with phenytoin is debatable. In our study, we aimed to determine the factors that cause seizure recurrence and to compare the efficacy of levetiracetam and phenytoin in the treatment of convulsive status epilepticus (CSE) and acute repetitive seizures (ARS).. In this study, 185 patients diagnosed with CSE or ARS and aged between 1 month and 18 years who received intravenous levetiracetam or phenytoin as a second-line AED were retrospectively evaluated.. A total of 185 patients were included in the study, 85 (45.9%) girls and 100 (54.1%) boys.While 54.1% (n = 100) of the patients were given phenytoin, levetiracetam was administered to 45.9% (n = 85) of them. The rates of cessation of seizure and prevention of seizure recurrence for 24 h were 84% for phenytoin and 78.8% for levetiracetam, without a significant difference (p > 0.05). Having active seizures on admission to the emergency department and an age of < 36 months were significantly related to seizure recurrence (p < 0.01).. Our results support that the intravenous administration of levetiracetam as the second-line treatment for CSE and ARS in children is as effective as the intravenous administration of phenytoin.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Retrospective Studies; Seizures; Status Epilepticus

Valproic acid (VPA) is frequently used and effective in juvenile myoclonic epilepsy (JME). Recently, levetiracetam (LEV) has been suggested as a monotherapy in JME. This study aimed to evaluate antiseizure medication (ASM) use in patients with JME.. Treatment choices in a total of 257 patients (age range 8-18 years, 152 girls, 105 boys) with JME diagnosed and treated between 2010 and 2020 were evaluated retrospectively. Seizure remission was defined as complete seizure control for at least 12 months.. Across the study period and entire patient group, VPA was most commonly chosen as the initial ASM (50.9%), followed by LEV (44.4%), and lamotrigine (4.7%). VPA was also the most frequent first choice in the subgroup of boys (73.3%), while LEV was the commonest first choice in girls (57.9%). The sex difference regarding the ASM of the first choice was statistically significant (p<0.001). While VPA was the most frequent initial ASM in the first 5 years of the study period (2010-2015,n = 66, 64%), LEV had taken over as the most popular first ASM in the last 5 years (n = 83, 53.9%, p = 0.005). The most frequent reasons for discontinuation were inefficacy for LEV and adverse effects for VPA (p = 0.001). During follow-up, 237 patients (92.2%) were seizure-free for at least 12 months, and 159 (61.9%) were also in electrographic remission. Seizure remission occurred earlier than electroencephalographic remission (p<0.001).. This study revealed that LEV has become the most frequently chosen initial ASM in the treatment of JME. Although LEV appears to have a better adverse effect profile, VPA seems more likely to be effective in achieving seizure control.

Topics: Adolescent; Anticonvulsants; Child; Female; Humans; Lamotrigine; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Retrospective Studies; Seizures; Sex Factors; Treatment Outcome; Turkey; Valproic Acid

There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure relapse or increased adverse effects. Considering recent findings that excipients, namely purported inactive ingredients, may nevertheless exert biological effects, it is possible that the variation in adverse event profile of antiseizure drugs may be related to differences in excipients. To test our hypothesis, we constructed a new research tool to connect FDA-compiled adverse event reports to the excipient in the medicine. Analysis of adverse events to formulations of five different second-generation antiseizure drugs - gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate - showed several significant associations between specific excipient in the formulations and an adverse event when compared to the same medicine formulated with other excipients. Epilepsy and seizure adverse events were associated with multiple excipients across gabapentin, lamotrigine, and levetiracetam formulations. A different group of excipients were associated with reports of hypersensitivity reactions including urticaria, rash, erythema, and Stevens-Johnson syndrome. Our study provides a novel approach to analyzing post-market surveillance reports by including excipients. It may be useful to clinicians when evaluating select patient groups that may be refractory to pharmacological treatment or experience worsening adverse events when switching formulations of the same antiseizure medicine.

Topics: Anticonvulsants; Drug Compounding; Excipients; Gabapentin; Humans; Lamotrigine; Levetiracetam; Seizures

The US Food and Drug Administration (FDA) has concluded that the efficacy of drugs approved for the treatment of partial onset seizures (POS) in adults can be extrapolated to pediatric patients 1 month of age and above and that independent efficacy trials in this pediatric population are no longer needed. This paper focuses on the dosing, pharmacokinetic (PK), exposure-response, and clinical information that were leveraged from the approved drugs for the treatment of POS to conduct analyses that supported extrapolation of efficacy in pediatric patients. Clinical data from trials for eight drugs (levetiracetam, oxcarbazepine, topiramate, lamotrigine, gabapentin, perampanel, tiagabine, and vigabatrin) approved in both adults and pediatric patients for the treatment of POS were analyzed. Comparisons of exposures at approved doses, placebo response, and model-based exposure-response relationships were performed. Based on disease similarity, similar response to intervention, and similar exposure-response relationships in adults and pediatric patients, it was concluded that extrapolation of efficacy in pediatric patients aged 1 month and above is acceptable. PK analysis to determine pediatric dose and regimens that provide drug exposure similar to that known to be effective in adult patients with POS will be required, along with long-term open-label safety data in pediatric patients.

Topics: Adult; Anticonvulsants; Child; Humans; Lamotrigine; Levetiracetam; Pharmaceutical Preparations; Seizures; United States

Glioblastoma multiforme (GBM) is an aggressive brain tumor, often occurring with seizures managed with antiepileptic drugs, such as levetiracetam (LEV). This study is aimed at associating progression-free survival (PFS) and overall survival (OS) of GBM patients with LEV plasma concentration, MGMT promoter methylation, and sex. In this retrospective, non-interventional, and explorative clinical study, GBM patients underwent surgery and/or radiotherapy and received LEV during adjuvant temozolomide (TMZ) treatment. A high-performance liquid chromatography with UV-detection was used for therapeutic drug monitoring of LEV plasma concentrations. Follow-up average drug concentration was related to patients' clinical characteristics and outcomes. Forty patients (42.5 % female; mean age=54.73 ± 11.70 years) were included, and GBM MGMT methylation status was assessed. All were treated with adjuvant TMZ, and LEV for seizure control. Patients harboring methylated MGMT promoter showed a longer median PFS (460 vs. 275 days, log-rank p < 0.001). The beneficial effect of MGMT promoter methylation was more evident for females (p < 0.001) and in patients with LEV concentration ≤ 20.6 µg/mL (562 days vs. 274.5 days, p = 0.032). Female patients also showed longer OS (1220 vs. 574 days, p = 0.03). Also, higher LEV concentration (>20.6 µg/mL) synergized with MGMT promoter methylation by extending the OS (1014 vs. 406 days of patients with no methylation and low LEV average concentration, p = 0.021). Beneficial effect of higher LEV plasma levels was more evident in males (p = 0.024). Plasma concentrations of LEV may support better outcomes for chemoradiotherapy when other positive prognostic factors are lacking and may promote overall survival by synergizing with MGMT promoter methylation and male sex.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Dacarbazine; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Prognosis; Retrospective Studies; Seizures; Temozolomide; Tumor Suppressor Proteins

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

Topics: Animals; Anticonvulsants; Camphor; Cardiotonic Agents; Digoxin; Levetiracetam; Male; Mice; Picrotoxin; Seizures; Strychnine; Topiramate; Valproic Acid

Nonadherence to levetiracetam (LEV) use can result in subtherapeutic concentrations and increase the risk of the occurrence of seizures. The impact of missing LEV doses on its pharmacokinetics and evidence of the appropriate remedial dose is lacking. This study has determined the influence of missed LEV doses on its pharmacokinetics and has explored the appropriate remedial dosage regimens.. Monte Carlo simulation was used to assess the impacts of different remedial dosage regimens on LEV concentrations. Simulated LEV concentrations outside the individual therapeutic range were calculated for the compliance scenario and for each of the remedial dosage regimens. The percentage of deviation from the full compliance scenario was also calculated. The regimen with the lowest percentage of deviation was considered the most appropriate.. The suitable LEV remedial dose varied across the delay times. For one missed dose, a remedial regimen with a regular dose followed by the usual dose was suitable for a delay time of less than 6 h, while a replacement with a regular dose followed by a partial dose appeared to be appropriate for a delay time of 6 h and longer. This was justified based on the concerns of LEV toxicity when the remedial dose is close to the next scheduled dose. For two consecutive missed doses, a remedial dose with one and a half of the regular dose was suitable if the gap between that and the next dose was greater than 6 h.. The appropriate remedial dosage regimen for one and two consecutive missed doses of LEV have been proposed. These remedial regimens, however, should be applied with clinicians' judgment based on the clinical status of the patients.

Topics: Anticonvulsants; Computer Simulation; Humans; Levetiracetam; Monte Carlo Method; Piracetam; Seizures

Epileptic spikes and seizures seem present early in the disease process of Alzheimer's disease (AD). However, it is unclear how soluble and insoluble amyloid beta (Aβ) and tau proteins affect seizure development in vivo. We aim to contribute to this field by assessing the vulnerability to 6 Hz corneal kindling of young female mice from two well-characterized transgenic AD models and by testing their responsiveness to selected antiseizure drugs (ASDs).. We used 7-week-old triple transgenic (3xTg) mice that have both amyloid and tau mutations, and amyloid precursor protein Swedish/presenillin 1 dE9 (APP/PS1) mice, bearing only amyloid-related mutations. We assessed the absence of plaques via immunohistochemistry and analyzed the concentrations of both soluble and insoluble forms of Aβ. Mutations increasing Aβ only or both Aβ and tau in the brain enhance susceptibility for seizures and kindling in mice. The effect of ASDs on seizures measured by the Racine scale is less pronounced in both investigated AD models and suggests that seizures of young AD mice are more difficult to treat.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anticonvulsants; Disease Models, Animal; Female; Lamotrigine; Levetiracetam; Mice; Mice, Transgenic; Seizures; tau Proteins

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5-12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Topics: Adult; Australia; Humans; Levetiracetam; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

In seizure-naive brain tumor patients, the efficacy of perioperative prophylactic antiepileptic drug treatment remains controversial. In case of administration, the common preferred drug is levetiracetam (LEV) because of its favorable pharmacological profile. Research to date has not sufficiently determined how LEV affects cognition in the short term, as is the case in the perioperative period. The objective of this prospective study was to examine the neurocognitive functioning of seizure-naive brain tumor patients after receiving LEV perioperatively.. Fortythree patients with supratentorial brain tumor scheduled for surgery received LEV three days before until six days after surgery as seizure prophylaxis. Cognitive functioning (NeuroCogFX), LEV plasma-levels, hematotoxicity, side-effects, as well as health-related quality of life (HRQoL, Qolie31), were recorded preoperatively before (Baseline) and after onset of LEV (Pre-Op), 4-6 days postoperatively (Post-Op) and 21 days postoperatively (Follow-Up).. No significant changes in cognitive functioning and HRQoL were seen after onset of preoperative LEV. There was a significant improvement of NeuroCogFX total-score at Follow-Up (p = 0.004) compared to Baseline. The overall-score Qolie31 showed simultaneous improvement patterns as cognitive functioning (p < 0.001). The most frequent side effect related to study drug was somnolence (in 28.6% of patients).. A significant improvement of cognitive functioning, as well as an improvement in HRQoL, were detected postoperatively. This is presumably due to the debulking effect of the surgery. Nevertheless, LEV has no detrimental effect on cognitive functioning in the perioperative phase in seizure-naive brain tumor patients.. This study was registered prospectively (Date: 25/11/2015; EudraCT: 2015-003,916-19).

Topics: Anticonvulsants; Brain Neoplasms; Humans; Levetiracetam; Piracetam; Prospective Studies; Quality of Life; Seizures; Supratentorial Neoplasms

Specific antiseizure medications (ASM) would improve the outcome in post-stroke epilepsy (PSE). The aim of this multicenter observational study was to compare different antiseizure monotherapies in PSE.. We collected the data from 207 patients with PSE who did not change their initial antiseizure monotherapy during the period of 12 months. Efficacy was assessed by a standardized three month seizure frequency and seizure freedom. Safety was estimated by the reported side effects.. The mean three month seizure frequency was 1.9 ± 3.1 on eslicarbazepine, 2.1 ± 3.2 on lacosamide, 3.4 ± 4.4 on levetiracetam, 4.3 ± 6.8 on lamotrigine, and 5.1 ± 7.3 on valproate (p < 0.05 for eslicarbazepine or lacosamide in comparison with levetiracetam, lamotrigine and valproate, respectively). The lowest seizure frequency and the highest seizure freedom was observed on ASMs acting via the slow inactivation of sodium channels in comparison to other mechanisms of action (0.7 ± 0.9 vs 2.2 ± 2.4, p < 0.01). Among side effects, the most frequently reported were vertigo (25%) and tiredness (15.9%). They were similar in all investigated groups of ASM. The independent factors increasing seizure frequency that were identified in multiple regression analyses were increased size of infarction, cortical involvement, hemorrhagic transformation, neurological deficits at admission and functional impairment. Administration of ASM with the mechanism of action via the slow inactivation of sodium channels was an independent factor decreasing the seizure frequency.. Our data show that antiseizure medications acting via the slow inactivation of sodium channels, such as lacosamide and eslicarbazepine, are well tolerated and might be associated with better seizure control in PSE.

Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Humans; Lacosamide; Lamotrigine; Levetiracetam; Seizures; Sodium Channels; Stroke; Valproic Acid

Approximately 80-90% of patients with Angelman syndrome (AS) develop childhood-onset intractable seizures with major negative impact on the quality of life. Thus adequate management of seizures is the most critical priority to improve health-related quality of life in children with AS.. The primary focus of the review is on pharmacotherapeutic management of seizures. To better comprehend pharmacotherapeutic decision-making, the first section of the paper briefly examines epileptogenesis and polymorphic seizure morphologies related to AS. Next, the review explores individual antiseizure medications (ASMs) and their potential therapeutic utility. Lastly, some future and emerging treatment options are discussed that can transform the management of seizures in patients with AS.. Evidence for treating seizures in AS mainly derives from low-quality studies. Levetiracetam and clobazam are the most commonly used ASMs. Although the potential utility of several other ASMs(valproate, topiramate, lamotrigine, ethosuximide, clonazepam) has been well documented for some time, the treatment landscape may rapidly evolve due to the availability of newer and better tolerated ASMs(cannabidiol oil, brivaracetam, perampanel). In addition, a better understanding of the underlying pathogenesis and the development of molecular therapeutics offer hope for precision therapies for seizures.

Topics: Anticonvulsants; Cannabidiol; Child; Clobazam; Clonazepam; Ethosuximide; Humans; Lamotrigine; Levetiracetam; Quality of Life; Seizures; Topiramate; Valproic Acid

Angelman's syndrome (AS) is accompanied by specific changes in the EEG and genetically determined epilepsy. To analyze the neurological status, changes on EEG, MRI, the course of epilepsy in patients with Angelman syndrome (observed at the Svt. uca`s Institute of Child Neurology and Epilepsy).. 47 patients with a genetically verified diagnosis of AS (aged 2 to 20 years, mean age 8.5 years; 26 boys and 21 girls) were included. The diagnosis was established by DNA methylation in 32 patients and sequencing in 15 patients (12 cases of deletion and 3 cases of nucleotide substitution were identified).. Of the 47 patients, 45 have epilepsy. The seizures start up to 5 years of age, inclusive. For treatment, patients received various antiepileptic drugs. Long-term follow-up of epilepsy was followed in 40 of 47 patients, and 36 of 40 achieved drug remission. After several years without seizures, 24 out of 30 had a relapse, which was quickly stopped in 23 out of 30 patients. The severity of the disease is influenced by the nature of the mutation and the length of the deletion, as well as persistent epileptic seizures. The most effective AEDs in patients in our study are: in monotherapy, valproic acid, levetiraceiam, ethosuximide; in duotherapy, valproic acid in combination with levetiracetam or ethosuximide, less often levetiracetam with ethosuximide.. Early genetic diagnosis of AS facilitates the selection of AET.. Изучение неврологического статуса, клинико-ЭЭГ-картины, нейровизуализации и течения эпилепсии у детей с генетически подтвержденным синдромом Ангельмана.. Проанализированы данные 47 пациентов (26 мальчиков и 21 девочка в возрасте от 2 до 20 лет, средний возраст 8,5 года) с генетически верифицированным диагнозом «синдром Ангельмана». Диагноз установлен методом метилирования ДНК у 32 пациентов и секвенирования у 15 (при этом выявлено 12 случаев делеции и 3 — нуклеотидной замены).. У 45 из 47 пациентов отмечается эпилепсия. Приступы дебютировали до 5 лет включительно. Для лечения пациенты получали различные антиэпилептические препараты. Длительный катамнез по эпилепсии удалось проследить у 40 из 47 пациентов, у 36 из 40 — достигнута медикаментозная ремиссия. Через несколько лет ремиссии у 24 из 36 пациентов произошел рецидив, который удалось быстро купировать у 23 пациентов. На степень тяжести заболевания влияют характер мутации и протяженность делеции, а также персистирующие эпилептические приступы. Максимально эффективными антиэпилептическими препаратами у пациентов в исследовании оказались вальпроевая кислота, леветирацетам, этосуксимид в монотерапии; вальпроевая кислота в сочетании с леветирацетамом или этосуксимидом, реже леветирацетам с этосуксимидом в дуотерапии.. Ранняя генетическая диагностика синдрома Ангельмана облегчает подбор противоэпилептической терапии.

Topics: Angelman Syndrome; Anticonvulsants; Child; Electroencephalography; Epilepsy; Ethosuximide; Female; Humans; Levetiracetam; Male; Seizures; Valproic Acid

To investigate the response to various antiseizure medications (ASMs) in the treatment of focal status epilepticus (SE) in the established phase, and the effect of administering several ASMs prior to sedation.. All SE cases in patients aged > 16 years treated with non-BZDs ASMs were prospectively collected in our centre from February 2011 to April 2019. In total, 281 episodes were analysed.. Median age at SE onset was 65.1 years; 47 % were focal motor and 53 % focal non-motor episodes. SE cessation was achieved in 79 % episodes with second-line drugs, whereas a third line (anesthetics) was required in 47 episodes. SE cessation was achieved in only 27 % with the first ASM, 48 % with the second, and 51 % with the third. Prompt resolution of the SE episode with a first or second ASM was associated with a better outcome than episodes requiring a larger number of drugs (p = 0.024). The first option in our sample was levetiracetam in 70 % of cases. Among the total of non-responding SE cases treated with levetiracetam as the first ASM option, 107 were subsequently given lacosamide (seizure cessation in 53.3 %) and 34 valproic acid (seizure cessation in 29.4 %) (p = 0.015).. Our findings further support the notion that early termination of SE with a first or second ASM confers a better functional outcome. The large difference in response between the first ASM and consecutive ones suggests that the sum of different ASMs might be the key to resolving focal SE.

Topics: Anticonvulsants; Humans; Levetiracetam; Seizures; Status Epilepticus; Tertiary Care Centers; Treatment Outcome

Palliative care patients experience seizures in different stages of their disease and may not tolerate oral medications toward the end of life. Subcutaneous infusions of levetiracetam and sodium valproate are increasingly used off-label. This retrospective analysis (conducted from January 2019 to July 2020 in Australia) reports the effectiveness and adverse effects of levetiracetam and sodium valproate delivered via subcutaneous infusion. The doses ranged from 500 to 3000 mg/d of levetiracetam and 500 to 2500 mg/d of sodium valproate. The concentrations ranged from 20 to 83 mg/mL of levetiracetam and 20 to 50 mg/mL of sodium valproate. Subcutaneous levetiracetam was given for a median duration of 6.5 days, with no seizure recurrences in 75% of patients and no reported adverse effects in any patients. Subcutaneous sodium valproate was given for a median duration of 3.5 days, with no reported seizure recurrences in 83% of patients and one report of a localized skin reaction. This analysis suggests that subcutaneous levetiracetam and sodium valproate can effectively control seizures in palliative care populations, with minimal localized reactions.

Topics: Anticonvulsants; Humans; Levetiracetam; Palliative Care; Piracetam; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid

To assess the effects of synaptic vesicle protein 2A (SV2A) modulators brivaracetam and levetiracetam on amygdala kindling epileptogenesis in Tg2576 mice, a model of Alzheimer's disease which exhibits sensitivity to seizures.. First, aged Tg2576 mice (13-25 months; n = 17) were treated subcutaneously with either brivaracetam (10 mg/kg/day), levetiracetam (150 mg/kg/day) or vehicle via osmotic pumps for 28 days prior to, and during electrical amygdala kindling epileptogenesis. Next, we treated young (4-6 months; n = 24) Tg2576 mice with brivaracetam (10 mg/kg/day) or vehicle for 28 days and allowed one week's 'washout' before commencing kindling. Progression of seizure severity and duration were compared between treatment groups and wildtype mice (WT).. In older Tg2576 mice, treatment with brivaracetam (p < 0.001) and levetiracetam (p < 0.05) before and during kindling significantly delayed the progression of seizure severity, compared to vehicle. Animals treated with brivaracetam required significantly more stimulations to reach the first class V (convulsive) seizure and had a lower mortality rate (p < 0.05) compared to those treated with vehicle. Young Tg2576 mice also exhibited increased susceptibility to kindling epileptogenesis compared to WT. Treatment with brivaracetam in younger animals only prior to kindling also delayed kindling acquisition compared to vehicle treatment, increasing the number of stimulations required to experience class V seizures (p < 0.05).. Brivaracetam treatment displayed marked anti-epileptogenic effects in both aged and young Tg2576 mice, including when treatment is ceased prior to initiating kindling. Targeting SV2A might represent a strategy for prevention of epilepsy in patients with Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Anticonvulsants; Disease Models, Animal; Kindling, Neurologic; Levetiracetam; Mice; Seizures; Synaptic Vesicles

Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either from the failure of the mechanisms responsible for seizure termination or initiation, leading to abnormally prolonged seizures. The definition has different time points for convulsive, focal and absence SE. Time is brain. There are changes in synaptic receptors leading to a more proconvulsant state and increased risk of brain lesion and sequelae with long duration. Management of SE must include three pillars: stop seizures, stabilize patients to avoid secondary lesions and treat underlying causes. Convulsive SE is defined after 5 minutes and is a major emergency. Benzodiazepines are the initial treatment, and should be given fast and an adequate dose. Phenytoin/fosphenytoin, levetiracetam and valproic acid are evidence choices for second line treatment. If SE persists, anesthetic drugs are probably the best option for third line treatment, despite lack of evidence. Midazolam is usually the best initial choice and barbiturates should be considered for refractory cases. Nonconvulsive status epilepticus has a similar initial approach, with benzodiazepines and second line intravenous (IV) agents, but after that, aggressiveness should be balanced considering risk of lesion due to seizures and medical complications caused by aggressive treatment. Usually, the best approach is the use of sequential IV antiepileptic drugs (oral/tube are options if IV options are not available). EEG monitoring is crucial for diagnosis of nonconvulsive SE, after initial control of convulsive SE and treatment control. Institutional protocols are advised to improve care.

Topics: Anticonvulsants; Benzodiazepines; Humans; Levetiracetam; Seizures; Status Epilepticus

Brivaracetam (BRV) is licensed as an adjunctive treatment for focal epilepsy. We describe our clinical experience with BRV at a large UK tertiary center.. Adults initiated on BRV between July 2015 and July 2020 were followed up until they discontinued BRV or September 2021. Data on epilepsy syndrome, duration, seizure types, concomitant and previous antiseizure medication (ASM) use, BRV dosing, efficacy, and side effects were recorded. Efficacy was categorized as temporary (minimum three months) or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefits (e.g., no convulsions or daytime seizures). Brivaracetam retention was estimated using Kaplan-Meier survival analysis.. Two-hundred people were treated with BRV, of whom 81% had focal epilepsy. The mean (interquartile range [IQR]) follow-up time was 707 (688) days, and the dose range was 50-600 mg daily. The mean (IQR) of the previous number of used ASMs was 6.9 (6.0), and concomitant use was 2.2 (1.0). One-hundred and eighty-eight people (94%) had previously discontinued levetiracetam (LEV), mainly due to side effects. 13/200 (6.5%) were seizure free for a minimum of six months during treatment, and 46/200 (23%) had a ≥50% reduction in seizure frequency for six months or more. Retention rates were 83% at six months, 71% at 12 months, and 57% at 36 months. Brivaracetam was mostly discontinued due to side effects (38/75, 51%) or lack of efficacy (28/75, 37%). Concomitant use of carbamazepine significantly increased the hazard ratio of discontinuing BRV due to side effects (p = 0.006). The most commonly reported side effects were low mood (20.5%), fatigue (18%) and aggressive behavior (8.5%). These side effects were less prevalent than when the same individuals took LEV (low mood, 59%; aggressive behavior, 43%). Intellectual disability was a risk factor for behavioral side effects (p = 0.004), and a pre-existing mood disorder significantly increased the likelihood of further episodes of low mood (p = 0.019).. Brivaracetam was effective at a broad range of doses in managing drug-resistant epilepsy across various phenotypes, but less effective than LEV in those who switched due to poor tolerability on LEV. There were no new tolerability issues, but 77% of the individuals experiencing side effects on BRV also experienced similar side effects on LEV.

Topics: Anticonvulsants; Carbamazepine; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Partial; Humans; Levetiracetam; Pyrrolidinones; Seizures; Tertiary Care Centers; Treatment Outcome

Pharmacokinetics (PK) of a drug drive its exposure, efficacy, and tolerability. A thorough preclinical PK assessment of antiseizure medications (ASMs) is therefore essential to evaluate the clinical potential. We tested protection against evoked seizures of prototype ASMs in conjunction with analysis of plasma and brain PK as a proof-of-principle study to enhance our understanding of drug efficacy and duration of action using rodent seizure models.. In vivo seizure protection assays were performed in adult male CF-1 mice and Sprague Dawley rats. Clobazam (CLB), N-desmethyl CLB (NCLB), carbamazepine (CBZ), CBZ-10,11-epoxide (CBZE), sodium valproate (VPA), and levetiracetam (LEV) concentrations were quantified in plasma and brain using liquid chromatography-tandem mass spectrometry. Mean concentrations of each analyte were calculated and used to determine PK parameters via noncompartmental analysis in Phoenix WinNonLin.. NCLB concentrations were approximately 10-fold greater than CLB in mice. The antiseizure profile of CLB was partially sustained by NCLB in mice. CLB concentrations were lower in rats than in mice. CBZE plasma exposures were approximately 70% of CBZ in both mice and rats, likely contributing to the antiseizure effect of CBZ. VPA showed a relatively short half-life in both mice and rats, which correlated with a sharp decline in efficacy. LEV had a prolonged brain and plasma half-life, associated with a prolonged duration of action in mice.. The study demonstrates the utility of PK analyses for understanding the seizure protection time course in mice and rats. The data indicate that distinct PK profiles of ASMs between mice and rats likely drive differences in drug efficacy between rodent models.

Topics: Animals; Anticonvulsants; Benzodiazepines; Carbamazepine; Clobazam; Epilepsy; Levetiracetam; Male; Mice; Rats; Rats, Sprague-Dawley; Seizures

The use of many antiseizure medications (ASMs) is limited due to pharmacoresistance and dose-limiting side effects, suggesting an unmet need for novel therapeutic approaches. The neuropeptide galanin reduces seizures in several preclinical seizure and epilepsy models, but its clinical utility is limited due to rapid metabolism and poor blood-brain barrier penetration. The lead galanin analog 810-2 is systemically bioavailable and reduces seizures when administered alone. Further development of this analog, with the potential for use as an add-on therapy in patients with epilepsy, requires a better understanding of the use of this analog in combination with approved ASMs. We sought to evaluate 810-2 in combination with commonly used ASMs in rodent models of seizures.. The mouse 6-Hz seizure assay was used to test efficacy of 810-2 in combination with levetiracetam (LEV), valproic acid (VPA), or lacosamide (LCM) using a 1:1 dose ratio in isobolographic studies. Further characterization was performed for the combination of 810-2 and LEV in the mouse corneal kindling and rat 6-Hz assays.. Whereas the combination of 810-2 with VPA and LCM yielded additive interactions, the combination of 810-2 with LEV demonstrated a synergistic interaction in the mouse 6-Hz assay. Supra-additive effects were also observed in the mouse corneal kindling and rat 6-Hz assays for this combination.. The combination of 810-2 with LEV suggests the potential for this galanin analog to be further developed as an add-on therapy for patients with epilepsy, particularly when coadministered with LEV.

Topics: Animals; Epilepsy; Levetiracetam; Mice; Rats; Rodentia; Seizures

About 30% of patients with glioma need an add-on antiseizure medication (ASM) due to uncontrolled seizures on ASM monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV + VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in patients with glioma.. In this multicenter retrospective observational cohort study, treatment failure (i.e., replacement by, addition of, or withdrawal of an ASM) for any reason was the primary outcome. Secondary outcomes included (1) treatment failure due to uncontrolled seizures and (2) treatment failure due to adverse effects. Time to treatment failure was estimated from the moment of ASM duotherapy initiation. Multivariable cause-specific Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months.. A total of 1,435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received ASM duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV + VPA was prescribed in 66% (236/355) and other ASM duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy vs LEV + VPA had a higher risk of treatment failure for any reason (cause-specific adjusted hazard ratio [aHR] 1.50 [95% CI 1.07-2.12],. This observational cohort study suggests that LEV + VPA has better efficacy than other ASM combinations. Similar toxicities were experienced in the 2 groups.. This study provides Class III evidence that for patients with glioma with uncontrolled seizures on ASM monotherapy, LEV + VPA has better efficacy than other ASM combinations.

Topics: Anticonvulsants; Cohort Studies; Glioma; Humans; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Valproic Acid

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Anti-epileptic drugs (AEDs) are the mainstay of epilepsy treatment but these may be a potential risk factor for behavioral disturbances particularly depression which requires treatment. In this study, the effect of antidepressant sertraline (SRT) in combination with AEDs sodium valproate (SV) and levetiracetam (LEV) on seizures, cognitive impairment and oxidative stress in rats was evaluated. After administration of 24th injection of pentylenetetrazole (PTZ), 77.8% rats were kindled. Administration of SRT showed no protective effect on kindling development while SV was 100% protective. With LEV 42.9% were kindled. On combining SRT with SV or LEV 25% and 20% rats were kindled. A significant increase in latency to reach platform zone in Morris water maze(MWM), and increased transfer latencies in Elevated plus maze(EPM) was observed in PTZ kindled rats as compared to normal control on day 49 and when LEV was combined with SRT. In EPM test, however none of the drug treatments had any effect on transfer latencies except LEV pretreated kindled group. In Passive avoidance (PA) test, kindling was associated with a significant decrease in retention time(p = 0.018) while LEV and SV had no effect. The PTZ kindled rats showed significantly higher malondialdehyde(MDA) levels in brain hippocampus(p = 0.0286) while both SRT and SV were associated with significantly lower MDA levels as compared to kindled control group. In case of glutathione (GSH), kindling had no significant effect. The use of sertraline for depression in persons with epilepsy on AEDs needs to be carefully evaluated and monitored due to likelihood of individual variation.

Topics: Animals; Anticonvulsants; Avoidance Learning; Cognition Disorders; Convulsants; Glutathione; Kindling, Neurologic; Levetiracetam; Male; Maze Learning; Oxidative Stress; Pentylenetetrazole; Rats; Rats, Wistar; Seizures; Selective Serotonin Reuptake Inhibitors; Sertraline; Valproic Acid

We present a case of a 14-year-old, previously healthy female, admitted with acute coronavirus disease 2019 infection and new-onset seizures secondary to virus-associated necrotizing disseminated acute leukoencephalopathy. Her symptoms resolved completely with intravenous immunoglobulin and steroids. Pathophysiology and prognosis of neurologic manifestations of coronavirus disease 2019 remain unclear.

Topics: Adolescent; Anticonvulsants; COVID-19; COVID-19 Drug Treatment; Female; Humans; Immunoglobulins, Intravenous; Intracranial Hemorrhages; Leukoencephalopathies; Levetiracetam; Lorazepam; SARS-CoV-2; Seizures

Topics: Adult; Anticonvulsants; Blood Chemical Analysis; Brain; Consciousness Disorders; Diagnosis, Differential; Electroencephalography; Humans; Immunoblotting; Levetiracetam; Magnetic Resonance Imaging; Male; Neurocysticercosis; Parasitic Diseases; Seizures; Tomography, X-Ray Computed

Epilepsy, a neuronal disorder has affected 1% of the world's population. Almost 35-40% of these patients get resistant to available anti-epileptic drugs (AEDs). Recent studies have shown the role of inflammation in the pathophysiology of epilepsy and a combination of anti-inflammatory and antiepileptic drugs could prove beneficial against epileptic seizures. Therefore, we aimed to examine the effect of levetiracetam (LEV) and diclofenac sodium (DFS) combination on pilocarpine (PLC) induced epileptic seizures in mice. Mice were divided into control and treatment groups. LEV alone and in combination with DFS was given for 3 days. On 3rd day after administering the required drugs, pilocarpine challenge was given intraperitoneally. Then, behavioral changes were observed for 90 minutes, including latency to first seizure, continuous seizures, duration of continuous seizures, and survival rate. Results showed significant improvement in the latencies to first (P<0.001) and continuous seizures (P<0.05), duration of the continuous seizure (p=0.001), and survival rate (P<0.01) in the combination treatment group as compared to the control or individual drug treatment groups. DFS enhances the efficacy of LEV, however, further mechanistic studies will be required to conclude if DFS can be given in combination with LEV for epilepsy treatment.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Behavior, Animal; Convulsants; Diclofenac; Drug Synergism; Epilepsy; Levetiracetam; Male; Mice; Pilocarpine; Seizures; Survival Analysis

Sleep is a reversible behavioural state of perceptual disengagement from and unresponsiveness to the environment, which is required for neural plasticity and memory consolidation. Sleep disorders are common in patients with epilepsy. The main causes of sleep disturbances are coexisting sleep disorders, impact of seizures and epileptic activity, and the effects of antiepileptic drugs. Sleep and epilepsy have reciprocal effects - on one hand electrical brain activity during sleep is a strong modulator of epileptic activity and on the other epileptic activity during sleep may disrupt sleep architecture. The most common side effects of anticonvulsants include alterations in sleep architecture and variation in the degree of daytime sleepiness. Their effects on sleep and daytime sleepiness are variable and it is often difficult to distinguish whether the improved seizure control and epileptic activity is a direct result of anticonvulsants or associated with improved sleep quality. Levetiracetam is a new generation anticonvulsant used to treat both focal and generalized epilepsy. Its satisfactory safety and tolerability explain its wide usage in the clinical practice and necessitates more profound knowledge on its effects on sleep quality. There have been few reports about its effects on sleep architecture and daytime sleepiness. A short summary of the studies concerning this topic is presented. Main disadvantages of the studies are: the small sample size, comparison of the results obtained in healthy volunteers with patients with epilepsy, short observation duration, variations of dosage, different evaluation modalities and concomitant AED therapy. Future prospective studies on subjective and objective effects of Levetiracetam on sleep architecture and daytime sleepiness are needed to better understand its impact on sleep in order to improve epilepsy patients' quality of life, seizure control and sleep disturbances.

Topics: Anticonvulsants; Disorders of Excessive Somnolence; Epilepsy; Humans; Levetiracetam; Prospective Studies; Quality of Life; Seizures; Sleep; Sleep Wake Disorders

Appropriate treatment of neonatal seizures with an effective therapy is important in reducing long-term neurologic disabilities. Sixty-seven neonates, who received intravenous (IV) levetiracetam (LEV) as first-line therapy for treating seizures between 2013 and 2017 were evaluated retrospectively to investigate the efficacy of LEV and its neurodevelopmental outcome at 12 months of age. Of the 67 neonates (44 preterm and 23 term babies) evaluated for seizures, 55 (82%) had a defined etiology. EEG confirmation was obtained in 36 (57.1%) of the neonates with clinical seizures. On the 7th day of the treatment (mean seizure control time 7.4 ± 15.1 days), LEV was effective as monotherapy in 43 (64%), whereas add-on therapy was required in 24 (36%) neonates. At the 1-year follow-up, 76% of infants achieved drug-free state, nine (18%) infants remained on LEV monotherapy and three (6%) needed add-on therapy. Neurodevelopmental outcome of the infants was assessed with Ankara Development Screening Inventory and results suggested favorable neurodevelopmental outcome in 69.7% of the infants with at the end of the 1-year follow-up with LEV monotherapy. In conclusion, this retrospective cross-sectional study demonstrated that IV LEV is an effective first-line therapy for treating neonatal clinical seizures and LEV monotherapy effect was sustained during the first year follow-up.

Topics: Anticonvulsants; Child Development; Cross-Sectional Studies; Electroencephalography; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Levetiracetam; Retrospective Studies; Seizures; Treatment Outcome

The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease.. Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam.. Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood-brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established.. Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood-brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.

Topics: Aged; Aged, 80 and over; Anticonvulsants; COVID-19; Critical Illness; Electroencephalography; Epidural Abscess; Humans; Laminectomy; Levetiracetam; Lumbar Vertebrae; Male; Radiculopathy; Respiration, Artificial; Respiratory Insufficiency; Sacrum; SARS-CoV-2; Seizures; Surgical Wound Infection

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Topics: Acute Kidney Injury; Adolescent; Airway Extubation; Anticonvulsants; Blood Coagulation Disorders; Bone Marrow Failure Disorders; Brain Diseases; Brain Edema; C-Reactive Protein; COVID-19; De Lange Syndrome; Disease Progression; Electroencephalography; Epilepsy; Female; Ferritins; Humans; Influenza B virus; Influenza, Human; Levetiracetam; Magnetic Resonance Imaging; Midazolam; Necrosis; Phenobarbital; Pseudomonas Infections; Respiration, Artificial; Rhabdomyolysis; SARS-CoV-2; Seizures; Sepsis; Systemic Inflammatory Response Syndrome; Tachycardia, Ventricular

Topics: Anticonvulsants; Brain Neoplasms; Cerebral Cortex; Constriction, Pathologic; Electrodes, Implanted; Electroencephalography; Epilepsy; Glioma; Humans; Laryngeal Diseases; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Seizures

This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based cohort comprising 471 adult GGE patients. A total of 1046 treatment attempts were analyzed (lamotrigine: 351, valproic acid: 295, levetiracetam: 249, primidone/phenobarbital: 94, zonisamide: 57). Under lamotrigine, seizure aggravation was observed in 15 patients (two patients during levetiracetam, one patient during zonisamide, none during phenobarbital and valproic acid). All but two patients with paradoxical reactions to lamotrigine were diagnosed with juvenile myoclonic epilepsy (JME), otherwise, the clinical and electroencephalographic characteristics of patients with paradoxical reactions did not differ. At treatment start, the estimated risk of a paradoxical reaction to lamotrigine was 7.9 % in JME patients (n = 190). For all GGE patients (incl. JME), the estimated risk of clinically relevant seizure aggravation under treatment with lamotrigine was 3.7 % (1.8 % for zonisamide and 0.8 % for levetiracetam). In conclusion, clinical significant aggravation of seizure frequency is common in lamotrigine-treated JME patients but rare in patients with other GGE subsyndromes or under treatment with other recommended anti-seizure medication.

Topics: Adult; Anticonvulsants; Epilepsy, Generalized; Humans; Lamotrigine; Levetiracetam; Myoclonic Epilepsy, Juvenile; Phenobarbital; Retrospective Studies; Risk Factors; Seizures; Valproic Acid; Zonisamide

Brain metastases originate from other primary cancers within the body, most commonly lung, breast, and melanoma. Because patients with brain metastasis, stroke, or intracranial hemorrhage may present with similar acute neurologic symptoms, clinicians must have a high suspicion for brain metastasis and perform an immediate workup to rule out life-threatening conditions. This case report focuses on the clinical symptoms, diagnostics, and treatment options for brain metastasis in a patient with multiple malignancies.

Topics: Brain Neoplasms; Cranial Irradiation; Dexamethasone; Esophageal Neoplasms; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Melanoma; Neoplasms, Multiple Primary; Nervous System Diseases; Prostatic Neoplasms; Radiosurgery; Scalp; Seizures; Skin Neoplasms; Tomography, X-Ray Computed

We report the case of a 70-year-old diabetic woman who presented to the emergency department with multiple seizure episodes and coma, prompting the need for sedation and mechanical ventilation. She was transferred to our institution for neurosurgical evaluation as the initial CT scan identified hyperdense lesions in the left basal ganglia, interpreted as acute intracranial haemorrhage. On admission, laboratory tests were mostly normal except for blood glucose of 413 mg/dL. Medical records revealed a history of poorly controlled diabetes mellitus and non-adherence to therapy. After seizure control and lifting sedation, right-sided ataxia/involuntary movements were observed. Considering the patient's history and these findings, the CT scan was reviewed and the striatal region hyperdensities interpreted as lesions typical of non-ketotic hemichorea-hemiballismus. MRI was latter performed and confirmed the diagnosis, even though the unusual presentation. Levetiracetam initiation and glycaemic control optimisation led to great neurological improvement without seizure recurrence.

Topics: Aged; Anticonvulsants; Basal Ganglia; Blood Glucose; Coma; Diabetes Mellitus, Type 2; Diagnosis, Differential; Dyskinesias; Female; Humans; Hyperglycemia; Intracranial Hemorrhages; Levetiracetam; Magnetic Resonance Imaging; Medication Adherence; Seizures; Tomography, X-Ray Computed

There are only a few reports on Go-induced epilepsy. We hereby report a case of Go-induced epilepsy and its ictal electroencephalography (EEG) findings, and treatment. A 71-year-old man reported to our hospital for seizures that lasted for several minutes after he had played Go for approximately an hour. Ictal EEG showed focal to bilateral tonic-clonic seizures of right parietal origin. He was administered levetiracetam 500 mg before the games, and he participated without seizures for more than a year. Go-induced epilepsy is considered to have a focal onset, and it may be controlled with antiepileptic drugs before the games.

Topics: Aged; Electroencephalography; Epilepsies, Partial; Games, Recreational; Humans; Levetiracetam; Male; Parietal Lobe; Seizures; Time Factors

Topics: Anticonvulsants; Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

To assess the spike characteristics and temporal spike evolution on serial EEG of children with childhood epilepsy with centrotemporal spikes (CECTS) treated with anti-seizure medication.. The study cohort consisted of 127 children with CECTS divided into three groups based on anti-seizure medication responsiveness: group I: seizure-free with monotherapy (n: 61, 48%), group II: seizure-controlled with monotherapy (n: 52, 41%) and group III: seizure-controlled with dual therapy (n: 14, 11%). The clinical profiles and sequential four-year follow-up visual EEG recordings of the children were evaluated. Each EEG was reanalyzed with three spike characteristics on the epochs: (1) spike-wave rate, (2) spike topography, and (3) spike localization. We calculated the spike clearance velocity, which is defined as a decrease in the spike-wave rate over time in four-year sequential follow-up EEGs.. There was no statistical significance across the study groups with respect to initial EEG spike characteristics (spike-wave rate, spike localization, and spike topography). Seizure recurrence occurred in 15 patients (12.8%) who discontinued anti-seizure medication. There was no statistically significant difference between the spike characteristics on EEG just before the discontinuation of anti-seizure medication and seizure recurrence. However, the spike clearance velocity was significantly slower in group III than in group I in four-year sequential follow-up EEGs (p = 0.002). A statistically significant decrease in the mean spike-wave rate was observed in group I in the first year of anti-seizure medication (p<0.001). The spike clearance velocity was also more prominent during the second year of treatment in group II and the third year of treatment in group III. However, the spike clearance velocity was not different across the anti-seizure medication groups (oxcarbazepine, valproic acid, and levetiracetam).. Spike clearance velocity might be a valuable EEG marker to guide anti-seizure medication in children with CECTS.

Topics: Child; Electroencephalography; Epilepsy, Rolandic; Humans; Levetiracetam; Recurrence; Seizures

This study aimed at estimating the cumulative incidence of antiepileptic drug (AED) treatment failure of first-line monotherapy levetiracetam vs valproic acid in glioma patients with epilepsy.. In this retrospective observational study, a competing risks model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as a competing event. Patients were matched on baseline covariates potentially related to treatment assignment and outcomes of interest according to the nearest neighbor propensity score matching technique. Maximum duration of follow-up was 36 months.. In total, 776 patients using levetiracetam and 659 using valproic acid were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure for any reason was significantly lower for levetiracetam compared to valproic acid (12 months: 33% [95% confidence interval (CI) 29%-38%] vs 50% [95% CI 45%-55%]; P < .001). When looking at specific reasons of treatment failure, treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95% CI 12%-19%] vs 28% [95% CI 23%-32%]; P < 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95% CI 11%-18%] vs 15% [95% CI 11%-18%]; P = .636).. Our results suggest that levetiracetam may have favorable efficacy compared to valproic acid, whereas level of toxicity seems similar. Therefore, levetiracetam seems to be the preferred choice for first-line AED treatment in patients with glioma.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid

We experienced 3 adult patients with intractable focal epilepsy treated by levetiracetam (LEV) as polytherapy, who showed paradoxical effect (PE). Starting dose of LEV was small (62.5, 250 mg/day) and we gradually increased by less than 250 mg/day, every more than 2 weeks. Within 6 months after LEV was added, LEV of 750 to 1,000 mg/day brought reduction of seizure frequency. Serum concentration of LEV was 13.3 and 14.0 μg/ml. In order to obtain better seizure control, LEV was increased up to 1,000-2,500 mg/day (19.3-35.0 μg/ml) within one year, and they developed PE. They all showed increased habitual seizures, occurring in cluster. Once dose of LEV deceased down to what produced the maximum seizure suppression, all of the patients regained the better seizure control. It is most likely that at least in some patients like present 3 cases, PE of LEV may express U curve association between dose and effect and that it was only delineated by slow titration.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Seizures; Treatment Outcome

Busulfan is a chemotherapy agent used in hematopoietic stem cell transplant (HSCT) conditioning regimens. Busulfan is associated with tonic-clonic seizures in ~10% of patients if administered without seizure prophylaxis. Historically, phenytoin was the most commonly utilized seizure prophylaxis agent; however, phenytoin is associated with CYP450 drug interactions and potentially increases the clearance of busulfan. Levetiracetam is being used more recently for busulfan seizure prophylaxis and is not associated with drug-drug interactions; however, data supporting use in pediatric patients are limited. The primary objective is to determine whether there is any difference in seizure rates or safety profile between phenytoin and levetiracetam when used for seizure prophylaxis.. We conducted a retrospective chart review including patients who received busulfan between 2010 and 2019 were identified. The data were evaluated to compare the incidence of busulfan-induced seizures in HSCT patients receiving either phenytoin or levetiracetam and to determine the impact of drug-drug interactions on treatment outcomes/adverse events.. A total of 342 patients were included with a median age of six years. Overall, five patients within the phenytoin group (n = 126) (4%) and zero patients in the levetiracetam group (n = 216) experienced a seizure (P = .007). There were no differences in liver enzyme elevations, recurrence rates of primary disease, and veno-occlusive disease.. Levetiracetam is effective at preventing seizures associated with busulfan administration with no clinically significant adverse effects when compared to phenytoin.

Topics: Adolescent; Adult; Anticonvulsants; Busulfan; Child; Child, Preschool; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Levetiracetam; Male; Myeloablative Agonists; Phenytoin; Retrospective Studies; Seizures; Transplantation Conditioning; Treatment Outcome; Young Adult

Despite the availability of more than 20 clinical antiepileptic drugs, approximately 30% of patients with epilepsy do not respond to antiepileptic drug treatment. Therefore, it is important to develop antiepileptic products that function via novel mechanisms. In the present study, we evaluated data from one of the largest global databases to identify drugs with antiepileptic effects, and subsequently attempted to understand the effect of the combination of antiepileptic drugs and valacyclovir in epileptic seizures using a kindling model. To induce kindling in mice, pentylenetetrazol at a dose of 40 mg/kg was administered once every 48 h. Valacyclovir was orally administered 30 min before antiepileptic drug injection in kindled mice, and behavioral seizures were monitored for 20 min following pentylenetetrazol administration. Additionally, c-Fos expression in the hippocampal dentate gyrus was measured in kindled mice. Valacyclovir showed inhibitory effects on pentylenetetrazol-induced kindled seizures. In addition, simultaneous use of levetiracetam and valacyclovir caused more potent inhibition of seizure activity, and neither valproic acid nor diazepam augmented the anti-seizure effect in kindled mice. Furthermore, kindled mice showed increased c-Fos levels in the dentate gyrus. The increase in c-Fos expression was significantly inhibited by the simultaneous use of levetiracetam and valacyclovir. The findings of the present study indicate that a combination of levetiracetam and valacyclovir had possible anticonvulsive effects on pentylenetetrazol-induced kindled epileptic seizures. These results suggest that valacyclovir may have an antiseizure effect in patients with epilepsy.

Topics: Animals; Anticonvulsants; Cefepime; Databases, Factual; Disease Models, Animal; Drug Repositioning; Drug Therapy, Combination; Hippocampus; Humans; Kindling, Neurologic; Levetiracetam; Male; Mice; Pentylenetetrazole; Proto-Oncogene Proteins c-fos; Seizures; Valacyclovir

There are no reliable prospective studies on the effectiveness of LEV in Bulgarian adult patients with drug-resistant epilepsy.. The study aimed at conducting an open, prospective study on various aspects of levetiracetam (LEV) effectiveness in Bulgarian patients with drug-resistant epilepsy.. The study was performed with patients with epilepsy recruited from those attending the Department of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LEV and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings.. LEV was applied as an add-on therapy in 135 patients (86 males, mean age 35 years). There was a relatively mild and persisting dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 49.6% of participants, a persisting mean seizure frequency reduction (48-58%) from 6 to 36 months of treatment and a high responder rate (53-60%) during the same period. New seizure types (focal with impaired awareness with /without evolution to bilateral tonic-clonic seizures) occurred in 4 patients. There were adverse events (dizziness, memory impairment, aggressiveness, numbness, non-epileptic seizures, depression, anxiety, speech disturbances, visual hallucinations, sleepiness, pelvic muscles weakness, confusion, sleep disturbances, loss of appetite, unstable gait, hair loss, acne, generalized rash) in 13.33% of patients.. LEV treatment is associated with: low and persisting improvement of seizure severity, a good and persisting improvement of seizure frequency, a possible worsening of seizure control, a possible appearance of new seizure types, a good safety and tolerability.

Topics: Adult; Anticonvulsants; Bulgaria; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Pharmaceutical Preparations; Prospective Studies; Seizures; Treatment Outcome

We aimed to evaluate the blood concentration of levetiracetam (LEV), as a second-line drug, in patients with status epilepticus (SE) in an emergency clinical setting.. We prospectively evaluated 20 consecutive patients with SE admitted to our department between July 2017 and July 2019. LEV (2500 mg) was administered via bolus infusion after diazepam infusion, followed by 500 mg every 12 h for 48 h and then 500 mg orally. The primary outcomes were LEV blood concentration 15 min, 12 h, 48 h, and 96 h after administration and the proportion of patients showing trough LEV concentration within the therapeutic range. The secondary outcomes were the discontinuation of apparent convulsive seizure, epileptic wave on electroencephalogram, tracheal intubation, adverse events related to blood parameters, and abnormal findings in vital signs examination.. Median blood LEV (2500 mg) concentration at 15 min after administration was 81.6 μg/mL. The median trough concentration after 12, 48, and 96 h was 28.8, 10.5, and 9.1 μg/mL, respectively. Moreover, 95% of patients had trough concentration above the lower limit of the therapeutic blood concentration (>12 μg/mL) after 12 h. Regarding secondary outcomes, endotracheal intubation, seizure suppression, and abnormal electroencephalogram findings were observed in approximately 40%, 90%-95%, and 41% of patients, respectively. No abnormal findings were noted in blood tests and vital sign examination, although the AST/ALT levels increased in 10% of the patients.. After bolus administration of 2500 mg, the blood LEV concentration reached the therapeutic window in patients with early-stage SE.

Topics: Anticonvulsants; Diazepam; Humans; Levetiracetam; Piracetam; Seizures; Status Epilepticus

Topics: Anticonvulsants; Brain Injuries, Traumatic; Humans; Incidence; Levetiracetam; Nervous System Diseases; Phenytoin; Retrospective Studies; Seizures

Awake craniotomy is an established procedure for resecting brain tumors in eloquent lesions, and intraoperative seizure is one of the most important complications. Phenytoin is normally used to control intraoperative seizures. Recently, phenytoin was replaced with levetiracetam at our institution because the latter has fewer side effects. While the phenytoin dose is calibrated in accordance with the serum concentration, there is currently no consensus on a method of monitoring the serum concentration of levetiracetam or the effective concentration range needed to control intraoperative seizures during awake craniotomy. The present study therefore aimed to determine whether monitoring the serum levetiracetam concentration is useful for controlling intraoperative seizures during awake craniotomy. The intraoperative serum concentration of levetiracetam during awake craniotomy was measured in 34 patients and compared with that of phenytoin in 33 patients undergoing the same procedure. The levetiracetam concentration inversely correlated with body surface area (BSA) and estimated glomerular filtration rate (eGFR). Levetiracetam was superior to phenytoin in terms of the correlation between the serum concentration and the dose adjusted for BSA and eGFR (correlation coefficient, 0.49 vs 0.21). Furthermore, the serum levetiracetam concentration in patients with intraoperative seizures was below the 95% confidence interval (CI) of the regression line whereas the serum phenytoin concentration of two patients with seizures was within the 95% CI, indicating that evaluating the serum levetiracetam concentration against the BSA and eGFR-adjusted dosage may be useful in preventing intraoperative seizures during awake craniotomy by allowing prediction of the seizure risk and enabling more accurate dosage calibration.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Craniotomy; Humans; Levetiracetam; Middle Aged; Phenytoin; Seizures; Wakefulness

Topics: Aged; Anticonvulsants; Asymptomatic Diseases; Electroencephalography; Female; Humans; Hydrocephalus; Levetiracetam; Seizures; Tomography, X-Ray Computed; Treatment Outcome; Urinary Tract Infections

Operational delays have the potential to lead to suboptimal time to seizure control during status epilepticus. Levetiracetam (LEV) is an urgent control antiepileptic medication that offers relative lack of adverse effects and ease of monitoring. There are limited data published demonstrating safety and tolerability of undiluted rapid intravenous (IV) push of LEV in doses of 1000 mg or less. The purpose of this study was to evaluate the safety of IV push administration of LEV doses up to 4500 mg.. This is a retrospective, observational, cohort analysis of adult patients who received at least one dose of undiluted IV push LEV from October 15, 2019 to August 31, 2020 at a large academic medical center in Phoenix, Arizona. Outcomes of interest include safety and tolerability of rapid administration of undiluted LEV.. There were 953 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizure in 51.9% of patients, and 40.7% of patients had a documented history of epilepsy or seizure disorder. There were 8561 undiluted IV push LEV doses administered, 3674 (42.9%) of which were greater than 1000 mg. LEV was administered most often through a peripheral IV (79.1%). There were 12 patients with documented adverse drug events during the study period, with four potentially directly related to IV push LEV administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line.. Rapid IV administration of undiluted LEV is both safe and tolerable in doses of up to 4500 mg, allowing for rapid drug administration, which is paramount during neurologic emergencies.

Topics: Adult; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Levetiracetam; Piracetam; Seizures; Status Epilepticus; Treatment Outcome

Levetiracetam (LEV) is a second-generation antiseizure medicine (ASM) with broad-spectrum efficacy and tolerability. Few studies have compared the efficacy of valproate (VPA) and LEV as monotherapy in the pediatric population. Herein, we compare the efficacy, tolerability and safety of LEV monotherapy with those of VPA monotherapy in ASM-naïve pediatric patients with idiopathic generalized epilepsy with tonic-clonic (GTC) seizures.. We retrospectively analyzed the clinical and electroencephalographic (EEG) data of these ASM-naïve pediatric patients who were treated with either oral VPA or oral LEV as monotherapy for over 2 years at our center.. This study included 60 patients with a seizure onset age between 2 months and 12 years. The patients on VPA (29 patients) and LEV monotherapy (31 patients) showed similar favorable 6-month treatment outcomes (complete seizure control in 79.31% vs 80.64%, p = 0.468052). Age at epilepsy onset, epilepsy syndrome, EEG features and ASM dose were not significant predictors of the 6-month treatment outcomes in either group. Lower seizure frequency at presentation was a predictor of favorable 6-month treatment outcomes in the LEV group but not in the VPA group. VPA and LEV treatment showed similar favorable 6-month treatment outcomes in the febrile seizures plus and patients with unidentified epilepsy syndrome subgroups. None of the patients discontinued VPA or LEV due to treatment-associated adverse effects.. Our study showed that compared to VPA monotherapy, LEV monotherapy in ASM-naïve infants and children with idiopathic generalized epilepsy with GTC seizures has a similarly favorable efficacy and tolerability, independent of age, EEG features and epilepsy syndrome.

Topics: Anticonvulsants; Child; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Humans; Infant; Levetiracetam; Retrospective Studies; Seizures; Valproic Acid

There have been recommendations to improve therapy discovery for epilepsy by incorporating chronic epilepsy models into the preclinical process, but unpredictable seizures and difficulties in maintaining drug levels over prolonged periods have been obstacles to using these animals. We report new protocols in which drugs are administered through a new chronic gastric tube to rats with higher seizure frequencies to minimize these obstacles.. Adult rats with spontaneous limbic seizures following an episode of limbic status epilepticus induced by electrical hippocampal stimulation were monitored with long-term video- electroencephalography (EEG). Animals with a predetermined baseline seizure frequency received an intragastric tube for drug administration. Carbamazepine, levetiracetam, phenobarbital, and phenytoin were tested with either an acute protocol (an increasing single dose every other day for a maximum of three doses) or with a chronic protocol (multiple administrations of one dose for a week). Drug levels were obtained to correlate the effect with the level.. With the acute protocol, all four drugs induced a clear dose-related response. Similar dose-related responses were seen following the week-long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range. The response to chronic levetiracetam was much less robust. The gastric tube route of administration was well tolerated over a number of months.. Using rats with stable, higher seizure frequencies made it possible to identify the potential of a drug to suppress seizures in a realistic model of epilepsy with drug levels that are similar to those of human therapeutic levels. The acute protocol provided a full dose response in 1 week. The chronic administration protocol further differentiated drugs that may be effective long term. The gastric tube facilitates a less stressful, humane, and consistent administration of multiple doses.

Topics: Animals; Anticonvulsants; Carbamazepine; Disease Models, Animal; Epilepsy; Levetiracetam; Pharmaceutical Preparations; Phenobarbital; Phenytoin; Rats; Seizures

Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response.. We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits.. Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.. Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.. Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Topics: Anticonvulsants; Carcinoma, Papillary; Clonazepam; Drug Therapy, Combination; Electroencephalography; Heart Arrest; Humans; Hypoxia, Brain; Levetiracetam; Male; Middle Aged; Myoclonus; Nitriles; Postoperative Complications; Pyridones; Seizures; Thyroid Neoplasms; Thyroidectomy; Valproic Acid

Several studies with larvae and adult zebrafish have shown that old and new antiseizure drugs (ASDs) produce discrepant results in seizure tests, locomotor activity or anxiety models. In this study, the pentylenetetrazole seizure test (PTZ) was performed to assess the effectiveness of four new ASDs: lamotrigine (LTG), topiramate (TPM), felbamate (FBM), and levetiracetam (LEV) in the subsequent stages of seizures in adult fish. All ASDs were administered intraperitoneally (i.p.). The time of maximal anticonvulsant effect and the dose-response relationship of the drugs were assessed. The effects of studied ASDs on the locomotor activity and the anxiety-like behavior in the color preference test were also investigated. Furthermore, drug concentrations in zebrafish homogenates were determined. LTG, TPM, and LEV significantly increased the seizure latency at three subsequent stages of seizures (SI-SIII), while FBM was effective only at SI. Locomotor activity decreased after TPM treatment. TPM and FBM exhibited a strong anxiolytic-like effect in the color preference test. LEV at the highest dose tested had a weak anxiolytic-like effect. The HPLC analysis showed average concentrations of the studied ASDs in the fish body during their maximum anticonvulsant activity. The present study shows that FBM cannot inhibit all subsequent PTZ seizure stages in the adult fish. Except for LTG, the studied drugs affected the anxiety-like behavior of treated animals. Furthermore, only TPM significantly changed locomotion parameters. Our findings support the need to accurately characterize the efficacy of new ASDs at different stages of the PTZ-induced seizures in adult zebrafish.

Topics: Age Factors; Animals; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Dose-Response Relationship, Drug; Felbamate; Female; Lamotrigine; Levetiracetam; Locomotion; Male; Pentylenetetrazole; Seizures; Topiramate; Zebrafish

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZ-induced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 μM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 μM).

Topics: Animals; Anticonvulsants; Behavior, Animal; Dose-Response Relationship, Drug; Epilepsy; Ethosuximide; Lacosamide; Levetiracetam; Male; Mice; Pentylenetetrazole; Pyrrolidines; Seizures; Valproic Acid; Zebrafish

Topics: Anticonvulsants; Female; Humans; Infant, Newborn; Levetiracetam; Male; Off-Label Use; Proportional Hazards Models; Retrospective Studies; Seizures; Treatment Outcome

Ocimum sanctum L. commonly known as tulsi (synonym of Ocimum tenuiflorum L.) is widely used in Ayurveda medicine and is having multitude neuromodulatory effect including the anticonvulsant effect in acute seizure models as per previous studies. In India, it is used for the treatment of epilepsy as traditional medicine. However, its role in chronic seizure model and interaction with newer antiepileptic drugs has not been investigated, which will enhance its translational value.. Current study investigated the effect of Ocimum on chronic seizure model and its interaction with levetiracetam (LEV), a newer antiepileptic drug.. The adjuvant role of Ocimum sanctum hydroalcoholic extracts (OSHE) 1000 mg/kg along with LEV 300 mg/kg was studied in adult male Wistar rats with mean weight of 227.84 ± 21.68 g using pentylenetetrazole (30 mg/kg, i.p.) kindling (K) (with maximum 24 injections on alternate days and challenge on 7th-day). Along with seizure score, neurobehavioral, brain tissue oxidative stress and histopathology status were assessed. Pharmacokinetic interaction was assessed between LEV and OSHE after 14 days of drug treatment.. Ocimum per se and combination with levetiracetam treatment exerted better seizure control, memory retention, oxidative stress reduction, and neuronal structure preservation than kindling control group. There was a very minimal drug interaction between Ocimum and LEV. So, Ocimum as an adjuvant to LEV may be shelpful in enhancing the antiepileptic effect and also in minimizing the adverse effects.

Topics: Animals; Anticonvulsants; Avoidance Learning; Disease Models, Animal; Drug Therapy, Combination; Epilepsy; Herb-Drug Interactions; Kindling, Neurologic; Levetiracetam; Male; Maze Learning; Ocimum sanctum; Oxidative Stress; Pentylenetetrazole; Plant Extracts; Rats; Rats, Wistar; Seizures

Nonketotic hyperglycemia-related seizures are not uncommonly encountered in clinical practice. Their presentation varies, and they may cause serious consequences if they remain unnoticed.. We report a case of nonketotic hyperglycemia-related seizures of unique left parieto-occipital origin and semiology, presenting as focal aware (simple partial) and impaired awareness (complex partial) seizures, including contralateral limb convulsion and apraxialike behavior.. Nonketotic hyperglycemia-related seizures can present with a relatively unique semiology. Careful education to the patients and family regarding attention to the paroxysmal symptoms and an effort to maintain good glycemic control are mandatory in clinical practice.

Topics: Administration, Intravenous; Electroencephalography; Female; Humans; Hyperglycemia; Insulin; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Neuroscience Nursing; Occipital Lobe; Paresis; Parietal Lobe; Seizures

Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely unknown beyond survey data.. To describe patterns and predictors of postoperative AED prophylaxis following intracranial tumor surgery.. The MarketScan Database was used to analyze pharmacy claims data and clinical characteristics in a national sample over a 5-year period.. Among 5895 patients in the cohort, levetiracetam was the most widely used AED for prophylaxis (78.5%) followed by phenytoin (20.5%). Prophylaxis was common but highly variable for patients who underwent open resection of supratentorial intraparenchymal tumors (62.5%, reference) or meningiomas (61.9%). In multivariate analysis, biopsies were less likely to receive prophylaxis (44.8%, OR 0.47, 95% CI 0.33-0.67), and there was near consensus against prophylaxis for infratentorial (9.7%, OR 0.07, CI 0.05-0.09) and transsphenoidal procedures (0.4%, OR 0.003, CI 0.001-0.010). Primary malignancies (52.1%, reference) and secondary metastases (42.2%) were more likely to receive prophylaxis than benign tumors (23.0%, OR 0.63, CI 0.48-0.83), as were patients discharged with home services and patients in the Northeast. There was a large spike in duration of AED use at approximately 30 days.. Use of seizure prophylaxis following intracranial biopsies and supratentorial resections is highly variable, consistent with a lack of guidelines or consensus. Current practice patterns do not support a clear standard of care and may be driven in part by geographic variation, availability of post-discharge services, and electronic prescribing defaults rather than evidence. Given uncertainty regarding effectiveness, indications, and appropriate duration of AED prophylaxis, well-powered trials are needed.

Topics: Adolescent; Adult; Anticonvulsants; Brain Neoplasms; Craniotomy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Neurosurgical Procedures; Phenytoin; Practice Patterns, Physicians'; Prognosis; Retrospective Studies; Seizures; Supratentorial Neoplasms; Young Adult

This study was carried out to determine changes over time in use of folic acid, anti-epileptic drugs (AED), seizures during pregnancy and malformation rate over two decades in women with epilepsy enrolled in the Kerala registry of Epilepsy and Pregnancy (KREP).. All completed pregnancies with known outcome between 1998 and 2017 (n = 1962) were analyzed for the use of folic acid and AEDs in the first trimester, seizure count for the entire pregnancy and the presence of major congenital malformation (MCM). The results were presented for three epochs (1998-2004, 2005-2011 and 2012-2017).. There was significant increase (p = .001) in the use of folic acid 5 mg/day or more in pre-pregnancy month (43.9 to 81 %) and first trimester (52.7 to 86.6 %). Occurrence of seizures during pregnancy had declined significantly (57.2 to 32.9 %, p = 0.001) over time. Those who were off AEDs during pregnancy declined from 17.4 to 8.5 % (p = .001). Newer AEDs - lamotrigine, levetiracetam, oxcarbazepine and topiramate) were increasingly preferred in the last seven years instead of older AEDs (phenobarbitone, phenytoin and clonazepam). There was no significant change in the use of carbamazepine or valproate. MCM rates did not show any significant change (7.5 to 7.3 %).. Seizure control and high dose folic acid usage during pregnancy had improved over two decades. Despite the changes in the AED usage over time the MCM rates had remained unchanged probably due to continued use of valproate, increased use of topiramate and clobazam that are associated with higher MCM rates and lack of reduction in polytherapy.

Topics: Adult; Anticonvulsants; Carbamazepine; Female; Folic Acid; Humans; India; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenytoin; Pregnancy; Pregnancy Complications; Registries; Seizures; Topiramate; Valproic Acid

Antiseizure prophylaxis is required during busulfan administration for hematopoietic stem cell transplantation. However, antiseizure agents such as benzodiazepines and phenytoin may produce adverse effects through interaction with other drugs. We retrospectively assessed the prophylactic efficacy and safety of levetiracetam and clonazepam against busulfan-induced seizures between 2013 and 2018. Thirty patients (after 2015) received levetiracetam, and 13 patients (before 2015) received clonazepam in this study. Levetiracetam was well-tolerated and had a significantly lower frequency of adverse effects, such as somnolence, compared with clonazepam, although two patients in the levetiracetam group experienced seizures. Levetiracetam is a feasible option for preventing busulfan-induced seizures.

Topics: Adolescent; Busulfan; Child; Child, Preschool; Clonazepam; Female; Hematopoietic Stem Cell Transplantation; Humans; Levetiracetam; Male; Retrospective Studies; Seizures; Treatment Outcome

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients' anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.

Topics: Adult; Anticonvulsants; Cerebellar Ataxia; Child; Dystonic Disorders; Epilepsy; Female; Hearing Loss, Sensorineural; Hemiplegia; Humans; Levetiracetam; Male; Mutation; Optic Atrophy; Reflex, Abnormal; Retrospective Studies; Seizures; Sodium-Potassium-Exchanging ATPase; Topiramate; Valproic Acid

This case report will provide further evidence for the fact that breach rhythm is not the effect of a bone abnormality only. We present the case of an 84-year-old woman, who had a craniotomy 14 month before admission to our emergency department with a focal inhibitory status epilepticus. Even after clinical recovery, electroencephalography revealed frequent subclinical seizure patterns. When seizure activity was suppressed by anticonvulsive medication with levetiracetam, breach rhythm appeared. Breach rhythm develops usually some months after craniotomy and therefore should have been established in our patient at the time of admission. Therefore, it is reasonable to assume that it was in some way suppressed by the seizure activity in our primary EEG recordings. The appearance of the breach rhythm after the complete suppression of seizure activity by antiepileptic drug treatment shows that breach rhythm is not purely the result of a skull defect but is related to the functional state of the brain tissue beneath.

Topics: Aged, 80 and over; Anticonvulsants; Brain; Craniotomy; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Paralysis; Seizures

Emerging studies suggest that levetiracetam pharmacokinetics can be difficult to predict in certain special patient populations, including the elderly, critically ill patients, and pregnant women.. To determine clinical characteristics that predict the attainment of target serum concentrations in a heterogeneous group of patients prescribed levetiracetam.. A retrospective observational study was conducted in adult neurological patients prescribed levetiracetam for the treatment or prophylaxis of seizures. Serum samples were collected after steady-state was reached, with a trough/steady-state serum concentration between 6 and 20 mg/L considered therapeutic. Logistic regression was used to identify significant predictors associated with the attainment of therapeutic concentrations.. One-hundred thirty patients (63 male) were included. The median (interquartile ranges) serum trough/steady-state concentration (Cmin/ss) was 16.2 (9.8-26.1) mg/L. The dose-normalized median (interquartile range) Cmin/ss was 11.5 (7.0-16.5) mg/L. The coefficient of variation of Cmin/ss and dose-normalized Cmin/ss were 69.4% and 64.2%, respectively. A weak correlation was observed between levetiracetam Cmin/ss and patient age (r = 0.21; P = 0.020), creatinine clearance (r = -0.26; P = 0.004), and daily dose (r = 0.42; P < 0.001). Logistic regression analysis identified age and daily levetiracetam dose as significant factors predicting target Cmin/ss attainment. The influence of concomitant antiepileptic therapy was not determined.. Age and daily dose were the most significant predictors of levetiracetam target-concentration attainment and should be considered in further investigations to develop a dosing algorithm for optimal levetiracetam therapy.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Critical Illness; Female; Humans; Levetiracetam; Male; Middle Aged; Pregnancy; Retrospective Studies; Seizures

Neonatal seizures are difficult to diagnose and, when they are, tradition dictates first line treatment is phenobarbital. There is little data on how consultants diagnose neonatal seizures, choose when to treat or how they choose aetiological investigations or drug treatments. The purpose of this study was to assess the variation across the UK in the management of neonatal seizures and explore paediatricians' views on their diagnosis and treatment.. An explanatory sequential mixed methods approach was used (QUAN→QUAL) with equal waiting between stages. We collected quantitative data from neonatology staff and paediatric neurologists using a questionnaire sent to neonatal units and via emails from the British Paediatric Neurology Association. We asked for copies of neonatal unit guidelines on the management of seizures. The data from questionnaires was used to identify16 consultants using semi-structured interviews. Thematic analysis was used to interpret qualitative data, which was triangulated with quantitative questionnaire data.. One hundred questionnaires were returned: 47.7% thought levetiracetam was as, or equally, effective as phenobarbital; 9.2% thought it was less effective. 79.6% of clinicians had seen no side effects in neonates with levetiracetam. 97.8% of unit guidelines recommended phenobarbital first line, with wide variation in subsequent drug choice, aetiological investigations, and advice on when to start treatment. Thematic analysis revealed three themes: 'Managing uncertainty with neonatal seizures', 'Moving practice forward' and 'Multidisciplinary team working'. Consultants noted collecting evidence on anti-convulsant drugs in neonates is problematic, and recommended a number of solutions, including collaboration to reach consensus guidelines, to reduce diagnostic and management uncertainty.. There is wide variation in the management of neonatal seizures and clinicians face many uncertainties. Our data has helped reveal some of the reasons for current practice and decision making. Suggestions to improve certainty include: educational initiatives to improve the ability of neonatal staff to describe suspicious events, greater use of video, closer working between neonatologists and neurologists, further research, and a national discussion to reach a consensus on a standardised approach to managing neonatal epileptic seizures.

Topics: Anticonvulsants; Attitude of Health Personnel; Diagnostic Techniques and Procedures; Electroencephalography; Humans; Infant, Newborn; Infant, Newborn, Diseases; Interviews as Topic; Levetiracetam; Neonatologists; Patient Care Team; Pediatricians; Phenobarbital; Practice Patterns, Physicians'; Seizures; Surveys and Questionnaires; United Kingdom

Background Antiseizure prophylaxis is recommended when high-dose of busulfan is given as part of the conditioning regimens in the allogenic hematopoietic stem cell transplant. Phenytoin has been widely used but its pharmacokinetics and pharmacodynamics profile makes its use complicated. Levetiracetam is a safe, effective and well tolerated antiseizure drug with good results in epileptic patients. Objective To describe our experience using oral (p.o) levetiracetam 1000 mg every 12 h (q12h) as an antiseizure prophylaxis, evaluating its preventive effects and adverse event rates after a high-dose of intravenous (i.v.) busulfan, as part of the conditioning regimen Methods Retrospective study of patients who underwent an allogenic hematopoietic stem cell transplant with a conditioning regimen based on high-dose of busulfan between January and November 2017. Results The study population comprised 36 patients, of whom 18 (50%) had acute myeloid leukemia as diagnosis. No seizures occurred in any patient. Levetiracetam was well tolerated and no serious adverse events were reported. Conclusions Our results suggest that giving levetiracetam at 1000 mg q12h p.o starting 12 h before the administration of i.v. busulfan until 48 h after the last dose, can be used as an alternative in the prevention of busulfan-induced seizures in adults.

Topics: Adult; Anticonvulsants; Busulfan; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Levetiracetam; Male; Retrospective Studies; Seizures; Transplantation Conditioning; Young Adult

To retrospectively evaluate the pharmacological profiles of antiepileptic drugs (AEDs) in epilepsy patients during haemodialysis using therapeutic drug monitoring data. The serum concentration of AEDs was collected before and after haemodialysis, and the clearance rate and concentration-to-dose ratio were calculated as pharmacological parameters. Thirty-six patients were enrolled in the study (25 males, 11 females; age: 65.3 ± 14.8 years). In 24 of the 36 patients, epilepsy was associated with cerebrovascular disorders, and diabetes was the most common reason for haemodialysis in 16 patients. With regards to seizure type, focal aware seizures were less frequent than focal impaired awareness seizures and focal-to-bilateral tonic-clonic seizures. Interictal EEG showed intermittent rhythmic slow waves and intermittent slow waves more often than spikes or sharp waves. Levetiracetam was the most commonly used AED and led to the highest percentage of responders (80%; 16/20 patients). However, the clearance rate of levetiracetam during dialysis was highest among the antiepileptic drugs used, requiring supplementary doses after haemodialysis in all 20 patients. Valproic acid was not effective for focal epilepsy for patients on haemodialysis, and non-responders to phenytoin had low serum concentration of phenytoin both before and after haemodialysis. The pre-haemodialysis concentration of levetiracetam tended to be higher than the reference range, suggesting a potential risk of overdosing before haemodialysis. The pre- and post-haemodialysis concentrations of valproic acid tended to be lower than the reference range, suggesting a potential risk of underdosing. The concentration-to-dose ratios for levetiracetam, valproic acid, phenytoin, and carbamazepine were significantly lower after than before haemodialysis. The majority of patients with epilepsy on haemodialysis had cerebrovascular diseases, and therapeutic drug monitoring for levetiracetam, valproic acid, and phenytoin, before and after haemodialysis, is needed to ensure proper dosing.

Topics: Aged; Anticonvulsants; Cerebrovascular Disorders; Comorbidity; Drug Monitoring; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Seizures

Seizures are a morbid complication of intracerebral hemorrhage (ICH) and increase the risk for herniation, status epilepticus, and worse patient outcomes. Prophylactic levetiracetam is administered to approximately 40% of patients with ICH. It is unclear which patients are consciously selected for treatment by physicians. We sought to determine how patients are selected for treatment with prophylactic levetiracetam after ICH.. We administered an adaptive conjoint analysis using decision making software to an NIH Stroke Trials Network Working Group. The adaptive conjoint analysis determines the most influential attributes for making a decision in an iterative, algorithm-driven process. We asked respondents which would most influence a decision to administer prophylactic levetiracetam. The attributes and their levels were taken from published phenotypes associated with prophylactic seizure medications and the likelihood of seizures after ICH: hematoma location (lobar or basal ganglia), hematoma volume (<=10 mL or >10 mL), level of consciousness (Glasgow Coma Scale 5-12 or Glasgow Coma Scale 13-15), age (<65 or ≥65 years), and race (White or Caucasian or Black/African American). The algorithm terminated when the attributes were ranked from most to least influential.. The study sample included 27 respondents who completed the adaptive conjoint analysis out of 42 who responded to the survey with a mean age of 43.4 ± 9.4 years. The attribute with the greatest weight was hematoma location (30%), followed by reduced level of consciousness (24%), hematoma volume (19%), race (14%), and age (13%). Ranks of attributes were different (P < .001).. The decision to administer prophylactic levetiracetam to patients with ICH is driven by lobar hematoma location and depressed level of consciousness. Future research on prophylactic seizure medication could focus on patients most likely to receive it.

Topics: Adult; Aged; Anticonvulsants; Attitude of Health Personnel; Cerebral Hemorrhage; Clinical Decision-Making; Decision Support Techniques; Drug Administration Schedule; Drug Utilization; Female; Health Care Surveys; Health Knowledge, Attitudes, Practice; Humans; Levetiracetam; Male; Middle Aged; Patient Selection; Practice Patterns, Physicians'; Predictive Value of Tests; Risk Assessment; Risk Factors; Seizures

Certain antiepileptic drugs (AEDs) may be more suitable for elderly patients with epilepsy (EWE) relative to others. However, little is known regarding which antiepileptic drugs (AEDs) are being used to treat EWE in the United States and how it has changed over time.. We performed a serial cross-sectional study evaluating noninstitutionalized US adults aged 65 years or older with a diagnosis of epilepsy using data from the Medical Expenditure Panel Survey (MEPS) from 2004 through 2015. Trends in AEDs used among EWE were examined. Using each AED as a dependent variable, we determined the p-value for the trend by performing a linear regression with the time interval as the explanatory variable.. There was a weighted total of 399,801 EWE. Between the years 2004-2006 and 2013-2015 use of phenytoin, carbamazepine and phenobarbital decreased from 60.7% to 31.1% (p ≤ 0.001), 13.7 % to 5.22 % (p = 0.03) and 12.5 % to 5.91 % (p = 0.04), respectively. Use of levetiracetam concomitantly increased from 6.70 % to 43.1 % (p ≤ 0.001). Patients with more medical comorbidities as measured by the Charlson Comorbidity Index had higher odds of levetiracetam use (OR = 2.52, 95 % CI = 1.19-5.34) and lower odds of phenytoin use (OR = 0.46, 95 % CI = 0.24-0.88).. There have been significant changes in AED prescriptions to EWE between 2004-2015. However, potentially harmful AEDs (e.g. phenytoin, carbamazepine, phenobarbital, primidone and valproate) were still being prescribed to 42.9 % of all patients between 2013-2015. Increased work to educate providers regarding the use of more appropriate AEDs in this population is needed.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Seizures; Zonisamide

Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance).. A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed.. The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test).. In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Injuries, Traumatic; Dizziness; Female; Glasgow Coma Scale; Humans; Length of Stay; Levetiracetam; Male; Middle Aged; Phenytoin; Postural Balance; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

To compare the safety and efficacy of phenobarbital and levetiracetam in a cohort of neonates with seizures following cardiac surgery.. We performed a retrospective single-center study of consecutive neonates with electrographically confirmed seizures managed with antiseizure medication after cardiac surgery from June 15, 2012 to December 31, 2018. We compared the safety and efficacy of phenobarbital and levetiracetam as first-line therapy.. First-line therapy was phenobarbital in 31 neonates and levetiracetam in 22 neonates. Phenobarbital was associated with more adverse events (P = .006). Eight neonates (14%) experienced an adverse event related to phenobarbital use, including seven with hypotension and one with respiratory depression. No adverse events were reported with levetiracetam use. The cessation of electrographic seizures was similar in both groups, including 18 neonates (58%) with seizure cessation after phenobarbital and 12 neonates (55%) with seizure cessation after levetiracetam (P = 1.0). The combined cessation rates of phenobarbital and levetiracetam when used as first- or second-line therapy were 58% and 47%, respectively (P = .47).. Phenobarbital was associated with more adverse events than levetiracetam, and the two drugs were equally but incompletely effective in treating electrographically confirmed seizures in neonates following cardiac surgery. Given its more acceptable safety profile and potential noninferiority, levetiracetam may be a reasonable option for first-line therapy for treatment of seizures in this population. Further prospective studies are needed to confirm these results.

Topics: Anticonvulsants; Cardiac Surgical Procedures; Female; Humans; Infant, Newborn; Levetiracetam; Male; Phenobarbital; Postoperative Complications; Retrospective Studies; Seizures

Ring chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory seizure, mental retardation, and behavioral problems. Although there are reports of the effective treatment of patients with antiepileptic drugs (AEDs), no study has reported the effects of lacosamide(LCM) in children with this syndrome. We report a 7-year-old boy with this syndrome whose refractory and behavioral abnormalities have been remarkably improved by treatment with LCM.. The patient was a 7-year-old boy with no medical or family history of epilepsy. He developed epilepsy with cessation of movement and derivation of the eyes followed by hyperkinetic seizures that made him squeak strangely and cling to his parents. The seizures lasted for less than a minute and were frequent (they occurred more than 30 times a day), particularly at night. Behavioral abnormalities such as hyperactivity also presented. Brain magnetic resonance imaging revealed no structural abnormalities, but an interictal electroencephalogram (EEG) indicated spikes and waves in the frontal lobe dominantly, and ictal single-photon emission computed tomography (SPECT) revealed a blood flow increase in the bilateral orbital frontal area in comparison to interictal SPECT. After chromosome examination, we diagnosed the patient with ring chromosome 20 syndrome (4/30 mosaic). Carbamazepine was ineffective, and seizures were exacerbated with levetiracetam (LEV). LCM was added to the treatment regimen with valproic acid (VPA) and lamotrigine (LTG); consequently, the seizures disappeared, and EEG results also improved. The patient's behavioral disorders, such as hyperactivity, were improved, and he was able to return to elementary school.. Although VPA and LTG are generally effective for the treatment of ring chromosome 20 syndrome, they do not completely suppress seizures. LCM can be considered an effective option for seizure control in patients with this syndrome.

Topics: Anticonvulsants; Carbamazepine; Child; Electroencephalography; Epilepsy; Humans; Lacosamide; Lamotrigine; Levetiracetam; Male; Ring Chromosomes; Seizures; Treatment Outcome; Valproic Acid

A 13-year-old female white-crowned pionus (. Bloodwork performed during the initial seizure workup revealed hypercalcemia and hypercholesterolemia, which were attributed to vitellogenesis given the bird's previous egg-laying history and recent onset of reproductive behavior. Magnetic resonance imaging of the brain revealed diffuse right pallium atrophy with multifocal hydrocephalus ex vacuo, which were believed to be the result of the previous TBI. Findings were most consistent with post-traumatic seizures (PTS).. Levetiracetam (100 mg/kg [45 mg/lb], PO, q 12 h) was initiated for PTS management. A 4.7-mg deslorelin implant was injected SC to suppress reproductive behavior. The bird was reexamined for presumed status epilepticus 5 times over 22 months. Seizure episodes coincided with onset of reproductive behavior. The levetiracetam dosage was increased (150 mg/kg [68 mg/lb], PO, q 8 h), and zonisamide (20 mg/kg [9.1 mg/lb], PO, q 12 h) was added to the treatment regimen. Additional deslorelin implants were administered every 2 to 6 months to suppress reproductive behavior. The owner was trained to administer midazolam intranasally or IM as needed at home. The treatment regimen helped control but did not eliminate seizure activity. The bird was euthanized 22 months after PTS diagnosis for reasons unrelated to the TBI or PTS.. Long-term management of PTS in a pionus was achieved with levetiracetam and zonisamide administration.

Topics: Animals; Anticonvulsants; Brain Injuries, Traumatic; Female; Levetiracetam; Parrots; Seizures; Zonisamide

The aim of this study was to clarify the pattern and efficacy of antiepileptic drugs (AEDs) in acute encephalitis and discuss how long AEDs should be used after the acute phase.. Patients with acute encephalitis who presented with seizure were enrolled. The clinical features were systematically gathered, and the information about AEDs and seizures was obtained by a clinical follow-up and (or) a telephone interview based on a structured form.. A total of 327 patients were enrolled, and the mean follow-up period was 63.8 (14-123) months. The risk of seizure relapse was estimated as 43.6% five years after the acute phase and the first three months was the peak time for relapse. Univariate analysis showed that status epilepticus, more than one seizure, cerebral spinal fluid protein level, abnormal MRI finding, temporal lobe involvement, and epileptiform discharge were related to seizure relapse. But only more than one seizure (OR = 2.80 (95% CI 1.29-6.09), p = 0.009) and temporal lobe involvement (5.34 (2.68-10.64), p < 0.001) remain predictive on multivariate regression analysis. For patients with only one seizure and no temporal lobe involvement, the risk of seizure relapse was similar between those with or without AED (2/29 vs. 4/28, p = 0.423). For the rest, the risks of relapse were similar among those who took sodium valproate and levetiracetam.. For patients with only one seizure and no temporal lobe involvement, AEDs may not be strictly needed. The first three months after acute phase was the peak time for relapse and AEDs may should be used during this period. Both sodium valproate and levetiracetam could be selected.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Seizures; Valproic Acid; Young Adult

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity.

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Atazanavir Sulfate; Betacoronavirus; Brain; Consciousness Disorders; Coronavirus Infections; COVID-19; Diffusion Magnetic Resonance Imaging; Disease Progression; Encephalitis; Female; Glucocorticoids; HIV Protease Inhibitors; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Intensive Care Units; Levetiracetam; Lung; Magnetic Resonance Imaging; Methylprednisolone; Pandemics; Pneumonia, Viral; Pons; Respiration, Artificial; SARS-CoV-2; Seizures; Temporal Lobe; Thalamus; Tomography, X-Ray Computed

The role of prophylactic antiepileptic drugs (AEDs) in preventing seizures and/or improving the outcomes after intracerebral hemorrhage (ICH) has remained controversial. The current guidelines have recommended against AED prophylaxis. However, these recommendations were based on older studies that had primarily used phenytoin as the AED of choice. Newer medications, such as levetiracetam, have yet to be extensively studied.. We performed a retrospective review of patients with ICH from 2010 to 2015. The patient demographic data, seizure data, and outcomes were collected. The results were analyzed using descriptive statistics, binary logistic regression, and quantile regression. The primary outcome was seizure incidence.. A total of 360 patients with a median age of 70 years had met the inclusion criteria. Of the 360 patients, 30 (8.3%) had had recorded seizure events, 54% were men, and 81% had a history of hypertension. The median admission National Institutes of Health stroke scale (NIHSS) score was 7 (interquartile range [IQR], 14), and the median discharge NIHSS score was 5.0 (IQR, 13). The median hematoma size was 7.1 mL (IQR, 13 mL), and 143 patients (40%) had had cortical involvement. Of the 360 patients, 273 (76%) had received prophylaxis and 87 (24%) had not. After adjustment for the admission NIHSS and the presence of cortical involvement, the rate of new seizure events after ICH remained significantly lower for the patients who had received AED prophylaxis (adjusted odds ratio, 0.28; 95% confidence interval, 0.11-0.71; P = 0.008).. The administration of, predominantly, levetiracetam for AED prophylaxis after ICH reduced the odds of new seizure events, independently of the admission NIHSS score and the presence of cortical involvement.

Topics: Aged; Anticonvulsants; Cerebral Hemorrhage; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures

Pharmacotherapy with two antiepileptic drugs in combination is usually prescribed to epilepsy patients with refractory seizures. The choice of antiepileptic drugs in combination should be based on synergistic cooperation of the drugs with respect to suppression of seizures. The selection of synergistic interactions between antiepileptic drugs is challenging issue for physicians, especially, if 25 antiepileptic drugs are currently available and approved to treat epilepsy patients. The aim of this study was to determine all possible interactions among 5 second-generation antiepileptic drugs (gabapentin (GBP), lacosamide (LCM), levetiracetam (LEV), pregabalin (PGB) and retigabine (RTG)) in the 6-Hz corneal stimulation-induced seizure model in adult male albino Swiss mice. The anticonvulsant effects of 10 various two-drug combinations of antiepileptic drugs were evaluated with type I isobolographic analysis associated with graphical presentation of polygonogram to visualize the types of interactions. Isobolographic analysis revealed that 7 two-drug combinations of LEV+RTG, LEV+LCM, GBP+RTG, PGB+LEV, GBP+LEV, PGB+RTG, PGB+LCM were synergistic in the 6-Hz corneal stimulation-induced seizure model in mice. The additive interaction was observed for the combinations of GBP+LCM, GBP+PGB, and RTG+LCM in this seizure model in mice. The most beneficial combination, offering the highest level of synergistic suppression of seizures in mice was that of LEV+RTG, whereas the most additive combination that protected the animals from seizures was that reporting additivity for RTG+LCM. The strength of interaction for two-drug combinations can be arranged from the synergistic to the additive, as follows: LEV+RTG > LEV+LCM > GBP+RTG > PGB+LEV > GBP+LEV > PGB+RTG > PGB+LCM > GBP+LCM > GBP+PGB > RTG+LCM.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Electroshock; Gabapentin; Lacosamide; Levetiracetam; Male; Mice; Muscle Strength; Seizures

This study aims to compare the neurocognitive outcome in term infants who were treated using phenobarbital (PB) and levetiracetam (LEV) monotherapy for neonatal clinical seizures.. Term infants who were treated using PB or LEV monotherapy as the first-line anti-epileptic treatment for neonatal clinical seizures and followed-up in a pediatric neurology outpatient clinic were enrolled in this study. Neurodevelopmental outcome assessments were carried out using the Bayley Scales of Infant Development, third edition (BSID-III), including cognitive, receptive language, expressive language, fine motor and gross motor subscales.. The study group consisted of 62 infants who received monotherapy with PB monotherapy (n = 22) and LEV (n = 40). The mean duration of monotherapy treatment was 8 ± 6 months. There was no statistically significant difference between PB and LEV monotherapy groups concerning each outcome parameter on the BSID-III. There was also no statistically significant difference between PB and LEV monotherapy subgroups excluding the infants with neurodevelopmental impairment with a BSID-III scale score<7 or a composite score<85.. Our findings suggest that both LEV and PB therapy can be equally safe as monotherapy for neonatal clinical seizures for the neurodevelopmental outcome assessment with BSID-III.

Topics: Anticonvulsants; Child; Epilepsy; Humans; Infant; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Objective Reversible splenial lesion syndrome (RESLES) is a clinical radiological syndrome characterized by a reversible lesion of the splenium of the corpus callosum with a decreased apparent diffusion coefficient (ADC) value. The clinical manifestations of RESLES are diverse. Methods Fifteen cases of adult RESLES patients (10 males and 5 females) were retrospectively selected from the radiology system using the key word "corpus callosum" at a university-affiliated tertiary care hospital between May 1, 2015 and December 31, 2019. The possible precipitating factors, clinicoradiological findings and modified Rankin Scale (mRS) on follow-up were then analyzed. Results The patient ages ranged from 22 to 53 years old. The mean age was 34 years old. The most common neurological symptoms included headache (3/15), dizziness (3/15), first onset of seizure (3/15), paroxysmal blurred vision (2/15), vertigo (2/15), amnesia (2/15), and confused consciousness without seizure (2/15), followed by drowsiness (1/15), paresthesia (1/15), dysmetria (1/15) and dysarthria (1/15). The precipitating factors included infection, seizure, anti-epileptic treatment with levetiracetam, carbamazepine, valproate, hyperglycemia, hypoglycemia, cerebral venous sinus thrombosis, and rabies vaccine injection prior to the onset of RESLES. All cases were carefully followed up and had excellent prognoses. Conclusion RESLES manifests as variety of symptoms with less specificity and precipitating factors. Paroxysmal blurred vision may be a relatively specific symptom of RESLES. Levetiracetam, carbamazepine or valproate could be the cause of RESLES, exposure to the rabies vaccine could be another predisposing factors for RESLES as well. RESLES type 1 was therefore found to be highly "reversible" with an excellent prognosis.

Topics: Adult; Anticonvulsants; Brain Diseases; Carbamazepine; Causality; Corpus Callosum; Female; Headache; Humans; Levetiracetam; Male; Middle Aged; Paraspinal Muscles; Prognosis; Retrospective Studies; Seizures; Valproic Acid; Vertigo; Young Adult

Although phenytoin is one of the most commonly used antiepileptic drugs (AEDs), it has potential serious side effects and drug interactions. Levetiracetam is a relatively newer AED with favorable pharmacokinetics and could be an effective and safer option for the treatment of convulsive status epilepticus (CSE). We aimed to compare the efficacy and safety profile of intravenous levetiracetam and phenytoin as second-line treatment agents in children with CSE and acute repetitive seizures (ARS).. Two hundred seventy-seven patients aged between 1 month and 18 years who received intravenous levetiracetam or phenytoin as a second-line AED with the diagnosis of CSE or ARS were retrospectively evaluated. Drug efficacy was defined as control of seizures without the need for any additional medication after completion of the infusion and no recurrence in the following 12 h. The primary outcome was drug efficacy. The secondary outcomes included application of an additional second-line AED, induction of anesthesia, and admission to the intensive care unit (ICU), and drug-related adverse reactions.. No differences were found between the two treatment groups with regard to patient characteristics and seizure type. The efficacy of levetiracetam was higher than that of phenytoin (77.6% vs 57.7%, P = 0.011) in children with CSE. There was no significant difference between the efficacy rates of levetiracetam and phenytoin for ARS (55.8% vs 58.8%, P = 0.791). Overall, drug efficacy was 70.9% for levetiracetam and 58.1% for phenytoin (P = 0.048). For CSE, the need for additional second-line treatment, anesthesia induction, and ICU admission was higher in the phenytoin group (P = 0.001, P = 0.038, P = 0.02, respectively). Drug-related adverse reactions were more frequent in the phenytoin group than the levetiracetam group (23.3% vs 1.4%; P < 0.001). The most common adverse reaction in the phenytoin group was hypotension. Phenytoin-related anaphylaxis was detected in one patient. No serious adverse effects related to levetiracetam were observed.. Intravenous levetiracetam seems as effective as intravenous phenytoin in emergency treatment of children with ARS and more effective for CSE in stopping the seizure with less risk of recurrence. Levetiracetam has fewer cardiovascular side effects and has a safer profile than phenytoin. Intravenous levetiracetam is a favorable option as a first second-line AED for pediatric seizures.

Topics: Administration, Intravenous; Adolescent; Anticonvulsants; Child; Child, Preschool; Emergency Medical Services; Female; Humans; Infant; Levetiracetam; Male; Phenytoin; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

Cerebral cavernous malformation (CCM) of the familial type is caused by abnormalities in the CCM1, CCM2, and CCM3 genes. These 3 proteins forming a complex associate with the maintenance of vascular endothelial cell-cell junctions. Dysfunction of these proteins results in the development of hemangiomas and abnormal intercellular junctions.. We report a 68-year-old man with familial cerebral cavernous malformation with initial presentation as convulsions at an advanced age. Brain magnetic resonance imaging revealed multiple cavernous hemangiomas in the right occipital lobe. The convulsions were considered to be induced by hemorrhage from cavernous hemangioma in the right occipital lobe.. Genetic screening of the CCM1, CCM2, and CCM3 genes revealed a novel mutation in the CCM2 gene (exon4 c: 359 T>A, p: V120D). No abnormalities were found in CCM1 or CCM3. Therefore, we diagnosed the patient with familial CCM caused by a CCM2 mutation.. This patient was treated with the administration of levetiracetam at a dosage of 1000 mg/day.. No seizures have been observed since the antiepileptic drug was administered. We performed brain magnetic resonance imaging (MRI) regularly to follow-up on appearance of new cerebral hemorrhages and cavernous hemangiomas.. This report reviews cases of familial cerebral cavernous malformations caused by abnormalities in the CCM2 gene. This mutation site mediates interactions with CCM1 and CCM3. The mutation occurs in the phosphotyrosine binding (PTB) site, which is considered functionally important to CCM2.

Topics: Aged; Anticonvulsants; Carrier Proteins; Genetic Testing; Hemangioma, Cavernous; Hemangioma, Cavernous, Central Nervous System; Hemorrhage; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Mutation; Seizures; Treatment Outcome

Initial identification of new investigational drugs for the treatment of epilepsy is commonly conducted in well-established mouse acute and chronic seizure models: for example, maximal electroshock (MES), 6 Hz, and corneal kindling. Comparison of the median effective dose (ED50) of approved antiseizure drugs (ASDs) vs investigational agents in these models provides evidence of their potential for clinical efficacy. Inbred and outbred mouse strains exhibit differential seizure susceptibility. However, few comparisons exist of the ED50 or median behaviorally impairing dose (TD50) of prototype ASDs in these models in inbred C57Bl/6 vs outbred CF-1 mice, both of which are often used for ASD discovery.. We defined the strain-related ED50s and TD50s of several mechanistically distinct ASDs across established acute seizure models (MES, 6 Hz, and corneal-kindled mouse). We further quantified the strain-related effect of the MES ED50 of each ASD on gross behavior in a locomotor activity assay. Finally, we describe a novel pharmacoresistant corneal-kindling protocol that is suitable for moderate-throughput ASD screening and demonstrates highly differentiated ASD sensitivity.. We report significant strain-related differences in the MES ED50 of valproic acid (CF-1 ED50: 90 mg/kg [95% confidence interval (CI) 165-214] vs C57Bl/6: 276 mg/kg [226-366]), as well as significant differences in the ED50 of levetiracetam in the pharmacoresistant 6 Hz test (CF-1: 22.5 mg/kg [14.7-30.2] vs C57Bl/6: >500 mg/kg [CI not defined]). There were no differences in the calculated TD50 of these ASDs between strains. Furthermore, the MES ED50 of phenobarbital significantly enhanced locomotor activity of outbred CF-1, but not C57Bl/6, mice.. Altogether, this study provides strain-related information to differentiate investigational agents from ASD standards-of-care in commonly employed preclinical discovery models and describes a novel kindled seizure model to further explore the mechanisms of drug-resistant epilepsy.

Topics: Animals; Animals, Outbred Strains; Anticonvulsants; Behavior, Animal; Brain; Carbamazepine; Cornea; Diazepam; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery; Drug Evaluation, Preclinical; Drug Resistant Epilepsy; Electroshock; Kindling, Neurologic; Lamotrigine; Levetiracetam; Locomotion; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Open Field Test; Phenobarbital; Seizures; Treatment Outcome; Valproic Acid

Adult-onset Still's disease (AOSD) is an uncommon inflammatory condition characterised by a triad of fevers, arthralgias and a salmon-coloured rash. It is also strongly associated with high ferritin levels, whose role in its pathogenesis is not entirely clear. Central nervous system (CNS) manifestations are exceedingly rare in this disease, accounting for only a handful of reported cases. Herein, we describe a case of a 63-year-old woman who developed new-onset psychiatric symptoms in the months preceding her diagnosis. 2 months after her diagnosis, she experienced an exacerbation of psychiatric symptoms followed by new-onset seizures in conjunction with an acute lung infection. In addition, we discuss two other previously reported cases of AOSD patients with psychiatric symptoms as their initial presentation.

Topics: Aggression; Anticonvulsants; Arthralgia; Diagnosis, Differential; Electroencephalography; Female; Fever; Glucocorticoids; Humans; Levetiracetam; Lorazepam; Mania; Methotrexate; Middle Aged; Paranoid Behavior; Seizures; Still's Disease, Adult-Onset; Treatment Outcome

The aim of this study was to describe the prevalence of the use and prescribing patterns of anti-seizure medications (ASMs) over a six-year period, and to provide real-world evidence on medicine utilization of pediatric patients with epilepsy in China.. ASM prescriptions for pediatric patients written from 2013 to 2018 were extracted from the database of the Hospital Prescription Analysis Cooperative Project. Trends of ASM use were analyzed by total prescriptions, cost, age, sex, ASM class and specific ASM. Prescribing patterns of ASMs were also analyzed.. A total of 44,675 ASM prescriptions were extracted for analysis in this study. Throughout the study period, a slight increase of ASM prescriptions was observed from 6170 in 2013 to 8211 in 2018. Children aged between 6 and 18 years, accounted for 78 % of total prescriptions every year. ASM use in boys was about 1.5 times higher than that in girls. Newer ASMs were prescribed more than older ASMs during this period. Sodium valproate was the most frequently prescribed ASM in 2013, and its use decreased in girls in 2016. Levetiracetam increased from 19.10 % in 2013 to 28.09 % in 2018 and became the most common ASM at the end of this study. Meanwhile, the use of oxcarbazepine increased from 19.31 % to 22.04 %, whereas the use of lamotrigine had declined from 18.43 % to 10.72 %. Monotherapy (66.24 %) was more frequently used than combined therapy, which included dual combination (25.80 %) and triple or more combinations (7.96 %).. There is an increased ASM prescription trend in childhood usage. Levetiracetam has replaced sodium valproate as the most frequently prescribed ASM in pediatric patients. Newer ASMs with fewer side effects and drug interactions are increasingly utilized, which is consistent with evolving recommendations by the medical community.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; China; Epilepsy; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Piracetam; Seizures; Valproic Acid

Neonatal seizures are frequently encountered in the neonatal intensive care unit and may be associated with serious long-term neurological sequelae. Response to treatment continues to be modest, and treatment guidelines remain unclear. The use of levetiracetam has been on the rise in the past several years due to its favorable safety profile in the face of limited data on its efficacy and optimal dosing regimens. Unlike the older age groups, the benefit of escalating to high-dose levetiracetam of 80-100 mg/kg/day in neonates not responding to the standard used dosing regimen (40-60 mg/kg/day) is not studied. We sought to investigate the safety and efficacy of levetiracetam escalation to high dose regimens for neonatal seizures.. A retrospective chart review over a 7-year period was conducted at the American University of Beirut to identify neonates with electrographically proven seizures treated with levetiracetam. Data was collected on electroclinical seizure characteristics, underlying etiology, seizure control, other anti-seizure medications, and adverse effects.. Electronic chart review revealed a total of 15 neonates with electrographically confirmed seizures treated with levetiracetam, with escalation to high doses in seven. As a first line drug, levetiracetam monotherapy terminated seizures in six out 10 neonates, two of whom had complete seizure cessation only after escalation to high doses of 80 or 100 mg/kg/day. When used in combination with other anti-seizure medications, four out of five neonates achieved complete seizure cessation upon escalation to high doses of levetiracetam. No adverse effects were noted.. In neonates not responding to the standard used levetiracetam doses, incremental increases to 80-100 mg/kg/day may be considered. Prospective studies are needed to confirm the promising role of such high dosing regimens, and to better elucidate the role of levetiracetam in neonatal seizures.

Topics: Aged; Anticonvulsants; Humans; Infant, Newborn; Levetiracetam; Piracetam; Prospective Studies; Retrospective Studies; Seizures

Post-stroke paroxysmal activity is a neurophysiological indicator of epileptogenesis and increase of seizure susceptibility, so treatments with neuroprotective activity and anti-paroxysmal activity can be more beneficial during post-ischemic period. The goal of this study was evaluation of levetiracetam (100 mg/kg, 7 days of administration) effect on behavior and brain bioelectric activity changes in the post-ischemic period. Global ischemia model was carried out with bilateral ligation of carotid arteries in rats. Neurological deficit and electrophysiological changes of brain structures (striatum, cortex, hypothalamus, hippocampus) were analyzed during 28 days. Paroxysmal activity was not observed on the 1st day after ischemia and had early (2nd day) and late (28th day) onsets. Spectral analysis showed that rats, that died by the 10th day, had delta wave increase and theta decrease on the 1st day and delta activity reduction on the 2-7th days. LEV did not affect survival rate, however, it contributed to neurological disorder regression towards lighter forms on the 1st day after ischemia. It suppressed paroxysmal activity with an early onset and affected delta and theta waves on the 1st day in all structures except hippocampus. On the 7th and 28th days LEV increased delta activity due to 1-3 Hz frequency. Thus, LEV eliminates early onset post-ischemic paroxysmal activity and contributes to normalization of delta waves activity on the 1st day after ischemia, that positively affects neurological status of animals in post-ischemic period. It allows one to make a conclusion about possible LEV application in the post-ischemic period.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain Ischemia; Cerebral Cortex; Electroencephalography; Hippocampus; Levetiracetam; Male; Neuroprotective Agents; Rats; Seizures

Levetiracetam and phenytoin are comparable for acute posttraumatic seizure(PTS) prophylaxis. Levetiracetam-induced hyponatremia has been reported in non-trauma patients. We studied hyponatremia in posttraumatic intracranial hemorrhage(ICH) patients receiving either drug.. Retrospective review of patients with ICH receiving PTS prophylaxis was performed. Patients were categorized by degree of sodium nadir: normal, mild, moderate, or severe, and analyzed by levetiracetam versus phenytoin. Patients were matched 2:1 regarding age and injury severity score(ISS). Incidence and treatment for hyponatremia was examined.. 1735 ICH patients received PTS prophylaxis over an 8-year period. After exclusions and matching, there were 282 phenytoin and 564 levetiracetam patients. Age, ISS and initial sodium were comparable between the matched cohorts. There was no clinically significant difference in the rate or degree of hyponatremia. Treatment was more common in levetiracetam patients.. There was a small but clinically insignificant difference in the incidence of hyponatremia in traumatic ICH patients receiving levetiracetam vs. phenytoin for PTS prophylaxis. There was an increased rate of intervention for hyponatremia in the levetiracetam group, possibly due to a coincidental preventive paradigm shift.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Early Medical Intervention; Female; Humans; Hyponatremia; Incidence; Levetiracetam; Male; Middle Aged; Phenytoin; Retrospective Studies; Seizures; Young Adult

Although levetiracetam (LEV) is globally established as a leading antiseizure medication (ASM) it is still a controversial matter whether dose increases correspond with an increased efficacy if LEV in the recommended dose range did not show satisfying efficacy. In our clinical perception we questioned the value of dose increases in such non-responders.. In this retrospective monocenter study we analyzed the data of adult people with epilepsies (PWE) with focal-onset seizures who had been treated at the department of adults of the Kork Epilepsy Center between 2009 and 2019, who had been on a stable daily LEV dose and in whom LEV was further increased due to further seizures in spite of baseline LEV in a recommended daily dose range. For reasons of data homogeneity, we included only PWE with at least two definite seizures during the hospital stay under the baseline LEV dose who were treated and observed as in-patients after the increase of LEV for a period at least three-fold longer than the baseline interval before. Additional data acquisition comprised clinical data including adverse events, serum concentrations of LEV and other ASMs, and additional laboratory findings. The primary outcome variable was the change of seizure frequency prior to and after the increase of LEV.. Out of 518 PWE who had been on LEV during their hospital stay, a total of 61 PWE fulfilled the inclusion criteria. After a gradual dose increment, 91,8 % of PWE showed a reduced seizure frequency, 73,8 % had a reduction of seizures of 50 % or more, and 21,3 % were seizure-free during the observation period. A significant seizure reduction could be shown with a seizure count of 2,5/week prior to the increment and 0,7/week after dose increment (p < 0,00001). Seven PWE reported minor adverse events and ten PWE showed slight laboratory changes (within normal levels).. Contrary to our long-term clinical impression, LEV dose increments were reasonable and improved the seizure situation in PWE, usually without additional safety hazards.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Seizures; Treatment Outcome; Young Adult

To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy.. Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end.. Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate.. Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.

Topics: Adult; Anticonvulsants; Australia; Carbamazepine; Depression; Epilepsy; Female; Humans; Levetiracetam; Pregnancy; Pregnancy Complications; Seizures; Topiramate

The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations.. This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification. According to the year of marketing, AEDs were categorised as classic (before 1990) or new (after 1990). We performed a descriptive analysis of qualitative and quantitative variables.. Female patients accounted for 54.6% of the sample. Mean age was 42.7 years; mean age of onset was 22.4. Regarding epilepsy type, 75.7% of patients experienced partial seizures, 51.5% were symptomatic,32.4% had refractory epilepsy, 35.6% had been seizure-free for the previous year, and 59.2% had associated comorbidities.A total of 1103 AED prescriptions were made; 64.6% of prescriptions were for new AEDs; 85.4% of patients received new AEDs. Patients received a mean of 2 AEDs (range, 1-5). A total of 59.6% of patients received polytherapy.The most frequently prescribed AEDs were levetiracetam (42.6%), valproic acid (25.4%), lamotrigine (19.5%), carbamazepine (17.9%), and lacosamide (17.5%). No AED was employed exclusively as monotherapy. The most frequently prescribed AEDs for generalised and partial seizures were valproic acid (48.2%) and levetiracetam (43.2%), respectively. Valproic acid was less frequently prescribed to female patients. Patients with refractory epilepsy or with associated comorbidities were more frequently prescribed a combination of new and classic AEDs (48.7% and 45.6%, respectively) than only one type of AED.. The majority of patients received new AEDs. The combination of classic and new AEDs was more frequently prescribed to patients with refractory epilepsy or with associated comorbidities.

Topics: Adult; Anticonvulsants; Drug Therapy, Combination; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Male; Neurology; Referral and Consultation; Seizures; Spain; Valproic Acid

Topics: Adult; Anticonvulsants; Classical Lissencephalies and Subcortical Band Heterotopias; Electroencephalography; Humans; Lamotrigine; Levetiracetam; Magnetic Resonance Imaging; Male; Mutation; Seizures; Valproic Acid

Levetiracetam (LEV) is an antiepileptic drug used widely in patients with a favorable safety profile. Studies evaluating the safety and efficacy of intravenous (IV) LEV included volumes of at least 100 mL. Minimally diluted doses administered over 5-6 min were found to be both safe and effective. Given the complexities of admixing, this practice can be impractical and result in delays in antiepileptic therapy. This study aimed to retrospectively review the safety and tolerability of rapid administration of undiluted LEV doses ≤ 1000 mg.. This was a retrospective study evaluating adverse drug reactions associated with undiluted LEV from January 1, 2018-June 1, 2018. Patients were included if they received at least one dose of undiluted LEV and were ≥ 18 years old. Safety endpoints were reviewed and collected from the time administration until hospital discharge. Endpoints included injection site pain and discomfort, injection site erythema, extravasation, IV line replacement, and any documented adverse effect leading to IV LEV discontinuation. Descriptive statistics were used to analyze the data.. A total of 199 patients were included in the study totaling 1626 doses of LEV. Most patients were administered LEV 1000 mg (60.8%), through a peripheral line (64.3%), and were prescribed LEV for seizure prophylaxis (58.3%). Patients received a mean of 8.1 ± 8 doses for a mean duration of therapy of 5 ± 4.5 days. About 98.5% of patients did not experience an adverse effect, whereas 1.5% of patients experienced agitation, delirium, confusion, and/or lethargy, which is well known to LEV therapy.. Rapid administration of undiluted LEV doses ≤ 1000 mg were well tolerated with no concentration-related side effects. Further prospective research is needed to confirm this observation as well as the safety of higher doses.

Topics: Adult; Aged; Anticonvulsants; Confusion; Delirium; Female; Humans; Injection Site Reaction; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Solutions; Time-to-Treatment

Guidelines on the administration of prophylactic antiepileptic drugs (AED), and specifically levetiracetam, for brain tumor surgery are still lacking. In this two-center matched cohort study, we aim to compare the proportion of postoperative seizures during follow-up after supratentorial tumor surgery in patients receiving no seizure prophylaxis, and those treated with levetiracetam perioperatively. Three hundred sixteen consecutive patients undergoing supratentorial tumor surgery, without history of seizures were included: 207 patients did not receive AED (no AED group), and 109 patients received levetiracetam perioperatively (levetiracetam group). The primary outcome measure was the rate of postoperative seizures. Additionally, uni- and multivariate analyses assessing possible risk factors for postoperative seizures were performed. No statistically significant difference for the occurrence of postoperative seizures was found between the two groups (10.1%, n = 21 in the no AED group vs. 9.2%, n = 10, in the levetiracetam group; p = 0.69, OR 0.9 [0.4-2.0), NNT 103 [12.9-17.1]). After propensity score matching, the primary outcome was observed in 13 patients (12.4%) from the no AED group and in 9 patients (8.6%) from the levetiracetam group (p = 0.50, OR 0.7 [0.3-1.6], NNT 26.3 [8.3-22.4]). Among all analyzed possible risk factors for postoperative seizures, only postoperative infarction showed a statistically significant association with higher seizure rates in multivariate analysis (OR 8.2 [1.1-60.6], p = 0.04). Prophylactic treatment with levetiracetam after brain tumor surgery showed no statistically significant effect in preventing postoperative seizures. However, in case a postoperative infarction occurs, its administration might be indicated.

Topics: Adult; Aged; Anticonvulsants; Cohort Studies; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Seizures; Supratentorial Neoplasms

Topics: Adult; Anticonvulsants; Benzodiazepines; Case-Control Studies; Disease Progression; Female; Hospitalization; Humans; Levetiracetam; Logistic Models; Odds Ratio; Retrospective Studies; Risk Factors; Seizures; Status Epilepticus

Topics: Aged; Anti-Bacterial Agents; Anticonvulsants; Ceftriaxone; Diabetes Mellitus, Type 2; Electroencephalography; Female; Humans; Levetiracetam; Meningitis, Bacterial; Seizures; Streptococcal Infections; Streptococcus agalactiae

Nearly 75% of patients with metastatic melanoma develop brain metastases. We here report the case of an 83 year-old woman hospitalized for secondarily generalized clonic seizures of the left leg with partial convulsive seizures in the Resuscitation Department. Melanoma resection of the left ankle had been performed 6 months before her admission. Neurological examination showed left ataxic crural monoparesis. Electro-encephalogram showed central and right frontal focus with left-sided dissemination. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain showed multiple supratentorial and subtentorial encephalic lesions with varying size and shape, with T1 hypersignal (A and A'), haemorrhage on T2*-weighted sequences (B and B'), gadolinium-enhancing T1 with perilesional edema on Flair sequences. Positron emission tomography (PET) showed multiple lymph node and bone metastases. Lymph node biopsy was negative for VE1 antibody with no BRAFV600E mutation by immunohistochemistry. An increase in the number of metastatic lesions was observed during control brain CT scan despite 10 brain radiotherapy sessions motivating palliative care. Epileptic seizures were controlled with levetiracetam. In patient with multiple hemorrhagic and spontaneous brain lesions, it is essential to obtain informations on patient's history of melanoma and to perform a thorough dermatologic examination in order to investigate its cause and to establish adequate therapeutic treatment.

Topics: Aged, 80 and over; Anticonvulsants; Bone Neoplasms; Brain Neoplasms; Female; Humans; Levetiracetam; Lymphatic Metastasis; Magnetic Resonance Imaging; Melanoma; Positron-Emission Tomography; Seizures; Skin Neoplasms

A 62-year-old previously healthy male was admitted with new onset generalised tonic-clonic seizures. Treatment was initiated with the antiepileptic levetiracetam and he had no further episodes of seizures. Creatine kinase (CPK) level was 1812 IU/L 12-hour postadmission. Despite good hydration, his CPK levels continued to rise dramatically and reached a level of 19 000 IU/L on day 5. This rise was unexplained as he did not have any further seizures and had a normal renal function. In the absence of other risk factors, the rare possibility of levetiracetam being responsible for the disproportionately high CPK was considered. Within 12 hours of withdrawal of levetiracetam, there was a downward trend in the CPK levels, with a 10-fold decrease in CPK levels over the next 4 days. This is only the ninth case reported in literature regarding this rare and potentially serious adverse effect of levetiracetam.

Topics: Anticonvulsants; Creatine Kinase; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Humans; Levetiracetam; Male; Middle Aged; Neurologic Examination; Phenytoin; Rhabdomyolysis; Seizures; Treatment Outcome

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Piracetam; Seizures

Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a devastating disease, that despite being increasingly diagnosed, there are no consensus guidelines for the optimal management. A previously healthy 3-year-old-boy brought to the emergency department due to seizures. Neurological examination was normal, and electroencephalogram (EEG) suggested focal epilepsy. Anticonvulsive medication was initiated. He progressively lost age-appropriate language skills, presented behavioural changes and psychiatric symptoms. Neurological examination at that time revealed symmetric gross motor weakness of the lower limbs. Brain and spinal cord MRI and cerebrospinal fluid were normal. Repeated EEG showed global lentification. Steroid therapy was initiated for the suspicion of autoimmune encephalitis, later confirmed as NMDAR encephalitis. He became clinically improved after 10 days of treatment but only returned to his baseline after 3 months of disease onset. The authors emphasised the variable course of the disease and possible late response to treatment.

Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Anticonvulsants; Child, Preschool; Disease Progression; Glucocorticoids; Humans; Levetiracetam; Male; Methylprednisolone; Seizures

The aim of this study was to evaluate the effectiveness of monotherapy with levetiracetam (LEV) in achieving seizure cessation in a retrospective cohort of extreme preterm infants with seizures.. Charts of infants with a diagnosis of neonatal seizures admitted to the NICU between 2013 and 2017 were reviewed. Seizures were diagnosed using continuous video electroencephalography. All infants were initially started on LEV and reached a dose of 80 mg/kg/day. Other ASMs were added to LEV if seizures continued after 2 days. Data on additional clinical variables were collected for each infant.. Sixty-one infants born <28 weeks of gestation met inclusion criteria. Seventy-four percent of patients did not respond to LEV monotherapy and required additional medications.. LEV monotherapy stopped seizures in only a small portion of cases.

Topics: Anticonvulsants; Electroencephalography; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Levetiracetam; Male; Retrospective Studies; Seizures; Treatment Failure

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.. El objetivo fue describir la frecuencia, modo de presentación y características de la epilepsia en niños con hemiparesia congénita (HC). Estudio retrospectivo, descriptivo y multicéntrico, basado en la recolección de datos de las historias clínicas de pacientes de 0 a 19 años con HC secundaria a infarto perinatal en diferentes centros de la comunidad de Cataluña. Se incluyeron 310 niños (55% varones y 45% mujeres) de un total de 13 centros de Cataluña. Edad media del debut de las crisis fue de 2 ± 1 año. Presentaron epilepsia el 29.5% (n = 76), el subtipo vascular más frecuente fue el infarto presumiblemente perinatal (51.3%), seguido del accidente isquémico arterial neonatal (18.4%), infarto hemorrágico venoso periventricular (15.8%), infarto hemorrágico neonatal (10.5%) y trombosis venosa neonatal (3.9%). La semiología de las crisis más frecuente fue la focal motora en un 82%, seguida de las focales motoras con bilateralización secundaria en el 23%, focales discognitivas en 13.5%, generalizadas 2% y espasmos 6.5%. El 67.3% se controló con monoterapia y los fármacos empleados fueron el valproato, levetiracetam o carbamacepina. Se identificó el antecedente de estatus eléctrico durante el sueño en 3 pacientes, todos asociados a lesiones extensas que incluían al tálamo. Del total con epilepsia, el 35% debutaron con convulsiones neonatales en los primeros 3 días de vida. El 30% con accidente cerebrovascular perinatal y HC presentan riesgo de padecer epilepsia durante la infancia. Aquellos con infartos isquémicos tienen el riesgo más alto, por lo que requerirán un seguimiento dirigido a detectar precozmente la epilepsia e iniciar tratamiento.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Paresis; Retrospective Studies; Risk Factors; Seizures; Spain; Stroke; Valproic Acid; Young Adult

Topics: Administration, Intravenous; Anticonvulsants; Electroencephalography; Humans; Hypoxia; Levetiracetam; Male; Medication Adherence; Pulmonary Edema; Radiography, Thoracic; Seizures; Status Epilepticus; Treatment Outcome; Young Adult

Topics: Child; Epilepsy; Humans; Levetiracetam; Phenytoin; Seizures; Status Epilepticus

Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported.. A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs.. To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Chorea; Female; Glioblastoma; Humans; Levetiracetam; Seizures; Spinal Cord Neoplasms

Until today, classic human astroviruses have not been associated with central nervous system infections in immunocompetent patients.. A 16-month-old Caucasian girl presented with repetitive generalized seizures with a 4-day history of watery diarrhea, which had already gradually improved. Initially, the prolonged seizures ceased after systemic midazolam treatment and were thought to be fever associated. However, her mental status remained altered, and after seizure recurrence, she was transferred to our pediatric intensive care unit. Seizure control was achieved by a combination of high-dose levetiracetam and phenobarbital, but she remained unconscious. An electroencephalogram at this time revealed generalized high voltage theta activity. All laboratory analyses, including extended blood and cerebrospinal fluid analyses, and a brain magnetic resonance imaging were normal. On day 4, the child gradually became conscious, but was very agitated and not able to walk. Since an electroencephalogram at this time still revealed generalized high voltage theta activity, although she had not received sedative medications for 72 hours, she was diagnosed as having encephalopathy. At that time, results of diagnostic testing of the stool sample were positive for classic astrovirus infection, and we decided to analyze the initially obtained cerebrospinal fluid for astrovirus as well. Cerebrospinal fluid was also found positive for human astrovirus. Sequencing analysis revealed a classic astrovirus genotype 1 with exactly the same nucleotide sequence as in the feces. Clinically, the child gradually improved and was discharged on day 9.. Whereas the new human astrovirus subtypes have been recently associated with central nervous system infection, this is the first case of encephalitis in an immunocompetent child due to classic human astrovirus. Considering that classic human astroviruses are the third most common etiological agents of viral gastroenteritis in children, we believe that human astroviruses as causative agents for central nervous system infections should be considered more often, especially in children and infants with preceding gastroenteritis.

Topics: Anticonvulsants; Astroviridae Infections; Diarrhea; Encephalitis; Feces; Female; Gastroenteritis; Humans; Hypnotics and Sedatives; Infant; Levetiracetam; Mamastrovirus; Phenobarbital; Seizures; Treatment Outcome

Glioblastoma multiforme (GBM) is a lethal and aggressive malignant tumor of the central nervous system. The World Health Organization classifies it as a grade IV astrocytoma. Controlling seizures is essential during GBM treatment because they are often present and closely associated with the quality of life of GBM patients. Some antiepileptic drugs (AEDs) exhibit antitumor effects and could decrease the mortality of patients with GBM. In this retrospective cohort study, we examined 418 patients treated with surgery, radiotherapy, and chemotherapy with temozolomide (TMZ) at Severance Hospital in South Korea, per the current protocol. Median overall survival (OS) was 21 months [95% confidence interval (CI): 18.1-23.9] in the levetiracetam (LEV) treatment group, whereas it was 16 months [95% CI: 14.1-17.9] in the group without LEV, exhibiting a statistically significant difference between the two groups (P < 0.001). Of nine AED groups, only LEV treatment [P = 0.001; hazard ratio (HR), 0.65; 95% CI: 0.51-0.83] exhibited a statistically significant difference in the OS, in the univariate analysis. In the risk analysis of the baseline characteristics, age, administration of LEV, and O6-methylguanine-DNA methyltransferase (MGMT) promoter status correlated with OS. The use of LEV in the group with a methylated MGMT promoter resulted in a positive impact on the OS [P = 0.006; HR, 0.174; 95% CI: 0.050-0.608], but the effect of LEV on the OS was not statistically significant in the unmethylated MGMT promoter group (P = 0.623). This study suggests that, compared with other AEDs, the administration of LEV may prolong the survival period in GBM patients with methylated MGMT promoters, who are undergoing chemotherapy with TMZ.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Chemoradiotherapy; Child; Child, Preschool; Dose Fractionation, Radiation; Female; Follow-Up Studies; Glioblastoma; Humans; Kaplan-Meier Estimate; Levetiracetam; Male; Middle Aged; Quality of Life; Republic of Korea; Retrospective Studies; Risk Factors; Seizures; Temozolomide; Time Factors; Treatment Outcome; Young Adult

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Topics: Epilepsy; Humans; Infant, Newborn; Levetiracetam; Phenobarbital; Seizures

Incidence and prevalence of epilepsy increase with advancing age. Although the majority of late-onset epilepsies are of lesional origin, a considerable proportion of patients present with unknown etiology. The aim of this study was to evaluate the semiological, electroencephalographic (EEG), and cerebrospinal fluid (CSF) characteristics as well as the 12-month seizure outcome in a cohort of patients with nonlesional late-onset epilepsy (≥55 years).. A total of 54 patients with newly diagnosed nonlesional late-onset epilepsy (NLLOE) were retrospectively evaluated for seizure type using the most recent International League Against Epilepsy (ILAE) classification of seizure types, EEG characteristics, and CSF profile and followed-up for at least 12 months after epilepsy onset. Results were compared with a gender-matched control group of 58 patients with nonlesional early-onset epilepsy (NLEOE).. The predominant seizure types in NLLOE were focal to bilateral tonic-clonic seizures (30%) as well as focal onset impaired awareness motor seizures (IAMS) (22%) and focal onset impaired awareness nonmotor seizures (IANMS) (22%). The predominant seizure types in NLEOE were focal to bilateral tonic-clonic seizures (43%) as well as focal onset aware nonmotor seizures (ANMS) (31%) and IAMS (31%). Focal onset impaired awareness nonmotor seizures were found to be more characteristic in patients with NLLOE (p = 0.019; α < 0.05; NLLOE: 22.2% vs. NLEOE: 8.6%). Electroencephalography revealed no significant differences between groups. Of interest, three patients with NLLOE (8%) presented with oligoclonal bands (OCB) in CSF albeit absence of antineuronal antibodies. Seizure-free rate was 70%. Adverse effects from medication leading to antiepileptic drug (AED) change were reported in 12 patients (22%), valproate was the best tolerated AED in patients with NLLOE [adverse effects in 9%, compared with 12% (gabapentin) and 26% (levetiracetam)].. Using the most recent classification system, different patterns of semiological characteristics were identified: NLLOE more frequently present with IANMS, whereas patients with NLEOE rather have ANMS. Oligoclonal bands were only detected in patients with NLLOE, indicating that careful exclusion of autoimmune encephalitis in this patient group is warranted. Our findings may help to more accurately identify and characterize patients with NLLOE to improve targeted diagnostics and adequate treatment in this challenging group of patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsy; Female; Gabapentin; Humans; Late Onset Disorders; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid; Young Adult

Topics: Anticonvulsants; Behavior; Child, Preschool; Cognitive Dysfunction; Epilepsy; Humans; Levetiracetam; Male; Neuropsychiatry; Phenytoin; Seizures; Vasculitis

Patient selection for seizure prophylaxis after traumatic brain injury (TBI) and duration of anti-epileptic drug treatment for patients with early post-traumatic seizures (PTS), remain plagued with uncertainty. In early 2017, a collaborative group of neurosurgeons, neurologists, neurointensive care and rehabilitation medicine physicians was formed in the UK with the aim of assessing variability in current practice and gauging the degree of uncertainty to inform the design of future studies. Here we present the results of a survey of clinicians managing patients with TBI in the UK and Ireland.. An online survey was developed and piloted. Following approval by the Academic Committee of the Society of British Neurological Surgeons, it was distributed via appropriate electronic mailing lists.. One hundred and seventeen respondents answered the questionnaire, predominantly neurosurgeons (76%) from 30 (of 32) trauma-receiving hospitals in the UK and Ireland. Fifty-three percent of respondents do not routinely use seizure prophylaxis, but 38% prescribe prophylaxis for one week. Sixty percent feel there is uncertainty regarding the use of seizure prophylaxis, and 71% would participate in further research to address this question. Sixty-two percent of respondents use levetiracetam for treatment of seizures during the acute phase, and 42% continued for a total of 3 months. Overall, 90% were uncertain about the duration of treatment for seizures, and 78% would participate in further research to address this question.. The survey results demonstrate the variation in practice and uncertainty in both described aspects of management of patients who have suffered a TBI. The majority of respondents would want to participate in future research to help try and address this critical issue, and this shows the importance and relevance of these two clinical questions.

Topics: Anticonvulsants; Brain Injuries, Traumatic; Drug Utilization; Humans; Ireland; Levetiracetam; Seizures; Surveys and Questionnaires; United Kingdom

This is a case series of 25 patients with drug-resistant epilepsy and psychiatric comorbidities who started on brivaracetam (BRV) at St George's University Hospitals and Frimley Health in London. Median BRV dose was 150 mg for a median follow-up period of 8 months. Twenty had focal epilepsy, four had generalized epilepsies, and one had unclassified epilepsy; 76% had mood disorders (either depression or bipolar disorder), 12% intellectual disabilities with autism spectrum disorder and challenging behavior, and 12% psychoses. Forty percent of patients presented at least 50% seizure reduction, but none of them became seizure-free. A total of 44% of patients discontinued BRV, 20% because of adverse events, 20% because of inefficacy, and 4% because of both. Depression was reported by 8%, aggressive behavior by 8%, while 4% reported both. A total of 91.6% had received levetiracetam (LEV) before, in whom LEV was discontinued because of psychiatric adverse events (PAEs) in half. Seventy-seven percent of patients who developed PAEs with LEV did not do so on BRV suggesting that BRV is better tolerated than LEV in complex patients with psychiatric comorbidities and that the synaptic vesicle glycoprotein 2A (SV2A) protein modulation is unlikely to be implicated in LEV-related PAEs.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Autism Spectrum Disorder; Comorbidity; Drug Resistant Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; London; Male; Mental Disorders; Middle Aged; Pyrrolidinones; Retrospective Studies; Seizures; Young Adult

Patients with epilepsy have a higher risk of accidental injuries. The aim of this study was to determine the incidence of accidental injuries and quality of life in patients with epilepsy and generalized tonic-clonic seizures and their association with patient-related factors.. This is an observational, cross-sectional, multicenter study of patients with epilepsy and primary generalized tonic-clonic seizures and/or focal to bilateral tonic-clonic seizures in the routine clinical practice of epilepsy clinics. In a single visit, demographic and clinical data and information on the type and severity of injuries were collected, and patients' quality of life was evaluated with the QOLIE-10 questionnaire.. In total, 406 patients with a median age of 41.1 years (range: 13-87) were included; 47.5% were women. Age at onset of tonic-clonic seizures was 25.4 (range: 0-83) years. Epileptic seizures were primary tonic-clonic (67.2%), focal to bilateral tonic-clonic (32.8%), focal with impairment of awareness (23.6%), focal without impairment of awareness (13.5%), absences (14.8%), and myoclonic (9.6%). Etiology was symptomatic or with unknown etiology focal (42.9%), genetic generalized (36.9%), symptomatic or with unknown etiology generalized (18.0%), and others (2.2%). The number of generalized tonic-clonic seizures in the last 12 months was as follows: 1 (41.9%), 2-5 (42.4%), and >5 (15.8%). Antiepileptic treatment at the time of the visit was monotherapy in 44.1% of the patients. The most commonly used drugs were levetiracetam (45.1%), valproate (20.7%), lamotrigine (20.0%), and perampanel (18.7%). In total, 59.6% of the patients had experienced at least one accidental injury associated with tonic-clonic seizures in the last 12 months, the most common being head injuries (35.5%), dental injuries (4.9%), burns (4.9%), and fractures (3.9%). A total of 25.1% had suffered at least one serious injury. The multiple logistic regression model showed that the factors associated with suffering an injury were the following: etiology (symptomatic or with unknown etiology focal and genetic generalized vs. symptomatic or with unknown etiology generalized, p = 0.0008 and p = 0.0077, respectively), number of seizures in the last year (2-5 vs. 1, p = 0.0115; >5 vs. 1, p = 0.0004), and psychiatric comorbidities (p = 0.0151). Patients with injuries had a worse quality of life than patients without injuries, according to the overall QOLIE-10 score (p = 0.0003).. More than half of the patients had accidental injuries related with seizures. Symptomatic or with unknown etiology focal epilepsy and genetic generalized epilepsy, >1 seizure in the last year, and concomitant psychiatric disease are the risk factors associated with accidental injuries in patients with tonic-clonic seizures, with the consequent worsening of quality of life.

Topics: Accidental Injuries; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cross-Sectional Studies; Epilepsy, Tonic-Clonic; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Quality of Life; Seizures; Valproic Acid; Young Adult

Cranioplasty is a relatively simple and straightforward intervention; however, it is associated with a high incidence of postoperative seizures. Postcranioplasty seizures, especially early seizures, are common and associated with poor outcomes and longer hospital stays. Protocols for preventing and managing early seizures have not been well established.. The medical records of 595 patients who underwent cranioplasty were retrospectively reviewed. Of these patients, 259 had preexisting seizures and 336 had no seizures before cranioplasty. Prophylactic antiepileptic drugs (AEDs) were administered to patients who had no seizures before cranioplasty for 1 week, whereas an advanced AED regimen was administered to patients with preexisting seizures. Subsequently, clinical characteristics, occurrence of recurrent seizures, early seizures, and postoperative complications were analyzed.. Our previous study showed positive results for prophylaxis in new-onset early seizures. In the patients with preexisting seizures, 46.7% of the patients (121/259) experienced recurrent seizures after cranioplasty and 17.4% of the patients (45/259) experienced early recurrent seizures within 1 week of their operation. In the group who received the advanced AEDs, early recurrent seizures were significantly reduced to 8.7% compared with the regular group (20.5%; P = 0.027). Younger age and preoperative hydrocephalus engendered a higher risk of recurrent seizures. The number of previous craniotomies was observed to have a trend of increasing early recurrent seizures.. Cranioplasty is associated with a high incidence of postoperative seizures. Our management protocol for postcranioplasty seizures includes seizure prophylaxis and advanced use of AEDs, which can reduce the occurrence of early seizures.

Topics: Adult; Anticonvulsants; Clinical Protocols; Decompressive Craniectomy; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Levetiracetam; Male; Phenytoin; Postoperative Complications; Recurrence; Retrospective Studies; Seizures; Skull; Treatment Outcome; Valproic Acid

To report the incidence of postattenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV).. Multi-institutional retrospective study.. Nine hundred forty dogs.. Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within 7 days postoperatively. Dogs were divided into 3 groups: no LEV (LEV-); LEV at ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose perioperatively, followed by ≥15 mg/kg every 8 hours postoperatively (LEV1); and LEV at <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively (LEV2).. Seventy-five (8.0%) dogs developed PAS. Incidence of PAS was 35 of 523 (6.7%), 21 of 188 (11.2%), and 19 of 228 (8.3%) in groups LEV-, LEV1, and LEV2, respectively. This difference was not statistically significant (P = .14). No differences between groups of dogs that seized with respect to investigated variables were identified.. The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols that were investigated in our study was not associated with a reduced incidence of PAS.. Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first 7 days postoperatively for seizures.

Topics: Administration, Intravenous; Animals; Anticonvulsants; Dog Diseases; Dogs; Female; Incidence; Levetiracetam; Male; Portal System; Postoperative Complications; Postoperative Period; Retrospective Studies; Seizures; Vascular Malformations

Topics: Anticonvulsants; Child, Preschool; Consanguinity; Cysts; Exons; Female; Gait Disorders, Neurologic; Hereditary Central Nervous System Demyelinating Diseases; Humans; Levetiracetam; Magnetic Resonance Imaging; Megalencephaly; Membrane Proteins; Mutagenesis, Insertional; Neuroimaging; Seizures

Anticonvulsant administration is the standard of care for prevention of busulfan-induced seizures (BIS) in hematopoietic stem cell transplantation (HSCT). While valproate interacts with other drugs, including carbapenem antibiotics, levetiracetam has no known clinically significant interactions. Only a few reports have discussed the use of levetiracetam for the prevention of BIS in HSCT recipients. This retrospective study aimed to evaluate the efficacy and safety of valproate and levetiracetam for BIS prophylaxis in adult HSCT recipients. We identified patients who received valproate or levetiracetam to prevent BIS at the National Cancer Center Hospital from December 2015 to November 2017. Ninety-one patients were analyzed (valproate group 45; levetiracetam group 46). No BIS occurred in either group. The pattern of anticonvulsant-related adverse events was similar in both groups, except for a higher incidence of rash in the valproate group. Carbapenem antibiotics were more frequently used in the levetiracetam group than in the valproate group. In conclusion, valproate and levetiracetam are effective and safe for the prophylaxis of BIS. Levetiracetam may be more useful in patients colonized with extended-spectrum beta-lactamase-producing bacteria due to its lack of any clinically significant drug-drug interactions.

Topics: Adult; Aged; Anticonvulsants; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Levetiracetam; Male; Middle Aged; Retrospective Studies; Seizures; Treatment Outcome; Valproic Acid; Young Adult

Topics: Anticonvulsants; Humans; Levetiracetam; Liver Failure, Acute; Male; Middle Aged; Neurosurgical Procedures; Seizures

The target brain binding site of levetiracetam (LEV) is synaptic vesicle glycoprotein 2A (SV2A). Up to now, only a homozygous pathogenic SV2A gene mutation was reported in human. We now report a novel heterozygous pathogenic SV2A gene mutation both in a girl and her mother result in epilepsy and poor response to LEV. Furthermore, the girl developed a new seizure type after using LEV. Our report had a clinical relevance that LEV could potentially produce contradictory efficacy in patients with SV2A gene mutation. If patients' seizures became exacerbated while using LEV, SV2A gene testing is recommended.

Topics: Anticonvulsants; Brain; Child, Preschool; Female; Humans; Levetiracetam; Membrane Glycoproteins; Mutation; Nerve Tissue Proteins; Piracetam; Seizures

Improved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible changes in QoL and adverse events in connection with generic substitution of levetiracetam (LEV).. This was a prospective, naturalistic, two-cohort, twin-center study. After a baseline period of 10 weeks, outpatients with epilepsy on stable treatment with Keppra® either continued on this brand (reference group, n = 16) or switched to generic LEV (1A Pharma®) (study group, n = 16) for an eight-week study period. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and an adverse events' questionnaire were administered at inclusion, after baseline, and at the end of the study period. The study protocol included a close clinical follow-up with repeated LEV serum concentration measurements and nurse-led outpatient visits.. Clinically relevant improvements in overall QOLIE-31 scores according to minimally important change (MIC) estimates were seen in both groups. QOLIE-31 subscales in both groups showed significantly less worry about seizures at the end of the study compared to scores at inclusion (study group: p = 0.01; reference group: p = 0.02). No significant deterioration in QoL or adverse events were observed following generic substitution. No switchbacks occurred.. We found reduced seizure worries over time among people with epilepsy allocated to either generic switch or continued treatment with brand LEV. We hypothesize that the nurse-led structured follow-up had an impact on seizure worries and switchback rates because of reduced nocebo effects. Further studies on generic AED substitution, focusing on psychological outcome measures, are warranted to test this supposition.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Prospective Studies; Quality of Life; Seizures; Surveys and Questionnaires; Young Adult

Influenza-associated acute encephalopathy (IAE) is more prevalent in children than in adults and often results in neurological sequelae or even death. Diagnosis of IAE is difficult as clinical presentation varies significantly and the influenza virus is rarely detected in cerebrospinal fluid. Moreover, seizures in adults due to influenza infection are rare. Herein, we describe the case of an adult presenting with both acute encephalitis and seizures. A 38-year-old female was admitted to the emergency department with acute respiratory symptoms and fever, followed by quick progression to stupor within 24 h. A rapid antigen test was influenza A-positive, and polymerase chain reaction of nasal secretions confirmed the H3N2 subtype. Brain magnetic resonance imaging showed bilateral water restriction lesions at the thalamus and the cerebellum and an electroencephalogram showed frequent episodic generalized sharp-and-slow waves over the bilateral frontal region. Based on the neuroimaging and laboratory findings, we diagnosed the patient with adult influenza A (H3N2)-related encephalitis complicated by seizure. Treatment with oseltamivir and anticonvulsants led to complete neurologic recovery by day 14. This report describes two unusual neurological manifestations of influenza A, i.e., encephalitis and seizures, in an adult. We emphasize that, in adults presenting with acute viral encephalitis, clinicians should consider influenza infection as part of the differential diagnosis, and that typical neuroimaging in conjunction with laboratory detection of influenza virus and/or intrathecal antibody production suggestive of IAE, may help establish an accurate diagnosis.

Topics: Acute Disease; Adult; Anticonvulsants; Antiviral Agents; Brain; Diagnosis, Differential; Encephalitis, Viral; Female; Humans; Influenza A Virus, H3N2 Subtype; Influenza, Human; Levetiracetam; Magnetic Resonance Imaging; Oseltamivir; Seizures

Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinases; Cognitive Dysfunction; Disease Models, Animal; Electroencephalography; GAP-43 Protein; Hippocampus; Levetiracetam; Male; Phosphorylation; Protein Kinase C; Rats; Rats, Sprague-Dawley; Seizures; Signal Transduction; Valproic Acid

Infants with brain injury are susceptible to developmental delays. Survivors of neonatal seizures are at risk for developmental delay, epilepsy, and further neurological comorbidities. Despite advances in neonatal critical care, the prevalence of adverse long-term outcomes and seizure recurrence remains unchanged. Our goal is to determine if early treatment of neonatal seizures with phenobarbital or levetiracetam is associated with worse neurodevelopmental outcomes in brain-injured infants.. We conducted a retrospective cohort study of 119 infants admitted between 2013 and 2017 who were at risk for developmental delay and assessed in our clinic. We compared brain injury infants with neonatal seizures to brain injury infants without neonatal seizures using Bayley scores (BSID III) at 9-14 months gestational age. A comparison of Bayley scores between those exposed to phenobarbital and levetiracetam was conducted.. Twenty-two children with neonatal seizures scored lower than 53 children without seizures in all domains with significant values in composite scores for cognitive function (p = 0.003) and language (p = 0.031). We found no difference in scores at 9-14 months between infants exposed to phenobarbital versus levetiracetam.. Our results suggest that in infants with brain injury, the occurrence of neonatal seizures has an adverse effect on neurodevelopmental outcomes. The choice of antiseizure medication may not play a significant role in their outcomes.

Topics: Anticonvulsants; Brain Injuries; Case-Control Studies; Developmental Disabilities; Female; Gestational Age; Humans; Infant; Levetiracetam; Male; Phenobarbital; Retrospective Studies; Seizures

We tested the impact of antiepileptic drug (AED) administration on post-cardiac arrest epileptiform electroencephalographic (EEG) activity.. We studied an observational cohort of comatose subjects treated at a single academic medical center after cardiac arrest from September 2010 to January 2018. We aggregated the observed EEG patterns into 5 categories: suppressed; discontinuous background with superimposed epileptiform activity; discontinuous background without epileptiform features; continuous background with epileptiform activity; and continuous background without epileptiform activity. We calculated overall probabilities of transitions between EEG states in a multistate model, then used Aalen's additive regression to test if AEDs or hypothermia are associated with a change in these probabilities.. Overall, 828 subjects had EEG-monitoring for 42,840 h with a median of 40 [IQR 23-64] h per subject. Among patients with epileptiform findings on initial monitoring, 50% transitioned at least once to a non-epileptiform, non-suppressed state. By contrast, 19% with non-epileptiform initial activity transitioned to an epileptiform state at least once. Overall, 568 (78%) patients received at least one AED. Among patients with continuous EEG background activity, valproate, levetiracetam and lower body temperature were each associated with an increased probability of transition from epileptiform states to non-epileptiform states, where patients with discontinuous EEG background activity no agent linked to an increased probability of transitioning from epileptiform states.. After cardiac arrest, the impact of AEDs may depend on the presence of continuous cortical background activity. These data serve to inform experimental work to better define the opportunities to improve neurologic care post-cardiac arrest.

Topics: Anticonvulsants; Cohort Studies; Coma; Combined Modality Therapy; Electroencephalography; Female; Heart Arrest; Humans; Hypothermia, Induced; Hypoxia, Brain; Levetiracetam; Male; Middle Aged; Nervous System Diseases; Outcome and Process Assessment, Health Care; Resuscitation; Seizures; United States; Valproic Acid

Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges.. A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007-2018). Additional clinical interviews were performed, and a mixed method approach was applied.. Ninety patients with defined JME diagnosis, 54/36 women/men aged 14-39 (mean: 25) years, were included. Only 29 (33%) were seizure-free. Within the last year, 21% experienced generalized tonic-clonic seizures (GTCS), and 68% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two-thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life.. Despite the use of AEDs in the majority of patients, only one-third were seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME.

Topics: Adolescent; Adult; Anticonvulsants; Cohort Studies; Female; Humans; Lamotrigine; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Myoclonus; Norway; Quality of Life; Seizures; Valproic Acid; Young Adult

Status epilepticus (SE) is characterized by recurrent seizure activity and can be drug- resistant. Knowledge of neuronal and metabolic activity of the brain during SE may be helpful to improve medical care. We here report the effects of three anti-seizure drugs on changes of acetylcholine energy metabolites and oxidative stress during SE.. We used the lithium-pilocarpine model in rats to induce SE and in vivo- microdialysis to monitor cholinergic and metabolic activity in the hippocampus. We measured extracellular concentrations of acetylcholine, glucose, lactate, pyruvate, glycerol and isoprostanes before and during SE, and after acute treatment with pregabalin, valproic acid, and levetiracteam.. Upon onset of  SE, acetylcholine (ACh) release increased six- to eightfold. Glucose was increased only transiently by 30% but lactate levels rose four-fold, and extracellular concentrations of glycerol ten-fold. Isoprostanes are markers of oxidative stress and increased more than 20-fold. Two hours after pilocarpine adminstration, rats were treated with pregabalin (100 mg/kg), levetiracetam (200 mg/kg) or valproic acid (400 mg/kg) by i.p. injection. All three drugs stopped seizure activity in a delayed fashion, but at the doses indicated, only animals that received levetiracetam reached consciousness. All drugs reduced ACh release within 60-120 minutes. Lactate/pyruvate ratios, glycerol and isoprostanne levels were also reduced significantly after drug administration.. Hippocampal ACh release closely follows seizure activity in SE and is attenuated when SE subsides. Pregabalin, valproic acid and levetiracetam all terminate seizures in the rat SE model and attenuate cholinergic and metabolic changes within two hours.

Topics: Acetylcholine; Animals; Anticonvulsants; Behavior, Animal; Cholinergic Agents; Chromatography, High Pressure Liquid; Disease Models, Animal; Levetiracetam; Male; Oxidative Stress; Pregabalin; Rats; Rats, Sprague-Dawley; Seizures; Status Epilepticus; Valproic Acid

This study aimed to explore the clinical effect of levetiracetam in the treatment of children with epilepsy.. 136 children with epilepsy were selected from January 2017 to December 2017. According to the random number table method, they were divided into the experimental group and the conventional group, with 68 cases in each group. The conventional group was treated with valproate, while the experimental group was treated with levetiracetam. The effective rate, the cognitive function and the frequency of clonic seizures in the two groups were compared.. There was no significant difference in the total effective rate between the two groups (P>0.05). There was no significant difference in attention, executive ability, abstract and orientation scores between the two groups before treatment (P>0.05). After treatment, the focus of attention (106.54±6.56), executive ability (105.76±6.77), abstract and directional score (106.65±6.57) were significantly higher than that of the conventional group. The difference in the two groups was statistically significant (P<0.05). After 3 months of treatment, the frequency of myoclonic seizures (9.22±0.95) and the frequency of tonic-clonic seizures (11.68±1.36) were found to be significantly lower than those of the conventional group, and the difference between the two groups was statistically significant (P<0.05).. Levetiracetam is effective in the treatment of children with epilepsy. It can effectively improve the cognitive function of the patients, reduce the frequency of myoclonic seizures and tonic-clonic seizures, and has a high promotion value.

Topics: Age Factors; Anticonvulsants; Child; Child, Preschool; Cognition; Epilepsy; Female; Humans; Infant; Levetiracetam; Magnetic Resonance Imaging; Male; Seizures; Tomography, X-Ray Computed; Treatment Outcome

Cannabidiol and cannabidiol-enriched products have recently attracted much attention as an add-on therapy for epilepsy, especially drug-resistant seizures. It should be, however, remembered that concomitant use of cannabidiol and antiepileptic drugs may pose a risk of interactions between them. For this reason, the aim of our study was to assess the effect of cannabidiol on the activity of selected new antiepileptic drugs in the electrically-induced seizure models in mice. We studied the effect of cannabidiol on the anticonvulsant action of topiramate, oxcarbazepine, lamotrigine, and pregabalin in the maximal electroshock-induced seizure test as well as on the activity of levetiracetam, tiagabine, lacosamide, and gabapentin in the 6 Hz seizure test in mice. We showed that cannabidiol increased the activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin. It did not affect the anticonvulsant effect of lamotrigine and lacosamide. Interestingly, cannabidiol attenuated the anticonvulsant activity of levetiracetam. Co-administration of antiepileptic drugs with cannabidiol did not cause adverse effects such as impairment of motor coordination, changes in neuromuscular strength or potentiation of the cannabidiol-induced hypolocomotion. Serum and brain levels of antiepileptic drugs and cannabidiol were determined by using HPLC in order to ascertain any pharmacokinetic contribution to the observed behavioral effects. Only interaction with levetiracetam was purely pharmacodynamic in nature because no changes in serum and brain concentration of either levetiracetam or cannabidiol were observed. Increased anticonvulsant activity of topiramate, oxcarbazepine, pregabalin, tiagabine, and gabapentin could be, at least in part, related to pharmacokinetic interactions with cannabidiol because there were changes in serum and/or brain concentrations of antiepileptic drugs and/or cannabidiol. Pharmacokinetic interactions cannot be also excluded between lacosamide and cannabidiol because cannabidiol increased brain concentration of lacosamide and lacosamide increased brain concentration of cannabidiol. Further pharmacokinetic studies are required to evaluate the type of interactions between cannabidiol and novel antiepileptic drugs.

Topics: Animals; Anticonvulsants; Brain; Cannabidiol; Chromatography, High Pressure Liquid; Disease Models, Animal; Drug Interactions; Drug Resistant Epilepsy; Electric Stimulation; Gabapentin; Lacosamide; Lamotrigine; Levetiracetam; Male; Mice; Oxcarbazepine; Pregabalin; Seizures; Tiagabine; Topiramate

WAG/Rij rats represent a validated genetic animal model of epileptogenesis, absence epilepsy and depressive-like comorbidity. Some treatments (e.g. ethosuximide), using specific protocols, prevent the development of spontaneous absence seizures. Accordingly, ethosuximide increases remission occurrence in children with childhood absence epilepsy in comparison to valproic acid. Considering that in this animal model, antiepileptogenic effects are, in some cases, not retained over time, we studied whether the antiepileptogenic effects of both ethosuximide and levetiracetam (which also possesses antiepileptogenic effects in this and other animal epilepsy models) would be retained 5 months after drug suspension.. WAG/Rij rats of ˜1 month of age were treated long-term with one of the two drugs at a dose of ˜80 mg/kg/day for 17 consecutive weeks; 1 and 5 months after drug suspension, the development of absence seizures as well as depressive-like behaviour were assessed by EEG recordings and the forced swimming test (FST).. In agreement with a previous report, both drugs continued to show antiepileptogenic effects 1 month after their discontinuation. Furthermore, ethosuximide improved depressive-like behaviour, whereas in contrast, levetiracetam worsened this symptom. However, none of the drugs maintained their antiepileptogenic effects 5 months after suspension, and in addition, animal behaviour in the FST returned to control conditions.. Overall, these results demonstrate that the antiepileptogenic effects of both ethosuximide and levetiracetam on absence seizure development and associated depressive-like behaviour in this model are only temporary.

Topics: Animals; Anticonvulsants; Behavior, Animal; Depression; Disease Models, Animal; Duration of Therapy; Epilepsy, Absence; Ethosuximide; Levetiracetam; Male; Motor Activity; Rats; Rats, Inbred Strains; Seizures; Time Factors

The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures.. We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV.. Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy was 1.6 days (0-49).. Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results.

Topics: Adult; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; New Mexico; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

Topics: Aged; Anticonvulsants; Humans; Hyponatremia; Levetiracetam; Male; Seizures

In patients requiring hemodialysis, the extracorporeal circuit is expected to remove the majority of serum levetiracetam. The preferred levetiracetam dosing regimen in critically ill patients exhibiting complex pharmacokinetic profiles undergoing hemodialysis is unknown. The objective of this case is to describe levetiracetam pharmacokinetics in a critically ill anephric patient receiving intermittent hemodialysis.. This is a case report of a single patient.. A 43-year-old anephric female was admitted to the intensive care unit for concerns of new onset seizure activity. She was loaded with 2000 mg levetiracetam followed by a 750 mg daily maintenance dose. The levetiracetam volume of distribution was 0.48 L/kg, and the interdialytic elimination half-life was 31 h. Hemodialysis removed nearly 85% of serum levetiracetam, and the patient exhibited slightly higher than expected non-renal elimination. Pharmacokinetic simulations identified 500 mg daily with 750 mg post-dialysis supplements as the regimen most likely to reduce variability in serum levetiracetam concentrations and achieve levels in the therapeutic range.. Substantial elimination of levetiracetam by hemodialysis occurred in this case, and non-renal clearance was slightly higher than in previous reports. Insufficient intradialytic or post-dialysis levetiracetam concentrations may place patients at risk of breakthrough seizures. This case indicates that dialysis patients on levetiracetam may require higher post-dialysis supplemental doses than currently recommended and tailored therapy supported by therapeutic drug monitoring.

Topics: Adult; Anticonvulsants; Critical Illness; Female; Humans; Levetiracetam; Renal Dialysis; Renal Insufficiency; Seizures

Pharmacological prophylaxis for early seizures following traumatic brain injury (TBI) is a recommendation in the Brain Trauma Foundation Guidelines. However, several studies have challenged the efficacy and safety of this practice, resulting in varied practice across centers around the world. The purpose of the present study was to compare the incidence of early clinical seizures following TBI, between two large centers, a US Center that practises routine seizure prophylaxis and a Chinese Center that does not use seizure prophylaxis following TBI.. This was a prospective observational study including an urban level I trauma center in the USA and a large hospital in Shenzhen, China. At the US Center, all patients received seizure prophylaxis with levetiracetam. At the Chinese Center, no seizure prophylaxis was given. All patients with blunt TBI and positive computed tomography findings for epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intracerebral hemorrhage or diffuse axonal injury were included. Patients who died within 24 h of admission were excluded. The study population was monitored daily for clinical seizures for the first 7 post-injury days. Data collected included demographics, mechanism of injury, vital signs upon arrival, injury severity and emergency interventions. Primary outcome was the incidence of early seizures, defined as those occurring within 7 days of injury.. A total of 522 patients were included in the analysis: 272 patients at the US Center who received seizure prophylaxis and 250 patients at the Chinese Center who did not receive prophylaxis. Overall, 3.7% of patients who received seizure prophylaxis developed early seizures, compared to 2.8% of patients who did not receive any prophylaxis (p = 0.573). Decompressive craniectomy was associated with the highest incidence of early seizure (9.2%). In this subgroup, the seizure rate was 10.4% in the prophylaxis group and 7.1% in the no-prophylaxis group (p = 0.738). Patients with admission GCS < 9 had an overall early seizure incidence of 7.0%: 4.3% in the prophylaxis group and 14.3% in the no-prophylaxis group (p = 0.062). Analysis of the subgroup with isolated blunt TBI showed an incidence of early seizures of 3.4% in the prophylaxis group versus 2.4% in the no-prophylaxis group (p = 0.593). Further analyses of outcomes according to head AIS 3, 4 and 5 showed no significant difference in the seizure rate between the two groups: head AIS 3: 6.1% in the prophylaxis group versus 2.6% in the no-prophylaxis group, p = 0.329; head AIS 4: 0 versus 2.7%, p = 0.302; head AIS 5: 8.7 versus 4.0%, p = 0.601.. The present study failed to show any benefit of routine early seizure prophylaxis following blunt TBI. This practice should be reexamined in a large randomized clinical study.

Topics: Adult; Anticonvulsants; Brain Injuries, Traumatic; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures

Topics: Humans; Levetiracetam; Piracetam; Seizures

Topics: Humans; Levetiracetam; Piracetam; Seizures

Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic seizures occurring mainly during relaxation periods, a juvenile age of onset and generalized tonic-clonic seizures in one-third of patients. An 8-month-old female intact RR was presented for myoclonic seizures and staring episodes that both started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous mutant genotype. Unsedated wireless video-electroencephalography (EEG) identified frequent, bilaterally synchronous, generalized 4 Hz spike-and-wave complexes (SWC) during the staring episodes in addition to the characteristic myoclonic seizures with generalized 4-5 Hz SWC or 4-5 Hz slowing. Photic stimulation did not evoke a photoparoxysmal response. Repeat video-EEG 2 months after initiation of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic seizures, and absence seizures were no longer evident. Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which reinforces its parallels to JME in humans.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Electroencephalography; Epilepsies, Myoclonic; Female; GTP Phosphohydrolases; Levetiracetam; Mutation; Photic Stimulation; Piracetam; Seizures; Tumor Suppressor Proteins

Animal models are valuable tools for screening novel therapies for patients who suffer from epilepsy. However, a wide array of models are necessary to cover the diversity of human epilepsies. In humans, neonatal hypoxia (or hypoxia-ischemia) is one of the most common causes of epilepsy early in life. Hypoxia-induced seizures (HS) during the neonatal period can also lead to spontaneous seizures in adulthood. This phenomenon, i.e., early-life hypoxia leading to adult epilepsy - is also seen in experimental models, including rats. However, it is not known which anti-seizure medications are most effective at managing adult epilepsy resulting from neonatal HS. Here, we examined the efficacy of three anti-seizure medications against spontaneous seizures in adult rats with a history of neonatal HS: (1) phenobarbital (PHB), the oldest epilepsy medicine still in use today; (2) levetiracetam (LEV); and (3) tiagabine (TGB). Both LEV and TGB are relatively new anticonvulsant drugs that are ineffective in traditional seizure models, but strikingly effective in other models. We found that PHB and LEV decreased seizures in adult rats with a history of HS, whereas TGB exacerbated seizures. These divergent drug effects indicate that the HS model may be useful for differentiating the clinical efficacy of putative epilepsy therapies.

Topics: Animals; Animals, Newborn; Anticonvulsants; Brain; Disease Models, Animal; Hypoxia; Levetiracetam; Male; Phenobarbital; Prohibitins; Rats, Long-Evans; Seizures; Tiagabine

This study developed a population pharmacokinetic (PK) model of levetiracetam (LEV) for treating neonatal seizures (NS) and determined the influence of clinically relevant covariates to explain the interindividual variability and residual error.. Twenty newborns admitted to the Neonatal Intensive Care Unit at the Hospital Central "Dr. Ignacio Morones Prieto" were included. LEV doses were administered by intermittent infusion. Blood samples were drawn 3 times post-infusion. Levetiracetam was quantified by a chromatographic technique. NONMEM software was used to determine the population PK model of LEV in neonates and the influence of clinical covariates on drug disposition.. The LEV PK in neonates is described by a one-compartment open model with first-order elimination. The influence of creatinine clearance (CRCL) and body weight (BW) on clearance (CL[L/h] = 0.47*CRCL), as well as the volume of the distribution (Vd[L] = 0.65*BW) of LEV, were confirmed, considering interindividual variabilities of 36% and 22%, respectively, and a residual error of 13%.. Based on the PK of LEV in neonates and the influence of the final PK model, a priori dosing guidelines are proposed considering CRCL, BW and LEV plasma concentrations between 6 and 20 mg/L for NS treatment.

Topics: Anticonvulsants; Creatinine; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Levetiracetam; Male; Models, Biological; Piracetam; Prospective Studies; Seizures; Tissue Distribution

Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors. Our data indicate that both tested drugs had no effect on locomotion, anxiety levels, fear learning, depression-like behavior, and memory retention in rats. However, when considering social interactions, we first confirmed the epilepsy-induced strong increase in aggressive behaviors and specific hippocampal neuronal loss. We furthermore observed, in Sham rats, that LEV-treated animals were 2 times faster to attack at first encounter, had 5 times more aggressive behaviors, and had significantly less social behaviors than control rats. In all circumstances, BRV rats behaved like Saline rats, suggesting that BRV treatment in rats leads to significantly less aggressive behaviors than LEV treatment at the doses used, while there are limited differential effects between these two drugs on other types of behaviors. Since increased aggressiveness has been reported in patients well controlled on LEV, this study indicates based on our findings, that BRV could represent an effective alternative to LEV to limit aggressiveness problems due to this antiepileptic drug (AED) therapy.

Topics: Animals; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Hippocampus; Humans; Kainic Acid; Levetiracetam; Male; Pyrrolidinones; Rats; Seizures; Synaptic Transmission

Seizures constitute a determining aspect in quality of life and are frequently challenging in palliative care-a field where treatment has yet to be standardised. Levetiracetam-a new generation anticonvulsant-has proved efficacy both through oral, as well as intravenous administration in the general population. This case reports on the use of continuous subcutaneous levetiracetam to effectively control seizures in a terminally ill patient without patent oral route.

Topics: Aged, 80 and over; Anticonvulsants; Dementia, Vascular; Disease Progression; Female; Humans; Infusions, Subcutaneous; Levetiracetam; Piracetam; Quality of Life; Seizures; Terminal Care; Treatment Outcome

We previously demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate subtype 2 (mGlu. The anticonvulsant efficacy of JNJ-46356479 was evaluated in the 6-Hz model of psychomotor seizures in mice. JNJ-46356479 was administered in combination with LEV using 3 fixed dose-ratio treatment groups in the mouse 6-Hz (44-mA) seizure test. The combination of JNJ-46356479 with LEV was also evaluated in the mouse corneal kindling model. The potential interactions of JNJ-46356479 with the antiseizure drugs VPA and LTG were also evaluated using fixed dose-ratio combinations. Plasma levels were obtained for analysis of potential pharmacokinetic interactions for each combination studied in the mouse 6-Hz model.. JNJ-46356479 was active in the 6-Hz model at both 32-mA and 44-mA stimulus intensities (median effective dose = 2.8 and 10.2 mg/kg, respectively). Using 1:1, 1:3, and 3:1 fixed dose-ratio combinations (LEV:JNJ-46356479), coadministration was significantly more potent than predicted for additive effects, and plasma levels suggest this synergism was not due to pharmacokinetic interactions. Studies in kindled mice further demonstrate the positive pharmacodynamic interaction of LEV with JNJ-46356479. Using 1:1 dose-ratio combinations of JNJ-46356479 with either VPA or LTG, there were no significant differences observed for coadministration.. These studies demonstrate a synergistic interaction of JNJ-46356479 with LEV, whereas no such effect occurred for JNJ-46356479 with either VPA or LTG. The synergy seems therefore to be specific to LEV, and the combination LEV/mGlu

Topics: Allosteric Regulation; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Drug Synergism; Excitatory Amino Acid Agonists; Levetiracetam; Male; Mice; Piracetam; Receptors, Metabotropic Glutamate; Seizures

This study was conducted to develop a population pharmacokinetic (PK) model of levetiracetam in Korean neonates with seizures.. Data were obtained from a retrospective study of 18 neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of Severance Children's Hospital for the period of from 2013 to 2015. Sampling and dosing times were recorded by clinical research coordinators on case report forms. Demographic factors and laboratory results were tested as potential covariates for PK parameters. Model development was performed within a mixed-effect modeling framework using NONMEM.. With a one-compartment model with first-order elimination chosen as a basic PK model based on theory-based allometric relationships, postmenstrual age and serum creatinine were found to have significant influences on clearance (CL). Typical parameter estimates of the final PK model obtained, evaluated at covariate medians, were 1.08 L/kg for volume of distribution (V) and 0.073 L/h/kg (= 1.23 mL/min/kg) for CL, illustrating that V in Korean neonates is a little larger than in Western population while CL is similar.. A population PK model of levetiracetam for Korean neonates with seizures was developed in this study. The result of this study can be used as a basis to develop an optimal dosage regimen in Korean neonates with seizures.
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Topics: Age Factors; Anticonvulsants; Drug Dosage Calculations; Drug Monitoring; Female; Hospitals, Pediatric; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Levetiracetam; Male; Metabolic Clearance Rate; Models, Biological; Piracetam; Republic of Korea; Retrospective Studies; Seizures

Perampanel (PER) is a third generation antiepileptic drug (AED), recently approved as add-on therapy in both focal and generalized seizures. Levetiracetam (LEV) is a second generation AED, widely used in patients with epilepsy because of its favorable safety and efficacy profiles. Perampanel and LEV treatments have been associated with the occurrence of similar adverse events (AEs) (sleepiness, irritability, depression, anxiety, aggressiveness). The aim of the present retrospective single center study was to verify the efficacy and tolerability of PER and LEV used as first add-on therapy in patients with epilepsy affected by secondarily generalized seizures. We collected data from 15 patients treated with PER and 26 patients treated with LEV and followed at our site with follow-up visits at 3, 6, and 12months. This retrospective study documented the comparable efficacy of PER and LEV as first add-on treatments in patients affected by uncontrolled secondarily generalized seizures. However, more patients withdrawn LEV because of AEs compared with PER at the 3- and 12-month follow-up visits. The better tolerability of PER observed in this study could be related to the low therapeutic dose of PER prescribed when it is used as first adjunctive treatment for better controlling secondarily generalized seizures.

Topics: Adult; Aggression; Anticonvulsants; Anxiety; Depression; Dizziness; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Irritable Mood; Levetiracetam; Male; Middle Aged; Nitriles; Pyridones; Retrospective Studies; Seizures; Treatment Outcome; Wakefulness

Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety.. The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV.. A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05).. The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28).. The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.

Topics: Adult; Anticonvulsants; Dibenzazepines; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Psychiatric Status Rating Scales; Retrospective Studies; Seizures; Substance Withdrawal Syndrome; Treatment Outcome; Voltage-Gated Sodium Channel Blockers

Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a p<0.0001 after multiple comparison adjustment). This is the largest survey to date assessing WHS seizures. This study design is susceptible to possible bias, as the data are largely drawn from caregiver report and investigators had limited access to medical records. Despite this, our data suggest that the genetic etiology of seizures, together with an accurate electroclinical delineation, are important components of drug selection, even in contiguous gene syndromes which may have complex seizure etiologies.

Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Clobazam; Female; Humans; Infant; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Phenobarbital; Phenytoin; Quality of Life; Seizures; Topiramate; Wolf-Hirschhorn Syndrome; Young Adult

We previously demonstrated that insulin-induced severe hypoglycemia-associated sudden death is largely mediated by fatal cardiac arrhythmias. In the current study, a pharmacological approach was taken to explore the potential contribution of hypoglycemic seizures and the sympathoadrenergic system in mediating severe hypoglycemia-associated sudden death. Adult Sprague-Dawley rats were randomized into one of four treatment groups: 1) saline (SAL), 2) anti-arrhythmic (β

Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Anti-Arrhythmia Agents; Anticonvulsants; Arrhythmias, Cardiac; Atenolol; Death, Sudden, Cardiac; Drug Therapy, Combination; Electrocardiography; Hypoglycemia; Levetiracetam; Male; Rats; Rats, Sprague-Dawley; Seizures

To present a retrospective study of 13 children with benign epilepsy with centrotemporal spikes (BECTS), also known as benign rolandic epilepsy (BRE), associated with generalized spikes and waves as the only EEG manifestation at onset.. Charts of children with typical clinical criteria of BRE electroclinically followed-up between February 2000 and February 2015 were reviewed.. Among 309 patients who met the electroclinical criteria of BRE, we identified 13 children who presented with the typical clinical manifestations but who, on the EEG, only had generalized paroxysms at onset that continued along the course of the syndrome. Generalized spike-and-wave discharges were observed in all patients when awake and during sleep (100%). During the evolution no particular electroclinical pattern was observed. The patients responded well to antiepileptic drugs, such as valproic acid and levetiracetam. Outcome was good in all patients.. We found evidence that patients with BRE may have generalized EEG discharges at onset as the sole manifestation lasting throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of BRE. Response to valproic acid and levetiracetam was found to be particularly good.

Topics: Anticonvulsants; Brain; Child; Child, Preschool; Electroencephalography; Epilepsy, Rolandic; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Valproic Acid

Seizures may occur after stroke. Though the majority of clinicians are aware of this, a consensus-based treatment and management strategy for post-stroke seizures is not available because there have only been a few large-scale studies that have explored this. This study has surveyed the actual state of medical treatment for post-stroke seizure and epilepsy in Japan. We conducted a nationwide questionnaire survey of the top 500 institutions regarding the number of cerebral infarction cases between February 2015 and May 2015. The questionnaire contained 14 items regarding the number of patients, type of tests and treatments conducted, and patient response to the treatments. Surveys from 189 institutions were obtained. A history of previous stroke was reported in 41% of hospitalized patients with epilepsy. The sensitivity of diffusion-weighted MRI and electroencephalography was not sufficient to detect the abnormalities seen in epilepsy. Carbamazepine was the most chosen antiepileptic drug for secondary prophylaxis, followed by valproate acid, and levetiracetam.

Topics: Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Japan; Levetiracetam; Male; Piracetam; Seizures; Stroke; Surveys and Questionnaires; Valproic Acid

Withdrawal of antiepileptic drugs (AEDs) is a standard procedure during presurgical epilepsy assessment. Rapid and, at times, even pre-hospital withdrawal of medication is performed in some centres to enhance the yield of recorded seizures during video-EEG monitoring. AED withdrawal, however, affects the propensity and speed of propagation of epileptic activity, may evoke more severe seizures, and may cause pitfalls in EEG interpretation. We report a case which had been recommended to undergo intracranial EEG recordings in order to clarify apparently discordant MRI findings and ictal EEG patterns when monitoring was performed following complete AED withdrawal. Re-evaluation to assess scalp EEG patterns at several drug levels during slow AED tapering showed a loss of localizing information with AED withdrawal due to contralateral and bitemporal spread of frontal epileptic activity. Our report demonstrates that in individual cases, rapid AED withdrawal during presurgical video-EEG monitoring can impair the validity of EEG recordings and lead to unnecessary risks and investigations during workup.

Topics: Acetamides; Anticonvulsants; Brain; Electroencephalography; Epilepsy; Humans; Lacosamide; Levetiracetam; Male; Piracetam; Preoperative Period; Seizures; Young Adult

Neonatal seizures remain a significant clinical problem, and therapeutic options are still not diverse with limited efficacy. Levetiracetam (LEV) is a relatively new and wide spectrum anti-seizure medication with favorable pharmacokinetics and safety profile. In the recent decades, LEV has been increasingly used for the treatment of neonatal seizures. The aim of this study was to describe the experience of using LEV as the first line anti-seizure medication for preterm infants.. A retrospective analysis of 37 preterm infants who were treated with LEV as the first-line anti-seizure medication was performed.. Levetiracetam can be a good and safe choice for treatment of neonatal seizures in preterm infants. Prospective double blind controlled studies are needed in the future.

Topics: Anticonvulsants; Birth Weight; Brain; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Levetiracetam; Magnetic Resonance Imaging; Male; Phenobarbital; Retrospective Studies; Seizures

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological condition characterised by drug-resistance seizures, hemiparesis, mental retardation, facial asymmetry, and intellectual disabilities. On brain imaging, the disease is characterised by cerebral hemiatrophy with ipsilateral calvarial thickening and hyperpneumotisation of paranasal sinuses or mastoid air cells. Although more common in men and on the left side of the brain, the disease can affect both genders and cerebral hemispheres. It mainly presents in childhood. The adult presentation is unusual but has been reported in medical literature. Most of the patients need more than one antiepileptic agent for optimal control of seizures. Hemispherectomy is reserved for patients who have drug-resistant and disabling seizures. The good prognostic factors are disease onset before age of two and better seizure control. We report two cases of DDMS occurring in teenage boys who presented with status epilepticus. The clinical histories, radiological findings, and treatment of both patients are discussed below.

Topics: Adolescent; Atrophy; Brain; Carbamazepine; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Paresis; Seizures; Status Epilepticus

The study aims to retrospectively compare the efficacy of lacosamide (LCS) and levetiracetam (LEV) in add-on treatment in patients with partial-onset epilepsy.. Patients who have been followed-up for at least one year due to diagnosis of partial epilepsy between September 2014 and December 2017 and who had no seizure control, despite using at least two antiepileptic monotherapies, and therefore undergone LEV or LCS add-on treatment were retrospectively reviewed. Of the patients, total number of seizures and seizure control rates 6 months before and 3 and 6 months after the add-on treatment were compared.. There was no statistically significant difference between the 30 patients in the LEV group (12 females, 18 males, mean age 29.7±6.6) and 28 patients in the LCS group (12 females, 16 males, mean age 28.2±6.4) in terms of age, gender and the duration of illness. When the LEV and LCS groups were evaluated separately, the mean number of seizures within 3 and 6 months after the add- on treatment were significantly lower than the mean number of seizures in the last 6 months before the add-on treatment (p<0.005 and p<0.005 respectively). There was no statistically significant difference between the two groups when compared with each other in terms of the rate of decrease in number of seizures and seizure control before and after the add-on treatment (p=0.445 and p=0.238, respectively).. LCS appears to be as effective as the currently well-established LEV in the treatment of partial onset seizures. No comparative study was found in the literature similar to this subject matter. There is a need for prospective studies for the comparison of the efficacies of these two drugs.. A vizsgálat célja a lacosamid (LCS) és a levetiracetam (LEV) kiegészítő kezelés hatékonyságának retrospektív összehasonlítása parciális kezdetű epilepsziában szenvedő betegek esetén.. Olyan betegek szerepeltek a vizsgálatban, akik parciális kezdetű epilepszia diagnózisát 2014 szeptembere és 2017 decembere között állapították meg, és utánkövetésük legalább egy évig zajlott, továbbá akiknél nem lehetett rohamkontrollt elérni legalább két epilepsziaellenes monoterápia alkalmazásával, ezért vagy LEV, vagy LCS kiegészítő kezelésben részesültek. Összehasonlítottuk a betegek hat hónappal a kiegészítő kezelés előtt mért összes rohamszámát és rohamkontrollarányaikat a kiegészítő kezelés után három, illetve hat hónappal mért értékekkel.. A LEV-csoportba 30 beteg (12 nő, 18 férfi, átlagéletkor 29,7±6,6 év), az LCS-csoportba 28 beteg került (12 nő, 16 férfi, átlagéletkor 28,2±6,4 év); a két csoport között nem volt statisztikailag szignifikáns különbség az életkor, a nem és a betegség fennállásának időtartama szempontjából. A LEV- és az LCS-csoport önálló értékelése esetén a kiegészítő kezelés után három és hat hónappal mért átlagos rohamszám szignifikánsan alacsonyabb volt, mint a kiegészítő kezelés előtt hat hónappal (p<0,005 és p<0,005). A két csoport eredményeit egymással összehasonlítva nem volt szignifikáns különbség a rohamszám csökkenésében és a rohamkontroll kiegészítő kezelés előtti, illetve utáni értékében (p=0,445 és p=0,238).. Az LCS ugyanolyan hatékonynak bizonyult a parciális kezdetű epilepszia kiegészítő kezelésében, mint a jelenleg leginkább használatos LEV. A szakirodalomban nem találtunk hasonló összehasonlító vizsgálatot. A jövőben prospektív vizsgálatokban kell összehasonlítani a két szer hatékonyságát.

Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Lacosamide; Levetiracetam; Male; Retrospective Studies; Seizures; Treatment Outcome

Prophylactic levetiracetam is currently used in ~40% of patients with intracerebral hemorrhage, and the potential impact of levetircetam on health-related quality of life is unknown. We tested the hypothesis that prophylactic levetiracetam is independently associated with differences in cognitive function health-related quality of life.. Patients with intracerebral hemorrhage were enrolled in a prospective cohort study. We performed mixed models for T-scores of health-related quality of life, referenced to the U.S. population at 50 ± 10, accounting for severity of injury and time to follow-up.. Academic medical center.. One-hundred forty-two survivors of intracerebral hemorrhage.. None.. T-scores of Neuro-Quality of Life Cognitive Function v2.0 was the primary outcome, whereas Neuro-Quality of Life Mobility v1.0 and modified Rankin Scale (a global functional scale) were secondary measures. We prospectively documented if prophylactic levetiracetam was administered and retrieved administration data from the electronic health record. Patients who received prophylactic levetiracetam had worse cognitive function health-related quality of life (T-score 5.1 points lower; p = 0.01) after adjustment for age (p = 0.3), National Institutes of Health Stroke Scale (p < 0.000001), lobar hematoma (p = 0.9), and time of assessment; statistical models controlling for prophylactic levetiracetam and the Intracerebral Hemorrhage Score, a global measure of intracerebral hemorrhage severity, yielded similar results. Lower T-scores of cognitive function health-related quality of life at 3 months were correlated with more total levetiracetam dosage (p = 0.01) and more administered doses of levetiracetam in the hospital (p = 0.03). Patients who received prophylactic levetiracetam were more likely to have a lobar hematoma (27/38 vs 19/104; p < 0.001), undergo electroencephalography monitoring (15/38 vs 21/104; p = 0.02), but not more likely to have clinical seizures (4/38 vs 7/104; p = 0.5). Levetiracetam was not independently associated with the modified Rankin Scale scores or mobility health-related quality of life (p > 0.1).. Prophylactic levetiracetam was independently associated with lower cognitive function health-related quality of life at follow-up after intracerebral hemorrhage.

Topics: Anticonvulsants; Cerebral Hemorrhage; Cognition; Cognitive Dysfunction; Female; Humans; Levetiracetam; Male; Middle Aged; Prospective Studies; Quality of Life; Seizures

We present a case involving an 85-year-old man with acute confusion and new onset seizure following a 1-week history of respiratory prodrome. This case report describes a case of influenza B-related meningoencephalitis supported by evidence of an influenza B infection and temporal relation of the neurological event and respiratory illness in the absence of other identifiable cause. Diagnosis is guided by cerebrospinal fluid profile and nasopharyngeal PCR. Treatment is largely supportive and the effect of vaccination on prevention of this neurological complication remains unclear.

Topics: Aged, 80 and over; Antiviral Agents; Betainfluenzavirus; Confusion; Humans; Influenza, Human; Levetiracetam; Male; Meningoencephalitis; Nasopharynx; Piracetam; Seizures; Treatment Outcome; Valproic Acid

Modeling and simulations were used to support body weight-based dose selection for eslicarbazepine acetate (ESL) in pediatric subjects aged 4-17 years with partial-onset seizures. A one-compartment pediatric population pharmacokinetic model with formulation-specific first-order absorption, first-order elimination, and weight-based allometric scaling of clearance and distribution volume was developed with PK data from subjects 2-18 years of age treated with ESL 5-30 mg/kg/day. Covariate analysis was performed to quantify the effects of key demographic and clinical covariates (including body weight and concomitant use of carbamazepine, levetiracetam, and phenobarbital-like antiepileptic drugs [AEDs]) on variability in PK parameters. Model evaluation performed using a simulation-based visual predictive check and a non-parametric bootstrap procedure indicated no substantial bias in the overall model and in the accuracy of estimates. The model estimated that concomitant use of carbamazepine or phenobarbital-like AEDs with ESL would decrease the exposure of eslicarbazepine, and that concomitant use of levetiracetam with ESL would increase the exposure of eslicarbazepine, although the small effect of levetiracetam may not represent a true difference. Model-based simulations were subsequently performed to apply target exposure matching of selected ESL doses for pediatric subjects (aged 4-17 years) to attain eslicarbazepine exposures associated with effective and well-tolerated ESL doses in adults. Overall, model-based exposure matching allowed for extrapolation of efficacy to support pediatric dose selection as part of the submission to obtain FDA approval for ESL (adjunctive therapy and monotherapy) in subjects aged 4-17 years, without requiring an additional clinical study.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dibenzazepines; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Male; Phenobarbital; Seizures

Levetiracetam is one of the most widely used antiepileptic drugs, but the evidence related to the safety of substitution from brand name to generic levetiracetam is scarce. The present study evaluated the risk of increased frequency of seizures after replacement of a brand-name levetiracetam with a generic product.. We enrolled patients with epilepsy who were treated with branded levetiracetam for at least 6 months of sustained use. Patients were advised to switch to the generic levetiracetam. We analyzed data from 6 months before, to 6 months after, generic substitution. Increased seizure frequency was defined as a≥ 50% increase in seizure frequency after conversion date compared with seizure frequency before the conversion date. We analyzed changes in seizure frequency and performed subgroup analysis according to changes in seizure frequency.. We analyzed 148 epilepsy patients. Among the 148 patients, 109 (73.6%) were seizure-free before substitution and 105 patients remained seizure-free after switching. After generic substitution, an increased seizure frequency was noted in seven patients (4.7%), and a decreased seizure frequency was noted in 10 (6.8%). Patients with decreased seizure frequency were significantly younger (p = 0.035) than those with an unchanged seizure frequency.. This study suggests that the risk of increased seizure frequency after generic substitution was minimal. The generic substitution of levetiracetam was generally safe, although larger prospective studies are warranted to corroborate our findings.

Topics: Adult; Anticonvulsants; Drug Substitution; Drugs, Generic; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

Unverricht-Lundborg disease (ULD) is a form of progressive myoclonus epilepsy characterized by stimulation-induced myoclonus and seizures. This disease is an autosomal recessive disorder, and the gene CSTB, which encodes cystatin B, a cysteine protease inhibitor, is the only gene known to be associated with ULD. Although the prevalence of ULD is higher in the Baltic region of Europe and the Mediterranean, sporadic cases have occasionally been diagnosed worldwide. The patient described in the current report showed only abnormally enlarged restriction fragments of 62 dodecamer repeats, confirming ULD, that were transmitted from both her father and mother who carried the abnormally enlarged restriction fragment as heterozygotes with normal-sized fragments. We report the first case of a genetically confirmed patient with ULD in Korea.

Topics: Adult; Anticonvulsants; Blotting, Southern; Cystatin B; Female; Genetic Predisposition to Disease; Humans; Isoxazoles; Levetiracetam; Piracetam; Republic of Korea; Seizures; Treatment Outcome; Unverricht-Lundborg Syndrome; Valproic Acid; Zonisamide

Zolpidem is an imidazopyridine nonbenzodiazepine hypnotic drug with a high affinity to the α1 subunit of the gamma amino butyric acid A receptor It is the first pharmacological option in the short-term management of sleep-onset insomnia. Initially considered a safer drug compared to benzodiazepines because of lower liability for abuse and dependence, recently, an increasing body of reports has questioned zolpidem's proneness to misuse. In this report, we describe a case of serious zolpidem abuse requiring pharmacological washout during hospitalization because of previous withdrawal seizures in a patient with chronic sleep-onset and maintenance insomnia.

Topics: Aged; Anticonvulsants; Chronic Disease; Clonazepam; Female; Hospitalization; Humans; Levetiracetam; Pregabalin; Seizures; Selective Serotonin Reuptake Inhibitors; Sertraline; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders; Substance-Related Disorders; Zolpidem

To predict the probability of a seizure-free (SF) state in patients with epilepsy (PWEs) after treatment with levetiracetam and to identify the clinical and electroencephalographic (EEG) factors that affect outcomes.. Retrospective analysis of PWEs treated with levetiracetam for 3 years identified 22 patients who were SF and 24 who were not. Before starting levetiracetam, 11 clinical factors and four EEG features (sample entropy of α, β, θ, δ) were identified. Overall, 80% of each the two groups were chosen to establish a support vector machine (SVM) model with 5-fold cross-validation, hold-out validation and jack-knife validation. The other 20% were used to predict the efficacy of levetiracetam. The mean impact value (MIV) algorithm was used to rank the relativity between factors and outcomes.. Compared with SF patients, not SF patients displayed a specific decrease in EEG sample entropy in α band from the F4 channel, β band from Fp2 and F8 channels, θ band from C3 channel (P < 0.05). The SVM model based on the clinical and EEG features yielded 72.2% accuracy of 5-fold cross-validation, 75.0% accuracy of jack-knife validation, 67.7% accuracy of hold-out validation in the training set and had a high prediction accuracy of 90% in test set (sensitivity was 100%, area under the receiver operating characteristic curve was 0.96). The feature of β band from Fp2 weighs heavily in the prediction model according to the mean impact value algorithm.. The efficacy of levetiracetam on newly diagnosed PWEs could be predicted using an SVM model, which could guide antiepileptic drug selection.

Topics: Adolescent; Adult; Algorithms; Anticonvulsants; Child; Electroencephalography; Epilepsy; Humans; Levetiracetam; Precision Medicine; Retrospective Studies; Seizures; Sensitivity and Specificity; Support Vector Machine; Young Adult

Thermoregulatory derangements secondary to valproic acid (VPA) administration, specifically hypothermia, have been reported throughout the literature, but a handful of times. This case report describes a 28-year-old male presenting status-post multiple tonic-clonic seizures, treated for persistent seizure activity refractory to benzodiazepines with valproic acid (VPA), levetiracetam, and fosphenytoin. After just over an hour, the patient's core temperature fell from 36.8 °C to 34.9 °C. Temperatures were repeated for confirmation, no further doses of VPA were administered, and the patient's temperature returned to normal over the next 7 h with the use of warming blankets. Levetiracetam and fosphenytoin were continued with no further reported development of hypothermia during the patient's admission. After reviewing other potential causes, a thorough drug database review was performed that found VPA to be the only medication administered with published reports of inducing hypothermia. The mechanism of thermoregulatory derangement associated with VPA is not clearly defined and much of the evidence surrounds alterations in gamma-aminobutyric acid (GABA) activity in animal studies. To our knowledge, this case report is the first reported case of VPA-induced hypothermia following a single dose in the emergency department and offers the potential that prompt return to normothermia is likely following discontinuation of the offending agent.

Topics: Adult; Anticonvulsants; Humans; Hypothermia; Levetiracetam; Male; Phenytoin; Seizures; Valproic Acid

The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Clinical trials have shown that mTOR inhibitors such as everolimus reduce seizures in tuberous sclerosis complex patients with intractable epilepsy. Furthermore, accumulating preclinical data suggest that mTOR inhibitors may have anti-seizure or anti-epileptogenic actions in other types of epilepsy. However, the chronic use of rapalogs such as everolimus is limited by poor tolerability, particularly by immunosuppression, poor brain penetration and induction of feedback loops which might contribute to their limited therapeutic efficacy. Here we describe two novel, brain-permeable and well tolerated small molecule 1,3,5-triazine derivatives, the catalytic mTORC1/C2 inhibitor PQR620 and the dual pan-PI3K/mTOR inhibitor PQR530. These derivatives were compared with the mTORC1 inhibitors rapamycin and everolimus as well as the anti-seizure drugs phenobarbital and levetiracetam. The anti-seizure potential of these compounds was determined by evaluating the electroconvulsive seizure threshold in normal and epileptic mice. Rapamycin and everolimus only poorly penetrated into the brain (brain:plasma ratio 0.0057 for rapamycin and 0.016 for everolimus). In contrast, the novel compounds rapidly entered the brain, reaching brain:plasma ratios of ∼1.6. Furthermore, they significantly decreased phosphorylation of S6 ribosomal protein in the hippocampus of normal and epileptic mice, demonstrating effective mTOR inhibition. PQR620 and PQR530 significantly increased seizure threshold at tolerable doses. The effect of PQR620 was more marked in epileptic vs. nonepileptic mice, matching the efficacy of levetiracetam. Overall, the novel compounds described here have the potential to overcome the disadvantages of rapalogs for treatment of epilepsy and mTORopathies directly connected to mutations in the mTOR signaling cascade.

Topics: Animals; Anticonvulsants; Azabicyclo Compounds; Blood-Brain Barrier; Catalysis; Electroshock; Enzyme Inhibitors; Epilepsy; Everolimus; Female; Hippocampus; Levetiracetam; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Mice; Morpholines; Phenobarbital; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Pyridines; Ribosomal Proteins; Seizures; Sirolimus; Triazines

Busulfan is used as a conditioning regimen for hematopoietic stem cell transplantation and is known to cause seizures as a side effect. As various anticonvulsant drugs have been reported, we conducted a retrospective investigation regarding the preventive effects and adverse events associated with different anticonvulsants administered alongside intravenous busulfan (ivBu) in our institution.. We targeted 104 patients who received ivBu at our institution from May 1, 2010 to April 30, 2017. We investigated the seizure prevention rate and adverse events rate under anticonvulsant prophylaxis.. There were 70 cases (67.3%) of phenytoin administration and 34 cases (32.7%) of levetiracetam administration for anticonvulsant therapy. The seizure prevention rate was 98.6% for phenytoin and 100% for levetiracetam; seizures occurred in one out of 104 patients. There were no significant differences in the seizure prevention rate depending on the type of anticonvulsant. Further, there were no differences in adverse events.. Anticonvulsant prophylaxis is considered necessary for safe conditioning with ivBu. Adverse events associated with the use of levetiracetam are within an acceptable range. Further, levetiracetam is considered useful as a preventive drug against seizures during ivBu administration because it is easy to administer and has ideal pharmacokinetics for supportive care.

Topics: Administration, Intravenous; Anticonvulsants; Busulfan; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Levetiracetam; Male; Middle Aged; Phenytoin; Retrospective Studies; Seizures; Transplantation Conditioning; Treatment Outcome

Alzheimer's disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.

Topics: Alzheimer Disease; Amyloid; Animals; Inflammasomes; Interleukin-18; Interleukin-1beta; Levetiracetam; Mice; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Piracetam; Seizures; Synaptic Transmission

Status epilepticus (SE) is a neurological condition that frequently induces severe neuronal injury in the hippocampus, subsequent epileptogenesis and pharmacoresistant spontaneous recurrent seizures (SRS). The repeated administration of LEV (a broad-spectrum antiepileptic drug) during the post-SE period does not prevent the subsequent development of SRS. However, this treatment reduces SE-induced neurodegeneration in the hippocampus. Conversely, propylparaben (PPB) is a widely used antimicrobial that blocks voltage-dependent Na

Topics: Animals; Anticonvulsants; Behavior, Animal; Disease Models, Animal; Hippocampus; Levetiracetam; Lithium; Male; Neurons; Neuroprotective Agents; Parabens; Pilocarpine; Rats, Wistar; Seizures; Status Epilepticus; Time

Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort.. We retrospectively identified consecutive newborns with HIE who were monitored with continuous video-electroencephalogram (VEEG) for the duration of therapeutic hypothermia. After identification of seizures, infants were treated with PHB or LEV at the discretion of treating physicians. We assessed time to seizure freedom as a function of AED choice, with adjustment for HIE severity and initial seizure frequency using the Kaplan-Meier procedure and multivariate Cox proportional hazards regression.. We identified 78 infants with HIE. Among 44 (56%) patients who had VEEG-confirmed seizures, 34 became seizure-free during monitoring, and the remaining 10 died. Initial treatment with LEV, in comparison with PHB, predicted a shorter interval to seizure freedom in a univariate analysis (Hazard ratio (HR) = 2.58, P = 0.007), even after adjustment for initial seizure frequency and an unbiased ad hoc measure of HIE severity (adjusted HR = 2.57, P = 0.010). This effect was recapitulated in an analysis in which patients with treatment crossover were excluded. As expected, severity of HIE was an independent predictor of longer duration to seizure freedom (HR = 0.16, P < 0.001) and remained a significant predictor after adjustment for initial seizure burden and treatment agent.. Despite a relatively small sample size and retrospective design, this study suggests that LEV is a viable alternative to PHB in the treatment of neonatal seizures associated with HIE. A large-scale randomized controlled trial is needed to confirm these findings.

Topics: Anticonvulsants; Electroencephalography; Female; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Kaplan-Meier Estimate; Levetiracetam; Male; Phenobarbital; Prohibitins; Proportional Hazards Models; Retrospective Studies; Seizures; Treatment Outcome

Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy.. Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (≤1 seizure/month) and non-responders (>1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta.. Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 ± 0.59 kg.day/L) and Cmax/D ratio (2.25 ± 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 ± 0.12 kg.day/L and 1.49 ± 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy.. The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.

Topics: Adult; Anticonvulsants; Biomarkers; Epilepsy; Female; Humans; Interleukin-1beta; Levetiracetam; Male; Middle Aged; Seizures; Treatment Outcome; Young Adult

Objectives To study the clinical profile and outcome in patients with epilepsy who developed psychogenic non-epileptic seizures (PNES) associated with levetiracetam (LEV) use.   Methods In this prospective observational study, conducted over 1 year, 13 patients with epilepsy and PNES, documented by video electroencephalogram (VEEG) while on LEV, were included. Those with past history of psychiatric illnesses were excluded. VEEG, high-resolution magnetic resonance imaging, neuropsychological and psychiatric evaluation were performed. Patients in Group I (07) were treated with psychotherapy, psychiatric medications and immediate withdrawal of LEV while, those in Group II (06) received psychotherapy, anxiolytics and LEV for initial 2 months after which it was stopped. Follow-up period was six months. There was subsidence of PNES on discontinuation of LEV in these patients.   Results Mean (±SD) age of patients was 25 ± 12.28 years; there were 11 (84.62%) females. All were on antiepileptic agents which included LEV >1000 mg/day, except one. Mean dose of LEV was 1269.23 ± 483.71 mg/day. Three patient's scores were suggestive of depression or anxiety; one had both depression and anxiety. Eight patients had mood disorders; three had a history of emotional abuse or neglect. PNES subsided within 1-3 months and did not recur after withdrawal of LEV in any patient.   Conclusion LEV can induce PNES in susceptible populations. Awareness of this association is crucial for timely withdrawal of triggering factor and appropriate management. This will reduce inadvertent additional prescription of antiepileptic agents.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Child; Depression; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Psychotherapy; Risk Factors; Seizures; Young Adult

The prescription pattern of antiepileptic drugs (AEDs) during pregnancy is changing but to what extent this is occurring in Spain remains unknown. The efficacy of newer drugs for controlling seizures is a key issue and may have changed over the years as doctors gained familiarity with these drugs during pregnancy. To assess these 2 topics, we report the results from the Spanish EURAP register gathered over a 12-year period.. After signing informed consent forms, patients were included in the register and evaluated at onset of pregnancy, at the end of the second and third trimesters, after delivery, and one year after delivery. For the purposes of this study, we analysed AEDs, type of epilepsy, seizure frequency per trimester and throughout pregnancy, percentage of seizure-free pregnancies, and frequency of congenital malformations. We then compared data from 2 periods (June 2001-October 2007) and (January 2008-May 2015) RESULTS: We compared 304 monotherapies from the older period to 127 from the more recent one. There was a clear increase in the use of levetiracetam (LEV) with declining use of carbamazepine (CBZ), phenytoin, and phenobarbital; a slight decline in use of valproate (VPA), and a slight increase in the use of lamotrigine (LTG) and oxcarbazepine (OXC). Epilepsy types treated with CBZ and VPA remained unchanged, whereas fewer cases of generalised epilepsy were treated with LTG in the new period. This trend was not associated with significant changes in seizure frequency, but rather linked to better control over de novo seizures in the third trimester. LEV was similar to CBZ and VPA with regard to levels of seizure control, and more effective than LTG. Generalised epilepsy accounted for 64% of the cases treated with LEV.. The prescription pattern of AEDs during pregnancy has changed in Spain, with diminishing use of CBZ, phenytoin, and phenobarbital. Changes also reflect the type of epilepsy, since there is less use of LTG for generalised epilepsy. LEV provides similar seizure control to that of the older AEDs, and it is more effective and better than LTG.

Topics: Adult; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Longitudinal Studies; Oxcarbazepine; Piracetam; Pregnancy; Seizures; Spain; Triazines

Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of levetiracetam (LEV) alone, LEV and lacosamid (LCM) as compared to phenytoin (PHT).. After IRB approval, the charts of individuals who underwent craniotomy from April 2007 to September 2011 were reviewed. Those receiving PHT were compared to those receiving LEV alone and LEV/LCM. The patient data included demographic, indication and procedure related data. The cumulative dose of norepinephrine (NET), atropine (ATR) and the change in systolic blood pressure during and after the administration of the AED were analyzed.. Five hundred thirty-eight patients were screened of which 122 were included for analysis. 40 patients with primary or secondary supratentorial brain tumors received LEV (19 female, 21 male; mean age 56 years), 41 patients received LEV/ LCM (16 female, 25 male; mean age 56 years) and 41 patients received PHT (15 female, 26 male; mean age 50 years). The commonest indications for craniotomy were glioblastoma (N.=14 vs. N.=12 vs. N.=15), meningiomas (N.=9 vs. N.=7 vs. N.=10), low-grade gliomas (N.=6 vs. N.=13 vs. N.=6) and brain metastases (N.=5 vs. N.=4 vs. N.=5). 1 LEV/LCM patient (2%) and 4 PHT patients (4.5%) had a seizure despite prophylaxis. Possible side effects were observed in 2 patients associated with PHT. During anesthesia there was a significant drop in systolic blood pressure in the PHT group after administration of the AED perioperatively when compared to LEV (P=0.001) and LEV/LCM (P≤0.0001) respectively. The mean cumulative doses of NET and ATR over the course of the operation did not differ significantly.. LEV alone and in combination with LCM for patients without and with symptomatic epilepsy as seizure prophylaxis provides a safe and feasible alternative to PHT. PHT was associated with an unfavorable drop in blood pressure during anesthesia and more adverse reactions.

Topics: Acetamides; Adult; Anticonvulsants; Blood Pressure; Craniotomy; Female; Humans; Hypotension; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pre-Exposure Prophylaxis; Retrospective Studies; Seizures; Supratentorial Neoplasms

The aim of this paper was to describe the synthesis of a library of 28 new 1,3-substituted pyrrolidine-2,5-dione as potential anticonvulsant agents. The anticonvulsant activity was evaluated using three acute models of seizures in mice (MES-maximal electroshock, scPTZ-subcutaneous pentylenetetrazole, and 6Hz-psychomotor seizure tests). The neurotoxicity was determined by rotarod test. The most promising compound was found to be N-[{morpholin-1-yl}-methyl]-3-benzhydryl-pyrrolidine-2,5-dione (15), as it was active in the MES (ED

Topics: Animals; Anticonvulsants; Mannich Bases; Mice; Pyrrolidines; Seizures

Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome.. We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score.. We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication.. Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Cerebral Hemorrhage; Drug Prescriptions; Female; Guideline Adherence; Humans; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Piracetam; Prevalence; Retrospective Studies; Seizures

Lacosamide (LCM) due to no known drug interaction and the absence of metabolic enzyme induction is a good candidate for an add-on medication, especially in combination with lamotrigine, levetiracetam (LEV), oxcarbazepine, topiramate, and valproic acid (VPA). Here we report for the first time, to our knowledge, that LCM can lower VPA and LEV serum levels. At present, there are no known explicable mechanisms of action of LCM, which lowers VPA and LEV. Here observed drug interaction of LCM is of clinical significance, which might be useful for other colleagues in the field.

Topics: Acetamides; Adolescent; Anticonvulsants; Brain Neoplasms; Drug Interactions; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Neoplasms, Neuroepithelial; Piracetam; Seizures; Valproic Acid

Early myoclonus after cardiac arrest (CA) is traditionally viewed as a poor prognostic sign (status myoclonus). However, some patients may present early Lance-Adams syndrome (LAS): under appropriate treatment, they can reach a satisfactory functional outcome. Our aim was to describe their profile, focusing on pharmacologic management in the ICU, time to return of awareness, and long-term prognosis.. Adults with early LAS (defined as generalized myoclonus within 96h, with epileptiform EEG within 48h after CA) were retrospectively identified in our CA registry between 2006 and 2016. Functional outcome was assessed through cerebral performance categories (CPC) at 3 months, CPC 1-2 defined good outcome.. Among 458 consecutive patients, 7 (1.5%) developed early LAS (4 women, median age 59 years). Within 72h after CA, in normothemia and off sedation, all showed preserved brainstem reflexes and localized pain. All patients were initially treated with valproate, levetiracetam and clonazepam; additional agents, including propofol and midazolam, were prescribed in the majority. First signs of awareness occurred after 3-23 days (median 11.8); 3/7 reached a good outcome at 3 months.. Early after CA, myoclonus together with a reactive, epileptiform EEG, preserved evoked potentials and brainstem reflexes suggests LAS. This condition was managed with a combination of highly dosed, large spectrum antiepileptic agents including propofol and midazolam. Even if awakening was at times delayed, good outcome occurred in a substantial proportion of patients.

Topics: Adult; Aged, 80 and over; Anticonvulsants; Cardiopulmonary Resuscitation; Clonazepam; Drug Combinations; Electroencephalography; Female; Heart Arrest; Humans; Intensive Care Units; Levetiracetam; Male; Middle Aged; Myoclonus; Piracetam; Prospective Studies; Registries; Seizures; Syndrome; Time Factors; Valproic Acid

Topics: Amnesia; Anticonvulsants; Electroencephalography; Epilepsy; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

The aim of this study was to evaluate the risk factors, clinical implications, and prognosis of new-onset seizures that occurred after pediatric liver transplantation, and to assess the efficacy of levetiracetam treatment. The clinical and laboratory data of liver transplanted 28 children who had seizures after liver transplantation and specifically of 18 children who received levetiracetam were analyzed retrospectively. Sixteen patients (88.9%) remained seizure-free and in 2 (11.1%), more than 50% reduction in seizures were detected with levetiracetam treatment. In conclusion, seizures are generally the most common complication by a spectrum of seizure types, and sometimes cause symptomatic epilepsy. The most common risk factors for seizures in transplant recipients is immunosuppressant toxicity. Currently, there isn't a specific treatment involving the transplant patient population. Levetiracetam may be preferable in pediatric patients as it's reliable for liver disease and has advantages in the treatment of postoperative seizures due to its intravenous usage.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Humans; Infant; Levetiracetam; Liver Diseases; Liver Transplantation; Magnetic Resonance Imaging; Male; Piracetam; Risk Factors; Seizures

BACKGROUND Levetiracetam is an antiepileptic drug frequently used in critically ill patients. Levetiracetam is primarily eliminated as a parent compound via glomerular filtration and requires dose adjustment in renal insufficiency, but the literature on patients receiving continuous veno-venous hemofiltration (CVVH) is scant. CASE REPORT We report the levetiracetam pharmacokinetic profile of a patient being treated with levetiracetam 1000 mg intravenously every 12 h who required continuous veno-venous hemofiltration (CVVH). The patient underwent CVVH utilizing a high-flux polyethersulfone membrane filter. The blood flow rate was 250 ml/min, and the predilution replacement therapy fluid flow rate was 2000 ml/h. After achieving presumed steady-state on levetiracetam 1000 mg q12h, serial plasma samples (pre- and post-filter) and effluent samples were drawn at 2, 4, 6, 8, and 10 h. Levetiracetam concentrations were determined utilizing LC-MS/MS. The levetiracetam maximum concentration (Cmax), minimum concentration (Cmin), half-life, area under the concentration-time curve (AUC0-12), clearance (CL), and volume of distribution (Vd) were 30.7 µg/ml, 16.1 µg/ml, 12.9 h, 272 mg·hr/L, 3.68 L/h, and 0.73 L/kg, respectively. The sieving coefficient was 1.03±0.08. CVVH represented 61.3% of the total levetiracetam clearance. The patient was maintained on CVVH for 24 consecutive days and then transitioned to intermittent hemodialysis and remained seizure-free. CONCLUSIONS CVVH is highly effective in removing levetiracetam from circulating plasma. Due to the effective removal, standard doses of levetiracetam are required to maintain adequate plasma concentrations. Dose reductions utilizing HD or estimated creatinine clearance recommendations will likely lead to subtherapeutic levels, especially if higher CVVH flow rates are used.

Topics: Aged; Anticonvulsants; Hemofiltration; Humans; Intracranial Hemorrhages; Levetiracetam; Male; Piracetam; Seizures

Posttraumatic seizures are a medical problem affecting patients with traumatic brain injury. Yet effective treatment is lacking owing to the limitations of antiepileptic drugs (AEDs) applicable to these patients.. In this study, we evaluated the dose-response efficacy of levetiracetam (12.5-100.0 mg/kg) and gabapentin (1.25-25.0 mg/kg) administered either individually or in pairs at fixed-dose ratios as a combination in mitigating posttraumatic nonconvulsive seizures induced by severe penetrating ballistic-like brain injury (PBBI) in rats. Seizures were detected by continuous electroencephalogram (EEG) monitoring for 72 hours postinjury. Animals were treated twice per day for 3 days by intravenous injections.. Both levetiracetam (25-100 mg/kg) and gabapentin (6.25-25 mg/kg) significantly reduced PBBI-induced seizure frequency by 44% to 73% and 61% to 69%, and seizure duration by 45% to 64% and 70% to 78%, respectively. However, the two drugs manifested different dose-response profiles. Levetiracetam attenuated seizure activity in a dose-dependent fashion, whereas the beneficial effects of gabapentin plateaued across the three highest doses tested. Combined administration of levetiracetam and gabapentin mirrored the more classic dose-response profile of levetiracetam monotherapy. However, no additional benefit was derived from the addition of gabapentin. Furthermore, isobolographic analysis of the combination dose-response profile of levetiracetam and gabapentin failed to reach the expected level of additivity, suggesting an unlikelihood of favorable interactions between these two drugs against spontaneously occurring posttraumatic seizure activities at the particular set of dose ratios tested.. This study was the first attempt to apply isobolographic approach to studying AED combination therapy in the context of spontaneously occurring posttraumatic seizures. Despite the failure to achieve additivity from levetiracetam and gabapentin combination, it is important to recognize the objectivity of the isobolographic approach in the evaluation of AED combination therapy against seizures directly associated with brain injuries.

Topics: Amines; Animals; Cyclohexanecarboxylic Acids; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Gabapentin; gamma-Aminobutyric Acid; Head Injuries, Penetrating; Levetiracetam; Male; Piracetam; Rats; Rats, Sprague-Dawley; Seizures

Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have psychiatric issues prior to adjunctive AED treatment compared to other patients (208 of 936, 22.2%), but there were no statistically significant differences once the new AEDs were added (8 of 122 patients with learning disability, 6.6%; 64 of 936 other patients, 6.8%). Awareness of these issues may assist clinicians in avoiding, identifying and treating psychiatric comorbidities in people with epilepsy.

Topics: Acetamides; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Dibenzazepines; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Fructose; Humans; Lacosamide; Levetiracetam; Male; Medical Audit; Mental Disorders; Middle Aged; Nitriles; Piracetam; Pregabalin; Prospective Studies; Pyridones; Retrospective Studies; Seizures; Sodium Channel Blockers; Topiramate; Young Adult

Levetiracetam is used in the treatment of some forms of epilepsy. In renal impairment and patients on chronic haemodialysis, dose adjustment is required. We report a case.. This case report describes a woman on levetiracetam treatment who presented with generalized tonic-clonic seizures during a haemodialysis session. We report on treatment adjustment and on the impact of dialysis on levetiracetam levels.. Haemodialysis reduces serum levetiracetam concentration and can lead to subtherapeutic levels. Close monitoring is necessary when dialysis is used on patients receiving anticonvulsant drugs that are extensively eliminated by the procedure.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Humans; Levetiracetam; Piracetam; Renal Dialysis; Seizures

Levetiracetam (LEV) is primarily renally eliminated. In end-stage renal disease (ESRD) patients on hemodialysis (HD), pharmacokinetic studies recommend daily dosing with 50% supplemental doses after 4-hour HD sessions. However, poor medication adherence after HD could result in fluctuating plasma drug levels.. To compare two LEV dosing regimens, daily versus twice-daily (BID), in ESRD patients undergoing HD.. Consecutive ESRD patients (April 2013 to May 2014) receiving maintenance inpatient HD and prescribed LEV prior to admission to our academic tertiary hospital were prospectively analyzed. Demographics, initial lab values, adverse reactions, seizures, and LEV regimens were recorded. LEV levels were obtained pre-HD and post-HD along with levels after receiving post-HD doses. Recovery of plasma levels after HD was assessed by comparison of levels predialysis versus postdialysis and post-HD doses.. We identified 22 patients who met inclusion criteria; 14 BID and 8 daily dosing. Mean predialysis, postdialysis, and post-HD dose plasma levels were higher in patients receiving LEV BID compared with daily (43.1 ± 6.3, 19.4 ± 5.2, 34.9 ± 4.3 vs 21.1 ± 3.9, 6.9 ± 1.5, 11.9 ± 1.7 µg/mL; P < 0.05). BID post-HD levels were 41.9 ± 4.6% of predialysis levels versus 36.9 ± 7.3% with daily dosing ( P = 0.275). Post-HD dose levels were 81.4±4.3% of predialysis on LEV BID versus 65.7 ± 8.8% on LEV daily ( P = 0.045). No seizures were reported during hospital admission in either group.. Compared to LEV daily, BID dosing achieved significantly higher levels and a better recovery to predialysis levels. Although limited by small numbers, a similar relationship between postdialysis levels was not detected.

Topics: Adult; Aged; Anticonvulsants; Clinical Protocols; Drug Administration Schedule; Female; Humans; Kidney Failure, Chronic; Levetiracetam; Male; Middle Aged; Piracetam; Renal Dialysis; Seizures

High-dose benzodiazepine (BZD) dependence represents an emerging and under-reported addiction phenomenon and is associated with reduced quality of life. To date there are no guidelines for the treatment of high-dose BZD withdrawal. Low-dose slow flumazenil infusion was reported to be effective for high-dose BZD detoxification, but there is concern about the risk of convulsions during this treatment. We evaluated the occurrence of seizures in 450 consecutive high-dose BZD dependence patients admitted to our unit from April 2012 to April 2016 for detoxification with low-dose slow subcutaneous infusion of flumazenil associated with routine anticonvulsant prophylaxis. In our sample, 22 patients (4.9%) reported history of convulsions when previously attempting BZD withdrawal. Only four patients (0.9%) had seizures during ( n = 2) or immediately after ( n = 2) flumazenil infusion. The two patients with seizures during flumazenil infusion were poly-drug misusers. The most common antiepileptic drugs (AEDs) used for anticonvulsant prophylaxis were either valproate 1000 mg or levetiracetam 1000 mg. Our data indicate that, when routinely associated with AEDs prophylaxis, low-dose slow subcutaneous flumazenil infusion represents a safe procedure, with low risk of seizure occurrence.

Topics: Adolescent; Adult; Anti-Anxiety Agents; Anticonvulsants; Antidotes; Benzodiazepines; Female; Flumazenil; Humans; Hypnotics and Sedatives; Levetiracetam; Male; Middle Aged; Piracetam; Quality of Life; Seizures; Substance-Related Disorders; Valproic Acid; Young Adult

Benzodiazepines are used as first-line treatments for status epilepticus. Fosphenytoin (FPHT) is recommended for second-line therapy; however, intravenous injection of levetiracetam (LEV) may also be effective against status epilepticus. Herein, we compared the efficacy and safety of LEV as a second-line treatment for status epilepticus with FPHT in Japanese patients.Patients with status epilepticus were selected from the database of the Emergency and Critical Care Center of Hitachi General Hospital. The subjects were patients whose status epilepticus was successfully stopped by diazepam, and in whom FPHT or LEV was administered after diazepam. As LEV injections recently became clinically available in Japan, the choice of drug was determined by the treatment period. Thus, 21 patients who were intravenously injected with LEV as a second-line therapy and 42 matched patients (historical controls) who were treated with FPHT (1:2) were selected.The subjects had a mean age of 64.0 ± 2.2 years, and included 48 males and 15 females. The status epilepticus control rates of the FPHT and LEV groups did not differ significantly (81.0% [34/42] vs 85.1% [18/21], respectively; P  =  .69). As for serious adverse events, a reduction in blood pressure was observed in the FPHT group, but not in the LEV group. The oral anticonvulsant switching rates of the 2 groups were similar, but the same-drug switching rates of the FPHT and LEV groups were 8.1% and 77.8%, respectively.The efficacy of intravenous LEV injections after status epilepticus was equivalent to that of FPHT, and the incidence of adverse events was lower in the LEV group. LEV is effective and safe at preventing recurrent seizures after status epilepticus following benzodiazepine treatment.

Topics: Administration, Intravenous; Administration, Oral; Anticonvulsants; Blood Pressure; Databases, Factual; Diazepam; Drug Substitution; Emergency Medical Services; Female; Hospitals, General; Humans; Japan; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Recurrence; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

The aim was to study the impact of therapeutic drug monitoring (TDM) on patients on lamotrigine (LTG) therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations.. During the period of 2001-2014, 3118 predose samples were taken from 1137 patients >15 years of age as part of their routine TDM. Drug interactions were evaluated using calculation of LTG clearance (CL).. Valproic acid (VPA) decreased LTG CL by 66% in bitherapy, and by 35% and 31% in triple therapy with carbamazepine (CBZ) and phenytoin (PHT), respectively. CBZ and PHT increased LTG CL by 52% and 96% in respective bitherapies but by 88% in triple therapy. Clonazepam, levetiracetam, and topiramate had no effect. The LTG therapeutic range (TR) was exceeded in 1% of cases in monotherapy, and in 4%-5% of cases in combination therapy. Only 54% of results were within the TR during 2001-2005, whereas 60%-62% were within the TR during 2006-2014. Adverse drug reactions (ADRs) were reported in 88 cases and occurred more frequently during TR during 2001-2005. Higher number of supratherapeutic levels in combination therapy led to a 3-fold higher incidence of ADR and poorer seizure control, as seizures occurred more often monthly (2.5%) or a few per year (41%) and fewer patients were seizure free (18%). Seizures occurred more often daily and monthly during the first period and in patients with 3 or 4 drugs in combination.. A significantly higher number of supratherapeutic levels were found in combinations with VPA, despite lower doses of LTG. Hepatic enzyme inducers, such as CBZ and PHT only partially compensated for the inhibitory effect of VPA. Decrease of both the frequency of seizures and the incidence of ADRs after TDM implementation suggests that TDM may have given clinicians the opportunity to achieve more optimal patient treatment.

Topics: Adult; Anticonvulsants; Carbamazepine; Clonazepam; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Phenytoin; Piracetam; Seizures; Topiramate; Triazines; Valproic Acid

Reproductive disorders are more common in men with epilepsy taking anticonvulsant medications. Antiseizure/anticonvulsant drugs and seizures in medial temporal lobe structures may cause gonadal dysfunction, including infertility, decreased libido, and potency. Levels of circulating bioavailable testosterone are affected by the aromatase enzyme, which converts testosterone into estrogen and may be affected by seizure medications. However, the relationship of anticonvulsant drugs with central aromatase levels is not clear. This study investigated the possible effects of the highly efficient, new-generation antiseizure/anticonvulsant drug levetiracetam on central and gonadal aromatase expression and gonadal tissue functionality at 27 and 54 mg/kg/day doses. Epileptogenesis was generated in male Wistar rats by an intraperitoneal injection of the excitotoxic agent kainic acid. Aromatase levels were 1.5 times higher in the brain cortex of the kainic acid groups after 4 weeks and the hippocampus after 4 and 8 weeks compared with the controls. Decreased basal aromatase levels were observed after 1 week of levetiracetam treatment (27 mg/kg/day). Administration of 27 mg/kg/day levetiracetam did not alter vas deferens contractions at 1, 4, or 8 weeks compared with the controls. No histological changes were observed in the vas deferens, epididymis, or testis after 8 weeks of levetiracetam administration at both doses. Administration of 27 and 54 mg/kg/day levetiracetam downregulated testis aromatase expression at 8 weeks compared with the controls. These results suggest that levetiracetam decreases aromatase levels in the testis and increases the seizure threshold by a possible decrease in systemic estradiol levels.

Topics: Animals; Aromatase; Cerebral Cortex; Epididymis; Hippocampus; Kainic Acid; Levetiracetam; Male; Nerve Tissue Proteins; Oxidoreductases Acting on CH-CH Group Donors; Piracetam; Rats, Wistar; Seizures; Testis; Time Factors; Vas Deferens

Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency.. Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA. LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection.. Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.

Topics: Acetamides; Animals; Anticonvulsants; Electroencephalography; Female; GABA Antagonists; Lacosamide; Levetiracetam; Malformations of Cortical Development; Pentylenetetrazole; Piracetam; Pregnancy; Prenatal Exposure Delayed Effects; Radiation Exposure; Rats; Rats, Sprague-Dawley; Seizures

To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client-owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow-up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Follow-Up Studies; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Lesions of the thalamus and those extending into midbrain can cause various types of movement disorders such as dystonia, asterixis and ballism-chorea. Seizures are rare manifestation of thalamic disorder. Occurrence of seizures in bilateral thalamic infarct has been reported; but seizures in unilateral thalamic infarct have been reported very rarely. Literature review showed only single case of perinatal unilateral thalamic infarct presenting with seizures. We are reporting a unique case of convulsive seizure at the onset of unilateral thalamic infarct in an adult male, which has never been reported to the best of our knowledge.

Topics: Aspirin; Atorvastatin; Cerebral Angiography; Cerebral Infarction; Humans; Hydrocephalus; Levetiracetam; Magnetic Resonance Angiography; Male; Middle Aged; Piracetam; Seizures; Thalamus

Topics: Anticonvulsants; Autism Spectrum Disorder; Early Diagnosis; Electroencephalography; Humans; Infant; Levetiracetam; Methylprednisolone; Piracetam; Seizures; Speech Therapy; Time-to-Treatment

Objectives Currently, there are no published randomised, controlled veterinary trials evaluating the efficacy of antiepileptic medication in the treatment of myoclonic seizures. Myoclonic seizures are a hallmark of feline audiogenic seizures (FARS). Methods This prospective, randomised, open-label trial compared the efficacy and tolerability of levetiracetam (20-25 mg/kg q8h) with phenobarbital (3-5 mg/kg q12h) in cats with suspected FARS that experienced myoclonic seizures. Cats were included that had ⩾12 myoclonic seizure days during a prospective 12 week baseline period. This was followed by a 4 week titration phase (until a therapeutic serum concentration of phenobarbital was achieved) and a 12 week treatment phase. Results Fifty-seven cats completed the study: 28 in the levetiracetam group and 29 in the phenobarbital group. A reduction of ⩾50% in the number of myoclonic seizure days was seen in 100% of patients in the levetiracetam group and in 3% of patients in the phenobarbital group ( P <0.001) during the treatment period. Levetiracetam-treated cats had higher freedom from myoclonic seizures (50.0% vs 0%; P <0.001) during the treatment period. The most common adverse events were lethargy, inappetence and ataxia, with no difference in incidence between levetiracetam and phenobarbital. Adverse events were mild and transient with levetiracetam but persistent with phenobarbital. Conclusions and relevance These results suggest that levetiracetam is an effective and well tolerated treatment for cats with myoclonic seizures and is more effective than phenobarbital. Whether it will prevent the occurrence of generalised tonic-clonic seizures and other forebrain signs if used early in the course of FARS is not yet clear.

Topics: Animals; Anticonvulsants; Cat Diseases; Cats; Epilepsies, Myoclonic; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Seizures

Objective The objective of this study was to compare clinical outcomes in children undergoing hematopoietic cell transplantation who received levetiracetam versus those who received phenytoin for the prevention of busulfan-induced seizures. Methods This study was an IRB-approved, single-center, retrospective analysis of pediatric patients receiving intravenous busulfan for hematopoietic cell transplantation conditioning from January 2009 to July 2014. The primary study endpoint was the incidence of seizure during busulfan administration (day -8 to 0). Key transplant related-outcomes were also collected, including the incidence of graft rejection, sinusoidal obstruction syndrome, relapse, and death. Results A total of 20 patients met criteria for inclusion in the study. The population was heterogeneous with regard to the indication for hematopoietic cell transplantation, donor type, stem cell source, and conditioning regimen. Nine patients (45%) received levetiracetam and 11 (55%) received phenytoin for seizure prophylaxis. No seizures or graft rejections were observed in the study population. One relapse, one case of sinusoidal obstruction syndrome, and two deaths occurred in the levetiracetam group, while no relapses, two cases of sinusoidal obstruction syndrome, and one death occurred in the phenytoin group. Conclusion These data suggest similar safety and effectiveness between levetiracetam and phenytoin for the prevention of busulfan-induced seizures in a small, heterogeneous pediatric hematopoietic cell transplantation population.

Topics: Adolescent; Anticonvulsants; Busulfan; Child; Child, Preschool; Female; Graft Rejection; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Infant; Levetiracetam; Male; Myeloablative Agonists; Phenytoin; Piracetam; Recurrence; Retrospective Studies; Seizures; Transplantation Conditioning; Young Adult

Epilepsy with the main symptom of amnesia is known as transient epileptic amnesia (TEA). Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia. The concept that Lewy body disease includes Parkinson's disease with dementia and dementia with Lewy bodies was proposed in the 2005 revision of the Clinical Diagnostic Criteria. Here, we describe a woman with cognitive impairment, olfactory dysfunction, and reduced

Topics: 3-Iodobenzylguanidine; Aged; Amnesia; Anticonvulsants; Cognition Disorders; Electroencephalography; Female; Hallucinations; Humans; Levetiracetam; Lewy Body Disease; Myocardial Perfusion Imaging; Parkinsonian Disorders; Piracetam; Seizures; Tomography, Emission-Computed, Single-Photon

Ciguatera fish poisoning is the most frequently reported seafood toxin illness associated with the ingestion of contaminated tropical fish. Diagnosis relies on a history of recent tropical fish ingestion and subsequent development of gastrointestinal, cardiovascular, and neurological symptoms. Ciguatera poisoning usually has a self-limited time course, and its management involves symptomatic control and supportive care. This case report presents an uncommon case of ciguatera poisoning with prolonged intractable seizures refractory to standard antiseizure medications. The patient also had significant functional decline that responded to rigorous inpatient rehabilitation not previously described in literature.

Topics: Adolescent; Animals; Anticonvulsants; Ciguatera Poisoning; Gait Disorders, Neurologic; Humans; Levetiracetam; Male; Neuropsychological Tests; Physical Therapy Modalities; Piracetam; Seizures

Topics: Anticonvulsants; Female; Humans; Infant, Newborn; Levetiracetam; Male; Retrospective Studies; Seizures

To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register (www.ukaed.info).. Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile (LAEP).. The number of seizure-free patients in the last 4 weeks was overall CBZ/VPA/LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/VPA/LTG/LEV=59%/71%/67%/57%. Mean LAEP scores were CBZ/VPA/LTG/LEV/CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly higher in patients reporting depression and in patients with active epilepsy than in patients without depression and remission. Central nervous system (CNS) adverse effects including memory problems, difficulty concentrating, depression, unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of anger was significantly more frequent in LEV, and depression was significantly more frequent in CBZ compared to the other drugs.. In this Internet-based register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were similar. Self-reported CNS adverse effects were significantly more frequent than in controls. In addition, anger was associated with LEV and depression with CBZ. Confounding factors were depression and uncontrolled epilepsy.

Topics: Adult; Anticonvulsants; Carbamazepine; Depression; Epilepsy; Female; Humans; Internet; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Seizures; Self Report; Treatment Outcome; Triazines; United Kingdom; Valproic Acid

Cytisine (CYT) is a partial agonist of brain α4β2 nicotinic acetylcholine receptors widely used in Central/Eastern Europe for smoking cessation.. This study evaluated the effect of CYT on the ability of classical and novel antiepileptic drugs to prevent seizures evoked by the 6-Hz test, a model of psychomotor seizures in mice thought as a model of drug-resistant seizures.. CYT administered intraperitoneally (i.p.) in a dose of 2 mg kg. CYT-evoked alterations in the protection provided by some antiepileptic drugs against seizures can be of serious concern for epileptic smokers, who might demonstrate therapeutic failure to lacosamide, levetiracetam, and pregabalin, resulting in possible breakthrough seizure attacks.

Topics: Alkaloids; Animals; Anticonvulsants; Azocines; Dose-Response Relationship, Drug; Electroshock; Levetiracetam; Male; Memory, Long-Term; Mice; Nicotinic Agonists; Phenobarbital; Piracetam; Quinolizines; Seizures; Valproic Acid

Neonatal seizures are a common problem in the neonatal intensive care unit and are frequently treated with antiepileptic drugs. Limited data exist on current or changing antiepileptic drug use for seizures in the neonatal intensive care unit.We sought to describe trends of antiepileptic drug exposure in a large volume of US neonatal intensive care unit from 2005 to 2014 and we hypothesized increasing levetiracetam exposure over the 10-year study period.. Retrospective cohort study of infants from the Pediatrix Medical Group Clinical Data Warehouse, a large, multicenter, deidentified data set. Data were analyzed for trends in 2-year time periods. Our cohort included infants with a diagnosis of seizures who received an antiepileptic drug that were discharged from the neonatal intensive care unit from 1 January 2005 to 31 December 2014.. Among 778 395 infants from 341 facilities, we identified 9134 infants with a seizure diagnosis who received an antiepileptic drug. Phenobarbital was used in 98% of the cohort. From 2005-2006 to 2013-2014 phenobarbital exposure declined from 99 to 96% (P<0.001), phenytoin exposure decreased from 15 to 11% (P<0.001) and levetiracetam exposure increased 10-fold from 1.4 to 14% (P<0.001). Overall, <1% of infants were exposed to carbamazepine, lidocaine or topiramate.. Infants with seizures were overwhelmingly exposed to phenobarbital, despite a significant increase in levetiracetam exposure. The use of phenytoin declined and has been surpassed by levetiracetam as the second most widely used antiepileptic in the neonatal intensive care unit. These changes in antiepileptic drug usage patterns have occurred in the absence of novel efficacy data in neonates.

Topics: Anticonvulsants; Child; Drug Utilization; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Levetiracetam; Male; Phenobarbital; Phenytoin; Piracetam; Retrospective Studies; Seizures; Texas

Prophylactic medications can be a source of preventable harm, potentially affecting large numbers of patients. Few data exist about how clinicians change prescribing practices in response to new data and revisions to guidelines about preventable harm from a prophylactic medication. We sought to determine the changes in prescribing practice of seizure medications for patients with intracerebral hemorrhage (ICH) across a metropolitan area before and after new outcomes data and revised prescribing guidelines were published.. We conducted an observational study using electronic medical record data from 4 academic medical centers in a large US metropolitan area.. A total of 3,422 patients with ICH, diagnosed between 2007 and 2012, were included. In 2009, after a publication found an association of phenytoin with higher odds of dependence or death, the use of phenytoin declined from 9.6% in 2009 to 2.2% in 2012 (p < 0.00001). Conversely, the use of levetiracetam more than doubled, from 15.1% in 2007 to 35% in 2012 (p < 0.00001). Use of levetiracetam varied among the 4 institutions from 6.7% to 29.8% (p < 0.00001).. New data that led to revised prescribing guidelines for prophylactic seizure medications for patients with ICH were temporally associated with a significant decrease in use of the medication, potentially reducing adverse outcomes. However, a corresponding increase in the use of an alternative medication, levetiracetam, occurred despite limited knowledge about its potential effects on outcomes. Future guideline changes should anticipate and address alternatives.

Topics: Adult; Aged; Anticonvulsants; Cerebral Hemorrhage; Cohort Studies; Craniotomy; Electronic Health Records; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures

The objective of this study was to determine the efficacy and safety of levetiracetam in treatment of neonatal seizures due to hypoxic ischemic encephalopathy. Seizures often persist in neonates with hypoxic ischemic encephalopathy despite phenobarbital. A retrospective single-center study was conducted in neonates ≥36 weeks gestation with hypoxic ischemic encephalopathy. A total of 127 neonates were identified born 2008-2015. Clinical seizures occurred in 83 infants. Fifty-one neonates (61%) had cessation of seizures with only phenobarbital. Thirty-two neonates received levetiracetam after phenobarbital, and the seizures stopped in 27 of these neonates. The mean total loading dose of levetiracetam was 63 mg/kg. Mean maintenance dose of levetiracetam was 65 mg/kg/d. We found no negative side effects in neonates following levetiracetam use. Our study finds that levetiracetam is an efficacious medication in treatment of seizures in the setting of neonatal hypoxic ischemic encephalopathy. Future prospective studies should explore its use as a first-line medication.

Topics: Adult; Anticonvulsants; Female; Follow-Up Studies; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Levetiracetam; Male; Phenobarbital; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Levetiracetam (LEV) is commonly used as a mono- or adjunctive therapy for treating patients with partial and generalized epilepsy. This study aimed to develop a population pharmacokinetic (PK) model of LEV, based on sparse data, and to explore LEV efficacy relative to its PK properties in patients with epilepsy. We included 483 LEV concentrations from 425 patients with epilepsy that received multiple oral LEV doses. We performed a population PK analysis, implemented in NONMEM (version 7.2). In addition, we explored the relationships between seizure control and PK variables (i.e., LEV dose, trough concentration, and the number of concomitant anti-epileptic drugs). LEV concentration-time profiles were adequately described with a one-compartment, open linear model, with first-order absorption, and additive residual error. The typical population estimates of the apparent clearance (CL/F) and the volume of distribution (V/F) were 3.9L/h and 65.3L, respectively. Body weight was a significant covariate for CL/F and V/F; the estimated glomerular filtration rate only significantly affected CL/F; and concomitant intake of other anti-epileptic drugs did not significantly affect either parameter. A cumulative percentage analysis revealed that over 95% of patients that remained seizure-free received LEV doses of 2000mg/day or lower. LEV trough concentrations were not significantly different between seizure-free and seizure groups, for each LEV dose. In conclusion, we successfully developed a population PK model of LEV, which enabled investigation of LEV efficacy, relative to its PK properties. The findings in this study can be utilized to optimize LEV dosing regimens in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome; Young Adult

To assess the impact of the new AEDs on overall outcome for patients with epilepsy.. In 2004, the effect of combination therapy on seizure frequency in adult patients with focal epilepsy was evaluated in a cross-sectional study in our center. We repeated this analysis ten years and eight new antiepileptic drugs (AED) later.. In 2014, a higher percentage of patients with polytherapy (117 out of 396; 30%) were seizure-free compared with the original analysis (22%) (p=0.042). Eighty three out of 218 (38%) subjects on duo-therapy were seizure-free (27% in 2004) (p=0.040); in the 151 receiving triple therapy there were 30 (20%) seizure-free subjects (10% in 2004). Four out of 27 subjects (15%) with four AEDs were seizure-free (0% in 2004). The most common pairing of 52 different combinations for duo-therapy was levetiracetam-oxcarbazepine. Eighty different AEDs regimens were being used in the patients administered three AEDs.. Our combined data from these two studies indicate that some patients with focal epilepsy might benefit from newer AEDs as an adjunctive therapy in the hope they could acquire seizure freedom.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Levetiracetam is an antiepileptic drug used for the treatment of generalised or partial seizures, either alone or in a combination therapy. Adverse effects have been reported with its clinical use, including headache, dizziness, liver failure etc. A rare but an important adverse effect is an increase in creatine phosphokinase (CPK) levels with its use. Herein, we present a case of 43-year male, known intravenous (IV) drug abuser with a history of decompressive craniotomy. Patient presented with severe behavioural disorder for which risperidone was given. Five days later, he started having high grade fever, hyperventilation and uncontrolled generalised tonic-clonic seizures (GTCS). After initial management of seizures, levetiracetam was started in combination with topiramate for seizure control. Seizures remained subsided but CPK levels, which were normal at the start of therapy, began to rise and reached tremendous levels of 29,000 mg/dl within a span of a week. Levetiracetam, suspected as a cause of this increase CPK levels, was stopped immediately and the levels returned to baseline within one week. This report provided us with an important step in the management of seizures with levetiracetam.

Topics: Adult; Anticonvulsants; Creatine Kinase; Humans; Levetiracetam; Male; Piracetam; Seizures

The purpose of this study was to synthetize the focused library of 34 new piperazinamides of 3-methyl- and 3,3-dimethyl-(2,5-dioxopyrrolidin-1-yl)propanoic or butanoic acids as potential new hybrid anticonvulsants. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5-38 were prepared in a coupling reaction of the 3-methyl- or 3,3-dimethyl-2-(2,5-dioxopyrrolidin-1-yl)propanoic (1, 2) or butanoic acids (3, 4) with the appropriately substituted secondary amines in the presence of the N,N-carbonyldiimidazole reagent. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests as well as in the six-Hertz (6Hz) model of pharmacoresistant limbic seizures. The acute neurological toxicity was determined applying the chimney test. The broad spectra of activity across the preclinical seizure models in mice ip displayed compounds 7, 15, and 36. The most favorable anticonvulsant properties demonstrated 15 (ED50 MES=74.8mg/kg, ED50scPTZ=51.6mg/kg, ED50 6Hz=16.8mg/kg) which showed TD50=213.3mg/kg in the chimney test that yielded satisfying protective indexes (PI MES=2.85, PI scPTZ=4.13, PI 6Hz=12.70) at time point of 0.5h. As a result, compound 15 displayed comparable or better safety profile than clinically relevant AEDs: ethosuximide, lacosamide or valproic acid. In the in vitro assays compound 15 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and L-type calcium channels. Beyond the anticonvulsant properties, 6 compounds diminished the pain responses in the formalin model of tonic pain in mice.

Topics: Analgesics; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Injections, Intraperitoneal; Mice; Molecular Structure; Pain; Pain Measurement; Pentylenetetrazole; Piperazines; Pyrrolidinones; Seizures

This paper describes the synthesis of the library of 22 new 3-methyl- and 3-ethyl-3-methyl-2,5-dioxo-pyrrolidin-1-yl-acetamides as potential anticonvulsant agents. The maximal electroshock (MES) and the subcutaneous pentylenetetrazole (scPTZ) seizure models were used for screening all the compounds. The 6 Hz model of pharmacoresistant limbic seizures was applied for studying selected derivatives. Six amides were chosen for pharmacological characterization of their antinociceptive activity in the formalin model of tonic pain as well as local anesthetic activity was assessed in mice. The pharmacological data indicate on the broad spectra of activity across the preclinical seizure models. Compounds 10 (ED50=32.08 mg/kg, MES test) and 9 (ED50=40.34 mg/kg, scPTZ test) demonstrated the highest potency. These compounds displayed considerably better safety profiles than clinically relevant antiepileptic drugs phenytoin, ethosuximide, or valproic acid. Several molecules showed antinociceptive and local anesthetic properties. The in vitro radioligand binding studies demonstrated that the influence on the sodium and calcium channels may be one of the essential mechanisms of action.

Topics: Amides; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mice; Molecular Structure; Pentylenetetrazole; Pyrrolidines; Seizures

The focused library of 21 new N-phenyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamide, and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives as potential new hybrid anticonvulsant agents was synthesized. These hybrid molecules were obtained as close analogs of previously described N-benzyl derivatives and fuse the chemical fragments of clinically relevant antiepileptic drugs such as ethosuximide, levetiracetam, and lacosamide. The initial anticonvulsant screening was performed in mice (ip) using the 'classical' maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, as well as in the six-Hertz (6Hz) model of pharmacoresistant limbic seizures. Applying the rotarod test, the acute neurological toxicity was determined. The broad spectra of activity across the preclinical seizure models in mice (ip) displayed compounds 4, 5, 11, and 19. The most favorable anticonvulsant properties demonstrated 4 (ED50 MES=96.9mg/kg, ED50scPTZ=75.4mg/kg, ED50 6Hz=44.3mg/kg) which showed TD50=335.8mg/kg in the rotarod test that yielded satisfying protective indexes (PI MES=3.5, PI scPTZ=4.4, PI 6Hz=7.6). Consequently, compound 4 revealed comparable or better safety profile than model antiepileptic drugs (AEDs): ethosuximide, lacosamide, and valproic acid. In the in vitro assays, compound 4 was observed as relatively effective binder to the neuronal voltage-sensitive sodium and diltiazem site of L-type calcium channels.

Topics: Amides; Animals; Anticonvulsants; Calcium Channels; Drug Design; Humans; Injections, Intraperitoneal; Mice; Molecular Structure; Neurons; Pyrrolidines; Seizures

The 42-year-old woman who had been taking 300 mg phenytoin and 2,000 mg levetiracetam daily took 28.6 g of phenytoin and was transferred to our critical care center. The blood phenytoin concentration was 67.9 μg/mL on admission and decreased to 53.4 μg/mL on hospital day 2. Tonic seizures occurred several times on hospital day 2; thus, we resumed levetiracetam via a nasogastric tube. Thereafter, no further seizures were observed. We thought the seizure to have been caused by temporary withdrawal of levetiracetam because it did not occur on the day when the blood phenytoin concentration peaked and stopped altogether after resumption of levetiracetam. We considered that to treat the convulsion attack resulting from an overdose of the other antiepileptic drug with a different action mechanism, it was necessary to promptly restart the administration of the antiepileptic drug, which the patient was usually administered.

Topics: Acute Disease; Adult; Anticonvulsants; Drug Combinations; Drug Overdose; Female; Humans; Levetiracetam; Phenytoin; Seizures

Topics: Anticonvulsants; Antihypertensive Agents; Antineoplastic Agents; Biomarkers, Tumor; Bortezomib; Brain; Disease Management; Disease Progression; Female; Humans; Immunoglobulin kappa-Chains; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Multiple Myeloma; Neurologic Examination; Nimodipine; Nootropic Agents; Oligopeptides; Piracetam; Polyneuropathies; Posterior Leukoencephalopathy Syndrome; Secondary Prevention; Seizures

Traumatic brain injury increases the risk of both early and late seizures. Antiepileptic prophylaxis reduces early seizures, but their use beyond 1 week does not prevent the development of post-traumatic epilepsy. Furthermore, prolonged prophylaxis exposes patients to side effects of the drugs and has occupational implications. The American Academy of Neurology recommends that antiepileptic prophylaxis should be started for patients with severe traumatic brain injury and discontinued after 1 week. An audit is presented here that investigates the use of prophylaxis in a cohort of military patients admitted to the UK Defence Medical Rehabilitation Centre (DMRC).. Data were collected and analysed retrospectively from electronic and paper records between February 2009 and August 2012. The timing and duration of antiepileptic drug use and the incidence of seizures were recorded.. During the study period, 52 patients with severe traumatic brain injury were admitted to the rehabilitation centre: 25 patients (48%) were commenced on prophylaxis during the first week following injury while 27 (52%) did not receive prophylaxis. Only one patient (2%) received prophylaxis for the recommended period of 1 week, 22 patients (42%) received prophylaxis for longer than 1 week with a mean duration of 6.2 months. Two patients (4%) had post-traumatic epilepsy and started on treatment at DMRC.. The use of antiepileptic prophylaxis varies widely and is generally inconsistent with evidence-based guidance. This exposes some patients to a higher risk of early seizures and others to unnecessary use of antiepileptics. Better implementation of prophylaxis is required.

Topics: Adult; Anticonvulsants; Brain Injuries; Carbamazepine; Case-Control Studies; Chemoprevention; Cohort Studies; Humans; Levetiracetam; Military Personnel; Phenytoin; Piracetam; Retrospective Studies; Seizures; Trauma Severity Indices; Valproic Acid

Topics: Adolescent; Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Rhabdomyolysis; Seizures

This study evaluated the effects of different doses of atropine and new antiepileptics, levetiracetam and topiramate, on the development of convulsions triggered by food intake in antimuscarinic-treated fasted animals. Mice deprived of food for 24 h and treated i.p. with atropine at a dose of 2.4 or 24 mg/kg developed convulsions after being allowed to eat ad libitum. No convulsions were observed in fasted animals treated with 0.24 mg/kg atropine. There was no difference in the incidence of convulsions between the two atropine treatments, but latency to convulsions was longer in 24 mg/kg atropine treated animals. The lowest dose of atropine, 0.24 mg/kg, caused stage 1 and stage 2 activity, but did not provide the convulsive endpoint (stage 3, 4, 5 activity). Administration of levetiracetam (50 or 200 mg/kg) or topiramate (50 or 100 mg/kg) to another group of 24-h fasted mice was ineffective in reducing the incidence of convulsions developed in the animals after 2.4 mg/kg atropine treatment and food intake. However, the higher dose of levetiracetam prolonged the onset of convulsions. Present results demonstrated the efficacy of low and high doses of atropine on the development of convulsions in fasted animals and provided additional evidence for the ineffectiveness of antiepileptic treatment in these seizures.

Topics: Animals; Anticonvulsants; Atropine; Eating; Fasting; Fructose; Levetiracetam; Male; Mice, Inbred BALB C; Muscarinic Antagonists; Piracetam; Seizures; Topiramate

Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients.

Topics: Adult; Anesthesia, General; Cerebral Hemorrhage; Emergency Service, Hospital; Heart; Hemangioma, Cavernous, Central Nervous System; Humans; Hypertension; Hypotension; Levetiracetam; Male; Methamphetamine; Myocardial Stunning; Nicardipine; Perioperative Period; Phenylephrine; Piracetam; Seizures; Substance-Related Disorders; Takotsubo Cardiomyopathy

The primary objective of this study was to determine the effectiveness of a lower dose of levetiracetam (500 mg every 12 hours) to prevent early seizures after traumatic brain injury (TBI). It was hypothesized that the seizure rate would be low and comparable to previous studies using phenytoin.. This was a retrospective cohort study conducted in a tertiary care, academic institution that is designated as a level 1 trauma centre in the US. Consecutive patients with TBI were evaluated. Patients who were given a levetiracetam dose of 500 mg every 12 hours were included. The primary outcome was the occurrence of a seizure within 7 days of TBI.. There were a total of 169 patients included in the study, who were treated with levetiracetam 500 mg every 12 hours. The median time to first dose of levetiracetam was 3.5 hours after injury (interquartile range = 1-13 hours). After initiation of levetiracetam, there were four (2.4%) patients who had a seizure within 7 days. This was not significantly different than the hypothesized population value of 3.6% (p = 0.390).. A lower dose of levetiracetam 500 mg every 12 hours after TBI may be effective for early seizure prevention after TBI.

Topics: Adult; Aged; Anticonvulsants; Brain Injuries, Traumatic; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures; Trauma Centers

To evaluate the prevalence of early seizures after levetiracetam prophylaxis in children with moderate to severe traumatic brain injury.. Prospective observational study.. Level 1 pediatric trauma center.. We enrolled 34 patients between the ages of 0-18 years with moderate to severe traumatic brain injury admitted to the PICU at a level 1 trauma center who received levetiracetam for early posttraumatic seizure prophylaxis.. Primary outcome was the prevalence of early posttraumatic seizures that were defined as clinical seizures within 7 days of injury. In 6 of 34 patients (17%), clinical seizures developed despite levetiracetam prophylaxis. An additional two patients had nonconvulsive seizures. This prevalence is similar to that reported in the literature in this patient population who do not receive seizure prophylaxis (20-53%) and is higher than that in patients who receive phenytoin prophylaxis (2-15%). Patients with early posttraumatic seizures were younger (median age, 4 mo) (p < 0.001) and more likely to have suffered from abusive head trauma (p < 0.0004).. Early clinical posttraumatic seizures occurred frequently in children with moderate to severe traumatic brain injury despite seizure prophylaxis with levetiracetam. Younger children and those with abusive head trauma were at increased risk of seizures. Further studies are needed to evaluate the efficacy of levetiracetam before it is routinely used for seizure prophylaxis in these children, particularly in young children and those who have suffered from abusive head trauma.

Topics: Adolescent; Anticonvulsants; Brain Injuries; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Prevalence; Prospective Studies; Seizures; Trauma Centers; Treatment Outcome

We report the case of a man who developed seizures on a background of recurrent metastatic squamous cell carcinoma with intracranial involvement. Initial seizure control with enteral levetiracetam was achieved, and when enteral and intravenous (i.v.) access was no longer available, a continuous subcutaneous infusion (CSCI) of levetiracetam successfully controlled his seizures without the need for sedating anticonvulsants. As a result, end-of-life care was able to be given with the patient retaining the ability to communicate with his family and healthcare staff. This report adds to the sparse but growing evidence base for the use of subcutaneous levetiracetam to manage seizures in palliative and end-of-life care.

Topics: Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Infusions, Subcutaneous; Levetiracetam; Male; Palliative Care; Piracetam; Quality of Life; Scalp; Seizures; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Terminal Care; Treatment Outcome

Topics: Anticonvulsants; Drug Combinations; Female; Humans; Infusions, Subcutaneous; Levetiracetam; Middle Aged; Piracetam; Seizures

We assessed the therapeutic efficacy of FDA-approved anti-epileptic drug Levetiracetam (LEV) to reduce post-traumatic nonconvulsive seizure (NCS) activity and promote neurobehavioral recovery following 10% frontal penetrating ballistic-like brain injury (PBBI) in male Sprague-Dawley rats.. Experiment 1 anti-seizure study: 50 mg/kg LEV (25 mg/kg maintenance doses) was given twice daily for 3 days (LEV3D) following PBBI; outcome measures included seizures incidence, frequency, duration, and onset. Experiment 2 neuroprotection studies: 50 mg/kg LEV was given twice daily for either 3 (LEV3D) or 10 days (LEV10D) post-injury; outcome measures include motor (rotarod) and cognitive (water maze) functions.. LEV3D treatment attenuated seizure activity with significant reductions in NCS incidence (54%), frequency, duration, and delayed latency to seizure onset compared to vehicle treatment. LEV3D treatment failed to improve cognitive or motor performance; however extending the dosing regimen through 10 days post-injury afforded significant neuroprotective benefit. Animals treated with the extended LEV10D dosing regimen showed a twofold improvement in rotarod task latency to fall as well as significantly improved spatial learning performance (24%) in the MWM task.. These findings support the dual anti- seizure and neuroprotective role of LEV, but more importantly identify the importance of an extended dosing protocol which was specific to the therapeutic targets studied.

Topics: Analysis of Variance; Animals; Disease Models, Animal; Electroencephalography; Gait Disorders, Neurologic; Gene Expression Regulation; Head Injuries, Penetrating; Levetiracetam; Male; Maze Learning; Motor Activity; Neuroprotective Agents; Piracetam; Rats; Rats, Sprague-Dawley; Reaction Time; Seizures; Statistics, Nonparametric; Time Factors; Trauma Severity Indices; Treatment Outcome

Rufinamide is a novel antiepileptic drug used as adjunctive therapy in patients with Lennox-Gastaut syndrome and provides seizure control especially in tonic and atonic seizures. Rufinamide is expected to be effective in intractable epilepsy when atonic and tonic seizures exist. However, rufinamide induced seizure aggravation has been reported in a few patients, which was not associated with a specific type of seizure.. A 12-year-old boy with intractable epilepsy had tonic and atonic seizures despite treatment with valproic acid (3000mg/day), levetiracetam (3000mg/day) and clobazam (40mg/day). Rufinamide was administered as adjuvant therapy. After 2weeks on rufinamide, he experienced atonic seizure worsening, and the frequency of epileptic discharges increased. The deterioration in seizure frequency and epileptiform discharges resolved when rufinamide was discontinued.. Rufinamide may aggravate atonic seizures in patients with intractable epilepsy.

Topics: Anticonvulsants; Benzodiazepines; Brain; Child; Clobazam; Drug Resistant Epilepsy; Drug Therapy, Combination; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Seizures; Triazoles; Valproic Acid

Levetiracetam, a second-generation antiepileptic drug, is frequently used for managing partial-onset seizures. About 70% of the administered dose is excreted in urine unchanged, and dosage adjustment is recommended based on the individual's renal function. In this study, a population pharmacokinetic model of levetiracetam was developed using routinely monitored serum concentration data for individualized levetiracetam therapy.. Patients whose serum concentrations of levetiracetam at steady-state were routinely monitored at Kyoto University Hospital from April 2012 to March 2013 were enrolled. The influence of patient characteristics on levetiracetam pharmacokinetics was evaluated using the nonlinear mixed-effects modeling (NONMEM) program.. A total of 583 steady-state concentrations from 225 patients were used for the analysis. The median patient age and estimated glomerular filtration rate (eGFR) were 38 (range: 1-89) years and 98 (15-189) mL·min·1.73 m, respectively. Serum concentration-time data of levetiracetam were well described by a 1-compartment model with first-order absorption. Oral clearance was allometrically related to the individual body weight and eGFR. An increase in the dose significantly increased oral clearance. No improvement in model fit was observed by including the covariate of any concomitant antiepileptic drugs. The population mean clearance for an adult weighing 70 kg and with a normal renal function was 4.8 and 5.9 L/h for 500 mg bis in die (bid) and 1500 mg bid, respectively.. Oral clearance allometrically related with body weight and eGFR can well predict the routine therapeutic drug monitoring data from pediatric to aged patients with varying renal function. Dosage adjustments based on renal function are effective in controlling the trough and peak concentrations in similar ranges.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Body Weight; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Infant; Kidney Function Tests; Levetiracetam; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Piracetam; Retrospective Studies; Seizures; Young Adult

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats.

Topics: Animals; Anticonvulsants; Diazepam; Disease Models, Animal; Drug Resistance; Epilepsy; GABA Antagonists; Levetiracetam; Male; Mice; Pentylenetetrazole; Phenobarbital; Pilocarpine; Piracetam; Rats; Seizures; Status Epilepticus; Valproic Acid

This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.

Topics: Acetamides; Adult; Aged; Anticonvulsants; Combined Modality Therapy; Drug Therapy, Combination; Epilepsies, Partial; Female; Humans; Lacosamide; Levetiracetam; Longitudinal Studies; Male; Middle Aged; Piracetam; Seizures; Treatment Outcome

To determine whether post-traumatic seizure severity would be affected by the interval between seizures and head injury, we measured seizures after various times with or without fluid percussion brain injury (2atm fluid percussion injury; FPI). To determine efficacy of anti-seizure medication, we also determined if levetiracetam (LEV) would alter the relationship between injury and subsequent seizures. Early post-traumatic seizures were induced by Kainic acid (KA) at one week after 2atm fluid percussion injury (FPI) in one group (FPI-ES). Seizures were induced at two weeks after FPI by KA in another group (FPI-LS). In addition, one group had induced seizures by KA without FPI, (sham-ES). Finally one group of animals received the antiepileptic agent (levetiracetam) infusion for one week after FPI and then had seizures induced by KA (FPI-LEV-ES). We measured seizure onset time, ictal duration and severity of seizures using a modified Racine's scale. Histopathological changes in the hippocampus CA1 region were also analyzed. Severity of seizures were increased in the FPI-ES group compared with sham-ES animals. Severity was also enhanced in early post-injury seizures induced by KA (FPI-ES vs. FPI-LS); this exacerbation of seizure severity could be ameliorated by levetiracetam infusion (FPI-ES vs. FPI-LEV-ES). Neuronal degeneration in CA1 was more severe in the FPI-ES group and this degeneration was also diminished by LEV. We conclude that early post injury seizures exacerbate susceptibility and severity of post traumatic seizures and increase neuronal degeneration in the CA1 layer of hippocampus. These changes are partially reversed by LEV infusion after FPI.

Topics: Animals; Anticonvulsants; Brain Injuries, Traumatic; CA1 Region, Hippocampal; Disease Models, Animal; Drug Evaluation, Preclinical; Epilepsy, Post-Traumatic; Kainic Acid; Levetiracetam; Male; Neurons; Neuroprotective Agents; Piracetam; Rats, Sprague-Dawley; Seizures; Severity of Illness Index; Time Factors

Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 %. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures.. All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug.. 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 % (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3-5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 % (36/1795) vs. 0.08 % (3/3756); OR 25.6; 95 % CI 7.8-83.2; p < 0.0001]. Of the patients who had seizures after severe TBI, 25 % (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 %, p = 0.50).. In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 % in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.

Topics: Adolescent; Adult; Anticonvulsants; Brain Injuries, Traumatic; Chemoprevention; Databases, Factual; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Propensity Score; Retrospective Studies; Seizures; Treatment Failure; Young Adult

Traumatic brain injury (TBI) is a major cause of pediatric morbidity and mortality. Secondary injury that occurs as a result of a direct impact plays a crucial role in patient prognosis. The guidelines for the management of severe TBI target treatment of secondary injury. Posttraumatic seizure, one of the secondary injury sequelae, contributes to further damage to the injured brain. Continuous electroencephalography (cEEG) helps detect both clinical and subclinical seizure, which aids early detection and prompt treatment.. The aim of this study was to examine the relationship between cEEG findings in pediatric traumatic brain injury and neurocognitive/functional outcomes.. This study focuses on a subgroup of a larger prospective parent study that examined children admitted to a level-1 trauma hospital. The subgroup included sixteen children admitted to the pediatric intensive care unit (PICU) who received cEEG monitoring. Characteristics included demographics, cEEG reports, and antiseizure medication. We also examined outcome scores at the time of discharge and 4-6weeks postdischarge using the Glasgow Outcome Scale - Extended Pediatrics and center-based speech pathology neurocognitive/functional evaluation scores.. Sixteen patients were included in this study. Patients with severe TBI made up the majority of those that received cEEG monitoring. Nonaccidental trauma was the most frequent TBI etiology (75%), and subdural hematoma was the most common lesion diagnosed by CT scan (75%). Fifteen patients received antiseizure medication, and levetiracetam was the medication of choice. Four patients (25%) developed seizures during PICU admission, and 3 patients had subclinical seizures that were detected by cEEG. One of these patients also had both a clinical and subclinical seizure. Nonaccidental trauma was an etiology of TBI in all patients with seizures. Characteristics of a nonreactive pattern, severe/burst suppression, and lack of sleep architecture, on cEEG, were associated with poor neurocognitive/functional outcome.. Continuous electroencephalography demonstrated a pattern that associated seizures and poor outcomes in patients with moderate to severe traumatic brain injury, particularly in a subgroup of patients with nonaccidental trauma. Best practice should include institution-based TBI cEEG protocols, which may detect seizure activity early and promote outcomes. Future studies should include examination of individual cEEG characteristics to help improve outcomes in pediatric TBI.

Topics: Adolescent; Brain; Brain Injuries, Traumatic; Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Glasgow Outcome Scale; Humans; Infant; Infant, Newborn; Levetiracetam; Longitudinal Studies; Male; Piracetam; Prognosis; Prospective Studies; Seizures; Sleep

Anti-N-methyl-D-aspartate receptor encephalitis is an autoimmune syndrome that presents with personality changes, autonomic dysfunction, and neurologic deterioration. Most patients with this syndrome progress from psychosis to seizure to catatonia, often associated with abnormal movements, autonomic instability, and hypoventilation. First-line treatment constitutes resection of the associated neoplasm, corticosteroids, intravenous immunoglobulin, and plasma exchange. Second-line treatment includes rituximab and cyclophosphamide. A case of confirmed anti-N-methyl-D-aspartate receptor encephalitis is presented that illustrates the diagnostic and treatment challenges associated with this syndrome and underscores the nursing implications of medical management during immunosuppression. This case study recommends surface cooling and a pharmaceutical regimen for management of autonomic storming, which is a hallmark of this disorder.

Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Anticonvulsants; Cyclophosphamide; Fatal Outcome; Female; Headache; Humans; Immunologic Factors; Immunosuppressive Agents; Levetiracetam; Ovarian Neoplasms; Piracetam; Rituximab; Seizures

The library of 27 new 1-(4-phenylpiperazin-1-yl)- or 1-(morpholin-4-yl)-(2,5-dioxopyrrolidin-1-yl)propanamides and (2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents was synthesized. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. Compounds 5, 10, 11, and 24 displayed the broad spectra of activity across the preclinical seizure models, namely, the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-hertz (6 Hz) model of pharmacoresistant limbic seizures. The highest protection was demonstrated by 11 (ED50 MES = 88.4 mg/kg, ED50 scPTZ = 59.9 mg/kg, ED50 6 Hz = 21.0 mg/kg). This molecule did not impair the motor coordination of animals in the chimney test even at high doses (TD50 > 1500 mg/kg), yielding superb protective indexes (PI MES > 16.97, PI PTZ > 25.04, PI 6 Hz > 71.43). As a result, 11 displayed distinctly better safety profile than clinically relevant AEDs ethosuximide, lacosamide, or valproic acid.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Design; Electroshock; HEK293 Cells; Humans; Mice; Models, Molecular; Molecular Structure; Motor Activity; Piperazines; Seizures; Structure-Activity Relationship; Succinimides

Antiepileptic medications have been reported to cause disturbances in cardiac conduction. Lacosamide decreases seizure burden by modulating sodium channels. Although it has been demonstrated to have few side effects, there have been reports of clinically significant cardiac conduction disturbances. We report the case of a child with hypoplastic left-heart syndrome and well-controlled multifocal atrial tachycardia who developed haemodynamically significant atrial tachycardia after receiving two doses of lacosamide.

Topics: Acetamides; Anticonvulsants; Arrhythmias, Cardiac; Child, Preschool; Comorbidity; Humans; Hypoplastic Left Heart Syndrome; Isoxazoles; Lacosamide; Levetiracetam; Male; Piracetam; Seizures; Tachycardia, Sinus; Treatment Outcome; Zonisamide

To clarify the effect of levetiracetam (LEV) for acute and chronic seizure control in acute encephalitis with refractory, repetitive partial seizures (AERRPS).. We retrospectively reviewed the clinical course of six AERRPS cases treated with LEV, and explored the acute phase termination by withdrawal from barbiturate-induced coma under artificial ventilation, and the reduction in seizure frequency during the chronic phase. LEV was administrated orally or via nasogastric tubes as an add-on agent during acute (n=3; age 8-10 years) and chronic (n=3; age 19-30 years) AERRPS.. In the acute phase, administration of LEV (50-60 mg/kg/d) in combination with phenobarbital (n=3; peak 57.9-76.1 μg/ml) and potassium bromide (n=2; 30-36 mg/kg/d)) resulted in successful reduction of intravenous barbiturate dosage and withdrawal from artificial ventilation. In the chronic phase, seizure frequency reduced by >75% for 5-18 months with LEV 750-1500 mg/d.. LEV may affect seizure control in AERRPS, particularly during the chronic phase, through its unique action of inhibition of excitatory neurotransmitter release. The regimen of oral barbiturate, potassium bromide and LEV would be worth for trial during the acute phase of AERRPS.

Topics: Acute Disease; Adolescent; Adult; Anticonvulsants; Bromides; Child; Chronic Disease; Encephalitis; Female; Humans; Levetiracetam; Male; Phenobarbital; Piracetam; Potassium Compounds; Retrospective Studies; Seizures; Status Epilepticus; Young Adult

Brain tumor-related epilepsy (BTRE) is a unique condition that is distinct from primary epilepsy. The aim of this retrospective study was to clarify the epidemiology and results of treatment of BTRE in a single institution. From a database of 121 consecutive patients with supratentorial gliomas treated at Chiba Cancer Center from 2006-2012, the incidence and control of seizures before and after surgery were retrospectively evaluated. Epilepsy occurred in 33.9% of patients before surgery. All patients received prophylactic anti-epileptic drugs (AED) during surgery; however, seizures occurred in 9.1% of patients within the first postoperative week. During follow-up, seizures occurred in 48.3% of patients. The overall incidence of seizures was 73.7% in patients with World Health Organization Grade II gliomas, 66.7% in those with Grade III and 56.8% in those with Grade IV gliomas. Levetiracetam was very well tolerated. However, carbamazepine and phenytoin were poorly tolerated because of adverse effects. AED were discontinued in 56 patients. Fifteen of these patients (26.8%) had further seizures, half occurring within 3 months and 80% within 6 months of AED withdrawal. No clinical factors that indicated it was safe to discontinue AED were identified. The unpredictable epileptogenesis associated with gliomas and their excision requires prolonged administration of AED. To maintain quality of life and to safely and effectively control the tumor, it is necessary to select AED that do not adversely affect cognitive function or interact with other drugs, including anti-cancer agents.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Carbamazepine; Female; Glioma; Humans; Incidence; Japan; Levetiracetam; Male; Middle Aged; Neoplasm Grading; Phenytoin; Piracetam; Retrospective Studies; Seizures

Long-term prophylactic treatment with levetiracetam (LEV) has multiple neuroprotective effects in a traumatic brain injury (TBI) rat model. Although a rational time-frame of seizure prophylactic treatment with LEV for after TBI is not well established, clinical prophylaxis with LEV often includes treatment duration similar to clinical treatment guidelines with Phenytoin. Thus, this study investigated the effects of abbreviated LEV treatment on behavioural function and histological evidence of neuroprotection.. Pre-clinical trial of abbreviated LEV dosing in an experimental model of TBI Methods: After either controlled cortical impact (CCI) injury or sham surgery, rats received three 50 mg kg(-1) doses over 24 hours or vehicle. After injury/sham surgery, beam performance, spatial learning, contusion volume size and hippocampal neuron survival were assessed.. Abbreviated LEV did not improve motor or cognitive performance after TBI. Further, abbreviated LEV did not improve hippocampal neuron sparing or contusion volumes compared with vehicle controls.. Together with previous work assessing daily LEV treatment, these results suggest that longer-term therapy may be required to confer beneficial effects within these domains. These findings may guide (1) future experimental studies assessing minimal effective dosing for neuroprotection and anti-epileptogenesis and (2) treatment guideline updates for seizure prophylaxis post-TBI.

Topics: Animals; Brain Injuries; Contusions; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Hippocampus; Levetiracetam; Male; Neurons; Neuroprotective Agents; Phenytoin; Piracetam; Random Allocation; Rats; Rats, Sprague-Dawley; Seizures; Spatial Learning; Treatment Outcome

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

Topics: Adult; Aged; Anticonvulsants; Blood Cell Count; Blood Cells; Brain Neoplasms; Chemoradiotherapy; Female; Glioblastoma; Hemoglobins; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Valproic Acid; Young Adult

We report a 36-year-old pregnant patient with subtherapeutic trough plasma levels of levetiracetam (LVT) and a breakthrough nocturnal seizure while assuming 3 times a day dosing of the drug. An intensive pharmacokinetic study was performed from immediately before to 11 hours after the morning LVT dose administration and suggested that the patient was not adequately exposed to the drug during the night. After changing the dosing of LVT to 4 times a day, the patient experienced no seizures and delivered a healthy newborn without complications. Afterward, trough plasma levels of LVT remained always within the therapeutic range until delivery, and no major increase of the drug daily dose was required.

Topics: Adult; Anticonvulsants; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Levetiracetam; Piracetam; Pregnancy; Seizures

Despite more than 20 clinically approved antiepileptic drugs (AEDs), there remains a substantial unmet clinical need for patients with refractory (AED-resistant) epilepsy. Animal models of refractory epilepsy are needed for at least two goals; (1) better understanding of the mechanisms underlying resistance to AEDs, and (2) development of more efficacious AEDs for patients with refractory seizures. It is only incompletely understood why two patients with seemingly identical types of epilepsy and seizures may respond differently to the same AED. Prompted by this well-known clinical phenomenon, we previously evaluated whether epileptic rats respond differently to AEDs and discovered AED responsive and resistant animals in the same models. In the present study, we used the same approach for the widely used intrahippocampal kainate mouse model of mesial temporal lobe epilepsy. In a first step, we examined anti-seizure effects of 6 AEDs on spontaneous recurrent focal electrographic seizures and secondarily generalized convulsive seizures in epileptic mice, showing that the focal nonconvulsive seizures were resistant to carbamazepine and phenytoin, whereas valproate and levetiracetam exerted moderate and phenobarbital and diazepam marked anti-seizure effects. All AEDs seemed to suppress generalized convulsive seizures. Next we investigated the inter-individual variation in the anti-seizure effects of these AEDs and, in case of focal seizures, found responders and nonresponders to all AEDs except carbamazepine. Most nonresponders were resistant to more than one AED. Our data further validate the intrahippocampal kainate mouse model as a model of difficult-to-treat focal seizures that can be used to investigate the determinants of AED efficacy.

Topics: Animals; Anticonvulsants; Carbamazepine; Diazepam; Disease Models, Animal; Drug Resistance; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Female; Hippocampus; Kainic Acid; Levetiracetam; Mice; Phenobarbital; Phenytoin; Piracetam; Seizures; Valproic Acid

Levetiracetam is increasingly used as antiepileptic drug (AED) of choice in children as well as in adults with complex diseases due to its lack of interactions and a large spectrum of action. Secondary graft failure, i.e. loss of donor cells after initial engraftment, is a relatively uncommon but serious and life-theatening complication after pediatric hematopoietic stem cell transplantation.. We report a case of secondary graft failure after hematopoietic stem cell transplantation for treatment-related myelodysplastic syndrome during antiepileptic treatment with levetiracetam. Exclusion of all other possible etiologies left levetiracetam as the most likely cause of the imminent complete secondary graft failure after hematopoietic stem cell transplantation. Furthermore, the blood cell count improved just a few days after cessation of levetiracetam medication.. Thus, we recommend that in case of secondary graft failure after hematopoietic stem cell transplantation, all possible causes should carefully be excluded, including adverse events through new generation AED agents. Switching to different AEDs with less harming effect on bone marrow function should strongly be considered.

Topics: Adolescent; Anticonvulsants; Blood Cell Count; Graft Rejection; Hematopoietic Stem Cell Transplantation; Humans; Leukocyte Count; Levetiracetam; Male; Myelodysplastic Syndromes; Phenobarbital; Piracetam; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Seizures; Treatment Failure

We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration.

Topics: Anesthesia, General; Anesthesia, Local; Anticonvulsants; Aphasia; Benzodiazepines; Brain Diseases; Brain Mapping; Brain Neoplasms; Carnitine; Clobazam; Conscious Sedation; Consciousness Disorders; Craniotomy; Dominance, Cerebral; Frontal Lobe; Glioma; Humans; Hyperammonemia; Hypnotics and Sedatives; Intraoperative Complications; Language; Levetiracetam; Male; Middle Aged; Piperidines; Piracetam; Propofol; Remifentanil; Seizures; Temporal Lobe; Valproic Acid

The 6 Hz model of focal seizures has been increasingly used to identify anticonvulsant compounds with potential activity against therapy-resistant epilepsy, but the protective response to anticonvulsants in this model could be dependent on experimental conditions and selection of mouse strains.. Seizure thresholds in the 6 Hz model were compared in CF-1, NMRI, and C57Bl/6J male mice with two different electrical stimulators (Ugo Basile 5780 and Grass S48). Dose-response curves for phenytoin and levetiracetam were generated in the three strains at 32 and 44 mA current intensities using both devices. Plasma and brain exposure to the two drugs were measured in all three strains.. CF-1 mice had the lowest seizure threshold and responded to phenytoin at 32 mA stimulation intensity, but not at 44 mA. NMRI and C57Bl/6J mice had nearly identical threshold values, but NMRI mice responded well to phenytoin at 32 mA and showed limited responsiveness to this drug at 44 mA, whereas C57Bl/6J mice were nearly completely resistant to phenytoin. Furthermore, levetiracetam showed limited efficacy and low potency in CF-1 and C57Bl/6J mice, particularly at 44 mA, whereas in NMRI mice the drug showed much higher potency in all experimental conditions. No obvious difference in the pharmacokinetics of both phenytoin and levetiracetam was detected between the mouse strains that would have explained these unexpected variations in potency. We have also found that the protective effects of both drugs may be influenced by the device type.. Collectively these observations clearly indicate that treatment resistance of 6 Hz seizures should be interpreted with strain and experimental conditions in mind. Furthermore, it is important to note that strain differences, much like human genetic differences, may explain why some mice and patients respond to a given treatment and others do not.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroshock; Levetiracetam; Male; Mice; Phenytoin; Piracetam; Psychomotor Performance; Seizures; Treatment Outcome

There is strong evidence for the use of the ketogenic diet (KD) in Dravet syndrome (DS). The purpose of this study was to evaluate both effectiveness and tolerability in comparison with various antiepileptic drugs (AEDs).. 32 children (19 males) with genetically confirmed DS treated at our center since 1999 were analyzed retrospectively. Data collected from patients' files included type of mutation, age at treatment initiation and treatment lag, overall seizure frequency and frequency of different seizure types, especially prolonged seizures and status epilepticus (SE). Efficacy and safety of the KD were evaluated. In addition, the effect on seizure count was compared with that of various AED regimen and the vagus nerve stimulation (VNS).. Overall response to the KD was 70% at 3 months and 60% at 12 months. No SE occurred while patients were on the diet, and the frequencies of prolonged generalized and myoclonic seizures were reduced. No severe side effects requiring withdrawal of the KD were observed. Although the effect of the KD was independent of age at initiation, it had to be withdrawn due to noncompliance more frequently in solid fed older children compared with infants treated with the liquid ketogenic formula. The KD was not significantly inferior to the current gold standard AED triple combination of Stiripentol+Valproate+Clobazam (89%), Bromides (78%), Valproate alone (48%), Topiramate (35%) and VNS (37%) and significantly more effective than Levetiracetam (30%; p=0.037, Pearson's Chi-square).. These data suggest that the KD ranks among currently used AEDs as an effective treatment for seizures in DS. According to our results (good effect on SE and prolonged seizures, good tolerability, less compliance problems due to formula treatment) the KD should be considered as an early treatment option in infants with DS.

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Bromides; Child; Child, Preschool; Clobazam; Diet, Ketogenic; Dioxolanes; Epilepsies, Myoclonic; Female; Fructose; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Topiramate; Treatment Outcome; Vagus Nerve Stimulation; Valproic Acid; Young Adult

Epilepsy with electrical status epilepticus in sleep (ESES) is a devastating disease, and we sought to evaluate the efficacy of levetiracetam (LEV) for the treatment of patients with this epileptic encephalopathy in China.. Clinical data from all patients with ESES who received LEV therapy at our pediatric neurology outpatient clinic between 2007 and 2014 (n=71) were retrospectively analyzed. The LEV dosage was 30-50mg/kg/day. Electroencephalography recordings and neuropsychological evaluations were performed repeatedly for 3-75months after the start of LEV therapy.. Thirty-five (70%) of 50 patients who had seizures at the start of LEV therapy had a >50% reduction in seizure frequency. Positive response on EEG was found during the first 3-4months of LEV therapy in 32 (45%) of 71 patients, with normalization of EEG in 5 patients. Relapse occurred in 8 (25%) of the initial electrical responders. Hence, 47 patients (66%) still suffered from ESES and only 13 patients regained their baseline level of function at the last follow-up. The response to LEV was significantly associated with ESES duration, age at onset of ESES, and etiology of epilepsy. Although fatigue and anorexia were the primary adverse events, LEV was well-tolerated by all patients.. Levetiracetam is safe and may be efficient when used to treat ESES syndrome; however, the efficacy EEG neuropsychological outcomes is limited on the whole.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; China; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Seizures; Sleep Wake Disorders; Status Epilepticus; Treatment Outcome

Mesial temporal lobe epilepsy (MTLE) is the most prevalent type of partial epileptic disorders. In this study, we have analyzed the impact of levetiracetam (LEV) in the pilocarpine model of MTLE.. Sprague-Dawley rats (n=19) were injected with pilocarpine (380 mg/kg, i.p.) to induce a status epilepticus. Twelve animals were used as controls and seven were treated with LEV. They were implanted with bipolar electrodes in the CA3 subfield of the hippocampus, entorhinal cortex (EC), dentate gyrus (DG) and subiculum and EEG-video monitored continuously from day 4 to day 14 after SE.. Only 29% of LEV-treated animals had seizures compared to all controls following a latent period that was similar in duration. Seizure rates were lower in LEV-treated animals. In LEV-treated animals without seizures, lower interictal spike rates were found in all regions compared to controls. Analysis of interictal high-frequency oscillations (HFO s) revealed that LEV-treated animals without seizures had lower rates of interictal spikes with ripples (80-200 Hz) in CA3, EC and subiculum (p<0.01), whereas rates of interictal spikes with fast ripples (250-500 Hz) were significantly lower in CA3 and subiculum, compared to controls.. Our findings indicate that the anti-ictogenic properties of LEV are mirrored by decreases of interictal spike rate in temporal lobe regions, and are accompanied by subregion-specific decreases of HFO occurrence in CA3 and subiculum. Overall, this evidence suggest that LEV may inhibit neural network activity in regions that are known to play important roles in MTLE.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electrodes, Implanted; Electroencephalography; Epilepsy, Temporal Lobe; Hippocampus; Levetiracetam; Male; Periodicity; Pilocarpine; Piracetam; Rats, Sprague-Dawley; Seizures; Treatment Outcome; Video Recording

Intravenous levetiracetam is an option for treatment of status epilepticus (SE) and acute repetitive seizures (ARS). However, there have been relatively few studies with children and adolescents. Also, an appropriate dosage has yet to be determined.. This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents.. Retrospectively, the study reviewed the medical records of 19 male and 31 female patients under 18 years of age who had received intravenous levetiracetam treatment either for acute repetitive seizures or for convulsive status epilepticus. The patients were admitted between April 1st, 2010 and December 31st, 2011 to the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Data were collected on underlying illnesses, etiology of seizures, indication for levetiracetam therapy, initial dosage, rate of infusion, untoward effects during infusion and emerged complications. Efficacy of treatment was defined as the termination of seizure within 30 min of completing levetiracetam infusion and no seizure recurrence within 6 h of initial treatment.. The age range of the 50 patients was from one day to 18 years (mean 79.6 months). The analysis included 52 episodes of 34 acute repetitive seizures (63.4%) and 18 convulsive status epilepticus (34.6%). Infusion rates ranged from 2 to 66 mg/kg/min (mean 29.6). Cessation of seizure was obtained in 59.6% of 52 episodes. Patients with underlying drug resistant epilepsy did not respond to levetiracetam therapy as well as patients with other etiology of seizures. There were no adverse drug reactions or untoward effects observed during the therapy.. Intravenous administration of levetiracetam is safe and effective for treatment of acute repetitive seizures and convulsive status epilepticus in children and adolescents. Failure of treatment may be related to underlying drug resistant epilepsy. Further study of appropriate initial dosage and pharmacokinetic variations in the patients is needed as possible explanation of the unresponsiveness.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Status Epilepticus; Thailand

Treatment-resistant seizures affect about a third of patients suffering from epilepsy. To fulfill the need for new medications targeting treatment-resistant seizures, a number of rodent models offer the opportunity to assess a variety of potential treatment approaches. The use of such models, however, has proven to be time-consuming and labor-intensive. In this study, we performed pharmacological characterization of the allylglycine (AG) seizure model, a simple in vivo model for which we demonstrated a high level of treatment resistance. (d,l)-Allylglycine inhibits glutamic acid decarboxylase (GAD) - the key enzyme in γ-aminobutyric acid (GABA) biosynthesis - leading to GABA depletion, seizures, and neuronal damage. We performed a side-by-side comparison of mouse and zebrafish acute AG treatments including biochemical, electrographic, and behavioral assessments. Interestingly, seizure progression rate and GABA depletion kinetics were comparable in both species. Five mechanistically diverse antiepileptic drugs (AEDs) were used. Three out of the five AEDs (levetiracetam, phenytoin, and topiramate) showed only a limited protective effect (mainly mortality delay) at doses close to the TD50 (dose inducing motor impairment in 50% of animals) in mice. The two remaining AEDs (diazepam and sodium valproate) displayed protective activity against AG-induced seizures. Experiments performed in zebrafish larvae revealed behavioral AED activity profiles highly analogous to those obtained in mice. Having demonstrated cross-species similarities and limited efficacy of tested AEDs, we propose the use of AG in zebrafish as a convenient and high-throughput model of treatment-resistant seizures.

Topics: Allylglycine; Animals; Anticonvulsants; Diazepam; Disease Models, Animal; Fructose; Levetiracetam; Male; Mice; Phenytoin; Piracetam; Seizures; Topiramate; Treatment Outcome; Valproic Acid; Zebrafish

Retrospective studies can complement information derived from double-blinded randomized trials. There are multiple retrospective studies reporting good efficacy and tolerability of the anti-epileptic drug levetiracetam (LEV) in human patients with epilepsy; however, reports of LEV's tolerability and efficacy in dogs with epilepsy remain limited. The purpose of this retrospective study was to describe the use of LEV in a canine epilepsy clinic and determine the long-term efficacy and tolerability of LEV in veterinary clinical practice. The electronic database of a UK based referral hospital was searched for LEV usage in dogs with seizures. Information and data necessary for the evaluation were obtained from a combination of electronic and written hospital records, the referring veterinary surgeons' records and telephone interviews with dog owners. Only dogs that were reportedly diagnosed with idiopathic epilepsy were included in the study.. Fifty-two dogs were included in this retrospective study. Two treatment protocols were recognised; 29 dogs were treated continuously with LEV and 23 dogs received interval or pulse treatment for cluster seizures. LEV treatment resulted in 69% of dogs having a 50% or greater reduction of seizure frequency whilst 15% of all the dogs were completely free from seizures. Seizure frequency reduced significantly in the whole population. No dog was reported to experience life-threatening side effects. Mild side effects were experienced by 46% of dogs and a significantly higher number of these dogs were in the pulse treatment group. The most common side-effects reported were sedation and ataxia.. LEV appears to be effective and well tolerated for reduction of seizures.

Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy; Female; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Hypokalemia; Levetiracetam; Magnesium Deficiency; Piracetam; Seizures

TO determine neuroprotective properties of levetiracetam and simvastatin using rats with pilocaroine-induced epilepsy.. Epileptic rat models were randomly divided into 4 groups, each being exposed to saline, simvastatin, levetiracetam, or levetiracetam + simvastatin. Brain tissues of the rats were examined. Nissl staining was used to determine pilocarpine-induced neuronal loss in CA1 and CA3 of hippocampus. Western blot was used to detect calpain-1 expression of hippocampus.. Severe cell death was found 24 h after seizures, with a level significantly higher than the controls. Compared with the saline-treated cells, simvastatin did not decrease severe cell death (P>0.05), but levetiracetam and levetiracetam+simvastatin decreased severe cell death 24 h after seizures (P<0.05). No significant differences were found between those treated with levetiracetam and those with levetiracetam+simvastatin. Compared with controls, overexpressed calpain-1 was found in the rats 24 h after seizures, which indicates that calpain-1 may be involved in the pathophysiological mechanisms of epilepsy. Compared with those treated with pilocarpine + saline, simvastatin, levetiracetam and levetiracetam + simvastatin reduced the level of calpain-1 24 h after seizures (P<0.05).. Levetiracetam, not simvastatin, possesses neuroprotective properties, through changing calpain-1 expression levels. But levetiracetam plus simvastatin treatment does not have advantages over the choice of monotherapy. Simvastain does not possess neuroprotective properties at the early stage of epilepsy.

Topics: Animals; Calpain; Disease Models, Animal; Epilepsy; Hippocampus; Levetiracetam; Pilocarpine; Piracetam; Rats; Seizures; Simvastatin

Levetiracetam (LEV) is a unique, effective, relatively safe antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). This study aimed to explore the effect of combined treatment of LEV with omega 3 (OM3) on cognitive impairment and hippocampal oxidative stress and DNA damage induced by seizures in the PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats pretreated with single and combined treatment of LEV (30mg/kg, i.p.) and OM3 (200mg/kg, p.o.). Pretreatment with LEV and OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, the increase in hippocampal glutamate, malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase and superoxide dismutase activities induced by PTZ kindling, significantly decreased. These effects were higher with combined treatment of LEV with OM3 and significantly more than the observed effects of single LEV or OM3. In conclusion, the combined treatment of LEV with OM3 is more effective in seizure control and alleviating the cognitive impairment induced by PTZ kindling in the young rat model, the effects that result from the decrease in hippocampal oxidative stress and DNA damage which can be attributed to the antioxidant properties of both LEV and OM3. These results may be promising for the use of LEV and OM3 combination in the treatment of epileptic children.

Topics: Animals; Anticonvulsants; Anxiety; Avoidance Learning; Cognition Disorders; Convulsants; DNA Damage; Drug Synergism; Fatty Acids, Omega-3; Hippocampus; Kindling, Neurologic; Levetiracetam; Male; Oxidative Stress; Pentylenetetrazole; Piracetam; Rats; Rats, Wistar; Seizures

Brain metastases occur in about 30% of patients with non-small-cell lung carcinoma; seizures occur in approximately 20% of them. Antiepileptic drugs are commonly given for postoperative prophylaxis after brain or metastasis tumor surgery. The incidence of seizures following supratentorial craniotomy is estimated to be 15%-20%. Postoperative seizures are more common in the first month after cranial surgery. However, the use of antiepileptic drugs postoperatively has been investigated in randomized controlled trials. In case of seizures, the recommendations are continuing antiepileptic drugs after a 1- to 4-year seizure-free interval. This decision must weigh the risk of seizure recurrence against the possible benefits of the drug. Some antiepileptic drugs have been known to cause blood dyscrasias, including neutropenia, but this is a rare occurrence.. We report a case of neutropenia related to the use of levetiracetam at first exposure. After drug administration, neutropenia was detected. Additional tests were performed.. By exclusion, it was decided to withdraw the drug, and the patient had a reversal of neutropenia.. Levetiracetam-induced neutropenia is infrequent but possible. It is an exclusion diagnosis.

Topics: Adenocarcinoma; Anticonvulsants; Brain Neoplasms; Craniotomy; Drug Administration Schedule; Humans; Levetiracetam; Lung Neoplasms; Male; Middle Aged; Neutropenia; Piracetam; Seizures

To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography.. The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model.. The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures.

Topics: Animals; Brain; Carbamates; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Electroshock; Levetiracetam; Male; Mice; Models, Statistical; Phenylenediamines; Piracetam; Seizures

Several factors may influence the efficacy of antiepileptic drugs (AEDs) in patients with epilepsy, and treatment resistance could be related to genetics, neuronal network alterations, and modification of drug transporters or targets. Consequently, preclinical models used for the identification of potential new, more efficacious AEDs should reflect at least a few of these factors. Previous studies indicate that induction of status epilepticus (SE) may alter drug efficacy and that this effect could be long-lasting. In this context, we wanted to assess the protective effects of mechanistically diverse AEDs in mice subjected to pilocarpine-induced SE in another seizure model. We first determined seizure thresholds in mice subjected to pilocarpine-induced SE in the 6-Hz model, 2 weeks and 8 weeks following SE. We then evaluated the protective effects of mechanistically diverse AEDs in post-SE and control animals. No major differences in 6-Hz seizure susceptibility were observed between control groups, while the seizure threshold of pilocarpine mice at 8 weeks after SE was higher than at 2 weeks and higher than in control groups. Treatment with AEDs revealed major differences in drug response depending on their mechanism of action. Diazepam produced a dose-dependent protection against 6-Hz seizures in control and pilocarpine mice, both at 2 weeks and 8 weeks after SE, but with a more pronounced increase in potency in post-SE animals at 2 weeks. Levetiracetam induced a potent and dose-dependent protection in pilocarpine mice, 2 weeks after SE, while its protective effects were observed only at much higher doses in control mice. Its potency decreased in post-SE mice at 8 weeks and was very limited (30% protection at the highest tested dose) in the control group. Carbamazepine induced a dose-dependent protection at 2 weeks in control mice but only limited effect (50% at the highest tested dose) in pilocarpine mice. Its efficacy deeply decreased in post-SE mice at 8 weeks after SE. Perampanel and phenytoin showed almost comparable protective effects in all groups of mice. These experiments confirm that prior SE may have an impact on both potency and efficacy of AEDs and indicate that this effect may be dependent on the underlying epileptogenic processes. This article is part of a Special Issue entitled "Status Epilepticus".

Topics: Animals; Anticonvulsants; Carbamazepine; Diazepam; Disease Models, Animal; Levetiracetam; Male; Mice; Phenytoin; Pilocarpine; Piracetam; Seizures; Status Epilepticus; Treatment Outcome

Alpha lipoic acid is a powerful antioxidant widely used for the supplementary treatment of diabetic neuropathy. Intoxication with alpha lipoic acid is very rare. There is no reported dose of safety in children.. A 14-month-old previously healthy girl was referred to our hospital with the diagnosis of drug intoxication. She was admitted to the emergency department with lethargy and continuing involuntary movements for several hours after she had ingested an unknown amount of alpha lipoic acid. On admission she was lethargic and had myoclonic seizures involving all extremities. She had no fever and laboratory examinations were normal except for mild metabolic acidosis. The seizures were unresponsive to bolus midazolam, phenytoin infusion and levetiracetam infusion. She was taken to the pediatric intensive care unit with the diagnosis of status epilepticus. After failure of the treatment with midazolam infusion she was intubated and thiopental sodium infusion was started. Her myoclonic seizures were controlled with thiopental sodium infusion. After 48 h intubation and mechanical ventilation thiopental sodium was gradually reduced and then stopped. Following the withdraw of thiopental sodium, she was seizure free on her discharge on the 8th day.. Alpha lipoic acid and derivatives cause side effects in children like refractory convulsions. They are frequently rendered as vitamins by diabetic patients and are left at places where children can easily access them. Therefore, when faced with refractory convulsions in children who have had no disease before, intoxication by medicaments with alpha lipoic acid should be taken into consideration.

Topics: Anticonvulsants; Epilepsies, Myoclonic; Female; Humans; Infant; Levetiracetam; Midazolam; Piracetam; Respiration, Artificial; Seizures; Status Epilepticus; Thioctic Acid; Thiopental

The six hertz (6 Hz) refractory seizure model is considered an indispensable chain of the Anticonvulsant Screening Project. We here describe an adapted protocol using the intracerebroventricular (i.c.v.) delivery route, which will allow researchers to perform targetvalidation or proof-of-principle studies using promising compounds with unknown or limited blood-brain barrier permeability (e.g. neuropeptides and peptidomimetics) in this model. Seizures were induced by single application of a current intensity of 49 mA to i.c.v.-implanted NMRI mice using an ECT Unit 57800 Ugo Basile stimulator. By applying these key parameters, c-Fos immunohistochemistry revealed the recruitment of the dentate gyrus, ratifying this model as a valuable tool for testing i.c.v. administered compounds against therapy-resistant seizures. This finding was further strengthened, since i.c.v. administration of levetiracetam suppressed 6 Hz-evoked seizure severity but sodium phenytoin did not. We also propose to use "seizure duration" as an alternative, accurate parameter to express the results within this model.

Topics: Animals; Anticonvulsants; Blood-Brain Barrier; Capillary Permeability; Catheters, Indwelling; Cornea; Dentate Gyrus; Disease Models, Animal; Electric Stimulation; Immunohistochemistry; Injections, Intraventricular; Levetiracetam; Mice; Phenytoin; Piracetam; Proto-Oncogene Proteins c-fos; Seizures

Levetiracetam is considered by many clinicians to be one of the most benign antiepileptic medications available. We report the case of a 24-year-old man presenting with seizures for which he was started on levetiracetam. Despite an extensive work-up and treatment of possible infectious and noninfectious issues, the patient remained intermittently febrile. When a marked peripheral eosinophilia was noted, the patient's levetiracetam was discontinued and phenytoin prescribed. The fever resolved within 24 hours, and the patient's eosinophilia count returned to normal limits following discharge back to his long-term care facility. We estimate the probability of this reaction related to levetiracetam as probable based on a score of 7 on the Naranjo scale. Clinicians should be aware of the possibility that levetiracetam may be an offending agent in a patient with unexplained fever and eosinophilia. These may be early signs of the progression to a more serious drug hypersensitivity reaction, such as drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome.

Topics: Anticonvulsants; Eosinophilia; Fever; Humans; Levetiracetam; Male; Piracetam; Seizures; Young Adult

We performed a retrospective chart analysis in neonates routinely treated with levetiracetam (LEV) in a university setting. Patients and Methods We assessed clinical characteristics of the included neonates. Documented LEV doses and the duration of treatment were evaluated. To assess LEV effectiveness, we compared the need of any additional anticonvulsant as co- and rescue therapies before and following the initiation of LEV treatment. To assess LEV tolerance, we sought to identify documented adverse drug reactions resulting in a termination of LEV treatment.. We analyzed a total of 72 neonates receiving LEV with a median gestational age at initiation of LEV treatment of 30 (4/7) gestational weeks (min., 24(5/7)/max., 43(0/7) weeks). LEV was applied in target doses of 41.7 mg/kg/d (min., 14.4/max., 106.2 mg/kg/d). Patients received LEV treatment at hospital for a median of 28 days (min., 1/max., 195 days). Additional anticonvulsant therapy decreased a week after LEV treatment was initiated (p = 0.008). We did not find any cases of terminated LEV treatment resulting from adverse drug reactions.. Long term use of high LEV doses is rather frequent in immature neonates. Our data indicate good effectiveness and a low risk of adverse drug reactions.

Topics: Anticonvulsants; Female; Germany; Gestational Age; Hospitals, University; Humans; Infant, Newborn; Infant, Premature; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent.

Topics: Animals; Anticonvulsants; Antidotes; Body Weight; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Lethal Dose 50; Levetiracetam; Male; Nerve Agents; Organophosphate Poisoning; Organophosphates; Organophosphorus Compounds; Organothiophosphorus Compounds; Oximes; Piracetam; Procyclidine; Pyridinium Compounds; Rats; Rats, Wistar; Seizures; Soman

To elucidate the mechanisms that regulate p-glycoprotein (PGP) expression and function in pharmacoresistant epilepsy, we investigated the effect of an ETB receptor antagonist (BQ788) and a p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190) on intractable seizures in chronic epileptic rats.. Lithium-pilocarpine-induced chronic epileptic rats were used in the present study. Animals were given levetiracetam (LEV), LEV + SB202190, LEV + BQ788, SB202190 or BQ788 over a 3-day period using an osmotic pump. Seizure activity was recorded by video-EEG monitoring with 2h of recording per day at the same time of day. We also performed western blot after EEG analysis.. Compared to control animals, PGP, ETB receptor and p38MAPK expression was increased in the hippocampus of epileptic animals. Neither SB202190 nor BQ788 affected the spontaneous seizure activity in epileptic rats. Three of ten rats were responders and achieved complete seizure control or significant reduction in seizure activity by LEV. In four of ten rats, seizure frequency was unaltered by LEV (non-responders). LEV + SB202190 reduced seizure duration, but not seizure frequency, in both responders and non-responders. LEV + BQ788 alleviated seizure frequency and seizure duration in both responders and non-responders. Compared to responders, PGP and ETB receptor expression was enhanced in the hippocampus of non-responders.. To the best of our knowledge, these findings are the first indications of the role of ETB receptor in pharmacoresistant epilepsy. Therefore, the present data suggest that the regulation of the ETB receptor-mediated signaling pathway may be important for identification of new therapeutic strategies for improving antiepileptic drug efficacy.

Topics: Animals; Anticonvulsants; Brain; Chronic Disease; Disease Models, Animal; Endothelin B Receptor Antagonists; Enzyme Inhibitors; Epilepsy; Imidazoles; Levetiracetam; Male; Oligopeptides; p38 Mitogen-Activated Protein Kinases; Piperidines; Piracetam; Pyridines; Rats, Sprague-Dawley; Receptor, Endothelin B; Seizures; Treatment Outcome

After liver transplantation, patients may develop seizures or epilepsy due to a variety of etiologies. The ideal antiepileptic drugs for these patients are those with fewer drug interactions and less hepatic toxicity. In this study, we present patients using levetiracetam to control seizures after liver transplantation. We retrospectively enrolled patients who received levetiracetam for seizure control after liver transplantation. We analyzed the etiology of liver failure that required liver transplantation, etiology of the seizures, outcomes of seizure control, and the condition of the patient after follow-up at the outpatient department. Hematological and biochemical data before and after the use of levetiracetam were also collected. Fifteen patients who received intravenous or oral levetiracetam monotherapy for seizure control after liver transplantation were enrolled into this study. All of the patients remained seizure-free during levetiracetam treatment. Two patients died during the follow-up, and the other 13 patients were alive at the end of the study period and all were seizure-free without neurological sequelae that interfered with their daily activities. No patients experienced liver failure or rejection of the donor liver due to ineffective immunosuppressant medications. The dosage of immunosuppressants did not change before and after levetiracetam treatment, and there were no changes in hematological and biochemical data before and after treatment. Levetiracetam may be a suitable antiepileptic drug for patients who undergo liver transplantation due to fewer drug interactions and a favorable safety profile.

Topics: Adult; Anticonvulsants; Drug Monitoring; End Stage Liver Disease; Female; Humans; Levetiracetam; Liver Transplantation; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Taiwan; Treatment Outcome

An 11-year-old boy was admitted with fever followed by convulsions. He had developed aphasia subsequent to this illness. His birth history was unremarkable, and he had normal growth and development including of language, hearing and vision. His neurological examination was normal except for aphasia. Investigations including cerebrospinal fluid study and MRI were normal. However, EEG was abnormal and the boy was diagnosed as a case of Landau-Kleffner syndrome (LKS) and treated with sodium valproate, levetiracetam and steroids. He responded well to treatment and has been on follow-up for the last 4 months. We present this case of LKS to increase awareness about early diagnosis and to highlight the importance of appropriate management for a better outcome.

Topics: Anticonvulsants; Aphasia; Asia, Southeastern; Child; Electroencephalography; Humans; Landau-Kleffner Syndrome; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Seizures; Steroids; Valproic Acid

Topics: Drug Compounding; Drug Design; Humans; Levetiracetam; Piracetam; Printing, Three-Dimensional; Seizures; Tablets

A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing. A brain MRI showed gyral swelling with increased T2 fluid-attenuated inversion recovery signal and diffusion restriction in the left cerebral cortex. Neuroendocrine findings suggested panhypopituitarism with centrally derived adrenal insufficiency. Supportive treatment, hormone supplementation, antibiotics, antivirals and levetiracetam yielded clinical improvement. A follow-up brain MRI showed focal left parieto-occipital atrophy with findings of cortical laminar necrosis. In conclusion, we describe a case of NF1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like findings, hitherto unreported manifestations of NF1. Prompt recognition and treatment of these associated conditions can prevent devastating complications.

Topics: Adult; Anti-Bacterial Agents; Anticonvulsants; Antiviral Agents; Brain Diseases; Cafe-au-Lait Spots; Diarrhea; Fluid Therapy; Functional Neuroimaging; Hormone Replacement Therapy; Humans; Hypopituitarism; Levetiracetam; Magnetic Resonance Imaging; Male; Nerve Sheath Neoplasms; Neurofibromatosis 1; Piracetam; Seizures; Stroke; Testosterone; Treatment Outcome

A series of fluorinated analogs of the potent investigative anticonvulsant agent (4S,8aS)-4-phenylperhydropyrrolo[1,2-a]pyrazine-2,6-dione 1 was prepared and characterized by IR, 1H, 13C NMR and mass spectral data. The compounds have been evaluated in the in vivo rodent models of epilepsy. They displayed high activity in the 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests as well as in the 6Hz model of pharmacoresistant limbic seizures. The results showed that incorporating fluorine atoms into the phenyl ring of 1 can be beneficial for the anticonvulsant potency. The most promising meta-trifluoromethyl and meta-trifluoromethoxy derivatives (4S,8aS)-5h and (4S,8aS)-5l, respectively, displayed very broad spectra of activity across the preclinical seizure models.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Epilepsy; Halogenation; Hydrocarbons, Fluorinated; Male; Mice; Molecular Structure; Pentylenetetrazole; Pilocarpine; Pyrazines; Pyrroles; Rats; Rats, Sprague-Dawley; Seizures; Structure-Activity Relationship

The natural compounds carvacrol and thymol completely prevented seizures in the 6 Hz, 32 mA partial seizure model. Carvacrol and thymol, both exhibited an ED₅₀ = 35.8 mg/kg, ip and yielded protective indices of 5.3 and 3.4, respectively. At 44 mA current intensity, carvacrol and thymol exhibited ED₅₀s of 88.82 mg/kg (PI = 2.15) and 73.0 mg/kg (PI = 1.65), respectively. Thymol, but not carvacrol showed partial inhibitory activity in the maximal electroshock (MES), sc Metrazol (scMET) and Corneal-kindled models. These results suggest that carvacrol and thymol are more efficacious anticonvulsants than suggested by their lower efficacies in the conventional MES and scMET tests.

Topics: Animals; Anticonvulsants; Cymenes; Disease Models, Animal; Monoterpenes; Phenols; Psychomotor Performance; Seizures; Thymol

The aim of the presented study was to characterize the anticonvulsant effects of levetiracetam in combination with various antiepileptic drugs (carbamazepine, phenytoin, topiramate and vigabatrin) in the mouse 6Hz psychomotor seizure model. Limbic (psychomotor) seizure activity was evoked in albino Swiss mice by a current (32mA, 6Hz, 3s stimulus duration) delivered via ocular electrodes; type II isobolographic analysis was used to characterize the consequent anticonvulsant interactions between the various drug combinations for fixed-ratios of 1:1, 1:2, 1:5 and 1:10. With type II isobolographic analysis, the combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; P<0.01) in terms of seizure suppression, while the combinations for the fixed-ratios of 1:1 and 1:2 were additive. Levetiracetam combined with topiramate and vigabatrin for the fixed-ratio of 1:10 exerted supra-additive interaction (P<0.05), and simultaneously, the two-drug combinations for the fixed-ratios of 1:1, 1:2 and 1:5 produced additive interaction in the mouse 6Hz psychomotor seizure model. The combinations of levetiracetam with carbamazepine and phenytoin for the fixed-ratios of 1:5 and 1:10, as well as the combinations of levetiracetam with topiramate and vigabatrin for the fixed-ratio of 1:10 appear to be particularly favorable combinations exerting supra-additive interaction in the mouse 6Hz psychomotor seizure model. Finally, it may be concluded that because of the synergistic interactions between levetiracetam and carbamazepine, phenytoin, topiramate and vigabatrin, the combinations might be useful in clinical practice.

Topics: Animals; Anticonvulsants; Avoidance Learning; Carbamazepine; Disease Models, Animal; Drug Combinations; Drug Interactions; Fructose; Hand Strength; Levetiracetam; Male; Mice; Phenytoin; Piracetam; Psychomotor Performance; Seizures; Topiramate; Vigabatrin

Neonatal seizures are often refractory to treatment with initial antiseizure medications. Clinicians turn to agents such as levetiracetam despite the paucity of published data regarding its safety, tolerability, or efficacy in the neonatal population.. We describe a neonate who developed anaphylactic shock developing after receiving intravenous levetiracetam.. This is the first neonate to develop anaphylactic shock due to intravenous administration of levetiracetam.. Clinicians should be aware of this potentially fatal adverse effect occurring with intravenous levetiracetam in newborns.

Topics: Anaphylaxis; Anticonvulsants; Asphyxia Neonatorum; Contraindications; Drug Eruptions; Exanthema; Face; Fetal Distress; Humans; Infant, Newborn; Infusions, Intravenous; Leg; Levetiracetam; Piracetam; Pneumothorax; Scalp; Seizures

Seizure prophylaxis is used in a variety of conditions, including supratentorial intracranial hemorrhage (ICH). In adults, studies have demonstrated phenytoin as the drug of choice for seizure prophylaxis; in children, levetiracetam is often provided due to its favorable side effect profile and pharmacokinetics. This study evaluated the difference in efficacy between these treatment options.. This retrospective review included 126 patients between 1 month and 17 years of age with acute supratentorial ICH; all received seizure prophylaxis. Demographic data and outcome assessments were compared.. Seizure prophylaxis was provided with (fos)phenytoin in 40 children, levetiracetam in 61 children, and both drugs in 25 patients. Baseline characteristics of the treatment groups were similar, except that more patients treated with (fos)phenytoin had seizures on presentation. Patients treated solely with (fos)phenytoin had a higher probability of early seizures (within 7 days of ICH) compared with those treated only with LVT, controlling for relevant variables including seizures on presentation (OR 24.6, p = 0.002). Patients treated with (fos)phenytoin were more likely to need additional antiepileptic drugs for seizure control (p = 0.005). There was no significant difference in the incidence of late seizures (> 7 days after ICH) (p = 0.265). Adverse events necessitating a change in therapy were uncommon.. Levetiracetam is a reasonable alternative to (fos)phenytoin for prophylaxis of early posthemorrhagic seizures. Levetiracetam and (fos)phenytoin are well tolerated in children. Prospective studies are needed to determine superiority, optimal dosing, and impact on long-term outcomes.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Incidence; Infant; Intracranial Hemorrhages; Levetiracetam; Male; Phenytoin; Piracetam; Primary Prevention; Retrospective Studies; Seizures; Treatment Outcome

This study reviews our experience with the safety and tolerability of levetiracetam (LVM) with different methods of intravenous administration in intensive care unit (ICU) patients. We used retrospective chart review to identify 33 ICU patients who received intravenous LVM for treatment of seizures. Collected data included age, gender, diagnosis on admission, dosing regimen, documented seizure activity, adverse reactions, concomitant use of other antiepileptic drugs, and condition on discharge. A total of 33 ICU patients were given intravenous (IV) LVM as add-on treatment to standard regimen for treatment of breakthrough seizures or status epilepticus or given as preventive medication postoperatively. Among these 33 patients, 16 received intravenous LVM as bolus, and 17 received intravenous LVM as continuous infusion. Safety and tolerability of intravenous LVM were evaluated on the basis of the occurrence of adverse or side effects reported in daily progress notes of the physicians and nurses. There were no significant adverse or side effects reported in daily progress notes. The addition of intravenous LVM to the standard regimen for controlling seizures in ICU patients seems feasible and tolerable.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Infusions, Intravenous; Intensive Care Units; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome; Young Adult

Topics: Acetamides; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Humans; Lacosamide; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Neurologic Examination; Piracetam; Seizures; Toothbrushing

Although both levetiracetam and phenytoin are used for seizure prophylaxis in subdural hematomas (SDHs), there is little data on their comparative efficacies. We compared the efficacy and risk of using levetiracetam versus phenytoin for seizure prophylaxis following acute or subacute SDH diagnosis.. In this retrospective cohort study, the clinical data registry at a tertiary care hospital was searched for all cases of acute or subacute SDHs that were admitted to hospital in 2002, 2003, or 2011. Risk of clinical and/or electrographic seizures, and risk of adverse drug events were compared between the two exposure arms.. 124 subjects in the phenytoin arm and 164 subjects in the levetiracetam arm were included. There was no significant difference in clinical and/or electrographic seizure risk, though there was a decreased risk of adverse events in the levetiracetam arm (p < 0.001). In subjects with midline shift >0 mm, levetiracetam was associated with an increased risk of electrographic seizures during hospitalization (p = 0.028) and a decreased risk of adverse drug effects (p = 0.001), compared with phenytoin use.. Levetiracetam generally appears to have a similar efficacy to phenytoin in preventing clinical and/or electrographic seizures following acute/subacute SDH diagnosis, though patients with midline shift >0 mm may have associated with a higher risk of electrographic seizures on levetiracetam compared with patients on phenytoin. Levetiracetam is associated with a lower risk of adverse drug effects. A prospective, randomized study would more definitively determine any difference in efficacy and risk between phenytoin and levetiracetam.

Topics: Aged; Anticonvulsants; Female; Hematoma, Subdural; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures

A 41-year-old man, during a neurological consultation, reported "chin twitching" over a period of a week, which was diagnosed as intermittent perioral myoclonia. With only one tonic-clonic seizure seven years before, he had mentioned several episodes of chin twitching over the years. In the clinic, there were intermittent chin movements without apparent confusion, as he was able to provide a complete history and was fully oriented with intact memory. His video-EEG showed paroxysms of polyspike and slow-wave activity, with the longest burst-free interval being 20 seconds. Discharges were maximal over the fronto-central regions, correlating with the chin myoclonus. He was able to tap his hand continuously, and remained alert. The case represents an atypical presentation of idiopathic generalised epilepsy without manifestation of absence or limb myoclonus. Although juvenile myoclonic epilepsy and other idiopathic epilepsies are rarely associated with perioral myoclonia, this sign was the principal clinical feature for this patient. Oral treatment with levetiracetam resolved his seizures.

Topics: Adult; Diagnosis, Differential; Electroencephalography; Humans; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Piracetam; Seizures; Treatment Outcome; Video Recording

Levetiracetam (LEV) therapeutic range (20-40mg/L) and potential drug interactions were assessed in people with epilepsy (PWE).. Fifty-two PWE had LEV and concomitant medications [carbamazepine (CBZ); valproate (VPA); lamotrigine (LTG)] blood levels measured and compared to seizure activity. Lacosamide (LCM) levels were unavailable. Adopted therapeutic ranges were: 20-40mg/L - LEV; 25-50μmol/L - total CBZ; 6-13μmol/L - free CBZ; 300-750μmol/L - total VPA; 30-75μmol/L - free VPA; and 40-60μmol/L - LTG. Seizure-freedom was assessed and patients followed for almost two years.. 23 of 52 PWE (44%) used LEV monotherapy and 16/23 (70%) had 'therapeutic' LEV with 13/16 (81%) seizure-free. 29 of 52 (56%) used polytherapy and 16/29 (55%) had 'therapeutic' LEV with 7/16 (44%) seizure-free. 11 of 29 (38%) used CBZ: 4/11 (36%) had therapeutic mean LEV levels and 7/11 (64%) were seizure-free. Fourteen (48%) used VPA: 9/14 (64%) had therapeutic mean LEV levels and 8/14 (57%) were seizure-free. 13 of 29 (45%) used LTG: 8/13 (62%) had therapeutic mean LEV levels and 5/13 (38%) were seizure-free. LEV did not alter CBZ, but CBZ affected LEV. LEV elevated VPA free levels but not VPA total levels. Dosage/concentration was lowered with polytherapy.. LEV range (20-40mg/L) assisted epilepsy management and anti-epileptic medication interactions were suggested with polytherapy thus possibly explaining the impaired efficacy of LEV with polytherapy.

Topics: Adult; Aged; Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Valproic Acid; Young Adult

Levetiracetam is a frequently used drug in the therapy of partial onset, myoclonic and generalized tonic-clonic seizures. The main route of elimination is via the kidneys, which eliminate 66% of the unchanged drug as well as 24% as inactive metabolite that stems from enzymatic hydrolysis. Therefore dose adjustments are needed in patients with chronic kidney disease stage 5 D, i.e. patients undergoing dialysis treatment. In this patient population a dose reduction by 50% is recommended, so that patients receive 250-750 mg every 12 hours. However "dialysis" can be performed in using different modalities and treatment intensities. For most of the drugs pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis are not available. This is the first report on levetiracetam pharmacokinetics in a peritoneal dialysis patient.. A 73-y-old Caucasian male (height: 160 cm, weight 93 kg, BMI 36.3 kg/m2) was admitted with a Glasgow Coma Scale of 10. Due to diabetic and hypertensive nephropathy he was undergoing peritoneal dialysis for two years. Eight weeks prior he was put on levetiracetam 500 mg twice daily for suspected partial seizures with secondary generalization. According to the patient's wife, levetiracetam lead to fatigue and somnolence leading to trauma with fracture of the metatarsal bone. Indeed, even 24 hours after discontinuation of levetiracetam blood level was still 29.8 mg/l (therapeutic range: 12 - 46 mg/l). Fatigue and stupor had disappeared five days after discontinuation of the levetiracepam. A single dose pharamockinetic after re-exposure showed an increased half life of 18.4 hours (normal half life 7 hours) and levetiracetam content in the peritoneal dialysate. Both half-life and dialysate content might help to guide dosing in this patient population.. If levetiracetam is used in peritoneal dialysis patients it should be regularly monitored to avoid supratherapeutic levels that could lead to severe sequelae.

Topics: Aged; Anticonvulsants; Fatigue; Humans; Levetiracetam; Male; Metabolic Clearance Rate; Peritoneal Dialysis; Piracetam; Renal Insufficiency, Chronic; Seizures; Treatment Outcome

Mediastinal lymphoma with neoplastic invasion into the heart was diagnosed in a 9-year-old castrated male domestic short hair cat. The neoplastic infiltrate was seen throughout the atria and atrial septum, surrounded the aortic root, and resulted in narrowing of the right ventricular outflow tract. Chemotherapy resulted in resolution of the echocardiographic abnormalities and the cat's clinical signs until the patient was euthanized 58 days later following development of neurologic signs. Mediastinal lymphoma with myocardial invasion and response to chemotherapy has not been documented previously in the veterinary literature.

Topics: Animals; Anticonvulsants; Antineoplastic Agents; Asparaginase; Cat Diseases; Cats; Drug Therapy, Combination; Echocardiography; Euthanasia, Animal; Fatal Outcome; Heart Neoplasms; Levetiracetam; Lomustine; Lymphoma; Male; Mediastinal Neoplasms; Neoplasm Invasiveness; Piracetam; Seizures

Topics: Anticonvulsants; Electroencephalography; Female; Humans; Infant; Levetiracetam; Mouth Protectors; Oral Ulcer; Piracetam; Recurrence; Seizures

The use of levetiracetam for the treatment of epilepsy in women of childbearing age has increased as more evidence of teratogenicity of other broad-spectrum antiepileptic medications becomes available. Levetiracetam appears to be associated with a low incidence of major congenital malformations based on data from pregnancy registries. Major pregnancy-related changes in the pharmacokinetics of levetiracetam have been described in several case series, demonstrating a role for careful therapeutic drug monitoring of levetiracetam in pregnant patients. Extended-release levetiracetam provides a way to improve medication adherence in adults with epilepsy by allowing once/day dosing and may be considered for use in pregnancy to minimize the fluctuation of levetiracetam levels throughout the day, thus potentially minimizing dose-related adverse effects. In this case report, we describe a 16-year-old, compliant, pregnant patient who experienced subtherapeutic levetiracetam blood concentrations that occurred with use of extended-release levetiracetam. She experienced a breakthrough seizure with once/day dosing during her third trimester with low subsequent trough levels despite multiple dose increases. After changing to twice/day dosing of extended-release levetiracetam at delivery, the patient experienced no seizures and delivered a healthy infant without complications. This is the first case report, to our knowledge, to describe seizure breakthrough during pregnancy with an extended-release formulation of an antiepileptic medication. Pharmacokinetic changes associated with pregnancy may increase apparent clearance of extended-release formulations of levetiracetam, leading to periods of subtherapeutic blood or central nervous system concentrations. These changes support the important role of therapeutic monitoring of levetiracetam plasma concentrations to help maintain seizure control in women with epilepsy during pregnancy.

Topics: Adolescent; Anticonvulsants; Delayed-Action Preparations; Female; Humans; Infant, Newborn; Levetiracetam; Male; Piracetam; Pregnancy; Pregnancy Complications; Seizures

Quercetin is one of the most widely occurring flavonoid which is also often present in plants as glycosidic form - rutin. These compounds are ingredients of plant diet and are also present in numerous pharmaceutical preparations and diet supplements which are taken by patients suffering from epilepsy and treating with antiepileptic drugs (AEDs). Influence of these compounds on central nervous system-related effects was proved both in experimental and clinical studies. Their influence on anxiety, depression, memory processes and convulsant activity was reported. The aim of the present study was to investigate the effect of quercetin and rutin in some models of seizures, i.e., in the model of psychomotor seizures induced by 6Hz stimulation, in the maximal electroshock seizure threshold and intravenous pentylenetetrazole tests in mice. We also examined a possible mechanism of anticonvulsant activity of quercetin and its influence on action of two AEDs, i.e., valproic acid and levetiracetam, in the 6Hz seizure test. Our results revealed only a weak anticonvulsant potential of the studied flavonoids because they showed anticonvulsant action at doses from 10 to 200mg/kg only in the 6Hz test and did not change seizure thresholds in the remaining tests. Moreover, anticonvulsant action of the studied flavonoids was short-term, noted only at pretreatment time ranging between 30 and 60min. The highest anticonvulsant activity of quercetin was correlated with its high plasma and brain concentration, which was revealed in a pharmacokinetic study. We did not note changes in the anticonvulsant action of the used AEDs combined with quercetin in the model of psychomotor seizures in mice. Neither quercetin and rutin nor combinations of quercetin with the studied AEDs produced any significant impairments of motor coordination (assessed in the chimney test), muscular strength (investigated in the grip-strength test) and long-term memory (evaluated in the passive avoidance test) in mice. The results of the present study suggest that quercetin and rutin have only weak and short-term anticonvulsant potential. These flavonoids seem to be safe for patients with epilepsy because they neither changed activity of the studied AEDs nor produced any adverse effects.

Topics: Animals; Anticonvulsants; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electric Stimulation; Levetiracetam; Male; Memory, Long-Term; Mice; Muscle Strength; Pentylenetetrazole; Piracetam; Psychomotor Performance; Quercetin; Rutin; Seizures; Time Factors; Valproic Acid

Levetiracetam (LEV), used for both partial and generalized seizures, is a frequently preferred antiepileptic because of its few side effects. We present a 23-year-old man who developed hypokalemia after switching from valproate to LEV. The patient was sent to our clinic due to hypokalemia 1 month after initiation of LEV, and his neurological examination was normal. Further examinations revealed hypokalemia (3.1 mmol/L) and hypomagnesaemia (0.56 mmol/L). His hemogram, blood urea nitrogen, creatinine, total cortisol, thyroid function tests, creatinine clearance, and renal Doppler ultrasound were normal. LEV was tapered off and treatment with 200mg/day lamotrigine begun. Potassium and magnesium levels returned to normal ranges in subsequent tests. While hypokalemia and hypomagnesaemia have not been reported before to our knowledge, interstitial nephritis and renal failure after the use of LEV have been. Hypokalemia, found in the early period in this case, may be an indicator of a recently developed renal tubular disorder. This experience indicates that unpredictable side effects of increasingly used new antiepileptic drugs should be taken into consideration.

Topics: Adult; Anticonvulsants; Humans; Hypokalemia; Lamotrigine; Levetiracetam; Magnesium; Male; Nephritis, Interstitial; Piracetam; Potassium; Risk Factors; Seizures; Triazines; Valproic Acid

Current guidelines recommend against the use of phenytoin following aneurysmal subarachnoid hemorrhage (aSAH) but consider other anticonvulsants, such as levetiracetam, acceptable. Our objective was to evaluate the risk of poor functional outcomes, delayed cerebral ischemia (DCI) and delayed seizures in aSAH patients treated with levetiracetam versus phenytoin. Medical records of patients with aSAH admitted between 2005-2012 receiving anticonvulsant prophylaxis with phenytoin or levetiracetam for >72 hours were reviewed. The primary outcome measure was poor functional outcome, defined as modified Rankin Scale (mRS) score >3 at first recorded follow-up. Secondary outcomes measures included DCI and the incidence of delayed seizures. The association between the use of levetiracetam and phenytoin and the outcomes of interest was studied using logistic regression. Medical records of 564 aSAH patients were reviewed and 259 included in the analysis after application of inclusion/exclusion criteria. Phenytoin was used exclusively in 43 (17%), levetiracetam exclusively in 132 (51%) while 84 (32%) patients were switched from phenytoin to levetiracetam. Six (2%) patients had delayed seizures, 94 (36%) developed DCI and 63 (24%) had mRS score >3 at follow-up. On multivariate analysis, only modified Fisher grade and seizure before anticonvulsant administration were associated with DCI while age, Hunt-Hess grade and presence of intraparenchymal hematoma were associated with mRS score >3. Choice of anticonvulsant was not associated with any of the outcomes of interest. There was no difference in the rate of delayed seizures, DCI or poor functional outcome in patients receiving phenytoin versus levetiracetam after aSAH. The high rate of crossover from phenytoin suggests that levetiracetam may be better tolerated.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Brain Ischemia; Female; Follow-Up Studies; Hematoma; Humans; Incidence; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures; Severity of Illness Index; Subarachnoid Hemorrhage; Time Factors; Treatment Outcome; Young Adult

Levetiracetam is an antiepileptic medication that has been reported to be both well-tolerated and effective in treating generalized tonic-clonic, myoclonic, and partial-onset seizures. The adverse effects most commonly reported in tolerability trials include somnolence, fatigue/asthenia, headaches, dizziness, and nausea. However, there have been a few reports suggesting possible detrimental effects of levetiracetam on renal function.. Here we describe the case of a previously healthy 23-year-old female patient who developed acute kidney injury 1 day after the initiation of levetiracetam therapy for new-onset seizures.. Based on the time course of the patient's rise in serum creatinine and the exclusion of other causes, this case suggests that levetiracetam use contributed to the acute kidney injury.. Levetiracetam is a widely used drug that has been reported to be generally tolerable and effective; however, it has the potential to negatively affect renal function. This potential consequence of therapy should be considered when deciding whether or not to prescribe this medication, and renal function should be monitored during treatment.

Topics: Acute Kidney Injury; Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Seizures; Young Adult

To assess the effectiveness of the newer antiepileptic drugs (AEDs)-in particular lamotrigine, topiramate, and levetiracetam-in controlling epileptic seizures in pregnant women.. Analysis of data in the Australian Register of Antiepileptic Drugs in Pregnancy concerning seizure control in 1,534 pregnancies in women with AED-treated epilepsies.. In AED monotherapy (1,111 pregnancies), use of levetiracetam in pregnancies in the Australian Register was associated with levels of seizure control similar to those that applied for the major older AEDs carbamazepine and valproate, but with levels of seizure control superior to those associated with use of lamotrigine and topiramate.. Levetiracetam shows promise as a satisfactory drug for controlling seizures in pregnancy.

Topics: Anticonvulsants; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Piracetam; Pregnancy; Registries; Seizures; Topiramate; Treatment Outcome; Triazines; Victoria

We present a case of a 24-year-old woman with abnormal behaviour of recent onset. She had been diagnosed previously with epilepsy and had been started on antiepileptic medication. Clinical examination confirmed features of psychosis including paranoid delusions and auditory hallucination. Neurological examination showed nystagmus and dysmetria. Further evaluation revealed the underlying cause for her symptoms. She responded promptly to appropriate therapy with complete resolution of psychosis.

Topics: Adult; Anticonvulsants; Epilepsy; Female; Hallucinations; Humans; Levetiracetam; Neuropsychological Tests; Phenytoin; Piracetam; Psychotic Disorders; Seizures; Treatment Outcome

Much debate exists on the optimal medication for posttraumatic seizure prophylaxis after traumatic brain injury (TBI). There is some evidence that levetiracetam (LEV) could be neuroprotective and provide long-term benefits in this patient population.. The primary objective was to compare the Glasgow Outcome Scale-Extended (GOS-E) 6 months or more after severe TBI. Secondary end points were presence of early seizures (0 to 7 days post-TBI) or late seizures (8 days post-TBI to phone interview), use of anticonvulsant medication when interviewed, medication-related hospital complications, and a summary of phenytoin (PHT) and LEV dosing regimens.. This was an IRB-approved, single-center, prospective cohort analysis. Patients were identified by cross-referencing a list of patients receiving LEV or PHT, with a list of patients with ICD-9 code consistent with TBI. After study inclusion, patients were contacted by telephone, and the GOS-E was administered. Data for secondary end points were gathered by retrospective chart review.. In all, 19 patients were included in the final analysis. There was no difference in the GOS-E score assessed ≥6 months after injury (5.07±1.69 vs 5.60±2.07, P=0.58). There was no difference in the secondary end points of early seizures (P=0.53) or late seizures (P=0.53). However, the PHT group experienced a higher rate of hospital days with recorded fever (0.20±0.22 vs 0±0; P=0.014).. Long-term functional outcome in patients who experienced a TBI was not affected by treatment with PHT or LEV; however, patients treated with PHT had a higher incidence of fever during hospitalization.

Topics: Adult; Aged; Anticonvulsants; Brain Injuries; Female; Humans; Levetiracetam; Male; Mental Status Schedule; Middle Aged; Phenytoin; Piracetam; Prospective Studies; Seizures

Levetiracetam has been proven to be effective in both partial and generalized seizures in children. However, few studies have reported its efficacy in the treatment of acute repetitive seizures. We aimed to investigate the efficacy and safety of levetiracetam in children with acute repetitive seizures.. The medical records of children from the age of 1 month-18 years who received levetiracetam because of acute repetitive seizures in the pediatric intensive care unit between 2010 and 2013 were reviewed retrospectively.. Of the 133 patients, levetiracetam terminated seizures in 104 (78.2%). Side effects such as agitation and aggression were observed in three patients (2.2%). The likelihood of treatment failure was increased by four times by younger age at seizure onset; by six times in the individuals with neurological abnormalities; and by 22 times in the patients with West syndrome. The patients who used levetiracetam as the first treatment option for acute repetitive seizures had a longer duration of epilepsy, a higher rate of neurological abnormality, and a higher proportion of medically resistant epilepsy compared with the individuals who used levetiracetam as an add-on treatment to the other intravenous antiepileptic drugs. However, no differences were detected between these two groups in terms of treatment response.. Intravenous levetiracetam appears to be effective and safe in the treatment of acute repetitive seizures. Randomized clinical trials are needed to determine whether intravenous levetiracetam may replace other antiepileptic drugs as the first-line therapy in the management of acute repetitive seizures.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Injections, Intravenous; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Retrospective Studies; ROC Curve; Seizures; Statistics, Nonparametric

Levetiracetam (LEV) and tiagabine (TGB) are utilized for the treatment of seizures, including neonatal seizures. However, relatively little is known about the preclinical therapeutic profile of these drugs during brain development. The relative paucity of information regarding these drugs in neonatal animals may be due to their unusual profile of anticonvulsant action in experimental models. LEV and TGB are without effect against seizures in several common screening models (e.g., the maximal electroshock test, maximal pentylenetetrazole seizures), instead showing preferential efficacy against models of partial seizures. We have recently described a method for reliably evoking partial seizures in neonatal animals by systemic administration of the chemoconvulsant, DMCM (Kulick et al., 2014, Eur. J. Pharmacol., doi:10.1016/j.ejphar.2014.06.012). DMCM is a negative allosteric modulator of GABAA receptors, and offers a wide separation between doses required to evoke complex partial as compared to tonic-clonic seizures. Here we used DMCM to evaluate the effect of LEV and TGB against seizures in postnatal day (P) 10 rat pups. We compared the profile of LEV and TGB to that of phenobarbital (PB), the most widely utilized anticonvulsant in neonates. We found that LEV significantly protected against DMCM seizures when administered in doses of 10mg/kg and greater. TGB protected against DMCM-evoked seizures when administered in doses of 1mg/kg or greater. PB protected against DMCM-evoked seizures when administered in doses of 5mg/kg or greater. These data provide preclinical evidence for the efficacy of LEV and TGB in neonates and underscore the utility of DMCM for screening anticonvulsant action in neonatal animals.

Topics: Animals; Animals, Newborn; Anticonvulsants; Carbolines; Levetiracetam; Male; Nipecotic Acids; Phenobarbital; Piracetam; Rats; Rats, Sprague-Dawley; Seizures; Tiagabine

Sudden unexplained/unexpected death (SUDEP) is related to high mortality in patients with epilepsy. The prolongation of QT interval, involved in cardiac arrhythmia-related SUDEP, may be precipitated by antiepileptic drugs (AEDs). In this study, we evaluated the effects of phenobarbital and levetiracetam on PR-QTc intervals in patients with post-stroke seizures.. We performed an open-label, parallel group, prospective, multicenter study between June 2009 and December 2013 in patients older than 18 years of age with a clinical diagnosis of post-stroke seizure and treated with phenobarbital or levetiracetam. In order to exclude a role of cerebral post-stroke injury on modulation of PR and QTc intervals, patients with cerebral post-stroke injury and without seizures were also enrolled as controls.. Interictal electrocardiography analysis revealed no significant difference in PR interval between patients treated with an AED (n = 49) and control patients (n = 50) (181.25 ± 12.05 vs. 182.4 ± 10.3 ms; p > 0.05). In contrast, a significantly longer QTc interval was recorded in patients treated with an AED compared with control patients (441.2 ± 56.6 vs. 396.8 ± 49.3 ms; p < 0.01). Patients treated with phenobarbital showed a significantly longer QTc interval than patients treated with levetiracetam (460.0 ± 57.2 vs. 421.5 ± 50.1 ms; p < 0.05).. The study reported that in patients with late post-stroke seizures, phenobarbital prolonged QTc interval more so than levetiracetam.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Levetiracetam; Long QT Syndrome; Male; Middle Aged; Phenobarbital; Piracetam; Prospective Studies; Risk Factors; Seizures; Single-Blind Method; Stroke; Treatment Outcome

Hypertension and heart failure belong to common comorbid conditions with epilepsy so drug interactions between antiepileptics and cardiovascular drugs are possible in clinical practice. The aim of this study was to evaluate the effects of angiotensin AT1 receptor antagonists (losartan potassium and candesartan cilexetil), angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril arginine) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of levetiracetam (LEV) in mice.. The protective action of LEV was examined in the maximal electroshock seizure threshold test. Drugs were administered intraperitoneally (ip). Additionally, combinations of cardiovascular drugs with LEV were tested for adverse effects in the passive avoidance task and the chimney test.. Losartan potassium (50mg/kg), candesartan cilexetil (8mg/kg), captopril (50mg/kg), hydrochlorothiazide (100mg/kg) and ethacrynic acid (100mg/kg) did not affect the anticonvulsant activity of LEV. Perindopril arginine (10mg/kg) raised the convulsive threshold for LEV administered at doses of 100, 300 and 500mg/kg. This interaction could be pharmacodynamic in nature because the brain concentration of LEV remained unchanged by perindopril. The adverse effects of the combined treatment with LEV and cardiovascular drugs were not observed in the passive avoidance task or the chimney test.. Although experimental data can be hardly extrapolated to clinical practice, it is suggested that perindopril arginine may positively influence the anticonvulsant action of LEV in epileptic patients. The use of losartan potassium, candesartan cilexetil, captopril, hydrochlorothiazide or ethacrynic acid in patients treated with LEV seems neutral regarding its anticonvulsant activity.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anticonvulsants; Avoidance Learning; Cardiovascular Agents; Disease Models, Animal; Diuretics; Dose-Response Relationship, Drug; Drug Interactions; Electroshock; Injections, Intraperitoneal; Levetiracetam; Mice; Piracetam; Seizures

To explore the effects of levetiracetam (LEV) on the changes of bone mineral density (BMD) and bone metabolism in the treatment of middle-aged and elderly patients with generalized tonic-clonic seizures.. A total of 112 patients with generalized tonic-clonic seizures from October 2012 to March 2014 were selected and divided into LEV and non-medication groups according to therapeutic methods (n = 56 each). LEV was administered to LEV group at an initial dosage of 500 mg twice daily. The same dose of LEV could be added every 2 or 3 weeks based on clonic seizure condition and tolerance. And the maximal dosage was 2 000 mg. The therapeutic duration was ≥ 6 months. No anti-seizure drug was offered for non-medication group. Another 50 healthy subjects served as control group. After 6-month treatment the clinical efficacy of LEV group was evaluated. BMD was detected with bone sonometer (DPX-L) and serum levels of blood calcium (Ca), blood phosphorus (P), alkaline phosphatase and parathyroid hormone were also detected in control group, pre-treatment in non-medication group and post-treatment in LEV group.. The rate of abnormal bone volume in non-medication (28.6%) and LEV groups (48.2%) were evidently higher than that in control group (4.0%) (P < 0.05). And it was apparently higher in LEV group than that in non-medication group (P < 0.05). BMD decreased obviously at post-treatment than pre-treatment (P < 0.05). And the post-treatment levels of Ca and P decreased markedly [(2.12 ± 0.19) vs (2.32 ± 0.23) mmol/L; (0.96 ± 0.01) vs (1.23 ± 0.12) mmol/L] while serum levels of alkaline phosphatase and parathyroid hormone increased significantly in LEV group than pre-treatment [(66 ± 6) vs (33 ± 3) µg/L; (62 ± 5) vs (34 ± 3) pmol/L, P < 0.05]. The clinical efficacy of LEV treatment at 1 month was similar to that at 6 months (both 98.21%). And the difference was insignificant (P > 0.05).. Single use of LEV is efficacious in the treatment of middle-aged and elderly patients with generalized tonic-clonic seizures. However, both disease and anti-seizure drugs have certain effects on BMD. And long-term application of LEV may lead to bone metabolism dysfunction to some extent.

Topics: Aged; Alkaline Phosphatase; Anticonvulsants; Bone and Bones; Bone Density; Humans; Levetiracetam; Middle Aged; Parathyroid Hormone; Piracetam; Seizures; Treatment Outcome

The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and then aminoalkylation reaction (Mannich-type) with formaldehyde and corresponding secondary amines, which let to obtain the final compounds 9a-d, 10a-d, 11a-d and 12a-d in good yields. Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The most effective compounds in mice were tested after oral administration in rats. The acute neurological toxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective especially in the MES test (model of human tonic-clonic seizures). The most active in the MES seizures in rats was 1-[(4-benzyl-1-piperidyl)methyl]-3-(2-chlorophenyl)pyrrolidine-2,5-dione (10c) which showed ED50 value of 37.64mg/kg. It should be stressed that this molecule along with 9a, 9d and 10d showed protection in the psychomotor seizure test (6-Hz), which is known as an animal model of therapy-resistant epilepsy. Furthermore compounds 9a, 9d and 10d were also tested in the pilocarpine-induced status prevention (PISP) test to assess their potential effectiveness in status epilepticus. For the most promising molecule 9d an influence on human CYP3A4 isoform of P-450 cytochrome was studied in vitro.

Topics: Administration, Oral; Animals; Anticonvulsants; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Disease Models, Animal; Drug Design; Electroshock; Humans; Male; Mannich Bases; Mice; Microsomes, Liver; Motor Activity; Pentylenetetrazole; Protein Binding; Pyrrolidines; Rats; Rats, Sprague-Dawley; Seizures; Structure-Activity Relationship

Current guidelines for traumatic brain injury (TBI) recommend antiepileptic drugs (AEDs) for 7 days after injury to decrease posttraumatic seizure risk. Phenytoin decreases seizure risk 73% vs placebo during this time. Levetiracetam (LEV) is an alternative; however, no published data validate comparable efficacy. Our objective was to evaluate seizure incidence 7 days after TBI in patients treated with phenytoin (PHT) vs LEV and to characterize practice of AED selection.. A retrospective observational study was conducted using a Trauma Registry (Collector Trauma Registry; Digital Innovation, Inc, Forrest Hill, Md) to evaluate patients with TBI. Patients with an initial Head/Neck Abbreviated Injury Scale score of 3 or higher and a Glasgow Coma Scale of 8 or less were included.. Of 109 patients, 89 received PHT, and 20, LEV. Two patients experienced posttraumatic seizure, 1 in each group. Sixty-eight patients survived to hospital discharge; 65% received prophylactic AED greater than 7 days. Ninety-eight percent of 81 patients admitted between 2000 and 2007 received PHT, whereas 64% of 28 patients admitted between 2008 and 2010 received LEV.. Only 2 patients experienced posttraumatic seizure after receiving AED, indicating low incidence. Most surviving to hospital discharge received AED prophylaxis greater than 7 days despite guideline recommendations. After approval of intravenous LEV, a trend favoring LEV was observed.

Topics: Abbreviated Injury Scale; Adult; Anticonvulsants; Brain Injuries; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Registries; Retrospective Studies; Seizures; Treatment Outcome

Prophylactic antiseizure drugs (PAD) are commonly prescribed for non-traumatic intracerebral hemorrhage (ICH) despite limited evidence for this indication. We sought to determine the current prescribing patterns of the use of a PAD for ICH.. A 36-item survey was distributed to physicians who manage ICH patients soliciting details of PAD prescription in their practice.. A total of 199 physicians responded to the survey, all of who manage 50 or more ICH patients per year. The respondents were neurologists (32%), neurosurgeons (11%), and intensivists (57%) in academia (69%) and private practice (31%). Prophylactic antiseizure drugs prescriptions used: never (33%), 1-33% (35%), 34-66% (14%), 67-99% (9%) of the time, or always (9%). Most respondents performed electroencephalographic and serum level monitoring in at least some patients. Levetiracetam was used most often (60%), followed by fosphenytoin (37%), for a usual duration of days (36%), weeks (47%), or months (17%). Prophylactic antiseizure drugs prescription varied by patient characteristics and physician specialty. Perception of physician community consensus regarding PAD use for ICH among respondents ranged from strongly (7%) or weakly (23%) against the practice, to a fairly equal division of opinion (41%), to weakly (27%) or strongly (4%) in favor of the practice.. We found variability of multiple aspects of the current prescribing patterns and opinions regarding the use of a PAD for ICH. This variability is likely secondary to insufficient data. Clinical equipoise exists for this issue, and controlled trials would be both justified and useful.

Topics: Anticonvulsants; Brain; Cerebral Hemorrhage; Drug Prescriptions; Drug Utilization; Electroencephalography; Humans; Levetiracetam; Phenytoin; Piracetam; Practice Patterns, Physicians'; Seizures; Surveys and Questionnaires

Topics: Anticonvulsants; Benzodiazepines; Bradycardia; Brain Diseases; Cerebral Cortex; Clobazam; Drug Resistance; Electroencephalography; Heart Arrest; Humans; Lamotrigine; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Seizures; Triazines

In this case series we report on eight neonates with refractory seizures who received intravenous levetiracetam when seizures did not respond to two or more conventional anticonvulsants. Six of the eight neonates had an excellent response with either cessation, or reduction in seizures by at least 80%. One neonate showed a partial response while one did not have any reduction in seizure frequency. We did not encounter any adverse effects that could be attributable to levetiracetam.

Topics: Administration, Intravenous; Anticonvulsants; Electroencephalography; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Levetiracetam; Piracetam; Seizures; Treatment Outcome

To examine the efficacy of valproic acid (VPA) given either with or without levetiracetam (LEV) on seizure control and on survival in patients with glioblastoma multiforme (GBM) treated with chemoradiation.. A retrospective analysis was performed on 291 patients with GBM. The efficacies of VPA and LEV alone and as polytherapy were analyzed in 181 (62%) patients with seizures with a minimum follow-up of 6 months. Cox-regression survival analysis was performed on 165 patients receiving chemoradiation with temozolomide of whom 108 receiving this in combination with VPA for at least 3 months.. Monotherapy with either VPA or LEV was instituted in 137/143 (95.8%) and in 59/86 (68.6%) on VPA/LEV polytherapy as the next regimen. Initial freedom from seizure was achieved in 41/100 (41%) on VPA, in 16/37 (43.3%) on LEV, and in 89/116 (76.7%) on subsequent VPA/LEV polytherapy. At the end of follow-up, seizure freedom was achieved in 77.8% (28/36) on VPA alone, in 25/36 (69.5%) on LEV alone, and in 38/63 (60.3%) on VPA/LEV polytherapy with ongoing seizures on monotherapy. Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.. Polytherapy with VPA and LEV more strongly contributes to seizure control than does either as monotherapy. Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Drug Therapy, Combination; Female; Follow-Up Studies; Glioblastoma; Humans; Levetiracetam; Male; Middle Aged; Neoplasm Recurrence, Local; Piracetam; Prognosis; Retrospective Studies; Seizures; Survival Rate; Temozolomide; Valproic Acid; Young Adult

Topics: Adult; Anticonvulsants; Autoantibodies; Autoantigens; Brain; Dystonia; Female; Functional Laterality; Humans; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Levetiracetam; Magnetic Resonance Imaging; Methylprednisolone; Piracetam; Positron-Emission Tomography; Proteins; Seizures

Levetiracetam is frequently used in the elderly considering its favorable pharmacological profile, efficacy, and good tolerance. We reported an encephalopathy with levetiracetam in an elderly subject who had no renal failure, no concomitant valproate medication, and no other additional co-morbidities. Levetiracetam should be discontinued when this condition is suspected.

Topics: Aged, 80 and over; Anticonvulsants; Female; Humans; Levetiracetam; Neurotoxicity Syndromes; Piracetam; Seizures

Topics: Anticonvulsants; Brain Neoplasms; Female; Glioblastoma; Humans; Levetiracetam; Male; Neoplasm Recurrence, Local; Piracetam; Seizures; Valproic Acid

Increased creatinine clearance and subsequent elevated antimicrobial clearance is evident in many traumatic brain injury (TBI) patients due to augmented renal clearance (ARC). Little is known about the effects of ARC on other renally-eliminated medications, such as the anti-epileptic drug levetiracetam.. This is a case report of serum monitoring of vancomycin and levetiracetam in a 22 year old female with ARC after severe TBI.. The patient exhibited ARC of vancomycin as evidenced by her low serum concentrations with standard vancomycin dosing. Her estimated creatinine clearance based on vancomycin clearance was 243.9 ml/min. Serum concentrations also suggested ARC of levetiracetam. No toxicities for either medication were noted, even after dose adjustment to account for possible ARC.. Vancomycin and levetiracetam both appear to be subject to ARC after TBI. Clinicians should be mindful that standard dosing of these agents may not achieve typical target concentrations in this clinical scenario.

Topics: Anti-Bacterial Agents; Anticonvulsants; Bacterial Infections; Brain Injuries; Drug Monitoring; Female; Humans; Kidney; Levetiracetam; Piracetam; Seizures; Urine; Vancomycin; Young Adult

Neonatal seizures are common in the first month of life and may impair neurodevelopmental outcome. Current antiepileptic drugs used in the treatment of neonatal seizures have limited efficacy and undesirable side effects. Intravenous levetiracetam is increasingly being used in the neonatal period to treat seizures. Presently, insufficient data about the efficacy and safety of intravenous levetiracetam in preterm neonates exist.. We retrospectively analyzed data from preterm neonates who were treated with intravenous levetiracetam at our institution between January 2007 and December 2011. Data were acquired from review of our institution's electronic medical record regarding patients who were treated with intravenous levetiracetam during the neonatal period (0 to 28 days) and were born at preterm gestation (<37 weeks).. Twelve patients received a levetiracetam load of 25 to 50 mg/kg for neonatal seizures. Nine of 11 patients (82%) reached seizure cessation within 24 hours of receiving levetiracetam. No serious side effects were evident. Seven patients (59%) were discharged on oral levetiracetam alone, four patients (33%) were discharged on no oral antiepileptic drug, and one patient (8%) was discharged on levetiracetam and phenobarbital. Eleven of 12 patients were followed up to 6 months after receiving intravenous levetiracetam. Of these, six patients (55%) had achieved seizure freedom and been completely weaned off of all antiepileptic drugs. Three patients (27%) had achieved seizure freedom while still on oral levetiracetam.. Intravenous levetiracetam appears to be efficacious for seizure management in preterm neonates.

Topics: Acute Disease; Anticonvulsants; Electroencephalography; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Injections, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures

Antiepileptic drugs are commonly given for perioperative prophylaxis after brain tumor surgery, and there has been growing interest in levetiracetam, a second-generation antiepileptic drug. This retrospective study compared the seizure outcomes, side effects and durability of levetiracetam with valproic acid after a craniotomy for supratentorial brain tumors.. Between 2009 and 2012, 282 consecutive patients with a supratentorial brain tumor underwent a craniotomy at Seoul National University Bundang Hospital. Of these patients, 51 (18.1%) and 231 (81.9%) were pre-operatively administered levetiracetam and valproic acid, respectively. The postoperative seizure outcomes (within 1 month after surgery) and the long-term side effects of both drugs were evaluated.. Of the 51 patients in the levetiracetam group, 4 (7.8%) experienced postoperative seizures after brain tumor surgery, and 15 (6.5%) of the 231 patients in the valproic acid group experienced postoperative seizures (p = 0.728). The long-term complication rate of the valproic acid group (26.8%; 62/231) was significantly higher than that of the levetiracetam group (9.8%; 5/51) [p = 0.010]. In the valproic acid group, 10 hepatotoxicities, 20 hyperammonemias and 10 hematologic abnormalities (6 thrombocytopenias, 3 pancytopenias, and 1 leucopenia) occurred. Moreover, 89 patients (38.5%) in the valproic acid group changed or added other anticonvulsants because of side effects or uncontrolled seizures, whereas only 9 patients (17.6%) in the levetiracetam group changed or added other anticonvulsants (p = 0.005).. The postoperative seizure control rates of levetiracetam and valproic acid were not statistically significantly different; however, levetiracetam may be superior to valproic acid in terms of its safety and durability after supratentorial tumor surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Supratentorial Neoplasms; Treatment Outcome; Valproic Acid; Young Adult

Current treatment of nerve agent poisoning with ionotropic drugs proves inadequate, and alternative treatment strategies are searched for. Based on positive findings with metabotropic glutamate modulators in microinfusion studies, the present study was initiated to examine anticonvulsant effects of MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride), a metabotropic glutamate receptor 5 antagonist, and DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine), a metabotropic glutamate receptor 2/3 agonist, when administered systemically in combinations with HI-6 (1-[([4-(aminocarbonyl)pyridino]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) and procyclidine or HI-6 and levetiracetam relative to the combination of HI-6, procyclidine, and levetiracetam. The results showed that MPEP or DCG-IV combined with HI-6 and procyclidine resulted in substantial antidotal efficacy when administered 20 min after onset of seizures elicited by soman. MPEP or DCG-IV combined with HI-6 and levetiracetam did not terminate seizures and preserve lives. When given 20 min before challenge with soman, DCG-IV in combination with HI-6 and procyclidine provided protection, whereas MPEP combined with HI-6 and procyclidine did not. Combinations with metabotropic glutamate receptor modulators did not achieve the same high level of antidotal efficacy as the combination of HI-6, procyclidine, and levetiracetam. MPEP alone inhibited pseudocholinesterase activity in the brain markedly. A positive correlation was found between latency to seizure onset or full protection and level of pseudocholinesterase activity in brain. MPEP and DCG-IV can serve as effective anticonvulsants against nerve agent poisoning when combined with HI-6 and procyclidine. Metabotropic glutamate receptor modulators may represent an alternative or supplement to treatment with ionotropic drugs.

Topics: Acetylcholinesterase; Animals; Anticonvulsants; Butyrylcholinesterase; Cyclopropanes; Drug Interactions; Glycine; Levetiracetam; Male; Oximes; Piracetam; Procyclidine; Pyridines; Pyridinium Compounds; Rats; Rats, Wistar; Receptor, Metabotropic Glutamate 5; Seizures; Soman

Compare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures.. Retrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP) and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age.. In 280 infants with comparable seizure etiology and cranial imaging results, increased exposure to PB was associated with worse BSID cognitive and motor scores (8.1- and 9-point decrease per 100 mg kg(-1); P=0.01). The effect was less with LEV (2.2- and 2.6-point decrease per 300 mg kg(-1) LEV (P=0.01)). CP probability increased by 2.3-fold per 100 mg kg(-1) PB and was not associated with increasing LEV.. Increased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.

Topics: Anticonvulsants; Child Development; Child, Preschool; Cohort Studies; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Levetiracetam; Phenobarbital; Piracetam; Retrospective Studies; Seizures

To identify risk factors for the development of tumor-associated epilepsy (TAE) and potential benefit of newer generation AEDs in seizure prevention.. We performed an IRB approved retrospective study of newly diagnosed GBM patients at the University of Rochester between 1/1/05 and 5/13/11. Records were reviewed to describe demographics, seizure incidence, occurrence of status epilepticus, and AED use and toxicity.. 172 patients with newly diagnosed GBM were included in the study. 53.4% developed TAE. 31.4% had seizure prior to diagnosis. 118 patients were seizure-free at diagnosis: 32.2% developed post-diagnosis TIE (PostTAE) and 60.2% remained seizure-free. 70 seizure-free patients received an AED peri-operatively. 36 were weaned off AEDs and 31 were continued. Incidence of PostTAE and time to first seizure were comparable in AED-treated and untreated patients. 4 PostTAE patients presented with status epilepticus (SE), all were not AED treated. AEDs were withdrawn in 10 patients due to toxicity: 9 from phenytoin and 1 from levetiracetam.. There is a high incidence of PostTAE in GBM. Prophylactic AED therapy did not reduce PostTAE but may have prevented SE. Minimal toxicity was observed on 2nd generation AEDs. The high burden of epilepsy in this population and tolerability of newer AEDS suggest that AAN guidelines should be revisited.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Risk Factors; Seizures; Status Epilepticus; Treatment Outcome

Several studies have addressed the antiepileptic mechanisms of levetiracetam (LEV); however, its effect on catecholamines and the inflammatory mediators that play a role in epilepsy remain elusive. In the current work, lithium (Li) pretreated animals were administered LEV (500 mg/kg i.p) 30 min before the induction of convulsions by pilocarpine (PIL). Li-PIL-induced seizures were accompanied by increased levels of hippocampal prostaglandin (PG) E2, myeloperoxidase (MPO), tumor necrosis factor-α, and interleukin-10. Moreover, it markedly elevated hippocampal lipid peroxides and nitric oxide levels, while it inhibited the glutathione content. Li-PIL also reduced hippocampal noradrenaline, as well as dopamine contents. Pretreatment with LEV protected against Li-PIL-induced seizures, where it suppressed the severity and delayed the onset of seizures in Li-PIL treated rats. Moreover, LEV reduced PGE2 and MPO, yet it did not affect the level of both cytokines in the hippocampus. LEV also normalized hippocampal noradrenaline, dopamine, glutathione, lipid peroxides, and nitric oxide contents. In conclusion, alongside its antioxidant property, LEV anticonvulsive effect involves catecholamines restoration, as well as inhibition of PGE2, MPO, and nitric oxide.

Topics: Animals; Anticonvulsants; Dinoprostone; Dopamine; Glutathione; Hippocampus; Interleukin-10; Levetiracetam; Lipid Peroxidation; Lithium Chloride; Male; Nitric Oxide; Norepinephrine; Peroxidase; Pilocarpine; Piracetam; Rats; Rats, Wistar; Seizures; Tumor Necrosis Factor-alpha

This paper introduces a new method for estimating the excitability of brain networks. The motivation for this research was to develop a system that can track pathological changes in excitability, in diseases such as epilepsy. The ability to track excitability may provide a method for anticipating seizures and intervening therapeutically. Four normally healthy canines were implanted with the Medtronic Activia PC+S deep brain stimulation and sensing system. The devices were used to probe the circuit of Papez, with electrical stimulation in the anterior nucleus of the thalamus to measure evoked potentials in the hippocampus. The canines were given three different dosage levels of anti-convulsant medication in an attempt to manipulate the excitability of the network. The results showed changes in the morphology of the evoked potentials, following a circadian profile and reflecting times of drug delivery.

Topics: Animals; Anticonvulsants; Brain; Brain Mapping; Circadian Rhythm; Deep Brain Stimulation; Dogs; Drug Delivery Systems; Electrodes; Electrodes, Implanted; Epilepsy; Evoked Potentials; Hippocampus; Levetiracetam; Piracetam; Seizures; Signal Processing, Computer-Assisted; Thalamus

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Electroencephalography; Epilepsy, Absence; Humans; Levetiracetam; Male; Piracetam; Seizures; Treatment Outcome; Valproic Acid

The antiepileptic drug Levetiracetam (Lev) has neuroprotective properties in experimental stroke, cerebral hemorrhage and neurotrauma. In these conditions, non-convulsive seizures (NCSs) propagate from the core of the focal lesion into perilesional tissue, enlarging the damaged area and promoting epileptogenesis. Here, we explore whether Lev neuroprotective effect is accompanied by changes in NCS generation or propagation. In particular, we performed continuous EEG recordings before and after the permanent occlusion of the middle cerebral artery (pMCAO) in rats that received Lev (100 mg/kg) or its vehicle immediately before surgery. Both in Lev-treated and in control rats, EEG activity was suppressed after pMCAO. In control but not in Lev-treated rats, EEG activity reappeared approximately 30-45 min after pMCAO. It initially consisted in single spikes and, then, evolved into spike-and-wave and polyspike-and-wave discharges. In Lev-treated rats, only rare spike events were observed and the EEG power was significantly smaller than in controls. Approximately 24 hours after pMCAO, EEG activity increased in Lev-treated rats because of the appearance of polyspike events whose power was, however, significantly smaller than in controls. In rats sacrificed 24 hours after pMCAO, the ischemic lesion was approximately 50% smaller in Lev-treated than in control rats. A similar neuroprotection was observed in rats sacrificed 72 hours after pMCAO. In conclusion, in rats subjected to pMCAO, a single Lev injection suppresses NCS occurrence for at least 24 hours. This electrophysiological effect could explain the long lasting reduction of ischemic brain damage caused by this drug.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroencephalography; Infarction, Middle Cerebral Artery; Levetiracetam; Male; Neuroprotective Agents; Piracetam; Rats; Seizures; Time Factors

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Levetiracetam; Male; Piracetam; Quality of Life; Seizures; Time Factors; Treatment Outcome

Topics: Anticonvulsants; Cholinesterase Inhibitors; Electroencephalography; Follow-Up Studies; Levetiracetam; Magnetic Resonance Imaging; Myasthenia Gravis; Paraneoplastic Syndromes, Nervous System; Piracetam; Pyridostigmine Bromide; Seizures; Thymectomy; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adolescent; Anticonvulsants; Antineoplastic Agents; Drug Interactions; Drug Therapy, Combination; Humans; Levetiracetam; Male; Methotrexate; Piracetam; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Seizures

Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking.. We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)-induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain.. LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood.. LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.

Topics: Animals; Animals, Newborn; Anticonvulsants; Blotting, Western; Brain; Immunohistochemistry; Kainic Acid; Levetiracetam; Membrane Glycoproteins; Nerve Tissue Proteins; Piracetam; Rats; Seizures

Synthesis and anticonvulsant activity of new N-Mannich bases of 3-(2-fluorophenyl)- and 3-(2-bromophenyl)-pyrrolidine-2,5-diones have been described. Initial anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetrazole seizures test (scPTZ). The neurotoxicity was determined applying the rotarod test. The in vivo results in mice showed that majority of compounds were effective in the MES test. Only seven molecules showed protection in the scPTZ test. The quantitative evaluation in the MES seizures after oral administration into rats showed that the most active were 1-[{4-(4-fluorophenyl)-piperazin-1-yl}-methyl]-3-(2-bromophenyl)-pyrrolidine-2,5-dione (14) with ED(50) of 7.4mg/kg and 1-[{4-(3-bromophenyl)-piperazin-1-yl}-methyl]-3-(2-bromophenyl)-pyrrolidine-2,5-dione (16) with ED(50) of 26.4mg/kg. These molecules were more potent and also less neurotoxic than phenytoin which was used as reference antiepileptic drug.

Topics: Administration, Oral; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Electroshock; Male; Mannich Bases; Mice; Mice, Inbred Strains; Molecular Structure; Pentylenetetrazole; Rats; Rats, Sprague-Dawley; Seizures; Succinimides

Topics: Anticonvulsants; Brain Injuries; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

The aim of this study was to characterize the anticonvulsant effects of pregabalin in combination with four second-generation antiepileptic drugs (i.e., gabapentin, levetiracetam, tiagabine, and vigabatrin) in the mouse maximal electroshock (MES)-induced seizure model by using the type II isobolographic analysis. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. The combination of pregabalin with gabapentin at the fixed-ratio of 1:1 was supra-additive (synergistic) in terms of seizure suppression while the combinations at the fixed-ratios of 2:1 and 4:1 were additive in the mouse MES model. Similarly, the combination of pregabalin with tiagabine at the fixed-ratio of 25:1 was supra-additive, whereas the combinations at the fixed-ratios of 100:1 and 50:1 were additive in the mouse MES model. Pregabalin with levetiracetam and vigabatrin at the fixed-ratios of 1:1, 2:1 and 4:1 were additive in this seizure model. The combinations of pregabalin with gabapentin (1:1) and pregabalin with tiagabine (25:1) appear to be favorable combinations exerting supra-additive interaction in suppressing MES-induced seizures. Pregabalin in combination with levetiracetam and vigabatrin appears to be neutral producing only additivity in the mouse MES model.

Topics: Amines; Animals; Anticonvulsants; Avoidance Learning; Confidence Intervals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Electroshock; Gabapentin; gamma-Aminobutyric Acid; Hand Strength; Levetiracetam; Male; Mice; Motor Activity; Piracetam; Pregabalin; Seizures; Vigabatrin

Pervasive developmental disorder is characterized by various symptoms that often include self-injurious behavior (SIB). Episodes of SIB occur in the context of high emotional arousal, anger, or fear and may be related to epilepsy. We report the case of a 20-year-old man with pervasive developmental disorder presenting with SIB non-responsive to antipsychotic medication. Positron emission tomography showed a right temporoparietal hypometabolic focal lesion suggestive of an epileptic focus. Two weeks after initiation of levetiracetam (Keppra®), SIB disappeared, without recurrence 24 months later. Levetiracetam (Keppra®) may be beneficial for such patients.

Topics: Anticonvulsants; Child; Child Development Disorders, Pervasive; Humans; Intellectual Disability; Levetiracetam; Male; Piracetam; Seizures; Self-Injurious Behavior; Treatment Outcome; Young Adult

A 45-year-old man with a new diagnosis of low grade glioma was started on an escalating dose of levetiracetam (Lev) for seizure management. He gradually developed intractable nausea/vomiting and a high creatinine concentration due to acute renal failure which was attributed to Lev-induced interstitial nephritis. The medication was changed and his renal function rapidly improved to his baseline.

Topics: Acute Kidney Injury; Anticonvulsants; Astrocytoma; Brain Neoplasms; Humans; Levetiracetam; Male; Middle Aged; Nephritis, Interstitial; Piracetam; Seizures

Anticonvulsant drugs are frequently given after craniotomy. Phenytoin (PHT) is the most commonly used agent; levetiracetam (LEV) is a new anticonvulsant drug with fewer side effects. To compare the incidence of seizures in patients receiving either prophylactic PHT or LEV perioperatively, 971 patients undergoing a craniotomy were analysed retrospectively during a 2-year period. PHT was used routinely and LEV was administered when PHT was contraindicated. Seizures documented during the first 7 days after craniotomy were considered. A total of 235 patients were treated with an antiepileptic drug: 81 patients received LEV, and 154 patients, PHT. Two patients receiving LEV (2.5%) and seven receiving PHT (4.5%) had a seizure despite this treatment. No patient had a documented side effect or drug interaction. The data show that LEV may be an alternative option in patients with contraindications to PHT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Child; Contraindications; Craniotomy; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Postoperative Complications; Retrospective Studies; Seizures; Young Adult

Topics: Adult; Anticonvulsants; Basal Ganglia Diseases; Brain; Calcinosis; Central Nervous System Cysts; Dystonia; Female; Gait Disorders, Neurologic; Humans; Infant, Newborn; Infant, Premature; Leukoencephalopathies; Levetiracetam; Magnetic Resonance Imaging; Muscle Spasticity; Neurologic Examination; Piracetam; Seizures; Spinal Puncture; Tomography, X-Ray Computed

Recent data indicate comparable efficacy and safety for levetiracetam (LEV) when compared with phenytoin (PHT) for prophylaxis of early seizures after traumatic brain injury. The purpose of this study was to conduct a cost-minimization analysis, from the perspective of both the acute care institution (cost) and patient (charges), comparing these two strategies.. A decision tree was constructed to include baseline event probabilities obtained from detailed literature review, costs, and charges. Monte Carlo simulation was used to derive the mean costs and charges per patient treated with the LEV when compared with the PHT strategy. Adverse event probabilities, costs, charges, and frequency of laboratory determination for the PHT group were varied in sensitivity analyses.. Literature review indicated equal efficacy of PHT versus LEV for early seizure prevention. The PHT strategy was superior to the LEV strategy from both the institutional (mean cost per patient $151.24 vs. $411.85, respectively) and patient (mean charge per patient $2,302.58 vs. $3,498.40, respectively) perspectives. Varying both baseline adverse event probabilities and frequency of laboratory testing did not alter the superiority of the PHT strategy. LEV replaced PHT as the dominant strategy only when the cost/charge of treating mental status deterioration was increased markedly above baseline.. From both institutional and patient perspectives, PHT is less expensive than LEV for routine pharmacoprophylaxis of early seizures among traumatic brain injury patients. Pending compelling efficacy data, LEV should not replace PHT as a first-line agent for this indication.

Topics: Adult; Anticonvulsants; Brain Injuries; Cost Control; Cost-Benefit Analysis; Decision Trees; Drug Costs; Humans; Levetiracetam; Monte Carlo Method; Phenytoin; Piracetam; Seizures

Continuous electroencephalography (cEEG) is increasingly used to detect both clinical and subclinical seizures in patients with traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). We assess whether EEG findings predict outcomes in TBI/SAH patients enrolled in a levetiracetam (LEV) vs. fosphenytoin (fos-PHT) seizure prevention trial (NCT00618436). This prospective, single-blinded, comparative trial randomized 52 patients with TBI or SAH to receive prophylactic LEV or fos-PHT. Continuous video EEG monitoring was conducted for the initial 72 h of medication administration. The association between EEG findings (degree of generalized and focal slowing, presence and frequency of epileptiform discharges and seizures) and outcomes (Glasgow Outcomes Scale-Extended (GOS-E) and Disability Rating Scale (DRS)) at discharge, 3 and 6 months was assessed using a generalized linear model. Severity of generalized slowing tended to be associated with outcomes in both treatment groups (discharge DRS, p=0.042; discharge GOS-E, p=0.026; 3 month DRS, p=0.051). The presence of focal slowing, the presence and frequency of epileptiform discharges and the presence of seizures were not predictive of outcome in either treatment group (all p>0.15). While it has been shown that LEV is associated with better outcome than fos-PHT when used as seizure prophylaxis in brain injury, aside from severity of generalized slowing, electrographic findings of focal slowing, epileptiform discharges, and seizures were not themselves associated with outcomes in patients with TBI or SAH enrolled in a randomized clinical trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Injuries; Disability Evaluation; Electroencephalography; Female; Glasgow Outcome Scale; Humans; Levetiracetam; Linear Models; Male; Middle Aged; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures; Statistics, Nonparametric; Subarachnoid Hemorrhage; Young Adult

Topics: Anticonvulsants; Female; Humans; Levetiracetam; Middle Aged; Piracetam; Recurrence; Seizures; Subarachnoid Hemorrhage; Time Factors

Anti-seizure prophylaxis is routinely utilized during busulfan administration for HSCT. We evaluated the feasibility and efficacy of levetiracetam in children undergoing HSCT. A total of 28 children and young adults received levetiracetam during HSCT and the outcomes and costs were compared to a historical, but similar cohort of 25 patients who had received fosphenytoin. Levetiracetam was well tolerated and was efficacious in preventing seizures. Cost of drug, administration, and monitoring were also similar among the two groups. Due to non-induction of the hepatic cytochrome P450 enzymes, levetiracetam may lead to better dose assurance of busulfan in targeted dose regimens for HSCT.

Topics: Adolescent; Adult; Anticonvulsants; Busulfan; Child; Child, Preschool; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant; Levetiracetam; Phenytoin; Piracetam; Seizures; Transplantation Conditioning; Young Adult

Levetiracetam (brand name: E Keppra®) is a new antiepileptic drug marketed in Japan since 2010 1, 2). Clinical reports of its use in Japan are few. Our experience with levetiracetam in a patient with secondarily generalized seizures yielded interesting findings. The patient was a 62-year-old man receiving 4 antiepileptic drugs and 9 psychotropic drugs for treatment of secondarily generalized seizures (due to a cerebral contusion that occurred 20 years ago) and associated depressive symptoms, mainly anxiety and insomnia. He begun to wobble and, his increasing gait disturbance led to frequent falls. He recently underwent emergency surgery for acute extradural hematoma due to head contusion. Concomitant administration of levetiracetam, initiated after surgery, resulted in control of the epilepsy, resolution of the depressive symptoms, and reduction of multiple drugs doses. The patient was able to return to normal activity. Control of his epilepsy was probably attributable to the following: (1) the antiepileptic effect of levetiracetam and (2) improvement of the seizure threshold by streamlining multiple concomitant drugs. Although the effect of levetiracetam on depression is unclear, it is worth noting that control of the patient's epilepsy produced an improvement in the symptoms of depression.

Topics: Anticonvulsants; Brain Injuries; Depression; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

To study the prognostic implications of antiepileptic drug (AED) use on seizure freedom following temporal lobe resections for intractable epilepsy.. Seizure outcome implications of epilepsy characteristics and AED use were studied in patients who underwent temporal lobectomy patients at the Cleveland Clinic between September 1995 and December 2006. Survival analysis and multivariate regression with Cox proportional hazard modeling were used. Complete seizure freedom was defined as a favorable outcome.. Records of 312 patients were analyzed (mean ± standard deviation follow-up 3.5 ± 1.7 years). The estimated probability of complete seizure freedom was 69% at 12 months (95% confidence interval [CI] 66-72%), and 48% at 36 months (95% CI 45-52%). The mean number of AEDs used per patient at the time of surgery was 1.78 (range 1-4), dropping to 1.02 at last follow-up (range 0-4). Following multivariate analysis, a lower preoperative seizure frequency and perioperative use of levetiracetam predicted a favorable outcome (risk ratio [RR] 0.62, 95% CI 0.43-0.89, and RR = 0.57, 95% CI 0.39-0.83, respectively), whereas nonspecific pathology (RR 1.71, 95% CI 1.15-2.47) and a higher number of AEDs used at the time of surgery correlated with higher rates of seizure recurrence (whole-model log-rank test p-value < 0.0001). Better outcomes within the levetiracetam group were seen despite a higher proportion of several poor prognostic indicators within this patient group, and started as early as 4 months after surgery, gradually increasing to a 15-20% survival advantage by 5 years. No similar outcome correlations were identified with another AED.. AED use may be a potential new modifiable seizure-outcome predictor after temporal lobectomy. This possible prognostic indicator is discussed in light of proposed seizure recurrence mechanisms.

Topics: Adolescent; Adult; Aged; Anterior Temporal Lobectomy; Anticonvulsants; Child; Child, Preschool; Epilepsy; Female; Humans; Levetiracetam; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Positron-Emission Tomography; Postoperative Complications; Recurrence; Retrospective Studies; Seizures; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Young Adult

Levetiracetam (LEV) is increasingly used in the treatment of neonatal seizures. The aim of this study was to determine pharmacokinetics in neonates with seizures and to obtain preliminary safety and efficacy data.. Eighteen term neonates with seizures persisting after 20 mg/kg of phenobarbital received intravenous LEV for 1 wk. LEV was administered as a 20 or 40 mg/kg bolus followed by 5-10 mg/kg/d. Pharmacokinetic data were analyzed using a nonlinear mixed-effects population approach. Continuous electroencephalogram monitoring allowed preliminary assessment of the efficacy of LEV in this population.. LEV clearance (CL) increased from a mean of 0.7 ml/min/kg (SD 0.27 ml/min/kg) on day 1 to 1.33 ml/min/kg (SD 0.35 ml/min/kg) by day 7. Mean half-life was 18.5 h (SD 7.1 h) on day 1 of the study and decreased to 9.1 h (SD 2.0 h) by day 7. The mean volume of distribution was 1.01 l/kg (SD 0.13 l/kg). No study-related serious adverse events were observed.. CL of LEV in neonates was higher than expected on the basis of immature renal function in term infants and increased significantly during the first week of life. More frequent dosing of LEV is needed in term infants to maintain serum concentrations in the range seen in children and adults.

Topics: Electroencephalography; Female; Gestational Age; Half-Life; Humans; Infant, Newborn; Injections, Intravenous; Levetiracetam; Male; Metabolic Clearance Rate; Piracetam; Seizures

Topics: Aged; Amygdala; Anticonvulsants; Astrocytoma; Brain Neoplasms; Electroencephalography; Hippocampus; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piloerection; Piracetam; Seizures; Temporal Lobe; Valproic Acid

Topics: Adult; Albendazole; Animals; Anti-Inflammatory Agents; Anticonvulsants; Antiparasitic Agents; Developing Countries; Diagnosis, Differential; Emigration and Immigration; Enzyme-Linked Immunosorbent Assay; Humans; Immunoblotting; Levetiracetam; Magnetic Resonance Imaging; Male; Muscle Weakness; Nepal; Neurocysticercosis; Piracetam; Prednisolone; Seizures; Spinal Puncture; Taenia solium; Tremor; United Kingdom

Topics: Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Pregnancy; Pregnancy Complications; Seizures

To report the effectiveness and safety of intravenous levetiracetam in the treatment of children with acute repeated seizures, and status epilepticus in a children's hospital.. This two-year observational study evaluated all in-patients who received intravenous levetiracetam to treat acute repeated seizures (ARS) or convulsive and non-convulsive status epilepticus (SE). Information was collected on seizure type, epilepsy syndrome and underlying cause, the initial loading dose of intravenous levetiracetam, its effectiveness and safety and whether the patient remained on the drug at final follow-up. Analysis was descriptive.. Fifty-one patients aged 0.2-18.8 (mean 7.1) years were evaluated, including 45 with acute ARS or SE and six unable to continue their usual orally administered anti-epileptic medication. The median initial dose of levetiracetam was 14.4 (range 5-30)mg/kg in the 45 patients treated for acute seizures and SE. Twenty three of the 39 (59%) patients with ARS became and remained seizure-free. Levetiracetam terminated status in three of four (75%) patients with convulsive, and the two patients with non-convulsive status epilepticus. Aggressive behaviour occurred in three children, one of whom discontinued treatment. Forty-two patients (81%), including 34 of the 45 patients (76%) treated for ARS or SE remained on levetiracetam at the time of final follow-up, between two and 18 months after receiving the drug.. This observational study has confirmed previous data that intravenous levetiracetam seems to be effective and safe in the treatment of acute repeated seizures and status epilepticus. A randomised clinical trial is justified to determine whether intravenous levetiracetam should replace intravenous phenytoin as the first long-acting anticonvulsant in the management of acute repetitive seizures and status epilepticus.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Hospitals, Pediatric; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Seizures; Status Epilepticus

Topics: Anticonvulsants; Brain; Child; Electroencephalography; Hepatitis A; Humans; Immunoglobulin M; Levetiracetam; Magnetic Resonance Imaging; Male; Meningoencephalitis; Piracetam; Radiography; Seizures

Fear of discontinuing concomitant anti-epileptic drugs (AEDs) may lead to potentially unnecessary and perhaps unsafe polypharmacy. The effect of withdrawing concomitant AEDs on epilepsy control was therefore studied in long-term users of levetiracetam.. The EULEV cohort followed patients initiating levetiracetam in France in 2005 or 2006 for one year. In those maintaining levetiracetam throughout the study period, the association of a reduction in the number of concomitant AEDs during the first six months with seizure-freedom during the last six months of follow-up was investigated using logistic regression.. Of the 356 patients continuing levetiracetam for at least 1 year, 140 (39.3%) were seizure-free during the last six months of follow-up. Partial symptomatic or generalised idiopathic epilepsy were associated with greater seizure-freedom than partial cryptogenic disease. Factors associated with seizures were: longer disease duration, initial incapacity, increased number of seizures in the six months preceding levetiracetam initiation, and number of consultations for epilepsy in the six months preceding levetiracetam initiation. There was a trend for the association between the early reduction in the number of concomitant AEDs and seizure-free status later during follow-up, which however did not reach statistical significance in the final propensity score-adjusted multivariate model (OR = 1.8, 95%CI [0.8;4.0]).. Taking into account the various risk factors for seizures, the early reduction of concomitant AEDs was not associated with worse seizure rates during follow-up in real-life users of levetiracetam.

Topics: Adult; Anticonvulsants; Cohort Studies; Drug Therapy, Combination; Female; Follow-Up Studies; France; Humans; Levetiracetam; Logistic Models; Male; Middle Aged; Multivariate Analysis; Pharmacoepidemiology; Piracetam; Propensity Score; Risk Factors; Seizures; Time Factors; Withholding Treatment

Topics: Anticonvulsants; Cardiovascular Surgical Procedures; Child, Preschool; Female; Heart Defects, Congenital; Humans; Levetiracetam; Piracetam; Postoperative Complications; Seizures; Stevens-Johnson Syndrome

A number of novel pyrrole[1,2-a]pyrazine derivatives were synthesized and evaluated in in vivo animal models of epilepsy. Among them, several compounds displayed promising seizure protection in the maximal electroshock seizure (MES), subcutaneous metrazol seizure (scMET), 6 Hz and pilocarpine-induced status prevention (PISP) tests, with ED(50) values comparable to the reference anticonvulsant drugs (AEDs). A critical influence of the stereochemistry and conformational preferences of the pyrrole[1,2-a]pyrazine core on in vivo pharmacological activity was observed. The mechanism of the anticonvulsant action of the agents synthesized is most probably not via inhibition of the voltage-dependent sodium (Na(+)) currents.

Topics: Animals; Anticonvulsants; Diketopiperazines; Electroshock; Epilepsy; Humans; Male; Mice; Models, Molecular; Pentylenetetrazole; Rats; Rats, Sprague-Dawley; Rats, Wistar; Seizures; Sodium Channel Blockers; Sodium Channels

Efficacy and tolerability of levetiracetam (LEV) as perioperative seizure prophylaxis in supratentorial brain tumor patients were retrospectively studied. Between February 2007 and April 2009 in a single institution, 78 patients with primary or secondary supratentorial brain tumors [40 female, 38 male; mean age 57 years, from 27 to 89 years; gliomas in 42 patients (53.8%), brain metastases in 17 (21.8%), meningiomas in 16 (20.5%), 1 primary central nervous system (CNS) lymphoma patient, and 2 patients with radiation necrosis] received between 1,000 mg and 3,000 mg LEV perioperatively. Preoperatively, 30 patients had experienced seizures (38.5%), most commonly glioma patients (47.6%), but also meningioma patients (31.3%) or patients with brain metastases (23.5%). No more seizures occurred in patients receiving 1-3 g LEV preoperatively. Within the first week postoperatively, a single seizure occurred in two patients (2.6%). At the end of the follow-up period (mean 10.5 months, range 0-31 months), 71 of the 78 patients (91%) were seizure free and 21 (26%) patients were not taking antiepileptic drugs. We observed side-effects in five patients (6.4%), including non-tumor-associated progressive somnolence in three patients (1.5 g, 1.5 g, and 2 g LEV daily) and reactive psychosis in two patients (1 and 1.5 g LEV daily), regressing after dose reduction. Perioperative LEV in supratentorial brain tumor patients was well tolerated. Compared with the literature, it resulted in low (2.6%) [corrected] seizure frequency in the early postoperative period. Additionally, its advantage of lacking cytochrome P450 enzyme induction allowed early initiation of effective postoperative chemotherapy in malignant glioma patients.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Neurosurgical Procedures; Perioperative Period; Piracetam; Postoperative Complications; Retrospective Studies; Seizures; Supratentorial Neoplasms

To date, common therapy in patients with intracranial hemorrhage (ICH) includes prophylaxis of seizure using antiepileptic drugs, commonly phenytoin. Phenytoin therapy is associated with a high incidence of cognitive disturbance. Levetiracetam is known to cause less cognitive disruption and may be a suitable alternative for seizure prophylaxis. Cognitive outcomes in ICH patients receiving seizure prophylaxis with levetiracetam or phenytoin are compared.. A retrospective chart review was conducted with 269 patients who received prophylactic levetiracetam or phenytoin between August 2005 and May 2008. A total of 85 reviewed patients met inclusion criteria (phenytoin n = 25, levetiracetam n = 60).. Statistically significant results included higher Glasgow Coma Scores (GCS) at dismissal (median, 14 vs. 11, P = 0.023), lower seizure incidence (0.0 vs. 8%, P = 0.03) for patients receiving levetiracetam than those treated with phenytoin and patients being discharged home (21.7% vs. 16%, P = 0.03). Observed trends included greater cognitive function retention rate (56.7% vs. 36%, P = 0.08).. Despite similarities in hemorrhage type and severity at onset, patients receiving levetiracetam had better cognition at discharge and fewer seizures than patients receiving phenytoin. These data suggest that levetiracetam is more effective than phenytoin for seizure prophylaxis without suppression of cognitive abilities in patients with ICH.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Cognition Disorders; Female; Humans; Intracranial Hemorrhages; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures; Young Adult

Neonatal seizures are common, especially in prematurity. Phenobarbital (PB) currently represents the antiepileptic drug (AED) of choice, despite being related to increased neuronal apoptosis in animal models and cognitive impairment in human subjects. Levetiracetam (LEV) may have a more favorable profile since it does not cause neuronal apoptosis in infant rodents.. In a prospective feasibility study, LEV was applied as first-line treatment in 38 newborns with EEG-confirmed seizures, after ruling out hypoglycemia, hypocalcaemia, hypomagnesaemia and pyridoxin dependency. Initial intravenous doses of 10 mg/kg LEV were gradually increased to 30 mg/kg over 3 days with a further titration to 45-60 mg/kg at the end of the week. Acute intervention with up to 2 intravenous doses of PB 20 mg/kg was tolerated during LEV titration. LEV was switched to oral as soon as the infants' condition allowed. Based on clinical observation, EEG tracings (aEEG/routine EEGs), and lab data, drug safety and anticonvulsant efficacy were assessed over 12 months.. In 19 newborns a single PB dose of 20 mg/kg was administered, while 3 newborns received 2 PB doses. 30 infants were seizure free under LEV at the end of the first week and 27 remained seizure free at four weeks, while EEGs markedly improved in 24 patients at 4 weeks. In 19 cases, LEV was discontinued after 2-4 weeks, while 7 infants received LEV up to 3 months. No severe adverse effects were observed.. These results illustrate the safety of LEV treatment in neonatal seizures, including prematurity and suggest LEV anticonvulsant efficacy. Additional PB treatment admittedly constitutes a methodological shortcoming due to the prolonged anticonvulsive efficacy of PB. Double blind prospective controlled studies and long-term evaluation of cognitive outcome are called for.

Topics: Administration, Oral; Anticonvulsants; Feasibility Studies; Female; Humans; Infant, Newborn; Infant, Premature; Injections, Intravenous; Levetiracetam; Male; Piracetam; Prospective Studies; Seizures

We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders; 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced ≥ 50% reductions in seizures.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Diethylcarbamazine; Dose-Response Relationship, Drug; Drug Chronotherapy; Electroencephalography; Electronic Health Records; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Seizures; Statistics, Nonparametric; Treatment Outcome

Neonatal seizures are often refractory to treatment with initial antiseizure medications. Consequently, clinicians turn to alternatives such as levetiracetam, despite the lack of published data regarding its safety, tolerability, or efficacy in the neonatal population. We report a retrospectively identified cohort of 23 neonates with electroencephalographically confirmed seizures who received levetiracetam. Levetiracetam was considered effective if administration was associated with a greater than 50% seizure reduction within 24 hours. Levetiracetam was initiated at a mean conceptional age of 41 weeks. The mean initial dose was 16 ± 6 mg/kg and the mean maximum dose was 45 ± 19 mg/kg/day. No respiratory or cardiovascular adverse effects were reported or detected. Levetiracetam was associated with a greater than 50% seizure reduction in 35% (8 of 23), including seizure termination in 7. Further study is warranted to determine optimal levetiracetam dosing in neonates and to compare efficacy with other antiseizure medications.

Topics: Anticonvulsants; Child, Preschool; Electroencephalography; Female; Gestational Age; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

Antiepileptic drugs used for the treatment of neonatal seizures have limited efficacy and undesirable side effects, leading to increased off-label use in neonates. Intravenous levetiracetam became available in August 2006 for use in patients above 16 years of age. Insufficient data are available about the efficacy and safety of intravenous levetiracetam in neonates. Data captured from our institution's electronic medical records were retrospectively analyzed for neonates treated with intravenous levetiracetam between January 2007 and December 2009. Data were acquired by reviewing our electronic medical records. Twenty-two patients received a levetiracetam load of 10-50 mg/kg for neonatal seizures. Nineteen of 22 patients (86%) demonstrated immediate seizure cessation at 1 hour. Seven of 22 patients (32%) achieved complete seizure cessation after administration of the loading dose, 14 (64%) achieved seizure cessation by 24 hours, 19 (86%) by 48 hours, and all 22 (100%) by 72 hours. No serious side effects were evident. Nineteen patients (86%) were discharged on oral levetiracetam, and only two patients (9%) were discharged with an additional oral antiepileptic drug. Intravenous levetiracetam can be used as monotherapy and adjunctively in acute seizure management during the neonatal period.

Topics: Anticonvulsants; Female; Follow-Up Studies; Humans; Infant; Injections, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

To describe the clinical outcomes of a compulsory switch from branded to generic levetiracetam (LEV) among people with epilepsy (PWE) in an outpatient setting.. We conducted a retrospective chart review of 760 unduplicated consecutive adult patients attending a tertiary care epilepsy clinic at Ben Taub General Hospital. On November 1, 2008 hospital policy required all patients receiving branded LEV to be automatically switched to generic LEV. We calculated the proportion of patients switching back to branded LEV and reasons for the switch back.. Of the 260 patients (34%) being prescribed LEV (generic and brand name) during the study period, 105 (42.9%) were switched back to brand name LEV by their treating physicians. Reasons for switch back included increase in seizure frequency (19.6% vs. 1.6%; p < 0.0001) and adverse effects (AEs) (3.3%). AEs included headache, fatigue, and aggression. Patient age was associated with switchback when controlling for gender, epilepsy classification, and treatment characteristics [relative risk (RR) 2.44; 95% confidence interval (CI) 2.09-2.84; p < 0.05)]. An increase in seizure frequency subsequent to generic substitution was associated with polytherapy compared to monotherapy (3.225; 1.512-6.880; p < 0.05).. A significant proportion of patients in our cohort on generic LEV required switch back to the branded drug. Careful monitoring is imperative because a compulsory switch from branded to generic LEV may lead to poor clinical outcomes, with risk of AEs and increased seizure frequency.

Topics: Adult; Anticonvulsants; Cohort Studies; Drug Substitution; Drugs, Generic; Epilepsy; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Treatment Failure

Topics: Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Drug Therapy, Combination; Electroencephalography; Encephalitis; Female; Humans; Intracellular Signaling Peptides and Proteins; Lamotrigine; Levetiracetam; Middle Aged; Phenytoin; Piracetam; Proteins; Seizures; Triazines

We report on 4 patients having an increased incidence of seizures when treatment was switched from brand name levetiracetam (Keppra) to generic levetiracetam formulations.. Patients reported an increase in seizure activity to their neurologists after treatment was switched from Keppra to generic levetiracetam formulations. To confirm the timeline of increased seizure activity with use of the generic drug and report these adverse events to MedWatch, we made a telephone call to each patient's pharmacy to collect information on dispensing dates and the generic formulations' manufacturers. Subsequent to the increase in seizure frequency with generic levetiracetam, treatment in all 4 patients was switched back to Keppra. Seizure frequency in all patients returned to baseline when Keppra was reinstituted.. The Food and Drug Administration (FDA) considers generic medications to be therapeutically equivalent to their corresponding brand name formulation when the generic meets bioequivalence criteria. Considering the linear pharmacokinetic profile of levetiracetam, loss of seizure control or fluctuations of serum concentrations are unexpected if the patient remains on a consistent dose. However, there is growing evidence to support the concept that brand name antiepileptic drugs (AEDs) are not clinically equivalent to their generic counterparts. Because the FDA relies on voluntary reporting of adverse events from health-care professionals and consumers to their MedWatch program, underreporting makes it difficult to quantify the significance of brand to generic switches, and, equally important, generic to generic switches.. Until the use of generic AEDs can be evaluated in a large randomized blinded controlled study, clinicians must be vigilant in their efforts to report to MedWatch adverse events resulting from the switch from an AED brand to generic formulation of an AED.

Topics: Adult; Aged, 80 and over; Anticonvulsants; Drug Substitution; Drugs, Generic; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Piracetam; Seizures; Treatment Failure; Young Adult

Results from studies based on microinfusions into seizure controlling brain sites (area tempestas, medial septum, perirhinal cortex, posterior piriform cortex) have shown that procyclidine, muscimol, caramiphen, and NBQX, but not ketamine, exert anticonvulsant effects against soman-induced seizures. The purpose of the present study was to examine whether levetiracetam (Keppra(®)) may enhance the anticonvulsant potency of the above drugs to become optimally effective when used systemically. Levetiracetam has a unique profile in preclinical models of epilepsy and has been shown to increase the potency of other antiepileptic drugs. The rats were pretreated with pyridostigmine (0.1mg/kg) to enhance survival and received anticonvulsants 20 min after onset of seizures evoked by soman (1.15 × LD(50)). The results showed that no single drug was able to terminate seizure activity. However, when levetiracetam (LEV; 50mg/kg) was combined with either procyclidine (PCD; 10mg/kg) or caramiphen (CMP; 10mg/kg) complete cessation of seizures was achieved, but the nicotinic antagonist mecamylamine was needed to induce full motor rest in some rats. In a subsequent experiment, rats were pretreated with HI-6 (125 mg/kg) to enhance survival and treatment started 40 min following seizure onset of a soman dose of 1.6 × LD(50). LEV (50mg/kg) combined with either PCD (20mg/kg) or CMP (20mg/kg) terminated seizure activity, but the survival rate was considerably higher for LEV+PCD than LEV+CMP. Both therapies could also save the lives of rats that were about to die 5-10 min after seizure onset. Thus, the combination of LEV and PCD or CMP may make up a model of a future autoinjector being effective regardless of the time of application.

Topics: Animals; Anticonvulsants; Antidotes; Chemical Warfare Agents; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cyclopentanes; Disease Models, Animal; Drug Therapy, Combination; Lethal Dose 50; Levetiracetam; Male; Motor Activity; Muscimol; Nicotinic Antagonists; Piracetam; Procyclidine; Quinoxalines; Rats; Rats, Wistar; Reaction Time; Seizures; Soman; Time Factors

The pharmacokinetics of levetiracetam were determined prospectively in 18 neonates with seizures. Neonates were found to have lower clearance, higher volume of distribution, and a longer half-life as compared with older children and adults. Mild somnolence was the only adverse effect.

Topics: Anticonvulsants; Body Weight; Chromatography, Liquid; Creatinine; Female; Half-Life; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Levetiracetam; Male; Multivariate Analysis; Piracetam; Prospective Studies; Seizures; Tandem Mass Spectrometry

Depression is most commonly associated with epilepsy. Recent reports have suggested a putative relationship between seizure development and onset of depressive behavior, whereas others proposed that two clinical entities might represent different neuropathologic aspects of the same neurologic disorder. The WAG/Rij rat absence epilepsy model has also been proposed as a suitable model to test antidepressant drugs. We previously reported on a long-term study of two antiepileptic drugs (AEDs) to assess their protective role in absence epileptogenesis. Here, we examined the effects of long-term treatment with several AEDs on absence seizure development and onset of depressive-like behavior in WAG/Rij rats at different ages, using a forced swimming test (FST).. Animals were divided into one untreated control group and four test groups, given ethosuximide, levetiracetam, zonisamide, or carbamazepine. Electroencephalography (EEG) readings were recorded at 6.5 months of age.. Ethosuximide-treated animals showed significant reductions in recorded spike-wave discharges (SWDs), and FST immobility time (IT) compared with untreated same age controls. However, zonisamide- and carbamazepine-treated animals had IT values similar to those of controls, but only zonisamide significantly decreased absence seizure development. Carbamazepine increased SWD incidence. Levetiracetam also protected against seizure development, while augmenting IT, suggesting a prodepressive effect.. Although treatment with ethosuximide, levetiracetam, or zonisamide reduced appearance of SWDs in WAG/Rij rats, this was not generally linked to a reduced onset of depressive characteristics, as assessed by FST. Therefore, expression of depressive-like behavior seems unrelated to seizure control in this model. Some possible alternative explanations for the observed data are discussed.

Topics: Animals; Anticonvulsants; Brain; Carbamazepine; Depression; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Absence; Ethosuximide; Isoxazoles; Levetiracetam; Male; Piracetam; Rats; Rats, Wistar; Seizures; Zonisamide

The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration.

Topics: Animals; Anticonvulsants; Brain-Derived Neurotrophic Factor; Hippocampus; Levetiracetam; Neurons; Neuroprotective Agents; Piracetam; Placebos; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Sclerosis; Seizures

Both valproic acid and levetiracetam are anti-epileptic drugs, often used either alone or in combination. The present study compares valproate (VPA) with levetiracetam (LEV) as an intravenous (i.v.) anticonvulsant treatment in intensive care patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) with a high risk of seizures.. A prospective, single-center patient registry of 35 intensive care unit (ICU) patients with onset seizure and/or high risk of seizures underwent an anticonvulsive, first-line single treatment regimen either with VPA or LEV. Plasma concentrations (pc), interactions between drugs in the ICU context, adverse effects and seizure occurrences were observed and recorded.. A significant decrease in the pc in patients treated with LEV was observed after changing from intravenous (160±51μmol/l) to enteral liquid application (113±58μmol/l), corresponding to a 70.3% bioavailability for enteral liquid applications. The pc in VPA patients decreased significantly, from (491±138μmol/l) to (141±50μmol/l), after adding meropenem to the therapy (p<0.05). Three epileptic seizures occurred during anticonvulsive therapy in the LEV group, and two in the VPA group, including one non-convulsive status epilepticus (NCSE).. Though this finding needs further verification, the enteral liquid application of levetiracetam seems to be associated with lower bioavailability than the common oral application of levetiracetam. The use of the antibiotic drug meropenem together with valproic acid leads to lower pc levels in patients treated with of valproic acid. For clinical practice, this indicates the need to monitor the levels of valproic acid in combination with meropenem.

Topics: Administration, Oral; Aged; Aneurysm, Ruptured; Anti-Bacterial Agents; Anticonvulsants; Biological Availability; Brain Ischemia; Critical Care; Drug Interactions; Enteral Nutrition; Epilepsy; Female; Humans; Intensive Care Units; Levetiracetam; Male; Meropenem; Middle Aged; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Thienamycins; Valproic Acid

Cerebral venous thrombosis is a rare entity in pregnancy and the postpartum period, with an incidence of 1:10,000 to 1:25,000.. A 19-year-old woman, gravida 1, para 1, presented to the emergency department on postpartum day 7, having experienced seizures. Severe preeclampsia had been diagnosed during the antepartum period. The patient initially was diagnosed with postpartum eclampsia and started on magnesium sulfate for seizure prophylaxis. Magnetic resonance imaging later showed cerebral venous thrombosis of the left transverse sinus and right frontal and left frontoparietal cortical veins.. Cerebral venous thrombosis and eclampsia may manifest in a similar manner. Physicians can optimize the care of patients presenting with seizures by considering etiologies rarer than eclampsia and pursuing tests that may distinguish them.

Topics: Anticoagulants; Anticonvulsants; Brain; Female; Heparin; Humans; Hypertension; Levetiracetam; Magnesium Sulfate; Magnetic Resonance Imaging; Piracetam; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Seizures; Sinus Thrombosis, Intracranial; Stroke; Tomography, X-Ray Computed; Treatment Outcome; Venous Thrombosis; Young Adult

The standard for early posttraumatic brain injury (TBI) seizure prophylaxis is phenytoin. Despite its effectiveness, some argue for the use of newer antiepileptics (e.g., levetiracetam) because phenytoin requires close monitoring to maintain its therapeutic window and is associated with rare cutaneous hypersensitivity reactions. The purpose of this study was to evaluate whether phenytoin or levetiracetam would be more cost-effective in preventing early post-TBI seizures and reducing their negative impact on TBI outcomes.. Cost-effectiveness analysis with the following base case assumptions: (1) phenytoin patients receive 1.0 g fosphenytoin load + 3 days of 100 mg three times a day (TID), have level drawn on day 3, "therapeutic" patients receive 100 mg TID on days 4 to 7, and "subtherapeutic" patients receive 200 mg TID on days 4 to 7; (2) levetiracetam patients receive 500 mg load + 7 days of 500 mg two times a day. Glasgow Outcome Scale (GOS) scores 4 to 5 represent good outcome, and GOS scores 2 to 3 represent poor outcome. Patients who develop early seizures: 40% good outcome, 50% poor outcome, and 10% death. Those who do not develop seizures: 75% good outcome, 20% poor outcome, and 5% death. Quality of life outcomes by GOS: good = 0.7, poor = 0.3, and death = 0.0. Severe adverse events and those impacting costs are rare for each agent. Assumptions were obtained through hospital query and exhaustive literature review.. The cost of a 7-day course of fosphenytoin, phenytoin, and free phenytoin level was $37.50, whereas the cost of a 7-day course of levetiracetam was $480.00. Literature review noted phenytoin to be as effective as levetiracetam in preventing early post-TBI seizures (and more effective in subclinical seizures). Quality-adjusted life years (QALY) were 23.6 for phenytoin and 23.2 for levetiracetam. As a result, the cost/effectiveness ratios were $1.58/QALY for phenytoin and $20.72/QALY for levetiracetam. All sensitivity analyses favored phenytoin unless levetiracetam prevented 100% of seizures and cost <$400 for 7-day course.. Phenytoin is more cost-effective than levetiracetam at all reasonable prices and at all clinically plausible reductions in post-TBI seizure potential.

Topics: Adult; Anticonvulsants; Brain Injuries; Cost-Benefit Analysis; Decision Trees; Female; Glasgow Outcome Scale; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures; Treatment Outcome

We describe the first detailed histological description of an excised calcified Taenia solium granuloma from a patient who developed recurrent seizures associated with perilesional edema surrounding a calcified cysticercus (PEC). The capsule, around a degenerated cysticercus, contained marked mononuclear infiltrates that extended to adjacent brain, which showed marked astrocytosis, microgliosis, and inflammatory perivascular infiltrates. The presence of large numbers of mononuclear cells supports an inflammatory cause of PEC. Immunosuppression or anti-inflammatory measures may be able to treat and prevent PEC and recurrent seizures.

Topics: Albendazole; Animals; Anthelmintics; Anticonvulsants; Calcinosis; Edema; Granuloma; Humans; Levetiracetam; Male; Neurocysticercosis; Piracetam; Seizures; Taenia solium; Valproic Acid; Young Adult

Topics: Anticonvulsants; Humans; Levetiracetam; Male; Piracetam; Psychotic Disorders; Seizures; Young Adult

Levetiracetam (LEV) inhibits partial refractory epilepsy in human, and both convulsive and absence-like seizures in the spontaneously epileptic rat (SER). Two-thirds of hippocampal CA3 neurons in SER show a long-lasting depolarization shift, with accompanying repetitive firing upon mossy fiber stimulation. This abnormal excitability is probably attributable to abnormalities in the L-type Ca(2+) channels. We performed electrophysiological studies to elucidate the mechanism underlying the antiepileptic effects of LEV via intracellular recording from the hippocampal CA3 neurons in slice preparations of SER and non-epileptic Wistar rats. LEV (100 μM) inhibited the depolarization shift with repetitive firing by mossy fiber stimulation (MFS), without affecting the first spike in SER CA3 neurons. At a higher dose (1mM), LEV suppressed the first spike in all SER neurons (including the CA3 neurons which showed only a single action potential by MFS), while the single action potential of Wistar rat CA3 neurons remained unaffected. SER CA3 neurons with MFS-induced abnormal firing exhibited a higher number of repetitive spikes when a depolarization pulse was applied in the SER CA3 neurons. LEV (100 μM, 1mM) reduced the repetitive firing induced by a depolarization pulse applied without affecting Ca(2+) spike in SER neurons. LEV is known not to bind glutamate and gamma-aminobutyric acid (GABA) receptors. These findings suggest that the therapeutic concentration of LEV inhibits abnormal firing of the CA3 neurons by modulating abnormal synaptic transmission and abnormal Na(+) channels in SER.

Topics: Action Potentials; Animals; Anticonvulsants; CA3 Region, Hippocampal; Calcium; Electrophysiology; Humans; Levetiracetam; Membrane Potentials; Mossy Fibers, Hippocampal; Neurons; Piracetam; Rats; Rats, Mutant Strains; Rats, Wistar; Seizures; Sodium Channels; Synaptic Transmission

The incidence of seizures is generally accepted to be greater in patients with multiple sclerosis (MS) than in the general population, and rarely, MS can initially present as seizure. To present a case report of seizure as the initial symptom of MS, to quantify the occurrence of seizures among MS patients, and to classify patients according to when seizures occur relative to onset of MS. The medical history of patients presenting with MS and seizure in our clinic was examined. In addition, 25 scientific papers were reviewed and the number and characteristics of patients with MS and seizure recorded. Data from the literature review and from our own clinical series were combined and examined. Of the MS patients, 1.95% experienced seizures at any time during life. Patients experiencing seizures before MS diagnosis were classified into three categories: (a) 25 (7.3% of patients with MS and seizures) with seizure as the initial presentation of MS; (b) 27 (7.9%) with seizures appearing with other signs and symptoms of MS; and (c) 68 (20%) with seizures occurring years or an unknown period of time before MS onset. Seizure occurring as a symptom of MS relapse was found in 29 patients. The prevalence of seizures among MS patients was higher than that in the general population, indicating a relationship between seizures and MS. Seizures occurred before MS diagnosis in a small percentage of patients.

Topics: Adult; Anticonvulsants; Brain; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Multiple Sclerosis; Piracetam; Seizures; Vitamin B 12; Vitamin B 6; Vitamins

Congenital acute lymphoblastic leukemia (ALL) is a relatively rare disorder that is characterized by frequent central nervous system involvement that may increase the risk for seizures. Appropriate choice of anticonvulsant therapy with respect to ongoing oncologic treatment is not established in this age group. We report the case of a neonate with ALL who was successfully treated for seizures with levetiracetam monotherapy. This full-term boy did well until 3 days of age when he had an episode of left extremity jerking (07/06/07). Computed tomography of the head demonstrated extensive multifocal intraparenchymal hemorrhages. Initial EEG demonstrated multifocal epileptiform activity. Patient was loaded with Phenobarbital at 20 mg/kg. Complete blood count revealed leukocytosis (78 x 103/mm(3)). Peripheral blood smear contained blastocytes and DNA analysis confirmed B-cell ALL. A second focal seizure was reported on the same day and he was re-loaded with Phenobarbital. Maintenance dosing of Phenobarbital was initiated and no further seizures were noted. A repeat EEG on 7/10/07 remained abnormal with excessive multifocal sharp waves. Continuation of anticonvulsant therapy was recommended. Given concern for interaction between Phenobarbital and planned chemotherapy regimen, oncology requested a non-enzyme inducing anticonvulsant. Phenobarbital was subsequently weaned and Levetiracetam monotherapy initiated at 40 mg/kg/day (07/10/2007). Currently, the patient is seizure free at 8 months of age on Levetiracetam monotherapy. The use of Levetiracetam as monotherapy in neonates has not been formally evaluated and experience is limited. We report the successful use of levetiracetam monotherapy after Phenobarbital load in a neonate with leukemia and localization-related epilepsy.

Topics: Anticonvulsants; Electroencephalography; Humans; Infant, Newborn; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Seizures

In the past decade, most studies on levetiracetam were conducted on patients aged > or = 4 years of age. The authors sought to assess the efficacy and safety of levetiracetam as an adjunctive treatment of children <4 years of age with refractory epilepsy. The mean levetiracetam dosage used on the 24 patients in this study was 38.85 mg/kg per day, and the mean duration of treatment was 40 weeks. During the study, levetiracetam was tapered off in 2 patients due to seizure worsening and was discontinued in other 2 patients due to unacceptable adverse effects. Levetiracetam therapy was effective in 58.3% of patients, with 20.8% achieving seizure freedom. Eight patients showed no obvious response and the remaining 2 patients showed divergent responses. Although adverse effects were seen in 37.5% of patients, all adverse effects were tolerable or resolved with time or discontinuation. Therefore, the authors conclude that levetiracetam treatment is effective and safe in young children with refractory epilepsy.

Topics: Anticonvulsants; Child, Preschool; Drug Therapy, Combination; Epilepsy; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

In this retrospective study of institutionalized patients with mental retardation, we present the efficacy and safety of sequential treatment with intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in comparison with either treatment alone for acute repetitive or prolonged seizures (ARPS). We defined ARPS as >or=3 seizures of any type within 1 h or a single seizure of any type lasting >or=3 min. Eighty-eight ARPS episodes were treated in 25 patients (14 female, age 21-72 years), with mainly symptomatic generalized epilepsy. There were no adverse events directly attributable to the administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the primary outcome measure, was significantly lower after combined sequential IRD + IVL treatment (3 of 36) compared to IRD alone (6 of 24, p = 0.048) or IVL alone (10 of 28, p = 0.039). There was no statistically significant difference between the individual IRD and IVL treatments (p = 0.604). The estimated odds ratio (OR) indicated that the risk of seizure recurrence was higher after IRD or IVL monotherapy compared to combined IRD + IVL treatment. Subsequent emergency room (ER) transfers following seizure recurrence were least likely after IVL treatment (10%) compared to combined IRD + IVL (67%) or IRD (83%) treatment. These findings suggest that although IRD or IVL monotherapy is efficacious, the combination is superior in controlling ARPS in this special group of institutionalized patients. In addition, we speculate that a more reliable onset of action after IVL treatment results in rapid seizure control and fewer ER transfers, despite seizure recurrence.

Topics: Acute Disease; Administration, Rectal; Adult; Aged; Diazepam; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Intellectual Disability; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Treatment Outcome; Young Adult

Rett syndrome (RTT) is a progressive neurological disorder characterized by a wide spectrum of phenotypes. Epilepsy is reported to occur in 50-90% of patients with RTT; some develop medically refractory epilepsy. The aim of this study is to investigate the efficacy of levetiracetam (LEV) in drug-resistant patients with RTT. This prospective, pragmatic, open-label study consisted of an 8-week baseline period and a 6-month evaluation period. Efficacy variable was the mean frequency of monthly seizures before, and after 3 and 6 months of treatment with LEV. Eight female patients, aged 7.5-19 years (M12.8+/-5) entered the study. Mean age at epilepsy onset was 25.8+/-14.1 months. All patients showed MeCP2 mutation. Patients had been treated with a mean of 3.4 AEDs (2-7) before LEV. The mean LEV dose was 44.84+/-18.02mg/kg/day. The mean monthly seizure frequency for all types of seizures during the baseline period was 21.3+/-8.1 (range 10-35); after 3 months it was 3.3+/-4.1 (range 0-9) and after 6 months of LEV treatment it was 1.5+/-2 (range 0-4), p<0.0001. The mean follow-up period was 20.2+/-13 months. Mild sleepiness occurred in two patients, one reported intermittent agitation. Levetiracetam appeared effective in our series of drug-resistant RTT patients. All reported a reduction in seizure frequency and consequently a better quality of life.

Topics: Adolescent; Analysis of Variance; Anticonvulsants; Child; Drug Administration Schedule; Electroencephalography; Female; Humans; Levetiracetam; Methyl-CpG-Binding Protein 2; Patient Selection; Piracetam; Prospective Studies; Quality of Life; Rett Syndrome; Seizures; Treatment Outcome; Young Adult

Breakthrough seizure activity has been reported with conversion from brand name to generic anticonvulsants. This has prompted several organizations to support physician notification of generic substitution and patient consent. Recently, a generic formulation of levetiracetam has become available. Risk of seizures with generic levetiracetam has yet to be reported. Literature was reviewed regarding risk of generic substitution. Four cases of seizure activity in primary brain tumor patients after conversion from Keppra to generic levetiracetam are reported. In all cases, there was no evidence of tumor growth or concurrent illness that would increase the risk of seizures. In three cases, the patients have remained seizure free with conversion back to Keppra. The final patient required an increased dose of levetiracetam. As has been described with generic substitution of other anticonvulsants, patients switched to generic levetiracetam may be at risk for breakthrough seizure activity.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Drugs, Generic; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

To assess the long-term efficacy and tolerability of levetiracetam in routine clinical practice.. We retrospectively analysed 218 patients, mostly adults, presenting mostly with localisation-related epilepsy, treated with levetiracetam as adjunctive therapy or monotherapy for up to 36 months. The primary points evaluated were: long-term retention rate, reasons for discontinuing levetiracetam and the percentage of seizure-free patients.. The retention rate at 6, 12, 24 and 36 months following the commencement of levetiracetam treatment was 91.7, 75.2, 60.1 and 53.7% respectively. Sixty-seven (30.7%) patients discontinued levetiracetam treatment. During the clinical audit evaluation period, surgical resection or implantation of VNS was performed in 31 (14.3%) patients. In 53 of the 67 patients (79.1%), the treatment was discontinued due to lack of efficacy; in 14 patients (20.9%) treatment was discontinued due to adverse events. In total, 24 of 218 patients (11.0%) were seizure-free for 36 months.. Levetiracetam is an effective and well-tolerated option for long-term treatment of epilepsy in adults.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Chemotherapy, Adjuvant; Cohort Studies; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures; Time Factors; Treatment Outcome; Young Adult

Topics: Acetamides; Animals; Anticonvulsants; Disease Models, Animal; Indoles; Levetiracetam; Ligands; Membrane Glycoproteins; Mice; Nerve Tissue Proteins; Piracetam; Pyrrolidinones; Rats; Seizures; Synaptic Vesicles

The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined.. Cyclooxygenase-2 (Cox-2), Protocadherin-8 (Pcdh8) and TGF-beta-inducible early response gene-1 (TIEG1) were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-alpha, RGS2, Egr2/krox-20 and beta-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs) as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD) duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration.. The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus.

Topics: Amygdala; Animals; Anticonvulsants; Disease Models, Animal; Electric Stimulation; Epilepsy, Temporal Lobe; Gene Expression; Genes, Immediate-Early; Hippocampus; Levetiracetam; Male; Neuronal Plasticity; Piracetam; Rats; Rats, Wistar; RNA, Messenger; Seizures; Synapses; Synaptic Transmission; Time Factors

Levetiracetam (LEV) is a unique antiepileptic drug that preferentially interacts with synaptic vesicle protein 2A (SV2A). To evaluate the antiepileptogenic action of LEV, we studied its effects on the development and acquisition of pentylenetetrazole (PTZ) kindling and compared them to those of sodium valproate (VPA). Anticonvulsive actions of LEV in PTZ-kindled animals were also determined. LEV did not affect PTZ seizures in naïve animals even at high doses (approximately 300 mg/kg, i.p.). However, combined treatment of LEV (30 and 100 mg/kg, i.p.) with PTZ significantly suppressed the development and acquisition of PTZ kindling. In addition, LEV at relatively low doses (3-30 mg/kg, i.p.) inhibited PTZ-evoked seizures in fully kindled animals. In contrast to LEV, VPA at sub-anticonvulsive doses (30 and 100 mg/kg, i.p.) failed to prevent the development of PTZ kindling and its anticonvulsive potency was similar in PTZ-kindled and naïve mice. The present study shows that LEV contrasts VPA by preventing the development of PTZ kindling and inhibiting seizures selectively in kindled animals.

Topics: Animals; Anticonvulsants; Convulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Injections, Intraperitoneal; Kindling, Neurologic; Levetiracetam; Male; Mice; Mice, Inbred Strains; Pentylenetetrazole; Piracetam; Seizures; Treatment Outcome; Valproic Acid

We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.

Topics: Child; Child, Preschool; Epilepsy; Female; Humans; Infant; Injections, Intravenous; Levetiracetam; Male; Piracetam; Seizures; Time Factors; Treatment Outcome

Antiepileptic medication use in noncancer hospice/palliative care patients is not well defined. The authors report the case of a human immunodeficiency virus (HIV) patient under hospice care with increased seizure frequency. The patient is a 22-year-old female with advanced HIV disease complicated by tonic-clonic seizures, hypoalbuminemia, gastroesophageal reflux disease (GERD), and gastritis. During an admission to the hospice inpatient unit, she developed increasing seizure frequency while receiving oral phenytoin. After collaboration between the clinical pharmacist and the hospice treating physician, they simplified her medication regimen, discontinued the phenytoin, and initiated oral levetiracetam. After these adjustments to her medication regimen, the patient's seizure frequency decreased significantly. This case illustrates the challenges of anticonvulsant use in advanced disease, including drug-drug interactions, impaired pharmacokinetics parameters, and increased risk of adverse effects. The importance of continuously monitoring patients for adverse drug events and assessing patient specific factors to help guide medication selection are also highlighted.

Topics: Anti-Retroviral Agents; Anticonvulsants; Drug Interactions; Female; HIV Infections; Hospice Care; Humans; Levetiracetam; Piracetam; Seizures; Young Adult

Despite anticonvulsant efficacy in animal models of generalized epilepsy, levetiracetam was not effective in the maximal subcutaneous PTZ model in mice and rats. Aim of this study was to assess the efficacy of levetiracetam (LEV) against submaximal, s.c. MET test (PTZ at the dose of 70 mg/kg) acute seizures in Wistar rats, in comparison to valproic acid (VPA). Thirty male Wistar rats (P42) were divided in three drug-treatment groups (10 rats in each group) as follows: valproic acid, levetiracetam, and controls. All animals were tested for seizure threshold at age P50. VPA (110 mg/kg) and LEV (108 mg/kg) were freshly dissolved in saline and injected i.p. in 2-3 ml/kg, 15 and 30 min, respectively, before pentylenetetrazol (PTZ) injection at the dose of 70 mg/kg. The average latency of the seizure type 3 (generalized clonic seizure with loss of righting reflexes) significantly differed between controls and the drug-treated animal groups (p < or = 0.02). The average duration of the seizure type 2 (threshold seizure) was significantly longer in both groups compared to controls (<0.02). In conclusion, LEV plays a role against seizures triggered by subcutaneous PTZ injection given at submaximal doses in rats, as demonstrated by a significant increase in duration of the seizure type 2 (threshold seizure).

Topics: Animals; Anticonvulsants; Convulsants; Dose-Response Relationship, Drug; Electroshock; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Injections, Subcutaneous; Levetiracetam; Male; Pentylenetetrazole; Piracetam; Rats; Rats, Wistar; Seizures; Valproic Acid

In 2006, intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy, 16 years or older. We have established the safety, tolerability, and dosage of intravenous levetiracetam in children. This prospective study included 30 children (6 months to <15 years of age). Patients were administered a single dose of intravenous levetiracetam (50 mg/kg, maximal dose 2500 mg) over 15 minutes. A blood level of levetiracetam was performed 10 minutes after the infusion. The treated children's average age was 6.3 years (range 0.5-14.8 years). The mean levetiracetam level was 83.3 microg/mL (range 47-128 microg/mL). There were no serious adverse reactions. Minor reactions included sleepiness, fatigue, and restlessness. An apparent decrease in seizure frequency across all seizure types was noted. The dose of 50 mg/kg was well tolerated by the patients and is a safe, appropriate loading dose.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Prospective Studies; Regression Analysis; Seizures; Time Factors; Treatment Outcome

We present a patient with cryptogenic focal epilepsy and another with Dravet syndrome, who experienced seizure aggravation and negative myoclonus, associated with continuous spikes and waves during slow sleep, induced by levetiracetam. For both patients levetiracetam was discontinued, and there was significant improvement of this particular electroclinical picture.

Topics: Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Evoked Potentials; Female; Humans; Levetiracetam; Male; Piracetam; Seizures; Sleep; Syndrome

Second-generation antiepileptic drugs (AEDs) are increasingly used in the care of patients with glioma. There is little data on how this practice compares with the use of traditional AEDs in this population. This noninferiority analysis compares seizure outcomes and side effects in patients with glioma treated with phenytoin and levetiracetam monotherapy.. The authors retrospectively reviewed the records of 500 consecutive patients with glioma who were treated in clinical trials from 2001 to 2008 at 3 Mayo Clinic campuses. To be eligible for the study, these patients had to have had at least 1 clinical seizure and to have undergone follow-up for at least 6 months. Seizure outcomes, defined by the occurrence of a second seizure, time to second seizure, and seizure frequency, along with AED side effects, were compared between cohorts treated with phenytoin or levetiracetam. Seventy-six patients were identified, 25 treated with phenytoin and 51 with levetiracetam. Sixty-four percent of the patients had a Grade 4 astrocytoma. There was no difference in seizure outcome between the phenytoin and levetiracetam groups when comparing time to second seizure (p=0.584), second seizure rates (p=0.561), and average seizures per month (p=0.776). When adjusting for age, sex, type of seizure, type of glioma, and dosage using univariate and multivariate models, there were no differences between the treatment groups and none of these covariates were statistically significant for explaining the second seizure rates between treatment groups (all p values>0.05). The incidence of side effects in the levetiracetam group was 6% versus 20% in the phenytoin group (p=0.106). Additionally, 36% of the patients in the phenytoin group had dose adjustments unrelated to breakthrough seizures compared with only 10% in the levetiracetam group (p=0.010). In this study, patients with glioma treated with levetiracetam and phenytoin had similar seizure control. Patients treated with levetiracetam experienced fewer side effects and required fewer nonseizure-related dose adjustments than patients treated with phenytoin. Levetiracetam is a safe, effective, and preferred alternative for seizure management in patients with glioma.

Topics: Adult; Aged; Anticonvulsants; Female; Glioma; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Seizures

Electroencephalographic (EEG) seizures and behavioral convulsions begin to appear spontaneously a few weeks after chemoconvulsant-induced status epilepticus (SE) and thereafter become more intense. This indicates the progressive development of a long-lasting epileptic focus. In addition, chemoconvulsant-induced SE increases neuronal proliferation in the dentate subgranular zone (SGZ) and ectopic migration of newborn neurons into the dentate hilus of adult animals. These seizure-induced newborn neurons, especially ectopic granule cells in the dentate hilus, are believed to facilitate the development of epileptic foci in animal models of temporal lobe epilepsy. In the present study, we examined the effects of a novel antiepileptic drug, levetiracetam, on the appearance of spontaneous EEG seizures and on the generation of newborn neurons, especially of ectopic granule cells in the dentate hilus, following kainate-induced SE. Levetiracetam treatment for 25 days, initiated 24 hours after induction of kainate-induced SE, significantly decreased the mean duration of spontaneous EEG seizures 58 days later. Levetiracetam treatment also prevented an SE-induced increase in the number of ectopic granule cells observed 58 days after kainate administration by suppressing neuronal proliferation in the dentate SGZ and abnormal migration of newborn neurons from the dentate SGZ to the hilus. These results are in accord with a previous report that an antimitotic agent that reduced the number of newborn neurons significantly decreased the frequency of spontaneous convulsions 1 month after pilocarpine-induced SE. This evidence from the kainate model of temporal lobe epilepsy suggests that levetiracetam may exert antiepileptogenic effects through the suppression of seizure-induced neurogenesis.

Topics: Animals; Animals, Newborn; Bromodeoxyuridine; Dentate Gyrus; Disease Models, Animal; Electroencephalography; Homeodomain Proteins; Immunohistochemistry; Kainic Acid; Levetiracetam; Neurons; Nootropic Agents; Piracetam; Rats; Seizures; Status Epilepticus; Tetanus Toxin; Time Factors; Tumor Suppressor Proteins

Levetiracetam may be effective in children with acute seizures or status epilepticus. We performed a retrospective chart review of children who received intravenous levetiracetam within 30 minutes of a seizure. Seventy-three patients during a 2-year study period met our inclusion criteria. The mean (+/- S.D.) age and weight of the patients were 5.59 +/- 5.6 years (range, 1 day to 17.8 years) and 23.1 +/- 21 kg (range, 1.97-97 kg), respectively. Patients received a mean (+/- S.D.) levetiracetam dose of 29.4 +/- 13.5 mg/kg. Most children (n = 49, or 67%) received additional antiepileptic drugs to abort their seizure. Overall, the mean (+/- S.D.) total (abortive plus chronic) number of concomitant antiepileptic drugs used by the population was 2.53 +/- 1.7 (1.07 +/- 0.98 as additional abortive therapy, and 1.42 +/- 1.29 as chronic therapy). Most patients received levetiracetam for serial seizures (79%), whereas 12% and 8% manifested a single seizure or status epilepticus, respectively. Clinical effectiveness at 1, 12, 24, 48, and 72 hours after the initial levetiracetam dose constituted the primary study outcome. Eighty-nine percent of patients remained seizure-free at 1 hour. This rate decreased at each evaluation time point. Most patients (71%) were placed on maintenance levetiracetam within 24 hours of their loading dose. The predictive ability of patient and drug regimen variables in outcomes was poor. Only the number of concomitant antiepileptic drugs consistently predicted outcomes. Levetiracetam was well tolerated at the doses studied, and appears most effective in single seizure events.

Topics: Acute Disease; Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Injections, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Time Factors; Treatment Outcome

The novel antiepileptic drug levetiracetam (keppra, 80 mg/kg, i.p.) produces a pronounced anticonvulsant effect on all parameters of the audiogenic locomotion response in Wistar rats, leading to the prevention of acoustic seizures approximately in 50% animals. Keppra injection also led to a decrease in the intensity of single audiogenic convulsive episode, a twofold prolongation of the latency of motor reaction, and a change in the pattern of seizure reaction toward increasing number of rats with "one-wave" response. In contrast, a lack of sound resistant animals and the change from one- to two-wave audiogenic response were observed in Krushinsky-Molodkina strain rats.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Levetiracetam; Male; Motor Activity; Piracetam; Rats; Rats, Wistar; Reaction Time; Seizures; Species Specificity

Topics: Anticonvulsants; Electroencephalography; Family Health; Humans; Levetiracetam; Mutation; Myoclonic Epilepsy, Juvenile; Piracetam; Receptors, GABA-A; Seizures

The mechanisms underlying the changes in blood-brain barrier (BBB) integrity and the generation of seizures in childhood associated with preexisting brain lesions like cortical dysplasia (CD) are poorly understood. We investigated the effects of levetiracetam (LEV) on BBB integrity and the survival during hyperthermic seizures in rats with CD.. Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. On postnatal day 28, hyperthermia-induced seizures were evoked in offspring with CD. To show the functional and morphological alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopy were performed.. Seizure scores and mortality rates were decreased by LEV during hyperthermia-induced seizures in rats with CD (P<0.01). Increased NaFlu extravasation into brain by hyperthermia-induced seizures in animals with CD was decreased by LEV (P<0.01). While glial fibrillary acidic protein (GFAP) immunoreactivity slightly increased in brain sections of animals with CD during hyperthermia-induced seizures, LEV led to GFAP immunoreactivity comparable to that of controls. Decreased occludin immunoreactivity and expression in CD plus hyperthermia-induced seizures was increased by LEV. Opening of tight junctions and abundance of pinocytotic vesicles representing ultrastructural evidences of BBB impairment and severe perivascular edema were observed in animals with CD exposed to hyperthermia-induced seizures and LEV treatment led to the attenuation of these findings.. These results indicate that LEV may present a novel approach for the protection of the BBB besides its antiepileptic impact on hyperthermic seizures in the setting of CD.

Topics: Animals; Anticonvulsants; Blood-Brain Barrier; Disease Models, Animal; Female; Fever; Fluorescein; Gamma Rays; Levetiracetam; Male; Malformations of Cortical Development; Microscopy, Electron; Piracetam; Pregnancy; Rats; Rats, Sprague-Dawley; Seizures; Tight Junctions

We describe two patients with epilepsy who presented with nonepileptic seizures (NES) when started on levetiracetam (LEV), which disappeared or significantly decreased when LEV was discontinued. NES are traditionally attributed to psychic trauma often after physical or sexual abuse, whereas the psychiatric side effects of levetiracetam largely encompass depression, hallucinations, and psychosis. We conclude that NES are a rare side effect of LEV treatment and part of the spectrum of behavioral changes observed with LEV treatment.

Topics: Adult; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Seizures

This cross-sectional, observational study evaluated the use of levetiracetam oral solution in usual clinical practice. Patients ≥ 16 years with partial-onset seizures (had received levetiracetam oral solution for ≥ 28 days) completed a study questionnaire assessing overall acceptability of levetiracetam oral solution, specific organoleptic characteristics (taste, taste intensity, aftertaste), ease of use and convenience. Tolerability was assessed by evaluating adverse events. Of 389 patients, 92.8% (361/389) were evaluable for acceptability, all (389) for tolerability; 65.3% (236/361) rated levetiracetam oral solution very acceptable or acceptable, 41.5% (150/361) pleasant or very pleasant, 54.3% (196/361) neither strong nor mild taste intensity and indicated the drug left an aftertaste (most stated aftertaste did not bother them), 75.3% very easy or easy to use and 61.8% very convenient or convenient to use. There was a positive relationship between overall acceptability of levetiracetam oral solution and favorable responses for organoleptic characteristics, ease of use, convenience and patients' evaluation of treatment compliance (P < 0.0001 for each). Of the 176/353 who previously received another antiepileptic drug and reported preference for a medication, 72.2% (127/176) preferred levetiracetam oral solution and 39/389 (10%) reported adverse events. Levetiracetam oral solution demonstrated a high degree of patient acceptability in adult patients with partial-onset seizures and was well tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Cross-Sectional Studies; Female; Humans; Levetiracetam; Male; Middle Aged; Patient Compliance; Patient Preference; Pharmaceutical Solutions; Piracetam; Seizures; Taste; Young Adult

Overdose of levetiracetam may produce neurotoxicity.. We reported a patient with epilepsy who took an overdose of 63 grams of levetiracetam with mild adverse events. The patient presented mild blurred vision and mild ataxia that rapidly subsided within one day with supportive care. The laboratory tests showed mild leucopenia and mild thrombocytopenia that gradually returned to normal within 2 months.. The pharmacokinetics, tolerability and adaptation of levetiracetam might play a role in the mild adverse events of levetiracetam overdose in our patient.

Topics: Adult; Humans; Levetiracetam; Male; Neurotoxicity Syndromes; Piracetam; Seizures

This case is the first report of a patient who had phenobarbital (PB) withdrawal seizures after having been seizure-free for 3 years following temporal lobe surgery. The patient had been taking PB for 14 years when a gradual taper of PB was started. When PB was at 60 mg/d, a titration of lamotrigine (LTG) was started. However, typical complex seizures occurred when the patient was on PB 60 mg/d, along with LTG 25mg/d. PB was increased back to 90 mg/d and levetiracetam (LEV) was titrated. Seizures appeared when the patient was on PB 30 mg/d and LEV 750 mg BID and continued for 3 weeks after PB was stopped and the patient was on LEV 1,000 mg BID. For the following 6 months, her aura frequency remained elevated in comparison to her baseline aura of two auras per month for the previous year before the start of the PB taper. She was followed for 24 months after her last PB withdrawal seizure. During the last 8 months, her aura frequency returned to her baseline. As suggested by animal studies, the PB withdrawal seizures and increase in aura frequency in this patient may be explained by changes in her levels of GABA(A) receptor subunits.

Topics: Anticonvulsants; Data Collection; Female; Humans; Lamotrigine; Levetiracetam; Middle Aged; Phenobarbital; Piracetam; Seizures; Substance Withdrawal Syndrome; Time Factors; Triazines

Children with brain tumors and other cancers can suffer from seizures. Unfortunately, most antiepileptic therapies are metabolized by the hepatic cytochrome P450 (CYP) system. Levetiracetam, a newer anticonvulsant, does not undergo CYP metabolism and does not alter the pharmacokinetics of chemotherapy, antiemetics, and corticosteroids, which are metabolized by the liver. We studied 23 patients with cancer and seizures treated with levetiracetam. Over 95% of patients had fewer seizures, with 65.2% becoming seizure free; only one patient experienced an adverse reaction. Levetiracetam is effective and well tolerated in children with brain tumors and other cancers, who are often on multiple enzyme-inducing drugs.

Topics: Adolescent; Anticonvulsants; Brain Neoplasms; Child; Drug Evaluation; Female; Humans; Levetiracetam; Male; Neoplasms; Piracetam; Retrospective Studies; Seizures; Treatment Outcome

To characterize the interactions between levetiracetam and the antiepileptic drugs gabapentin, tiagabine, and vigabatrin in suppressing pentylenetetrazole-induced clonic seizures in mice, type II isobolographic analysis was used. Clonic seizures were evoked in Albino Swiss mice by subcutaneous injection of pentylenetetrazole at its CD(97)(98 mg/kg). Adverse-effect profiles with respect to motor performance, long-term memory and skeletal muscular strength were measured along with total brain antiepileptic drug concentrations. The combination of gabapentin with levetiracetam at the fixed-ratios of 2:1, 1:1, 1:2, and 1:4 were supra-additive (synergistic) in terms of seizure suppression whilst the combination at the fixed-ratio of 4:1 was additive. Tiagabine with levetiracetam and vigabatrin with levetiracetam at the fixed-ratios of 1:25, 1:50, 1:100, 1:200, and 1:400 and at 2:1, 3:1, 4:1, 6:1, 8:1, and 16:1 were additive, respectively. No acute adverse effects were observed. Measurement of total brain antiepileptic drug concentrations revealed that levetiracetam in combination with gabapentin at the fixed-ratio of 1:4 significantly elevated (21%) total brain gabapentin concentrations. In contrast, levetiracetam was without affect on tiagabine or vigabatrin concentrations and co-administration with gabapentin, tiagabine or vigabatrin had no effect on levetiracetam brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse pentylenetetrazole model. The combination of gabapentin with levetiracetam at the fixed-ratios of 2:1, 1:1, 1:2, and 1:4 appears to be particularly favorable combination exerting supra-additive interaction in suppressing pentylenetetrazole-induced seizures, although there is a pharmacokinetic contribution to the interaction between levetiracetam and gabapentin at the fixed-ratio of 1:4. Levetiracetam in combination with tiagabine and vigabatrin appear to be neutral combinations producing only additivity in the mouse pentylenetetrazole model.

Topics: Amines; Animals; Anticonvulsants; Brain; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Interactions; Drug Synergism; Gabapentin; gamma-Aminobutyric Acid; Levetiracetam; Male; Mice; Nipecotic Acids; Pentylenetetrazole; Piracetam; Seizures; Tiagabine; Tissue Distribution; Vigabatrin

Intravenous (IV) levetiracetam (LEV) is approved for use in patients older than 16 years and may be useful in critically ill children, although there is little data available regarding pharmacokinetics. We aim to investigate the safety, an appropriate dosing, and efficacy of IV LEV in critically ill children.. We describe a cohort of critically ill children who received IV LEV for status epilepticus, including refractory or nonconvulsive status, or acute repetitive seizures.. There were no acute adverse effects noted. Children had temporary cessation of ongoing refractory status epilepticus, termination of ongoing nonconvulsive status epilepticus, cessation of acute repetitive seizures, or reduction in epileptiform discharges with clinical correlate.. IV LEV was effective in terminating status epilepticus or acute repetitive seizures and well tolerated in critically ill children. Further study is needed to elucidate the role of IV LEV in critically ill children.

Topics: Acute Disease; Adolescent; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Critical Illness; Electroencephalography; Humans; Infant; Infusions, Intravenous; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Status Epilepticus

Topics: Anticonvulsants; Behavioral Symptoms; Child; Drug Therapy, Combination; Humans; Levetiracetam; Male; Piracetam; Pyridoxine; Seizures; Vitamin B Complex

The aim of this pilot study was to investigate the effects of levetiracetam monotherapy on seizure control, quality of life and neurocognitive performance in patients with brain tumor-related epilepsy. We present here preliminary data from 18 patients with follow-up of 6 months. We evaluated seizure frequency at baseline. We used administered Mini Mental State Examination (MMSE), Karnofsky Performance Status (KPS), Barthel index (BI), QOLIE 31P (V2), EORTC QLQ-C30 and Adverse Events Profile. After 6 months, 16 patients were seizure free (88.9%), 2 (11.1%) had reduction in seizure frequency >50%. Compared to baseline, we observed a worsening of performance (KPS p = 0.011; BI = 0.008) and global lower cognitive performance (MMSE p = 0.011); distress related to seizure frequency (p = 0.003) and medication effects (p = 0.046) were significantly lower. Levetiracetam caused mild and reversible side effects. These preliminary data on LEV monotherapy in patients with brain tumor-related epilepsy show that this antiepileptic drug is efficacious and well tolerated.

Topics: Activities of Daily Living; Adult; Aged; Anticonvulsants; Blood Cell Count; Brain Neoplasms; Combined Modality Therapy; Epilepsy; Female; Humans; Karnofsky Performance Status; Levetiracetam; Logistic Models; Male; Middle Aged; Neuropsychological Tests; Personal Autonomy; Piracetam; Quality of Life; Seizures; Surveys and Questionnaires; Young Adult

Although seizures in brain tumor patients are common, the knowledge on optimal anti-seizure therapy in this patient group is limited. An observational study was carried out using a database of all patients from the neuro-oncology service during the period 2000-2005, with data on seizure characteristics, therapy with AEDs, the underlying brain tumor and its treatment. A total of 140 brain tumor patients were studied of whom 23.6% had a low-grade glioma, 53.6% a high-grade glioma, and 22.8% belonged to a mixed group existing of ependymoma, meningioma, and brain metastasis. Epilepsy as the presenting sign was more frequent in low-grade vs. high-grade gliomas (69.7 vs. 52%, P = 0.087), and a total of 75.8% of patients developed seizures with low-grade and of 80.0% with high-grade gliomas. Of all 99 patients with seizures, 80.1% received valproic acid (VPA) as first choice, and either levetiracetam (LEV), carbamazepine (CBZ) or lamotrigine (LMT) as the most frequent next choice. Patients treated with a combination of VPA and LEV showed the highest percentage of responders (81.5%), with a decline in seizure frequency of more than two categories in 55.6% and seizure freedom in 59%. No correlation was found between the use of VPA and survival. A combination of VPA and LEV seems effective, if seizure control cannot be achieved by VPA alone. This indicates that adding levetiracetam may be preferable over sequential trials of AED monotherapy in treatment-resistant seizures in patients with brain tumors.

Topics: Adult; Anticonvulsants; Brain Neoplasms; Carbamazepine; Drug Therapy, Combination; Female; Follow-Up Studies; Glioma; Humans; Kaplan-Meier Estimate; Lamotrigine; Levetiracetam; Male; Middle Aged; Neoplasm Staging; Piracetam; Seizures; Time Factors; Treatment Outcome; Triazines; Valproic Acid

Levetiracetam is an antiepileptic drug widely prescribed. We report here for the first time, an alteration of platelet function attributable to this drug. This effect has never been reported before. The responsibility of levetiracetam seems to be probable: restoration of platelet functionality was observed after withholding this treatment and this effect has been described for a structurally related molecule, piracetam.

Topics: Aged; Anticonvulsants; Blood Platelet Disorders; Clopidogrel; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Platelet Aggregation; Platelet Aggregation Inhibitors; Seizures; Ticlopidine

This study investigates the effects of levetiracetam (LEV) on the functional and structural properties of blood-brain barrier (BBB) in pentylenetetrazole (PTZ)-kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. In offsprings, kindling was induced by giving subconvulsive doses of PTZ three times per week for 45 days. While all kindled rats with CD died during epileptic seizures evoked by the administration of a convulsive dose of PTZ in 15 to 25 min, one week LEV (80 mg/kg) pretreatment decreased the mortality to 38% in the same setting. LEV caused a remarkable decrease (p<0.01) in extravasation of sodium fluorescein dye into the brain tissue of kindled animals with CD treated with convulsive dose of PTZ. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Immunoreactivity for glial fibrillary acidic protein (GFAP) was observed to be slightly increased by acute convulsive challenge in kindled rats with CD while LEV pretreatment led to GFAP immunoreactivity comparable to that of controls. An increased c-fos immunoreactivity in kindled rats with CD exposed to convulsive PTZ challenge was also observed with LEV pretreatment. Tight junctions were ultrastructurally intact, whereas LEV decreased the increased pinocytotic activity in brain endothelium of kindled rats with CD treated with convulsive dose of PTZ. The present study showed that LEV decreased the increased BBB permeability considerably by diminishing vesicular transport in epileptic seizures induced by convulsive PTZ challenge in kindled animals with CD.

Topics: Animals; Anticonvulsants; Blood-Brain Barrier; Brain; Capillary Permeability; Endothelium; Fluorescein; Glial Fibrillary Acidic Protein; Levetiracetam; Malformations of Cortical Development; Membrane Proteins; Occludin; Pentylenetetrazole; Pinocytosis; Piracetam; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Sprague-Dawley; Seizures; Tight Junctions

Status epilepticus is defined as a seizure lasting beyond 30 minutes. Children with intractable epilepsy undergo frequent hospital admissions secondary to status epilepticus or because of acute exacerbation of seizures. Intravenous levetiracetam became available in August 2006 for use in patients aged above 16 years. There are insufficient data about the efficacy and safety of intravenous levetiracetam in children. We retrospectively analyzed data from children treated with intravenous levetiracetam for status epilepticus and acute exacerbation of seizures. We acquired data from our institution's electronic medical records concerning patients with status epilepticus and acute exacerbation of seizures who received intravenous levetiracetam. Thirty-two patients (age range, 2 months to 18 years) had received a levetiracetam load of 25-50 mg/kg for status epilepticus. There were 17 (53.1%) males and 15 (46.8%) females. Response to intravenous levetiracetam in all patients was favorable. Status epilepticus ceased clinically and electrographically. Eighteen patients (56.5%) received intravenous levetiracetam after receiving fosphenytoin and Ativan with no response. No serious side effects were evident. Fifteen patients (46.8%) were discharged on levetiracetam monotherapy, and 9 (28.1%) received levetiracetam as adjunctive therapy after discharge from the hospital. Intravenous levetiracetam can be used adjunctively or as monotherapy in children with status epilepticus and acute exacerbation of seizures.

Topics: Adolescent; Anticonvulsants; Brain; Chemotherapy, Adjuvant; Child; Child, Preschool; Electroencephalography; Female; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Status Epilepticus; Treatment Outcome

A 17-year-old girl who had started on levetiracetam because of new onset partial complex seizures developed acute renal failure and biopsy-confirmed interstitial nephritis 10 days after starting the drug. She made a complete and rapid recovery after discontinuation of levetiracetam and administration of oral corticosteroids. Levetiracetam, known to be predominantly excreted by the kidneys, has not previously been reported to cause significant renal complications in children. Children taking levetiracetam who present with abdominal pain, malaise, vomiting, oliguria, rash, or urticaria may require screening laboratory evaluation for potential renal adverse effects.

Topics: Adolescent; Adrenal Cortex Hormones; Anticonvulsants; Contraindications; Female; Humans; Kidney; Levetiracetam; Nephritis, Interstitial; Piracetam; Renal Insufficiency; Seizures

Topics: Anticonvulsants; Brain; Humans; Levetiracetam; Phenytoin; Piracetam; Seizures

This study was designed so as to characterize the interactions between levetiracetam (LEV) and the conventional antiepileptic drugs (AEDs) clonazepam (CZP), ethosuximide (ETS), phenobarbital (PB), and valproate (VPA) in suppressing pentylenetetrazole (PTZ)-induced clonic seizures in mice by use of type II isobolographic analysis. Adverse-effect profiles of the drugs in combination were determined and brain AED concentrations were measured. The combinations of VPA and ETS with LEV at the fixed-ratio of 1:2, CZP with LEV (1:20,000), and PB with LEV (1:20) were supra-additive (synergistic) in suppressing seizures. In contrast, VPA and ETS with LEV (1:1, 2:1, and 4:1), CZP with LEV (1:1000, 1:5000, and 1:10,000), and PB with LEV (1:1, 1:5, and 1:10) were additive. No adverse effects were observed. ETS significantly reduced brain LEV concentrations but no other pharmacokinetic changes were observed. The combinations of CZP with LEV (1:20,000); VPA and ETS with LEV (1:2); and PB with LEV (1:20) appear to be favorable combinations exerting supra-additive interactions in suppressing PTZ-induced seizures.

Topics: Animals; Anticonvulsants; Clonazepam; Convulsants; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Ethosuximide; Levetiracetam; Male; Mice; Pentylenetetrazole; Phenobarbital; Piracetam; Seizures; Valproic Acid

Antiepileptic drugs are frequently used in children with brain tumors. This retrospective study reviewed chronic use of antiepileptic drugs in children with brain tumors at two children's hospitals between 2000 and 2007. Antiepileptic drugs were used in 32/334 pediatric brain tumor patients (10%). Almost all (94%) had supratentorial tumors, of which 78% were glial tumors. The most common localization was temporal (70%). The most frequently used initial antiepileptic drugs were phenytoin (n = 14) and oxcarbazepine (n = 7). Initial antiepileptic drugs were frequently changed, because of lack of efficacy and adverse effects, as well as concerns about possible drug interactions. At last follow-up, the most common antiepileptic drugs were oxcarbazepine (n = 11) and levetiracetam (n = 10). Levetiracetam was more likely to be used in children who received chemotherapy or radiation therapy (8/14, or 57%) than in those who did not receive adjuvant therapies (3/18, or 17%) (P = 0.03). The patients started on newer-generation antiepileptic drugs (levetiracetam, oxcarbazepine, lamotrigine) tended to remain on the same antiepileptic drugs more than did patients on older-generation antiepileptic drugs (valproic acid, phenytoin, phenobarbital) (73% vs 28%) (P = 0.04). Newer antiepileptic drugs, especially those without significant drug-drug interactions, may be a more appropriate first choice in children with brain tumors and seizures.

Topics: Anticonvulsants; Antineoplastic Agents; Brain Neoplasms; Carbamazepine; Child; Drug Interactions; Follow-Up Studies; Glioma; Humans; Levetiracetam; Oxcarbazepine; Phenytoin; Piracetam; Retrospective Studies; Seizures; Supratentorial Neoplasms; Treatment Outcome

To study the incidence and extent of the occasionally noted hypotension after intravenous (IV) infusions of fosphenytoin (FOS) and levetiracetam (LEV) in patients presenting with acute cerebral symptoms.. Retrospective data collection of consecutive patients with acute cerebral symptoms who received IV infusions of a single dose of 750 mg or more of either fosphenytoin or levetiracetam and had documented blood pressure values in the 2h prior and the 2h after their IV infusion.. More than 10 mmHg drop in the systolic, diastolic and MBP was observed in the FOS group following the IV infusion (-16.82 mmHg, -11.60 mmHg, and 13.34 mmHg, respectively). However, there was not a significant change in the MBP after LEV infusion (1.54 mmHg, 1.84 mmHg, and 1.74 mmHg for systolic, diastolic and MBP change, respectively). The difference in the systolic, diastolic and MBP changes between the two groups was statistical significant (all p values are <0.0001) after adjusting for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. Sixty two percent of patients who received FOS had >10 mmHg decrease in their MBP. In the LEV group, only 2 of the 50 patients (4%) had >10 mmHg decrease in their MBP. The difference in proportion of the patients with >10 mmHg drop in MBP between the two study groups is also statistically significant (p<0.001) for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital.. IV infusion of FOS in subjects presenting with acute cerebral symptoms may cause significant decreases in their blood pressure. This was not seen in patients receiving IV LEV infusions. Since maintaining adequate cerebral perfusion pressure is a key point in the management of patients with acute cerebral symptoms, the results of this study may carry a clinical impact on the management of this subgroup of patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Chi-Square Distribution; Female; Humans; Hypotension; Levetiracetam; Male; Medical Records; Middle Aged; Patient Selection; Phenytoin; Piracetam; Regression Analysis; Retrospective Studies; Seizures; Treatment Outcome

Understanding the molecular mechanisms underlying epilepsy is crucial to designing novel therapeutic regimens. This report focuses on alterations in the secretory machinery responsible for neurotransmitter (NT) release. Soluble N-ethylmaleimide sensitive factor (NSF) attachment protein receptor (SNARE) complexes mediate the fusion of synaptic vesicle and active zone membranes, thus mediating NT secretion. SNARE regulators control where and when SNARE complexes are formed. Previous studies showed an asymmetric accumulation of 7S SNARE complexes (7SC) in the ipsilateral hippocampus of kindled animals. The present studies probe the persistence of 7SC accumulation and the effect of the anticonvulsant, levetiracetam (LEV), on 7SC and SNARE regulators.. Quantitative Western blotting was used to monitor levels of 7SC and SNARE regulators in hippocampal synaptosomes from kindled animals both before and after LEV treatment.. The asymmetric accumulation of 7SC is present 1-year postamygdalar kindling. The synaptic vesicle protein, synaptic vesicle protein 2 (SV2), a primary LEV-binding protein, and the SNARE regulator Tomosyn increase, whereas NSF decreases in association with this accumulation. Treatment with LEV prevented kindling-induced accumulation of SV2, but did not affect the transient increase of Tomosyn or the long-term decrease NSF. LEV treatment retarded the electrical and behavioral concomitants of amygdalar kindling coincident with a decrease in accumulation of 7SC.. The ipsilateral hippocampal accumulation of SNARE complexes is an altered molecular process associated with kindling that appears permanent. Kindling epileptogenesis alters synaptosomal levels of the SNARE regulators: NSF, SV2, and Tomosyn. Concomitant treatment with LEV reverses the kindling-induced 7SC accumulation and increase of SV2.

Topics: Amygdala; Analysis of Variance; Animals; Anticonvulsants; Disease Models, Animal; Electric Stimulation; Gene Expression Regulation; Hippocampus; Kindling, Neurologic; Levetiracetam; Male; Membrane Glycoproteins; N-Ethylmaleimide-Sensitive Proteins; Nerve Tissue Proteins; Piracetam; R-SNARE Proteins; Rats; Rats, Sprague-Dawley; Seizures; SNARE Proteins; Time Factors

Medically refractory neonatal seizures represent a major therapeutic challenge in neonatal intensive care units. Conventional antiepileptic drugs demonstrate limited efficacy. Previous studies documented a high frequency of off-label drug therapy in neonates. We sought to determine if pediatric neurologists are recommending treatment of neonatal seizures with newer agents, despite a lack of information about their safety or efficacy in this population. Surveys were distributed at the 2007 Annual Meeting of the Child Neurology Society. Responses from 55 pediatric neurologists were analyzed. Seventy-three percent (40/55) recommended treatment of neonatal seizures with one or both of levetiracetam and topiramate; 47% (26/55) recommended levetiracetam; and 55% (30/55) recommended topiramate. Despite an absence of data on neonatal pharmacokinetics of either drug, neurologists made different dosing recommendations for these two drugs (P = 0.003, chi-square test). Respondents considered both agents to be efficacious in the majority of cases; adverse effects were recognized more frequently with topiramate. These results highlight the urgent need for rigorous clinical trials to understand the risks and benefits of new drug therapies for neonatal seizures.

Topics: Anticonvulsants; Drug Utilization; Guidelines as Topic; Health Surveys; Humans; Infant, Newborn; Levetiracetam; Piracetam; Practice Patterns, Physicians'; Seizures; Surveys and Questionnaires

Topics: Adult; Agammaglobulinemia; Anticonvulsants; Brain Abscess; Humans; Immunoglobulins; Levetiracetam; Male; Piracetam; Seizures

The purpose of the study was to assess changes in cognitive functions and quality of life in patients with epilepsy over one year of treatment with levetiracetam (LEV) as add-on therapy.. Thirty-two patients (16 women; 16 men) who received LEV as an add-on treatment were included, and 27 completed the one-year follow-up period. Extensive neuropsychological assessments, together with a quality-of-life questionnaire were administered at baseline and at one, three, six and twelve months after beginning the add-on treatment. Patients received LEV starting with 500 mg/day in the first week, increasing by a further 500 mg/day per week until a target dose of 2 000 mg/day was reached by the end of the first month.. At the one-year follow-up, a significant improvement was observed in measurements of prospective memory, working memory, motor functions, verbal fluency, attention and quality of life. Performance for neuropsychological and quality-of-life tests was not affected by external variables such as seizure reduction or changes in previous anti-epileptic treatment. Slight changes between patients were observed, but these were not clinically significant.The limited sample size and the lack of a control group should be mentioned as limitations of the study. No control group was evaluated as in our clinical practice it was difficult to establish a comparable group of patients. Changes in the different variables were assessed by comparing baseline information with follow-up results.Despite the study limitations, we consider that the one-year treatment period provides valuable information regarding the drug's long-term effects in this setting.. Results of the present study suggest that long-term LEV treatment as add-on therapy does not interfere with cognitive function and improves quality of life.

Topics: Adult; Aged; Anticonvulsants; Cognition; Epilepsy; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Prospective Studies; Quality of Life; Seizures; Young Adult

Following a collapse at home, a previously well 24-year-old Ukrainian man living in Ireland was brought to the emergency department. He complained of neck pain and cervical spine radiographs revealed loss of lordosis, scalloping of the posterior vertebral bodies and widening of the neural exit foramina at C7. In view of these unusual radiological findings, further examination of the patient demonstrated multiple flat uniformly hyperpigmented brown macules with multiple subcutaneous well-circumscribed lesions along the distribution of the peripheral nerves. An MRI scan of the neck revealed multiple neurofibromas in the vertebral canal with cord compression at C7-T1. A diagnosis of neurofibromatosis type 1 was made. Other investigations to determine the aetiology of the collapse were normal and the patient was discharged with follow-up at specialist neurology and neurosurgical clinics. In recent years there have been increased numbers of economic migrants presenting to the emergency department in the UK and Ireland from European Union accession states. This case highlights the need for increased awareness among emergency physicians to previously undiagnosed genetic and congenital conditions.

Topics: Anticonvulsants; Humans; Levetiracetam; Male; Neck Pain; Neurofibromatosis 1; Piracetam; Seizures; Soft Tissue Neoplasms; Young Adult

We analyzed the effect of combination therapy on seizure frequency in all adult patients (N=193) with focal epilepsy followed at a single institution in a cross-sectional study. One hundred and thirty-five patients were on two AEDs, of them, 37 (27%) were seizure-free, 50 patients were on three AEDs including 5 (10%) seizure-free patients (p<0.01 for seizure-freedom with two AEDs versus three AEDs). Thirty-five different combinations were used in patients on two AEDs and 40 combinations on patients on three drugs emphasizing the difficulties involved in evaluation of the efficacy and tolerability of specific combinations. The significant proportion of seizure-free cases (27%) on duotherapy is suggesting the usefulness of combination therapy in achieving seizure-freedom in epilepsies refractory to single drug treatment. The material in the study was not from a randomized trial and therefore the comparability of patients on different AEDs is uncertain, but on the other hand the clinical practice followed provides a natural experiment suitable for comparative, non-randomized assessment of treatment outcomes.

Topics: Adult; Anticonvulsants; Brain; Carbamazepine; Drug Therapy, Combination; Female; Frontal Lobe; Fructose; Humans; Lamotrigine; Levetiracetam; Male; Nipecotic Acids; Occipital Lobe; Oxcarbazepine; Parietal Lobe; Piracetam; Seizures; Temporal Lobe; Tiagabine; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Screening of 12,000 compounds for binding affinity to the synaptic vesicle protein 2A (SV2A), identified a high-affinity pyrrolidone derivative, brivaracetam (ucb 34714). This study examined its pharmacological profile in various in vitro and in vivo models of seizures and epilepsy, to evaluate its potential as a new antiepileptic drug.. The effects of brivaracetam and levetiracetam on epileptiform activity and seizure expression were examined in rat hippocampal slices, corneally kindled mice, audiogenic seizure-susceptible mice, maximal electroshock and pentylenetetrazol seizures in mice, hippocampal-kindled rats, amygdala-kindled rats and genetic absence epilepsy rats.. Brivaracetam and levetiracetam reduced epileptiform responses in rat hippocampal slices, brivaracetam being most potent. Brivaracetam also differed from levetiracetam by its ability to protect against seizures in normal mice induced by a maximal electroshock or maximal dose of pentylenetetrazol. In corneally kindled mice and hippocampal-kindled rats, brivaracetam induced potent protection against secondarily generalized motor seizures and showed anti-kindling properties superior to levetiracetam. In amygdala-kindled rats, brivaracetam induced a significant suppression in motor-seizure severity and, contrary to levetiracetam, reduced the after-discharge at a higher dose. Audiogenic seizure-susceptible mice were protected more potently against the expression of clonic convulsions by brivaracetam than by levetiracetam. Brivaracetam induced a more complete suppression of spontaneous spike-and-wave discharges in genetic absence epilepsy rats than levetiracetam.. Brivaracetam has higher potency and efficacy than levetiracetam as an anti-seizure and anti-epileptogenic agent in various experimental models of epilepsy, and a wide therapeutic index.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroshock; Epilepsy; Hippocampus; Levetiracetam; Ligands; Male; Membrane Glycoproteins; Mice; Nerve Tissue Proteins; Piracetam; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Seizures

: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.

Topics: Animals; Anticonvulsants; Antioxidants; Brain; Catalase; Glutathione; Levetiracetam; Lipid Peroxidation; Male; Malondialdehyde; Mice; Nitrates; Nitrites; Pilocarpine; Piracetam; Seizures; Thiobarbituric Acid Reactive Substances

Polytherapy with two or more antiepileptic drugs (AEDs) is generally required for approximately 30% of patients with epilepsy, who do not respond satisfactorily to monotherapy. The potential usefulness of AED combinations, producing synergistic anticonvulsant efficacy and minimal adverse effects, is therefore of significant importance. The present study sought to ascertain the potential usefulness of levetiracetam (LEV) and felbamate (FBM) in combination in the mouse maximal electroshock (MES)-induced seizure model.. The anticonvulsant interaction profile between LEV and FBM in the mouse MES-induced seizure model was determined using type II isobolographic analysis. Acute adverse effects (motor performance) were ascertained by use of the chimney test. LEV and FBM brain concentrations were measured by HPLC in order to determine any pharmacokinetic contribution to the observed antiseizure effect.. LEV in combination with FBM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, were supraadditive, whereas at the fixed ratio of 1:4, additivity was observed in the mouse MES model. Furthermore, none of the investigated combinations altered motor performance in the chimney test. Brain FBM concentrations were unaffected by concomitant LEV administration. In contrast, FBM significantly increased LEV brain concentrations.. LEV in combination with FBM was associated with pharmacodynamic supraadditivity in the MES test. However, this anticonvulsant supraadditivity was associated with a concurrent increase in brain LEV concentrations indicating a pharmacokinetic contribution to the observed pharmacodynamic interaction between LEV and FBM.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Chromatography, High Pressure Liquid; Disease Models, Animal; Drug Synergism; Electroshock; Epilepsy; Felbamate; Humans; Levetiracetam; Male; Mice; Motor Activity; Phenylcarbamates; Piracetam; Propylene Glycols; Seizures

For the treatment of patients with chronic refractory epilepsies, development of new antiepileptic drugs is crucial. Three regulatory trials have demonstrated that add-on levetiracetam is efficacious in patients with localization-related epilepsy. However, results from these highly controlled short-term clinical trials cannot simply be extrapolated to everyday clinical practice. Therefore, more information is needed about the long-term profile of a new antiepileptic drug in clinical practice.. We analyzed all patients who had been treated with levetiracetam in the Epilepsy Centre Kempenhaeghe from the introduction of the drug in early 2001 up to a final assessment point, at the end of 2003, using a medical information system.. In total, 301 patients were included. One hundred thirty-eight patients (45.8%) discontinued LEV treatment during the 24-month follow-up period. Reasons for discontinuation were lack of efficacy in 15.9% of patients, adverse events in 6.0% of patients, and a combination of lack of efficacy and adverse events in 16.3% of patients. By Kaplan-Meier survival analysis, the continuation rate was 65.6% after 1 year and 45.8% after 2 years. About 15% of patients in this highly refractory group had a 3-month remission, whereas 10% of patients became seizure-free for longer periods. The most frequently reported side effects at the time of discontinuation were mood disorders, tiredness, and sleepiness. Variables predicting (dis)continuation of levetiracetam treatment could not be identified.. Levetiracetam is a new antiepileptic drug that appears to be a useful add-on treatment in patients with refractory epilepsy. Its side effect profile is mild, with mood disorders being the most dominant adverse event.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Drug Therapy, Combination; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Levetiracetam; Male; Mental Disorders; Middle Aged; Piracetam; Referral and Consultation; Seizures; Survival Analysis

We present the case of a boy with tuberous sclerosis who was referred for evaluation and treatment of his intractable epileptic seizures, having failed multiple anti-epileptic drug trials. He was subsequently treated with Levetiracetam that was gradually titrated to an effective dose, achieving full suppression of his seizures. Thereafter, his concomitant anti-epileptic drugs were gradually reduced and eventually discontinued. He remained on monotherapy with Levetiracetam, which continued to fully control his seizures. His EEG tracings before and after treatment are presented and compared, showing normalization of the latter.. Levetiracetam appears to be effective in treatment-resistant seizures which are symptomatic to tuberous sclerosis when used adjunctively as well as in monotherapy. This is the first report in the English literature regarding its use and efficacy in this condition.

Topics: Anticonvulsants; Child; Follow-Up Studies; Humans; Levetiracetam; Male; Piracetam; Seizures; Tuberous Sclerosis

Enhancement of the glutamatergic excitatory synaptic transmission efficacy in the FeCl3 induced epilepsy model is associated with changes in the levels of glutamate and GABA transporter proteins. This study examined the effect of levetiracetam (LEV) on glutamate overflow and glutamate/GABA transporters expression in rats with epileptogenesis induced by the amygdalar injection of 1.0 microl of 100 mM FeCl3 (epileptic rat) and in control rats receiving amygdalar acidic saline injection (non-epileptic rat). In amygdalar acidic saline injected rats, 40 mM KCl-evoked glutamate overflow was significantly suppressed by both 32 and 100 microM LEV co-perfusion. In unilateral amygdalar FeCl3 injected rats, 32 microM LEV was ineffective, but the 100 microM LEV statistically suppressed glutamate overflow. Western blotting was employed to determine the hippocampal expression of glutamate/GABA transporters in epileptic or non-epileptic rats. The rats were treated for 14 days with 54 mg/kg LEV or vehicle intraperitoneally injection. Following 14 days of treatment, the ipsilateral hippocampus was removed for a Western blot analysis. In non-epileptic rats, the expression increased for all of the glutamate and GABA transporters (GLAST, GLT-1, EAAC-1, GAT-1 and GAT-3) while the glutamate transporter regulating protein (GTRAP3-18) decreased in comparison to those of normal rats that were treated with the vehicle. In epileptic rats receiving LEV, the EAAC-1 and GAT-3 levels increased while GTRAP3-18 (89%) decreased in comparison to those of the epileptic rats treated with the vehicle. GTRAP3-18 inhibitor regulates glutamate-binding affinity to EAAC-1. The anti-epileptic action of LEV may be partially due to a reduction of glutamate-induced excitotoxicity and an enhancement of the GABAergic inhibition as observed with the inhibitory effect on the 40 mM KCl-evoked glutamate overflow. These conclusions are supported by the increase in the expression of glial glutamate transporters (GLAST and GLT-1), and the increase in the expression of EAAC-1 and GAT-3 associated with a decrease in GTRAP3-18. The increased expression of EAAC-1 and the decreased expression of GTRAP3-18 in association with the up-regulation of GAT-3 due to such continual LEV administration was thus found to enhance GABA synthesis and reverse the transport of GABA both in non-epileptic and epileptic rats. The suppression of glutamate excitation and the enhancement of GABA inhibition in the rats with continual LEV

Topics: Amino Acid Transport System X-AG; Amygdala; Analysis of Variance; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Ferric Compounds; GABA Plasma Membrane Transport Proteins; Gene Expression Regulation; Hippocampus; Levetiracetam; Male; Microdialysis; Piracetam; Rats; Rats, Wistar; Seizures

Seizures are a common complication of metastatic brain tumors (MBT), affecting approximately 27-50% of all patients during the course of their illness. Treatment of tumor-induced seizures is often inadequate with traditional antiepileptic drugs (AED) due to a variety of factors, including activation of glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A, that has been previously shown to reduce seizure activity in patients with primary brain tumors. Due to its unique mechanism of action, it has been postulated that LEV may also be effective in controlling seizures from MBT. A retrospective chart review was performed of all Neuro-Oncology Center patients with MBT who had received LEV for seizure control. Thirteen patients were reviewed with a median age of 55.1 years (range: 34-70). Six patients had breast cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED in seven patients (54%) and as monotherapy in six patients (46%), with a median dose of 1,000 mg/day (range: 500-3,000). The baseline median seizure frequency was one ictal event every other day. After the addition of LEV, the median seizure frequency was reduced to 0 per week. The seizure frequency was reduced to less than 50% of the pre-LEV baseline in 100% of patients (P=0.0002, Sign test), with 10 patients (77%; confidence interval: 46-95%) noting complete seizure control. The most common adverse event was somnolence and headache, noted in 3 of 13 patients (23%). LEV was very effective and well tolerated in MBT patients with seizures and should be considered for add-on therapy or as a substitute AED for monotherapy.

Topics: Adult; Aged; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures

We report the case of a five-year-old girl, presenting with difficult-to-treat, symptomatic focal epilepsy, who developed status gelasticus following the introduction of levetiracetam as add-on treatment to oxcarbazepine and diazepam. Gelastic seizures were documented by video-EEG and were responsive to i.v. administration of diazepam. A possible causative role of levetiracetam is suggested. Specific susceptibility to some AEDs is also discussed, as this patient, at the age of four years, had presented an episode of non-convulsive status epilepticus, following introduction of tiagabine, in association with vigabatrin and nitrazepam.[Published with video sequences].

Topics: Anticonvulsants; Brain; Child, Preschool; Electroencephalography; Epilepsies, Partial; Female; Humans; Laughter; Levetiracetam; Magnetic Resonance Imaging; Piracetam; Seizures; Stereotyped Behavior

Seizures are a common occurrence in the neonatal intensive care unit, especially among low-birth-weight infants. The efficacy and safety of standard anticonvulsants have not been evaluated extensively in the neonate. In addition, there is concern for the adverse effects of phenobarbital on long-term development. Levetiracetam has been a commonly prescribed oral anticonvulsant for the use of adjunctive therapy for partial seizures in adults with favorable tolerability, and it has been recently approved for children older than age 4 years. There are no published studies regarding the safety and efficacy of this medication in the infant population. This report describes the initiation of levetiracetam in 3 infants, aged 2 days to 3 months, for refractory seizures or intolerance to other anticonvulsants. Each patient was without seizure on levetiracetam monotherapy, and there were no adverse effects.

Topics: Anticonvulsants; Electroencephalography; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Seizures

In the present study, we evaluated the anti-seizure and anti-myoclonic activity of levetiracetam and brivaracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus. We found that brivaracetam (0.3 mg/kg, the minimal effective dose) was more potent than levetiracetam (3 mg/kg, the minimal effective dose) against post-hypoxic seizures. The anti-seizure activity of both compounds occurred 30 min following intraperitoneal (i.p.) administration and was maintained over the entire 150 min post-dose observation period. Both brivaracetam and levetiracetam significantly reduced auditory stimulated post-hypoxic myoclonus from a dose 0.3 mg/kg. At that dose, the anti-myoclonic activity of brivaracetam was already maximal whereas it continued to increase in a dose-relation manner with levetiracetam, suggesting that brivaracetam is a more potent agent. The onset and the duration of anti-myoclonic activity of both compounds were similar. These findings demonstrate that brivaracetam possesses more potent anti-seizure and anti-myoclonic activity than levetiracetam in an established rat model of cardiac arrest-induced post-hypoxic myoclonus.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsies, Myoclonic; Heart Arrest; Hypoxia; Levetiracetam; Piracetam; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Seizures

Topics: Anticonvulsants; Child, Preschool; Drug Overdose; Female; Humans; Levetiracetam; Piracetam; Seizures

Levetiracetam (LEV) monotherapy was investigated in 25 patients with advanced Alzheimer's disease (AD) and new-onset epileptic seizures in a prospective open-label study. At a daily dose of 1000-1500 mg, 72% were seizure-free for at least one year; 16% discontinued for untolerability; 8% were unresponsive; 4% were lost to follow-up. These results suggest the need for controlled studies to confirm if LEV can be a first-choice drug in AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies; Seizures

Seizure incidence during the neonatal period is higher than any other period in the lifespan, yet we know little about this period in terms of the effect of seizures or of the drugs used in their treatment. The fact that several antiepileptic drugs (AEDs) induce pronounced apoptotic neuronal death in specific regions of the immature brain prompts a search for AEDs that may be devoid of this action. Furthermore, there is a clear need to find out if a history of seizures alters the proapoptotic action of the AEDs. Our studies are aimed at both of these issues. Phenytoin, valproate, phenobarbital, and MK801 each induced substantial regionally specific cell death, whereas levetiracetam even in high doses (up to 1,500 mg/kg) did not have this action. In view of our previously findings of neuroprotective actions of repeated seizures in the adult brain, we also examined repeated seizures for a possible antiapoptotic action in the infant rat. Rat pups were preexposed to electroshock seizures (ECS) for 3 days (age 5-7 days) before receiving MK801 on day 7. The effect of ECS, which was consistently a 30% decrease in MK801-induced programmed cell death (PCD), suggests that repeated seizures can exert an antiapoptotic action in the infant brain. In contrast, PCD induced by valproate was not attenuated by ECS preexposure, suggesting that valproate-induced PCD is mechanistically distinct from that induced by MK801 and may not be activity-dependent. Presently, we do not know if this neuroprotective effect of seizures is deleterious or beneficial. If the seizures also enhance the survival of neurons that are destined to undergo naturally occurring PCD, early childhood seizures may have deleterious effects by preventing this necessary component of normal development. While this effect of seizures might be counteracted by AEDs, the fact that several AEDs shift the PCD to the other extreme, and trigger excessive neuronal cell loss, raises concern about whether the drug therapy may be more detrimental than the seizures. In this context, it is encouraging that we have identified at least one AED that is devoid of a proapoptotic action in the infant brain, even in high doses. It is now important to evaluate the long-term consequences of the changes in PCD in infancy by examining behavioral outcomes and seizure susceptibility in the AED- and seizure-exposed neonates when they reach adulthood.

Topics: Animals; Animals, Newborn; Anticonvulsants; Apoptosis; Basal Ganglia; Behavior, Animal; Body Weight; Brain; Dizocilpine Maleate; Electroshock; Levetiracetam; Piracetam; Rats; Rats, Sprague-Dawley; Seizures; Thalamus

Approximately 30% of patients with epilepsy do not experience satisfactory seizure control with antiepileptic drug (AED) monotherapy and often require polytherapy. The potential usefulness of AED combinations, in terms of efficacy and adverse effects, is therefore of major importance. The present study sought to identify potentially useful AED combinations with levetiracetam (LEV) METHODS: With isobolographic analysis, the mouse maximal electroshock (MES)-induced seizure model was investigated with regard to the anticonvulsant effects of carbamazepine (CBZ), phenytoin, phenobarbital (PB), valproate, lamotrigine, topiramate (TPM), and oxcarbazepine (OXC), administered singly and in combination with LEV. Acute adverse effects were ascertained by use of the chimney test evaluating motor performance and the step-through passive-avoidance task assessing long-term memory. Brain AED concentrations were determined to ascertain any pharmacokinetic contribution to the observed antiseizure effect.. LEV in combination with TPM, at the fixed ratios of 1:2, 1:1, 2:1, and 4:1, was supraadditive (synergistic) in the MES test. Likewise, the combination of LEV with CBZ (at the fixed ratio of 16:1) and LEV with OXC (8:1 and 16:1) were supraadditive. In contrast, all other LEV/AED combinations displayed additivity. Furthermore, none of the investigated LEV/AED combinations altered motor performance and long-term memory. LEV brain concentrations were unaffected by concomitant AED administration, and LEV had no significant effect on brain concentrations of concomitant AEDs.. These preclinical data would suggest that LEV in combination with TPM is associated with beneficial anticonvulsant pharmacodynamic interactions. Similar, but less profound effects were seen with OXC and CBZ.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Carbamazepine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Electroshock; Epilepsy; Humans; Levetiracetam; Male; Memory; Mice; Motor Activity; Oxcarbazepine; Piracetam; Seizures

Some epilepsy patients quickly develop resistance to antiepileptic drugs (AEDs). We report a case of a patient with refractory epilepsy with daily seizures who initially responded to levetiracetam daily therapy, but then returned to baseline seizure frequency. However, when levetiracetam was given once weekly, the patient had significantly fewer seizures on the day of and after administration. These results suggest a useful treatment strategy for patients with refractory epilepsy who have developed resistance to AEDs.

Topics: Adult; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Levetiracetam; Piracetam; Seizures

Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). Because of this unique mechanism, it has been postulated that LEV may be effective in controlling tumor-induced seizures. A retrospective chart review was performed of all patients who had received LEV for seizure control. Forty-one patients were reviewed (22 female, 19 male), with a median age of 47.5 years (range 25-81). There were 34 patients with PBT and 7 with MBT. LEV was used as an add-on AED in 33 patients and as monotherapy in eight patients, with a median dose of 1500 mg/day (range 500-3500). The baseline median seizure frequency for the cohort was 1 per week. After the addition of LEV and follow-up for a minimum of 4 weeks, the median seizure frequency was reduced to 0 per week (59% of patients noted complete seizure control). Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Brain Neoplasms; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Seizures

Seizures are a common neurologic symptom of tuberous sclerosis complex. The use of levetiracetam as adjunctive antiepileptic therapy was assessed in 20 patients with tuberous sclerosis complex aged 2 to 19 years. In this retrospective evaluation, 40% of patients treated with levetiracetam achieved a seizure reduction of more than 50%. Levetiracetam was generally well tolerated, and adverse events were relatively uncommon in patients who responded to treatment. The most commonly reported adverse events were behavioral problems. Unstable gait, insomnia, poor appetite, and increased seizure frequency were also reported. Based on these results, the use of levetiracetam as adjunctive antiepileptic therapy can reduce seizure frequency in patients with tuberous sclerosis complex. (J Child Neurol 2006;21:53-57).

Topics: Adolescent; Adult; Anorexia; Anticonvulsants; Behavioral Symptoms; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gait Disorders, Neurologic; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Tuberous Sclerosis

Levetiracetam (LEV) is a new antiepileptic drug highly effective as add-on treatment in refractory partial epilepsies. In animal models, LEV is effective against absence seizures. A limited number of case reports and series indicate that LEV reduces seizure frequency in patients with generalized epilepsies.. We evaluated with continuous EEG eight adult patients with idiopathic generalized epilepsy (IGE). All patients were refractory to the conventional therapy for IGE. Four patients received LEV as add-on therapy, and in four, a conversion to LEV monotherapy was undergone. Epileptic activity was analyzed in order to determine spike-wave density as well as median and maximal duration of spike-wave discharges. Each patient underwent a 24h EEG baseline monitoring before starting LEV therapy. A second 24h EEG examination was performed after a mean follow-up period of 136 days.. Spike-wave density (spikes/h) was reduced by 78% after LEV administration. Median spike-wave duration decreased by 72% (p < 0.05). Maximal spike-wave duration was 6s before, and 1.5s after LEV with a percentage change of 81% (p < 0.05). The four patients on LEV monotherapy evidenced also a considerably improvement after conversion.. This study showed that LEV produces a consistent long-term reduction of interictal epileptic activity in patients with refractory IGE. The reduction in the spike-wave activity additionally correlated with a clinically relevant antiepileptic effect. Our results support the concept that LEV could be an alternative therapy in primary generalized epilepsies.

Topics: Adolescent; Adult; Anticonvulsants; Drug Therapy, Combination; Electroencephalography; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Seizures

Owing to their activation by increased intracellular Ca(2+) levels following burst firing, and the resultant hyperpolarisation and dampening of neuronal excitability, the small-conductance Ca(2+)-activated K(+) (SK(Ca)) channels have been proposed as a potential target for novel antiepileptic drugs. Indeed, the channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) has been shown to reduce epileptiform activity in vitro. Accordingly, this study has investigated the therapeutic potential of 1-EBIO using a range of in vivo seizure models, and assessed the adverse effect liability with the rotarod and locomotor activity paradigms. To aid benchmarking of 1-EBIO's therapeutic and adverse effect potential, it was tested alongside two currently marketed antiepileptic drugs, phenytoin and levetiracetam. 1-EBIO was found to be effective at reducing seizure incidence in mice following maximal electroshock (ED(50) 36.0 mg/kg) as well as increasing the threshold to electrically- and pentylenetetrazole-induced seizures (TID(10)s 7.3 and 21.5 mg/kg, respectively). However, results from the mouse rotarod test revealed a strong adverse effect potential within the therapeutic dose range (ID(50) 35.6 mg/kg), implying a significantly inferior therapeutic index with respect to the comparator compounds. These results, therefore, support the in vitro data detailing 1-EBIO's reduction of epileptiform activity. However, the use of in vivo models has revealed a significant adverse effect potential within the therapeutic dose range. Nevertheless, given the multiplicity of SK(Ca) channel subunits and that 1-EBIO has been shown to enhance additional, non-SK(Ca) carried currents, these findings do not preclude the possibility that more selective enhancers of SK(Ca) function could prove to be effective as antiepileptic medications.

Topics: Animals; Anticonvulsants; Benzimidazoles; Disease Models, Animal; Dose-Response Relationship, Drug; Electroshock; Levetiracetam; Male; Mice; Motor Activity; Pentylenetetrazole; Phenytoin; Pilocarpine; Piracetam; Seizures; Sensory Thresholds; Small-Conductance Calcium-Activated Potassium Channels

The objective of the study was to analyze the short-term efficacy and safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized patients.. During admission to a tertiary hospital, we retrospectively identified patients with repetitive seizures who were treated for the first time with LEV during a hospital stay. LEV was considered effective if seizure cessation or >75% seizure reduction occurred in the 24 h after starting LEV (compared with the previous 48 h), requiring no further antiepileptic drug (AED) treatment.. Thirty patients (12 men, 18 women) were included. Mean age was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30 patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant medical conditions included atrial fibrillation (three) and hepatic disease (three). Concomitant medications included oral anticoagulants (seven), corticosteroids (two), and chemotherapy (two). Four patients received LEV as the only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of seizures but not in SE received LEV as add-on treatment after lack of response to first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four patients who received it as the only AED, four of six patients with focal SE, and 16 of 20 patients with clusters of seizures. Three (10%) elderly patients with seizures secondary to stroke and chronic obstructive pulmonary disease (COPD) reported moderate/severe somnolence and dizziness, leading to treatment discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine (30%) as the only AED.. LEV is effective and safe to treat repetitive seizures in hospitalized patients, including patients in focal SE.

Topics: Adult; Aged; Anticonvulsants; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Secondary Prevention; Seizures; Status Epilepticus; Treatment Outcome

Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy.. The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test.. NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models.. These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electroshock; Levetiracetam; Male; Mice; Nootropic Agents; Pentylenetetrazole; Piracetam; Pyrrolidinones; Rats; Rats, Wistar; Seizures

Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy for partial seizures. It displays a unique pharmacological profile against experimental models of seizures, including pilocarpine-induced seizures in rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to cholinergic alterations, adult male mice received LEV injections before cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.) increased the latencies of seizures, but decreased status epilepticus and death on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200, 200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice hippocampus showed that LEV200 pretreatment reverts the downregulation on muscarinic acetylcholine receptors (mAChR), induced by P400 administration, bringing back these density values to control ones (0.9% NaCl, i.p.). However, subtype-specific-binding assays revealed that P400- and LEV-alone treatments result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute to explain the reduction on oxotremorine-induced tremors and the delay on pilocarpine-induced seizures, by an increase in the attenuation of neuronal activity mediated by the M1 receptors.

Topics: Animals; Anticonvulsants; Convulsants; Disease Models, Animal; Hippocampus; Levetiracetam; Male; Mice; Muscarinic Agonists; Oxotremorine; Pilocarpine; Piracetam; Receptors, Muscarinic; Seizures

The long-lasting antiseizure effects of levetiracetam (LEV) have been observed in the spontaneously epileptic rat (SER) that expresses both tonic and absence-like seizures. Furthermore, the antiepileptogenic effects of LEV in addition to antiseizure effects have been reported in the amygdala-kindling model in rats. This suggests that the long-lasting seizure protection of LEV may be at least partly due to its antiepileptogenic effects. Therefore this study aimed to differentiate the antiseizure and potential antiepileptogenic effects of LEV by administering LEV continuously to SERs before the appearance of any seizure expression.. LEV was administered to the SERs at 80 mg/kg/day (i.p.) from postnatal weeks 5 to 8. The period of observation for tonic convulsions was from postnatal week 5 to 13. Absence-like seizures were recorded by using conventional EEG in weeks 12 and 13.. After age 7-8 weeks, SERs exhibit spontaneous tonic convulsions. Development of tonic convulsions was significantly inhibited in the LEV group, compared with the control group, by the middle of week 9. A significant reduction of tonic convulsions also was observed in the LEV group until week 13 (5 weeks after termination of the administration). In week 12, the absence-like seizures were significantly lower in the LEV group, compared with the control group.. This study demonstrates a significant inhibition of seizures after prolonged treatment with LEV before the developmental expression of seizure activity in SERs. This effect is suggested to be due to an antiepileptogenic effect and not an antiseizure effect of LEV, because the half-life of the drug in plasma is short (2-3 h in rats) after single and long-term administration. Furthermore, the inhibition of seizure expression in SERs was still apparent 5 weeks after termination of LEV treatment. These results further suggest that LEV possesses not only antiseizure effects but also antiepileptogenic properties.

Topics: Animals; Animals, Newborn; Anticonvulsants; Disease Models, Animal; Drug Administration Schedule; Electrodes, Implanted; Electroencephalography; Epilepsy; Female; Frontal Lobe; Hippocampus; Injections, Intraperitoneal; Levetiracetam; Male; Piracetam; Rats; Rats, Mutant Strains; Seizures

Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the effects of NEF in amygdala-kindled seizures and its potential for antiepileptic therapy.. Effects of NEF on fully amygdala-kindled seizures and development of amygdala-kindled seizures were investigated in rats and compared with those of levetiracetam (LEV), a pyrrolidone-type antiepileptic drug (AED).. In fully amygdala-kindled rats, NEF (25, 50, and 100 mg/kg, p.o.) decreased afterdischarge induction, afterdischarge duration, seizure stage, and motor seizure duration in a dose-dependent manner. LEV (25, 50, and 100 mg/kg, p.o.) had no effects on afterdischarge induction and slightly decreased afterdischarge duration, whereas it markedly decreased seizure stage and motor seizure duration. In contrast to the results in fully amygdala-kindled rats, NEF (25 and 50 mg/kg/day, p.o.) had few or no effects on the development of amygdala-kindled seizures. As well as fully amygdala-kindled seizures, LEV (50 mg/kg/day, p.o.) markedly inhibited the development of behavioral seizures without reducing daily afterdischarge duration.. Although NEF possesses potent anticonvulsant effects on fully amygdala-kindled seizures, it has few or no effects on the development of amygdala-kindled seizures. LEV shows marked anticonvulsant effects on both phases of kindling. In fully amygdala-kindled rats, NEF inhibits both electroencephalographic and behavioral seizures, whereas LEV inhibits only behavioral seizures. This double dissociation suggests that NEF has a distinct anticonvulsant spectrum and mechanisms from those of LEV.

Topics: Administration, Oral; Amygdala; Animals; Anticonvulsants; Behavior, Animal; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; Electroencephalography; Epilepsy, Complex Partial; Humans; Kindling, Neurologic; Levetiracetam; Male; Nootropic Agents; Piracetam; Pyrrolidinones; Rats; Rats, Wistar; Seizures

To report the case of a patient who experienced adverse events in succession to antiepileptic medications being used for both antiepileptic and mood-stabilization benefit.. A 46-year-old white woman developed hyponatremia with carbamazepine, hyperammonemia with divalproex, cognitive impairment with topiramate, and hyponatremia with oxcarbazepine. The patient was stabilized physically and psychiatrically on levetiracetam without any noted adverse events.. The adverse events in this report have been associated with the medications in question. The patient's presentation is unique, as she developed adverse events in succession to antiepileptic drugs being used to treat both a seizure disorder and symptoms of mood instability. The Naranjo rankings for the reported adverse events indicated the associations were probable (carbamazepine, divalproex, oxcarbazepine) and possible (topiramate). After repeated incidences of intolerability to these drugs, levetiracetam was initiated and provided both seizure control and mood-stabilizing benefits, which eventually led to hospital discharge.. Levetiracetam may provide mood-stabilizing qualities through a mechanism that is unique from that of other antiepileptic agents used for their mood-stabilizing properties. There are potential advantages with levetiracetam, as no specific therapeutic drug monitoring parameters need to be followed after its introduction. Additionally, this case emphasizes the importance of therapeutic drug monitoring and frequent assessments to prevent physical and psychiatric adverse reactions.

Topics: Anticonvulsants; Carbamazepine; Drug Therapy, Combination; Female; Fructose; Humans; Levetiracetam; Middle Aged; Mood Disorders; Oxcarbazepine; Piracetam; Seizures; Topiramate; Treatment Outcome; Valproic Acid

This study assesses the use of the serial day Rapid Kindling with Recurrent Hippocampal Seizures (RKRHS) model in drug testing by investigating the anti-epileptic effect of levetiracetam (LEV), a novel anti-epileptic drug (AED) with a unique preclinical profile.. Male Wistar rats (n=16) were implanted with a stimulation/recording electrode unit in the right hippocampus and epidural recording electrodes. One week later, all rats received 12 stimulations each day for several consecutive days according to the serial day RKRHS protocol, until they were fully kindled. Fully kindled rats were then randomly assigned to an active (n=8) and a control (n=6) group and injected once (intraperitoneal, i.p.) with levetiracetam (54 mg/kg) or saline (0.9% NaCl, 2 ml/kg), respectively. One hour later, the rats received additional kindling stimulations, during which the effect of LEV was assessed.. One hour following injection of LEV, mean seizure stage dropped to 1.67+/-1.03 compared to 5+/-0 in controls (p<0.05). Mean ADD was also significantly shorter in the active group than in controls; 21.16+/-5.03 s versus 57.24+/-8.16s, respectively (p<0.05). A gradual, time-dependent decline was noted in the anti-epileptic effect of LEV but this effect stayed statistically significant at least up to 2.5 h (p<0.05).. LEV was demonstrated to have anti-epileptic properties in RKRHS that compared to those in traditional kindling and contrast with results from classical screening tests. RKRHS may represent a valuable and sensitive screening tool early in the drug screening process.

Topics: Animals; Anticonvulsants; Convulsants; Electric Stimulation; Electrodes, Implanted; Electroencephalography; Hippocampus; Kindling, Neurologic; Levetiracetam; Male; Pentylenetetrazole; Piracetam; Rats; Rats, Wistar; Seizures

Topics: Acute Disease; Anticonvulsants; Humans; Levetiracetam; Piracetam; Psychoses, Substance-Induced; Seizures

(S)-alpha-ethyl-2-oxopyrrolidine acetamide 2 (levetiracetam, Keppra, UCB S.A.), a structural analogue of piracetam, has recently been approved as an add-on treatment of refractory partial onset seizures in adults. This drug appears to combine significant efficacy and high tolerability due to a unique mechanism of action. The latter relates to a brain-specific binding site for 2 (LBS for levetiracetam binding site) that probably plays a major role in its antiepileptic properties. Using this novel molecular target, we initiated a drug-discovery program searching for ligands with significant affinity to LBS with the aim to characterize their therapeutic potential in epilepsy and other central nervous system diseases. We systematically investigated the various positions of the pyrrolidone acetamide scaffold. We found that (i) the carboxamide moiety on 2 is essential for affinity; (ii) among 100 different side chains, the preferred substitution alpha to the carboxamide is an ethyl group with the (S)-configuration; (iii) the 2-oxopyrrolidine ring is preferred over piperidine analogues or acyclic compounds; (iv) substitution of positions 3 or 5 of the lactam ring decreases the LBS affinity; and (v) 4-substitution of the lactam ring by small hydrophobic groups improves the in vitro and in vivo potency. Six interesting candidates substituted in the 4-position have been shown to be more potent antiseizure agents in vivo than 2. Further pharmacological studies from our group led to the selection of (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide 83alpha (ucb 34714) as the most interesting candidate. It is approximately 10 times more potent than 2 as an antiseizure agent in audiogenic seizure-prone mice. A clinical phase I program has been successfully concluded and 83alpha will commence several phase II trials during 2003.

Topics: Acoustic Stimulation; Amides; Animals; Anticonvulsants; Binding Sites; Butyrates; Caco-2 Cells; Cerebral Cortex; Crystallography, X-Ray; Female; Humans; In Vitro Techniques; Levetiracetam; Male; Mice; Mice, Inbred DBA; Microsomes, Liver; Models, Molecular; Molecular Conformation; Piracetam; Pyrrolidinones; Rats; Rats, Sprague-Dawley; Seizures; Structure-Activity Relationship

Here, we show that the synaptic vesicle protein SV2A is the brain binding site of levetiracetam (LEV), a new antiepileptic drug with a unique activity profile in animal models of seizure and epilepsy. The LEV-binding site is enriched in synaptic vesicles, and photoaffinity labeling of purified synaptic vesicles confirms that it has an apparent molecular mass of approximately 90 kDa. Brain membranes and purified synaptic vesicles from mice lacking SV2A do not bind a tritiated LEV derivative, indicating that SV2A is necessary for LEV binding. LEV and related compounds bind to SV2A expressed in fibroblasts, indicating that SV2A is sufficient for LEV binding. No binding was observed to the related isoforms SV2B and SV2C. Furthermore, there is a high degree of correlation between binding affinities of a series of LEV derivatives to SV2A in fibroblasts and to the LEV-binding site in brain. Finally, there is a strong correlation between the affinity of a compound for SV2A and its ability to protect against seizures in an audiogenic mouse animal model of epilepsy. These experimental results suggest that SV2A is the binding site of LEV in the brain and that LEV acts by modulating the function of SV2A, supporting previous indications that LEV possesses a mechanism of action distinct from that of other antiepileptic drugs. Further, these results indicate that proteins involved in vesicle exocytosis, and SV2 in particular, are promising targets for the development of new CNS drug therapies.

Topics: Animals; Anticonvulsants; Binding Sites; Brain; Fibroblasts; Gene Deletion; Humans; Inhibitory Concentration 50; Intracellular Membranes; Levetiracetam; Membrane Glycoproteins; Mice; Mice, Knockout; Molecular Weight; Nerve Tissue Proteins; Photoaffinity Labels; Piracetam; Precipitin Tests; Protein Binding; Rats; Seizures; Synaptic Vesicles

A novel mechanism of action has recently been described for levetiracetam, a member of a new class of anticonvulsants. Levetiracetam binds selectively and with high affinity to a synaptic vesicle protein known as SV2A, thought to be involved with synaptic vesicle exocytosis and presynaptic neurotransmitter release.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Exocytosis; Humans; Levetiracetam; Membrane Glycoproteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurotransmitter Agents; Piracetam; Protein Binding; Seizures; Synaptic Transmission; Synaptic Vesicles

Levetiracetam (LEV) is a new antiepileptic drug with efficacy in partial-onset seizures. We report a case in which generalized-onset absence seizures responded clinically and electrographically to LEV.. We evaluated with continuous video/electroencephalography an adult with generalized-onset seizures given 3 antiepileptic drugs, 1 of which was LEV. Levetiracetam initiation 2 months before admission decreased patient-reported seizures. Interictal electroencephalography revealed generalized 3.5-Hz spike-wave and polyspike-wave discharges. Spike-wave bursts lasting 2 seconds or longer caused a pause in continuous reading aloud, consistent with clinical absence seizures. Levetiracetam was discontinued on admission, lamotrigine was gradually discontinued across 2 days, and topiramate was not changed. One encephalographer counted from video/electroencephalography recordings the number of spike-wave bursts in 1-hour time samples that included wake and sleep time.. Spike-wave bursts increased from 4 to 56 per hour at baseline (4000 mg of LEV per day) to 406 to 914 per hour less than 48 hours after LEV discontinuation. Levetiracetam treatment was restarted, and 3 hours after the first dose of 1000 mg, spike-wave bursts dropped to 135 per hour. Response was sustained during the next 2 days.. This case showed a dramatic, rapid effect of LEV discontinuation and reinstitution on generalized spike-wave burst frequency and clinical absence. The effects were independent of reduction of lamotrigine and without change in topiramate doses and occurred in a time course consistent with LEV pharmacokinetics. Levetiracetam may be effective in generalized-onset epilepsy, and randomized, controlled trials are indicated.

Topics: Adult; Anticonvulsants; Delta Rhythm; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Female; Fructose; Humans; Lamotrigine; Levetiracetam; Piracetam; Retrospective Studies; Seizures; Topiramate; Triazines

In kindling models of epilepsy, the period during which repeated stimulation evokes intensifying seizures is attributed to an underlying epileptogenic process, and the point at which class 5 kindled seizures occur is considered the established epileptic state. Previous studies have indicated that a separation can occur between drug effects on these two components. For example, carbamazepine and phenytoin inhibit kindled seizures but have no effect on seizure development, whereas levetiracetam inhibits both components. We have investigated the profile of lamotrigine in the amygdala kindling model, including levetiracetam for comparison. As expected, both treatments dose-dependently inhibited class 5 kindled seizures. In a separate study, daily administration of either lamotrigine (20mgkg(-1) i.p.) or levetiracetam (50mgkg(-1) i.p.) demonstrated antiepileptogenic-like effects by blocking seizure development during the treatment period. Following cessation of drug treatment, further daily stimulation resulted in kindled seizure development, though there was a significant increase with both treatment groups, relative to the control group, in the total number of stimulations required to produce classes 3 and 5 seizures. In addition, prior levetiracetam treatment appeared to delay or prevent the expected increase in after-discharge duration (ADD). These results suggest that lamotrigine, like levetiracetam, possesses the ability to counteract kindling acquisition, which differentiates it from other drugs with sodium channel blocking activity.

Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Electric Stimulation; Electrodes, Implanted; Kindling, Neurologic; Lamotrigine; Levetiracetam; Male; Models, Neurological; Piracetam; Rats; Seizures; Triazines

Topics: Brain Neoplasms; Follow-Up Studies; Glioma; Humans; Levetiracetam; Piracetam; Prospective Studies; Seizures

We evaluated the anticonvulsant efficacy of the new antiepileptic drugs (AEDs) gabapentin and levetiracetam in amygdala kindled rats that had been preselected with respect to their response to phenytoin. Anticonvulsant response was tested by determining the afterdischarge threshold (ADT), i.e. a sensitive measure for drug effects on focal seizure activity. By repeated testing with the phenytoin prodrug fosphenytoin, three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (phenytoin responders), rats which showed no anticonvulsant response (phenytoin nonresponders), and rats with variable responses (variable phenytoin responders). The latter, largest group was used to evaluate at which doses gabapentin and levetiracetam exerted significant anticonvulsant effects on ADT 1 h after i.p. drug administration. Effective doses were then used for drug testing in phenytoin responders and nonresponders. Both gabapentin and levetiracetam proved to be effective anticonvulsant drugs in the kindling model by significantly increasing the ADT. In addition, both drugs markedly decreased seizure severity recorded at ADT currents, indicating that these drugs affect seizure threshold in the epileptic focus and seizure spread from the focus in the kindling model. When the threshold for secondary generalized seizures (GST) was determined in addition to ADT, gabapentin and levetiracetam strikingly increased this threshold compared to predrug control. In phenytoin nonresponders, gabapentin and levetiracetam significantly increased ADT and GST, which is in line with their proven efficacy in patients with refractory partial epilepsy in whom older AEDs have failed. In phenytoin responders, gabapentin tended to be more efficacious in increasing ADT and GST than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. In contrast to gabapentin, levetiracetam was more efficacious in increasing ADT in nonresponders than in responders. The data of this study substantiate that phenytoin nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.

Topics: Acetates; Amines; Animals; Anticonvulsants; Cyclohexanecarboxylic Acids; Drug Evaluation; Drug Resistance; Female; Gabapentin; gamma-Aminobutyric Acid; Kindling, Neurologic; Levetiracetam; Phenytoin; Piracetam; Rats; Rats, Wistar; Seizures

Epileptogenesis induced by electrical kindling of rats appears to be superior to the acute maximal electroshock seizure (MES) test in normal animals in predicting the efficacy and adverse effect potential of drugs in patients with partial epilepsy. Unfortunately, inclusion of such kindling models in primary screening is hampered by the laborious and expensive procedure of stimulation and recording with implanted brain electrodes. Furthermore the size of the rats excludes their use in initial testing where compound availability is often limited for the 'first batch synthesis'. The present study demonstrates that chronic electrical stimulation with corneal electrodes in mice can rapidly yield large numbers of kindled animals with a seizure phenomenology reflecting partial seizures in man. A pharmacological characterisation showed that corneally kindled mice can be used repeatedly for several drug experiments with reproducible results. The seizure protection and adverse effect potential obtained with proven antiepileptic drugs were similar to the effects observed in amygdala kindled rats and their corresponding clinical profile in partial epilepsy. Protection was obtained with vigabatrin and levetiracetam in this new model despite their lack of anticonvulsant activity in the acute MES test. Furthermore, in agreement with clinical findings with NMDA antagonists, MK-801 revealed more severe adverse effects in corneally kindled mice than in normal animals. These results suggest that corneal kindling of mice represents a sensitive and valid screening model for the identification of new therapies for partial epilepsy in man.

Topics: Amygdala; Animals; Anticonvulsants; Carbamazepine; Cornea; Disease Models, Animal; Dizocilpine Maleate; Drug Evaluation, Preclinical; Electric Stimulation; Electroshock; Epilepsies, Partial; gamma-Aminobutyric Acid; Kindling, Neurologic; Levetiracetam; Male; Mice; Piracetam; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Retina; Seizures; Sensitivity and Specificity; Time Factors; Valproic Acid; Vigabatrin

The protective and adverse effect potentials of levetiracetam ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) in rodent models of seizures and epilepsy were compared with the profile of several currently prescribed and newly developed antiepileptic drugs. Levetiracetam was devoid of anticonvulsant activity in the acute maximal electroshock seizure test and in the maximal pentylenetetrazol seizure test in mice (up to 540 mg/kg, i.p.) but exhibited potent protection against generalised epileptic seizures in electrically and pentylenetetrazol-kindled mice (ED50 values = 7 and 36 mg/kg, respectively, i.p.). This differs markedly from established and most new antiepileptic drugs which induce significant protection in both the acute seizure tests and the kindling models. Furthermore, levetiracetam was devoid of anticonvulsant activity in several maximal chemoconvulsive seizure tests although an interesting exception was the potent protection observed against secondarily generalised activity from focal seizures induced by pilocarpine in mice (ED50 value = 7 mg/kg, i.p.), pilocarpine and kainic acid in rats (minimum active dose = 17 and 54 mg/kg, respectively, i.p.). The protection afforded by levetiracetam on the threshold for methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM)-induced seizures persisted after chronic administration (17-170 mg/kg, i.p., twice daily/14 days) and levetiracetam did not lower the seizure threshold for the proconvulsant action of the inverse benzodiazepine receptor agonist, N-methyl-beta-carboline-3-carboxamide (FG 7142). The main metabolite of levetiracetam (ucb L057; (S)-alpha-ethyl-2-oxo-1-pyrrolidine acetic acid) was found to be inactive in sound-sensitive mice after acute administration of doses up to 548 mg/kg, i.p. Levetiracetam induced only minor behavioural alterations in both normal and amygdala-kindled rats (54-1700 mg/kg, i.p.) resulting in an unusually high safety margin between rotarod impairment and seizure suppression of 148 in corneally kindled mice and 235 in Genetic Absence Epilepsy Rats from Strasbourg. In comparison, existing antiepileptic drugs have ratios between 2 and 17 in the corneally kindled mouse model. These studies reveal a unique profile of levetiracetam in rodent models. Characteristics are a general lack of anticonvulsant activity against maximal, acute seizures and selective protection with a very high safety margin in genetic and kindled animals and against chemoconvulsants producing par

Topics: Amygdala; Animals; Anticonvulsants; Behavior, Animal; Carbolines; Convulsants; Diazepam; Disease Models, Animal; Electroconvulsive Therapy; Epilepsy; Excitatory Amino Acid Agonists; Flumazenil; GABA-A Receptor Antagonists; Kindling, Neurologic; Levetiracetam; Male; Mice; Pentylenetetrazole; Piracetam; Rats; Rats, Sprague-Dawley; Seizures

1. Extracellular recording of field potentials, evoked by commissural stimulation in hippocampal area CA3 of anaesthetized rats, was performed in order to study the mode of action of the novel antiepileptic drug levetiracetam (ucb LO59). 2. The amplitude of orthodromic field population spike (PS2) markedly increased and repetitive population spikes appeared when the recording micropipette contained either bicuculline methiodide (BMI), or the specific GABAA antagonist gabazine (SR-95531). 3. BMI-induced increases in PS2 were reduced in a dose-dependent manner by 1 to 320 mumol kg-1 levetiracetam i.v., with a U-shape dose-response relationship. However, levetiracetam did not reduce the increases in PS2 produced by gabazine. 4. Clonazepam (1 mg kg-1, i.p.), carbamazepine (20 mg kg-1, i.p.) and valproate (200 mg kg-1, i.v.) were ineffective in preventing BMI-induced increases in PS2, while the calcium channel antagonist flunarizine, 50 mumol kg-1, i.p., reduced PS2 increments caused by BMI. The L-type calcium channel blocker nifedipine, 100 mumol kg-1, i.p., was without effect. Similar to levetiracetam, flunarizine did not reduce the increases in PS2 induced by gabazine. 5. These data suggest that the increased excitability of CA3 neurones, caused by BMI administered in situ, involves calcium-dependent processes not associated with blockade of GABAA receptors. The inhibition by levetiracetam of this calcium-dependent effect of BMI might contribute to the antiepileptic effects of the drug.

Topics: Animals; Anticonvulsants; Bicuculline; Convulsants; Flunarizine; GABA Antagonists; Hippocampus; Levetiracetam; Male; Piracetam; Pyridazines; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Seizures

The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Convulsants; Dizocilpine Maleate; Female; Kindling, Neurologic; Levetiracetam; Male; Mice; Mice, Inbred DBA; Motor Activity; N-Methylaspartate; Piracetam; Rats; Rats, Sprague-Dawley; Seizures