levetiracetam and Status-Epilepticus

We aim to describe use of electroconvulsive therapy (ECT) to treat super refractory status epilepticus (SRSE) in pregnancy and review the literature regarding utility and safety of ECT in refractory status epilepticus.. Status epilepticus (SE) is a commonly encountered emergency in neuro-critical care world. Pharmacotherapy of status epilepticus in pregnancy is very challenging given the effect of the majority of antiepileptic drugs (AEDs) on fetal development. Although there has been growing evidence for use of ECT in status epilepticus, data about its utility in pregnancy is lacking.. A twenty-one year old Caucasian female with history of epilepsy presented at 8 weeks of gestation as status epilepticus (SE) after abrupt discontinuation of her AEDs. Treatment was initiated with standard regimen of benzodiazepine and levetiracetam, which was progressively expanded to include approximately 10 anti-epileptic drugs over the course of 30 days. The status epilepticus was super refractory to sedation. She underwent ECT on day 31 with remarkable improvement in electroencephalogram (EEG) pattern and resolution of status epilepticus following a single ECT session. We reviewed PubMed and collated case reports involving the use of ECT in status epilepticus with emphasis on differences in various confounding factors esp. etiology of status and age group.. Our case is the first reported case of ECT for successful treatment of SRSE in pregnancy. While majority AEDs pose a significant maternal and fetal risk during pregnancy, ECT could be a potential frontline therapy for SE in pregnancy.

Topics: Adult; Anticonvulsants; Electroconvulsive Therapy; Electroencephalography; Female; Humans; Levetiracetam; Pregnancy; Status Epilepticus; Young Adult

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

Status epilepticus (SE) is a neurological emergency that can occur in patients with or without epilepsy. Rapid treatment is paramount to mitigate risks of neuronal injury, morbidity/mortality, and healthcare-cost burdens associated with SE. Fosphenytoin is the prodrug of phenytoin designed to enable faster administration and improved tolerability as compared to intravenous (IV) phenytoin in the treatment of SE.. This review evaluates the chemistry, pharmacokinetics, pharmacodynamics, safety, and tolerability of fosphenytoin. Efficacy data for fosphenytoin in the treatment of SE in adults and children are analyzed from initial phase I trials in 1988 through current phase III trials, including the Established Status Epilepticus Treatment Trial (ESETT).. IV phenytoin is an established treatment of SE, but its alkaline aqueous vehicle is associated with dermatologic irritation and systemic complications when rapidly infused. The water-soluble nature of its prodrug, fosphenytoin, allows for rapid infusion, and it is rapidly converted to phenytoin when administered intravenously or intramuscularly. In the ESETT, IV fosphenytoin demonstrated similar efficacy in treatment of established SE when compared to IV levetiracetam and IV valproate in adults and children, making it a reasonable choice in the treatment of SE that is unresponsive to benzodiazepines.

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

The ability to administer medications via rapid intravenous bolus has the potential to allow for the rapid attainment of therapeutic drug levels and to limit the amount of unnecessary fluid volumes infused. The purpose of this review was to evaluate the efficacy and safety of undiluted or minimally diluted levetiracetam bolus doses.. A total of six pieces of the literature were evaluated in this review. Doses of up to 4,500 mg of intravenous levetiracetam were found to be both efficacious and safe when administered undiluted or minimally diluted in either a peripheral or central line. Product concentrations of levetiracetam ranged from 50 mg/mL to 100 mg/mL, with volumes ranging from 10 to 30 mL. Maintenance doses of up to 1,500 mg twice daily were demonstrated to be both efficacious and safe when administered undiluted or minimally diluted. Injection site pain and agitation were the most commonly reported adverse drug effects.. Although hospitals and clinicians must be judicious with regard to training and the safety concerns of bolus intravenous push doses, and will need to address numerous logistical concerns, this practice is supported by practice guidelines and should be readily employed.

Topics: Administration, Intravenous; Anticonvulsants; Drug-Related Side Effects and Adverse Reactions; Humans; Infusions, Intravenous; Levetiracetam; Piracetam; Status Epilepticus

Status epilepticus (SE) in pregnancy represents a life-threatening medical emergency for both mother and fetus. Pregnancy-related pharmacokinetic modifications and the risks for fetus associated with the use of antiseizure medications (ASMs) and anesthetic drugs complicate SE management. No standardized treatment protocol for SE in pregnancy is available to date.. In this review, we provide an overview of the current literature on the management of SE in pregnancy and we propose a multidisciplinary-based protocol approach.. Literature data are scarce (mainly anecdotal case reports or small case series). Prompt treatment of SE during pregnancy is paramount and a multidisciplinary team is needed. Benzodiazepines are the drugs of choice for SE in pregnancy. Levetiracetam and phenytoin represent the most suitable second-line agents. Valproic acid should be administered only if other ASMs failed and preferably avoided in the first trimester of pregnancy. For refractory SE, anesthetic drugs are needed, with propofol and midazolam as preferred drugs. Magnesium sulfate is the first-line treatment for SE in eclampsia. Termination of pregnancy, via delivery or abortion, is recommended in case of failure of general anesthetics. Further studies are needed to identify the safest and most effective treatment protocol.

Topics: Anticonvulsants; Female; Humans; Levetiracetam; Phenytoin; Pregnancy; Review Literature as Topic; Status Epilepticus; Valproic Acid

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

Randomized controlled trials investigating the initial pharmacological treatment of status epilepticus have been recently published. Furthermore, status epilepticus arising in comatose survivors after cardiac arrest has received increasing attention in the last years. This review offers an updated assessment of status epilepticus treatment in these different scenarios.. Initial benzodiazepines underdosing is common and correlates with development of status epilepticus refractoriness. The recently published ESETT trial provides high-level evidence regarding the equivalence of fosphenytoin, valproate, and levetiracetam as a second-line option. Myoclonus or epileptiform transients on electroencephalography occur in up to 1/3 of patients surviving a cardiac arrest. Contrary to previous assumptions regarding an almost invariable association with death, at least 1/10 of them may awaken with reasonably good prognosis, if treated. Multimodal prognostication including clinical examination, EEG, somatosensory evoked potentials, biochemical markers, and neuroimaging help identifying patients with a chance to recover consciousness, in whom a trial with antimyoclonic compounds and at times general anesthetics is indicated.. There is a continuous, albeit relatively slow progress in knowledge regarding different aspect of status epilepticus; recent findings refine some treatment strategies and help improving patients' outcomes. Further high-quality studies are clearly needed to further improve the management of these patients, especially those with severe, refractory status epilepticus forms.

Topics: Anticonvulsants; Electroencephalography; Humans; Levetiracetam; Randomized Controlled Trials as Topic; Status Epilepticus

To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus.. We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials.. Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials.. Independently and in duplicate, we performed data abstraction, risk of bias assessment, and certainty assessment using Grading of Recommendations, Assessment, Development, and Evaluation. We performed meta-analyses using random-effect models or, if insufficient data, presented findings narratively.. We identified seven randomized controlled trials (n = 1,575). Pooled analysis demonstrated low certainty evidence for no difference of levetiracetam on time to seizure cessation (mean difference, -3.11 min; 95% CI, -6.67 to 0.45), early seizure cessation (relative risk, 1.09, 95% CI, 0.95-1.26), or late seizure cessation (relative risk, 1.05; 95% CI, 0.93-1.18). Adverse event outcomes were limited by low event numbers. We found low certainty evidence for less respiratory depression with levetiracetam (relative risk, 0.28; 95% CI, 0.12-0.69).. The efficacy of levetiracetam is comparable with phenytoin or fosphenytoin in children with benzodiazepine-refractory status epilepticus (low certainty evidence). Levetiracetam may cause less respiratory depression. Clinicians and guideline developers should weigh safety profiles when choosing between these agents.

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

To systematically evaluate the efficacy and safety of levetiracetam (LEV) versus phenytoin (PHT) as second-line drugs for the treatment of convulsive status epilepticus (CSE) in children.. English and Chinese electronic databases were searched for the randomized controlled trials comparing the efficacy and safety of LEV and PHT as second-line drugs for the treatment of childhood CSE. RevMan 5.3 software was used for data analysis.. LEV has a better clinical effect than PHT in the treatment of children with CSE and does not increase the incidence rate of adverse events.

Topics: Anticonvulsants; Child; Humans; Levetiracetam; Pharmaceutical Preparations; Phenytoin; Status Epilepticus

Status epilepticus (SE) is the second most critical neurological illness after cerebrovascular disease. Phenytoin has traditionally been considered the second-line drug of first choice after failure of first-line treatment using benzodiazepines. In recent years, levetiracetam has been proposed as a potential substitute for phenytoin. To comprehensively evaluate the efficacy and safety of levetiracetam and phenytoin in the treatment of patients with established SE, we integrated the data from 11 eligible studies and conducted a systematic review and meta-analysis. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched to identify eligible articles reporting outcomes including clinical seizure cessation within 60 min, clinical recurrence rate within 24 h, good final outcome at discharge, and adverse events (AEs) of treatment with levetiracetam and phenytoin. Our study included a total of 11 trials including a total of 1933 patients. The outcomes showed that the pooled Risk Raito (RR) of clinical seizure cessation within 60 min was 1.08 (95% CI = 1.02-1.14, P = 0.01). The pooled RR of clinical recurrence rate within 24 h was 1.03 (95% CI = 0.66-1.59, P = 0.91). The pooled RR of AEs was 0.83 (95% CI = 0.57-1.21, P = 0.34). The pooled RRs of life-threatening hypotension and acute respiratory depression were 0.29 (95% CI = 0.10-0.81, P = 0.02) and 0.63 (95% CI = 0.40-0.98, P = 0.04), respectively. Levetiracetam might be more effective than phenytoin for the treatment of established SE and is associated with a lower incidence of more serious AEs. Levetiracetam can be used as an alternative to phenytoin for the treatment of benzodiazepine-refractory SE.

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

To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).. PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.. Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020.. The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO.. Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias.. The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.

Topics: Anticonvulsants; Child; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus

To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs.. We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0.. Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60).. Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.

Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus

We performed this analysis to evaluate the efficacy and safety of intravenous levetiracetam (IV LEV) in patients with status epilepticus.. Studies were searched in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for available randomized controlled trials(RCTs) comparing the efficacy and/or safety of IV LEV with other antiepileptic drugs (AEDs). Meta-analysis was performed using the random-effects model to calculate risk ratio with the RevMan 5.3 software.. Six RCTs with a total of 543 patients were included. There was no significant differences in clinical seizure cessation and hospital mortality, either between IV LEV and IV phenytoin (PHT) or between IV LEV and IV valproate (VPA). Compared with IV PHT, IV LEV had a lower risk of poor neurological outcome. For IV LEV compared with IV lorazepam (LOR), no significant difference in efficacy was found, but IV LEV patients had significantly lower need for ventilatory assistance. Adding IV LEV to clonazepam (CNP), compared with adding placebo showed no significant differences in seizure cessation at 15 min.. Our results suggested that IV LEV was comparable to IV PHT,VPA, or LOR in efficacy, and IV LEV as add-on therapy of CNP had no superiority in seizure cessation than CNP plus placebo. IV LEV may have a better tolerability than other AEDs do. More RCTs are needed to validate the role of IV LEV in status epilepticus.

Topics: Administration, Intravenous; Anticonvulsants; Humans; Levetiracetam; Randomized Controlled Trials as Topic; Status Epilepticus; Treatment Outcome

To compare the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus.. In this systematic review, we searched Medline, Embase, and Cochrane databases from their inception with no language restrictions until May 8, 2019 and updated on February 5, 2020, for randomized controlled trials comparing the efficacy and safety of levetiracetam and phenytoin for the treatment of established status epilepticus. A Meta-analysis was conducted to calculate the risk ratio (RR) using random-effects models.. Moderate-quality evidence suggested that levetiracetam was not significantly superior to phenytoin in seizure cessation in patients with established status epilepticus.

Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus

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

Recent studies have shown conflicting results regarding the effectiveness of levetiracetam for treating benzodiazepine-refractory status epilepticus (SE) compared with phenytoin. Therefore, a meta-analysis was carried out to assess the value of levetiracetam versus phenytoin in the pharmacotherapy of benzodiazepine-refractory SE.. The aim of this systematic review and meta-analysis was to compare the efficacy and safety of levetiracetam and phenytoin in the treatment of benzodiazepine-refractory SE.. The MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs) that had been conducted to evaluate levetiracetam versus phenytoin for benzodiazepine-refractory SE, to April 2020. The data were assessed using Review Manager 5.3 software. The risk ratio (RR) was analyzed using dichotomous outcomes, and calculated using a random-effect model.. We pooled 1850 patients from 12 RCTs. Patients in the levetiracetam group had a significantly higher rate of clinical seizure cessation than in the phenytoin group (75.2% vs. 67.8%; RR 1.14, 95% confidence interval [CI] 1.05-1.25, p = 0.003). Moreover, less adverse events were observed in the levetiracetam group than in the phenytoin group (17.8% vs. 21.4%; RR 0.82, 95% CI 0.70-0.97, p = 0.02). In subgroup analysis, clinical seizure cessation was achieved more frequently with a higher dose of levetiracetam (> 30 mg/kg) [RR 1.15, 95% CI 1.00-1.32, p = 0.05]. Furthermore, in the subgroup of children, levetiracetam showed a higher rate of clinical seizure cessation than phenytoin (RR 1.13, 95% CI 1.02-1.25, p = 0.02).. Pharmacotherapy for BZD-refractory SE by LEV is superior to PHT in efficacy and safety outcomes.

Topics: Anticonvulsants; Benzodiazepines; Child; Humans; Levetiracetam; Odds Ratio; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus

Convulsive status epilepticus (SE) is a relatively common emergency condition affecting individuals of all ages. The primary goal of treatment is prompt termination of seizures. Where first-line treatment with benzodiazepine has failed to achieve this, a condition known as established SE (ESE), there is uncertainty about which agent to use next. The Established Status Epilepticus Treatment Trial (ESETT) is a 3-arm (valproate (VPA), fosphenytoin (FOS), levetiracetam (LEV)), phase III, double-blind randomized comparative effectiveness study in patients aged 2 years and above with established convulsive SE. Enrollment was completed in January 2019, and the results are expected later this year. We discuss lessons learnt during the conduct of the study in relation to the following: ethical considerations; trial design and practical implementation in emergency settings, including pediatric and adult populations; quality assurance; and outcome determination where treating emergency clinicians may lack specialist expertise. We consider that the ESETT is already informing both clinical practice and future trial design. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Topics: Adult; Anticonvulsants; Benzodiazepines; Child, Preschool; Clinical Trials as Topic; Diagnostic Tests, Routine; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Levetiracetam; Male; Status Epilepticus; Treatment Outcome; Valproic Acid

Compare the cost and effectiveness of nonbenzodiazepine antiepileptic drugs (non-BZD AEDs) for treatment of BZD-resistant convulsive status epilepticus (SE).. Decision analysis model populated with effectiveness data from a systematic review and meta-analysis of the literature, and cost data from publicly available prices. The primary outcome was cost per seizure stopped ($/SS). Sensitivity analyses evaluated the robustness of the results across a wide variation of the input parameters.. VPA and PB were more effective than PHT for SE. There is substantial overlap in the cost-effectiveness of non-BZD AEDs for SE, but available evidence does not support the preeminence of PHT, neither in terms of effectiveness nor in terms of cost-effectiveness.

Topics: Anticonvulsants; Benzodiazepines; Cost-Benefit Analysis; Decision Support Techniques; Humans; Lacosamide; Levetiracetam; Phenobarbital; Phenytoin; Status Epilepticus; Treatment Failure; Valproic Acid

Since 2004 several reports on the treatment of status epilepticus with levetiracetam have been published. In this review, the results of a PubMed-based search of publications December 12, 2011 - July 6, 2018 are summarized and compared to those of earlier publications. In total, 28 treatment episodes in case reports, each on one or two cases of treatment episodes, and 412 treatment episodes in case series and prospective studies were analyzed. Case series and prospective studies reported an average success rate for termination of status probably of 55,0 %-59,4 %. Since preclinical data suggest a delayed effect of levetiracetam, its use in the treatment of generalized convulsive status epilepticus appears still questionable. A loading dose of 30 mg / kg seems to be reasonable.. Seit 2004 liegen Publikationen zum Einsatz von Levetiracetam beim Status epilepticus vor. In der vorliegenden Arbeit werden basierend auf einer PubMed-Literatur-Recherche vom 06.07.2018 die nach dem 12.12.2011 erschienenen Arbeiten zusammenfassend dargestellt und in der Diskussion mit den älteren Arbeiten verglichen. Es wurden 28 Behandlungsepisoden in Berichten über 1-2 Fälle und 412 Behandlungsepisoden in Fallserien und prospektiven Studien beschrieben. Dabei ließ sich aus den Fallserien und Studien ein hochwahrscheinlicher Mittelwert der Erfolgsrate für die Status-Durchbrechung von 55,0 %-59,4 % ableiten. Auf-grund des zu vermutenden verzögerten Wirkungseitritts des Levetiracetams ist sein Einsatz beim Status generalisierter tonisch-klonischer Anfälle dennoch zu hinterfragen. Als Loading-Dosis erscheinen 30 mg / kg KG angemessen.

Topics: Anticonvulsants; Humans; Levetiracetam; Prospective Studies; Research Design; Status Epilepticus

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.

Topics: Administration, Cutaneous; Administration, Intravenous; Anticonvulsants; Exanthema; Humans; Infusions, Intravenous; Levetiracetam; Phenytoin; Piracetam; Status Epilepticus; Treatment Outcome

Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed. Expert opinion: In early SE in children, in the prehospital setting, rectal diazepam or buccal midazolam are efficacious drugs; whereas in the hospital setting, intravenous lorazepam or diazepam are indicated. As regard estabilished stage of SE, in addition to the 'classic' compounds, such as phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam and lacosamide have been demonstrated efficacious. Treatment recommendations of refractory SE depend on retrospective case series and uncontrolled studies. We reported experiences about the use of midazolam, propofol, ketamine and lidocaine. They could be a valid option, but further prospective studies are necessary. Over the last few decades, important advances in basic mechanisms underlying refractory SE have been achieved, but few data are available regarding management of these stages.

Topics: Algorithms; Anticonvulsants; Child; Clinical Protocols; Humans; Ketamine; Levetiracetam; Midazolam; Piracetam; Prospective Studies; Retrospective Studies; Status Epilepticus; Valproic Acid

Convulsive status epilepticus is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment. Treatment of convulsive status epilepticus is usually divided into stages/steps. The International League Against Epilepsy has released a new definition of status epilepticus that may help to unify the definition in future studies. Over the last few years new information has become available regarding its management. The Rapid Anticonvulsant Medication Prior to Arrival Trial demonstrated non-inferiority of intramuscular midazolam in early status epilepticus compared with intravenous lorazepam. Valproate and levetiracetam have also emerged as possible alternatives to phenytoin in established status epilepticus. The potential role of lacosamide in this stage of status epilepticus remains to be defined. The ongoing Established Status Epilepticus Treatment Trial may help to determine the most effective treatment for benzodiazepine-resistant status epilepticus. Management of refractory status epilepticus and super-refractory status epilepticus remains mostly non-evidence-based. Increasing recognition of a possible autoimmune aetiology has led to the use of immune-modulation in super-refractory status epilepticus. Ketamine is also increasingly used in this challenging condition. There are also reports of potential use of a ketogenic diet and magnesium.

Topics: Acetamides; Anticonvulsants; Diet, Ketogenic; Hong Kong; Humans; Lacosamide; Levetiracetam; Magnesium; Midazolam; Piracetam; Practice Guidelines as Topic; Status Epilepticus; Treatment Outcome; 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

The aim of this study was to conduct a meta-analysis of published studies to directly compare intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) or IV valproate (VPA) as second-line treatment of status epilepticus (SE), to indirectly compare intravenous IV LEV with IV VPA using common reference-based indirect comparison meta-analysis, and to verify whether results of indirect comparisons are consistent with results of head-to-head randomized controlled trials (RCTs) directly comparing IV LEV with IV VPA.. Random-effects Mantel-Haenszel meta-analyses to obtain odds ratios (ORs) for efficacy and safety of LEV versus VPA and LEV or VPA versus PHT were used. Adjusted indirect comparisons between LEV and VPA were used.. Two RCTs comparing LEV with PHT (144 episodes of SE) and 3 RCTs comparing VPA with PHT (227 episodes of SE) were included. Direct comparisons showed no difference in clinical seizure cessation, neither between VPA and PHT (OR: 1.07; 95% CI: 0.57 to 2.03) nor between LEV and PHT (OR: 1.18; 95% CI: 0.50 to 2.79). Indirect comparisons showed no difference between LEV and VPA for clinical seizure cessation (OR: 1.16; 95% CI: 0.45 to 2.97). Results of indirect comparisons are consistent with results of a recent RCT directly comparing LEV with VPA.. The absence of a statistically significant difference in direct and indirect comparisons is due to the lack of sufficient statistical power to detect a difference. Conducting a RCT that has not enough people to detect a clinically important difference or to estimate an effect with sufficient precision can be regarded a waste of time and resources and may raise several ethical concerns, especially in RCT on SE.

Topics: Anticonvulsants; Humans; Levetiracetam; Phenytoin; Piracetam; Status Epilepticus; Valproic Acid

Status epilepticus (SE) is a common, severe neurological disorder, and prolonged seizures in SE may result in irreversible brain damage in association with high disability and mortality rates. Thus, termination of seizures as soon as possible is vital for the successful treatment of this disease. Levetiracetam, a new broad-spectrum anti-epileptic drug, can be used to rapidly and effectively control SE episodes with few side effects. Thus, an understanding of the use of this drug to treat SE will help clinicians to more effectively control SE and improve patient prognosis.

Topics: Anticonvulsants; Humans; Levetiracetam; Nootropic Agents; Piracetam; Status Epilepticus

Non-convulsive status epilepticus and epilepsia partialis continua are common epileptic conditions for which straightforward recommendations based on controlled randomised trials for treatment of therapy refractory courses are lacking. Therefore in these conditions sometimes antiepileptic drugs that are not approved by governmental authorities for the treatment of status epilepticus (SE) are used. Here we review all case reports and case series concerning the treatment of SE with levetiracetam (LEV), that had been listed in pub-med up to December 12th 2011. Additionally we analysed abstracts and papers in peer reviewed journals, that were listed in the references of the primarily reviewed papers. Furthermore we looked for LEV treatments in papers on the use of lacosamide (LCM) in SE. LEV was given in dosages ranging from 500 mg to 9000 mg per day. Side effects were especially sedation and irritability. Estimated on the basis of the case series the overall success-rate of LEV in terminating status epilepticus may be set in a range between 53.7% and 58.1%. Therefore LEV may be a useful alternative for the treatment of SE when the approved drugs are contraindicated or when these drugs have been taken without success.

Topics: Anticonvulsants; Epilepsia Partialis Continua; Humans; Levetiracetam; Piracetam; Status Epilepticus

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

We performed this systematic review to determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus (SE). A literature search was performed using Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). From 544 articles screened, 5 were identified as randomized controlled trials and were included for data extraction. The main outcomes were SE controlled and risk of seizure continuation. The meta-analysis was performed with the Random-effect model. The quality of the included studies was evaluated by GRADE (Grading of Recommendations Assessment, Development, and Evaluation). There was no significant statistics in SE controlled between intravenous sodium valproate and phenytoin. Compared with diazepam, sodium valproate had a statistically significant lower risk of time interval for control of refractory SE (RSE) after having drugs; however, there was no statistically significant difference in SE controlled within 30 min between the two groups. There was no statistically significant difference in cessation from status between intravenous sodium valproate and levetiracetam. Intravenous sodium valprate was as effective as intravenous phenytoin for SE controlled and risk of seizure continuation.

Topics: Anticonvulsants; Diazepam; Humans; Injections, Intravenous; Levetiracetam; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Status Epilepticus; Valproic Acid

The role of new antiepileptic drugs (AED) in the treatment of status epilepticus (SE) is of interest, especially in benzodiazepine-resistant status epilepticus where phenytoin is deemed inappropriate due to allergy or comorbidity. Levetiracetam (LEV) is a new AED with few side effects. It is easy to administer. Reports exist of its use in SE in adults.. To clarify the evidence for use of LEV as an alternative stage two AED in treatment of SE by a systematic review of the literature.. An online MEDLINE search identified 118 articles. The abstracts were screened for studies written in English, in which (1) at least two adults had been treated, and (2) LEV had been administered intravenously as the first AED, on its own or together with benzodiazepines. Ten studies were included.. Out of the ten studies, seven were retrospective observational, two prospective observational, and one prospective randomized. The studies described a total of 334 patients. The most common reason for administrating LEV was that standard treatment was deemed inappropriate. The efficacy ranged from 44% to 94%, with higher efficacy reported in the retrospective studies.. The evidence for use of LEV as an alternative stage two AED in SE is limited. The higher efficacy reported in retrospective studies indicates possible publication bias, and caution is advised when the results of these retrospective studies are considered in clinical decision-making.

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

Current standard treatment of established status epilepticus after failure of benzodiazepines is intravenous phenytoin/fosphenytoin, phenobarbital, or valproate. Since 2006 two new antiseizure drugs have become available as intravenous formulation: levetiracetam (2006) and lacosamide (2008). Both drugs have been taken up very rapidly by the clinicians to treat acute seizures and status epilepticus, despite lack of evidence from randomized controlled trials. The favorable pharmacokinetic profile and the good tolerability, especially the lack of sedating effects of both drugs make them promising potential alternatives to the standard antiseizure drugs. Future randomized controlled trials are needed to inform clinicians better about the best choice of treatment in established status epilepticus. The experimental evidence as well as the current clinical experience with levetiracetam and lacosamide are summarized in this review.

Topics: Acetamides; Humans; Injections, Intraventricular; Lacosamide; Levetiracetam; Lipoproteins; Piracetam; Status Epilepticus

The pharmacokinetics and pharmacodynamics of major antiepileptic agents are presented. The onset of action and the factors leading to extraction across the blood brain barrier are described as well as the mechanism and extent of metabolism, and the main interactions with other drugs. For each class, the dosing scheme and practical issues related to administration are described, based on evidence when available in the literature.

Topics: Anticonvulsants; Barbiturates; Benzodiazepines; Fructose; Humans; Hypnotics and Sedatives; Levetiracetam; Phenytoin; Piracetam; Propofol; Status Epilepticus; Topiramate; Valproic Acid

Topics: Anticonvulsants; Benzodiazepines; Humans; Levetiracetam; Phenobarbital; Phenytoin; Piracetam; Prodrugs; Status Epilepticus; Treatment Outcome; Valproic Acid

Topics: Anticonvulsants; Drug Approval; Fructose; Humans; Infusions, Intravenous; Injections, Intravenous; Levetiracetam; Piracetam; Status Epilepticus; Topiramate; United States; Valproic Acid

The intensive care unit management of status epilepticus focuses on patients who are refractory to initial treatment, who have an underlying condition that require critical care management, or who experience respiratory or cardiovascular complications of their therapies. The available data suggest that failure of a first-line anticonvulsant agent to terminate status should lead to the use of a definitive therapy in general anesthetic doses. Midazolam, propofol, and phenobarbital have been used most frequently; the place of newer agents (e.g., valproate, levetiracetam, or topiramate) remains to be determined.

Topics: Anesthesia, General; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Humans; Intensive Care Units; Levetiracetam; Midazolam; Patient Care Management; Phenobarbital; Piracetam; Propofol; Status Epilepticus

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

First, a short history is given of the use of the EEG as a biomarker of efficacy in anti-seizure medication (ASM) development. The generalized epileptiform EEG response to Intermittent Photic Stimulation (IPS), the photoparoxysmal EEG response or PPR, in particular, is a reliable reproducible measure since the 1950s. Over time, a "Photosensitivity Model", testing within the same patients the impact of potential new oral ASMs, along with dose-ranging data, on PPRs, has been developed successfully. The classical Photosensitivity Model consists of IPS and blood sampling for ASM measurement performed hourly between 8 AM and 5 PM over three consecutive days. This single-blind, placebo-controlled, pharmacokinetic-pharmacodynamic (PK/PD) Model is now commonly utilized as a Proof-of-Concept Phase 2a trial. For Generalized Tonic-Clonic Status Epilepticus (GTCSE), it is especially relevant to know the time for CNS entry and effect minutes after i.v. ASM treatment, since "time is brain". We, therefore, adapted successfully the Model to a time-efficient Model with the determination of photosensitivity ranges in minutes after equivalent doses of iv brivaracetam (BRV) and levetiracetam (LEV). This modified design allows one to monitor the time to CNS effect (i.e., PPR elimination) of a quickly-acting FDA-approved ASM given i.v., a crucial element in status epilepticus treatment. This paper was presented at the 8th London-Innsbruck Colloqium on Status Epilepticus and Acute Seizures held in September 2022.

Topics: Anticonvulsants; Humans; Levetiracetam; Photosensitivity Disorders; Pyrrolidinones; Single-Blind Method; Status Epilepticus; Treatment Outcome

Benzodiazepines are the first-line anti-seizure medication (ASM) for generalized convulsive status epilepticus (GCSE), but they fail to end seizures in a third of cases. Combining benzodiazepines with another ASM that acts by a different pathway could be a potential strategy for rapid control of GCSE.. To evaluate the efficacy of adding levetiracetam to midazolam in the initial treatment of pediatric GCSE.. Double-blind randomized controlled trial.. Pediatric emergency room at Sohag University Hospital between June, 2021 and August, 2022.. Children aged between 1 month and 16 years with GCSE lasting more than 5 min.. Intravenous levetiracetam (60 mg/kg over 5 min) and midazolam (Lev-Mid group) or placebo and midazolam (Pla-Mid group) as first-line anticonvulsive therapy.. Primary: cessation of clinical seizures at 20-min study time point. Secondary: cessation of clinical seizures at 40-min study time point, need for a second midazolam dose, seizure control at 24-hr, need for intubation, and adverse effects.. Cessation of clinical seizures at 20-min occurred in 55 children (76%) in Lev-Mid group compared with 50 (69%) in the Pla-Mid group [RR (95% CI) 1.1 (0.9-1.34); P=0.35]. No significant difference was found between the two groups regarding the need for a second midazolam dose [44.4% vs 55.6%; RR (95% CI) 0.8 (0.58-1.11); P=0.18] as well as cessation of clinical seizures at 40-min [96% vs 92%; RR (95% CI)1.05 (0.96-1.14); P=0.49] and seizure control at 24-hr [85% vs 76%; RR (95% CI) 1.12 (0.94-1.3); P=0.21]. Intubation was required for three patients in the Lev-Mid group and six patients in the Pla-Mid group [RR (95%CI) 0.5 (0.13- 1.92); P=0.49]. No other adverse effects or mortality were observed during the 24-hour study timeframe.. Combined levetiracetam and midazolam for initial management of pediatric GCSE presents no significant advantage over midazolam alone in cessation of clinical seizures at 20-min.

Topics: Anticonvulsants; Child; Humans; Infant; Levetiracetam; Midazolam; Status Epilepticus; Treatment Outcome

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

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

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged ≥2 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomly assigned to FOS, LEV, or VPA infused over 10 minutes. A sparse blood-sampling approach was used, with up to 2 samples collected per patient within 2 hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV, and VPA and plasma protein binding of PHT and VPA. Twenty-seven children with median (interquartile range) age of 4 (2.5-6.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 μg/mL for LEV, 11.3 to 26.7 μg/mL for PHT and 126 to 223 μg/mL for VPA. Free fraction ranged from 4% to 19% for PHT and 17% to 51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure-response relationships in this emergent condition.

Topics: Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Protein Binding; Status Epilepticus; Valproic Acid

Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE.. This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes.. The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application.. Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019.

Topics: Adult; Anticonvulsants; Diazepam; Humans; Japan; Levetiracetam; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Phenytoin; Randomized Controlled Trials as Topic; Status Epilepticus; Treatment Outcome

To investigate whether receiving a second-line anticonvulsant medication that is part of a patient's home regimen influences outcomes in benzodiazepine-refractory convulsive status epilepticus.. Using the Established Status Epilepticus Treatment Trial data, allocation to a study drug included in the patient's home anticonvulsant medication regimen was compared to receipt of an alternative second-line study medication. The primary outcome was cessation of clinical seizures with improved consciousness by 60 minutes after study drug initiation. Secondary outcomes were seizure cessation adjudicated from medical records and adverse events. We performed inverse probability of treatment-weighted (IPTW) logistic regressions.. Of 462 patients, 232 (50%) were taking 1-2 of the 3 study medications at home. The primary outcome was observed in 39/89 (44%) patients allocated to their home medication vs 76/143 (53%) allocated to a nonhome medication (IPTW odds ratio [OR] 0.66, 95% confidence interval [CI] 0.39-1.14). The adjudicated outcome occurred in 37/89 (42%) patients vs 82/143 (57%), respectively (IPTW OR 0.52, 95% CI 0.30-0.89). There was no interaction between study levetiracetam and home levetiracetam and there were no differences in adverse events.. There was no difference in the primary outcome for patients who received a home medication vs nonhome medication. However, the retrospective evaluation suggested an association between receiving a nonhome medication and seizure cessation.. This study provides Class II evidence that for patients with refractory convulsive status epilepticus, use of a home second-line anticonvulsant compared to a nonhome anticonvulsant did not significantly affect the probability of stopping seizures.

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Comparative Effectiveness Research; Double-Blind Method; Drug Resistant Epilepsy; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Outcome Assessment, Health Care; Phenytoin; Self Administration; Status Epilepticus; Valproic Acid; Young Adult

To determine whether levetiracetam is an alternative to fosphenytoin to control Benzodiazepine Refractory Status Epilepticus (BRSE) in pediatric population and also to compare the acute drug related side-effects and ventilation requirement among the both arms of anti-epileptic drug therapy.. All consecutive children admitted with BRSE were randomized to group A, who received fosphenytoin at 20 mg/kg phenytoin equivalents (PE) dose and group B who received levetiracetam at 40 mg/kg over 10 min. Time to terminate seizure (response latency) was measured. If seizure remained refractory after 20 min of test drug administration, appropriate drug escalation was made according to pediatrician's discretion. All primary and secondary outcome measures were compared between the two therapeutic groups.. Of 61 children enrolled over 18 mo period, 29 (47.5%) were randomized to group A and 32 (52.5%) were randomized to Group B. Baseline characteristics were comparable between the two groups. Among 61 children, 58(98%) required Pediatric Intensive Care Unit (PICU) admission and among those 5(8.2%) children required mechanical ventilation. Duration of PICU stay, hospital stay, the response latency and seizure recurrence were compared between both groups. Significant number of children received additional anti-epileptic drugs (AEDs) in fosphenytoin group [9/29(31%)] compared to levetiracetam group [2/32(7%)] to control seizure.. Levetiracetam may be an effective alternative to fosphenytoin in management of BRSE in children but multicentric trials with large sample size are needed to substantiate this observation.

Topics: Anticonvulsants; Benzodiazepines; Child; Humans; Levetiracetam; Neoplasm Recurrence, Local; Phenytoin; Status Epilepticus; Treatment Outcome

To compare the efficacy of phenytoin, valproate, and levetiracetam in the management of pediatric convulsive status epilepticus.. Randomized double-blind controlled clinical trial.. Pediatric critical care division in a tertiary care institute from June, 2016 to December, 2018.. 110 children aged three month to 12 year with convulsive status epilepticus.. Patients not responding to 0.1 mg/kg intravenous lorazepam were randomly assigned (1:1:1) to receive 20 mg/kg of phenytoin (n=35) or valproate (n=35) or levetiracetam (n=32) over 20 minutes. Patients with nonconvulsive status epilepticus, recent hemorrhage, platelet count less than 50,000 or International normalized ratio (INR) more than 2, head injury or neurosurgery in the past one-month, liver or kidney disease, suspected or known neurometabolic or mitochondrial disorders or structural malformations, and allergy to study drugs; and those who were already on any one of the study drugs for more than one month or had received one of the study drugs for current episode, were excluded.. The primary outcome was the proportion of patients that achieved control of convulsive status epilepticus at the end of 15 minutes after completion of the study drug infusion. Secondary outcomes were time to control of seizure, rate of adverse events, and the requirement of additional drugs to control seizure, length of ventilation, hospital stay, and functional status after three months (Glasgow Outcome Scale).. The study was stopped after the planned mid-interim analysis for futility. Intention to treat analysis was done. There was no difference in primary outcome in phenytoin (31/35, 89%), valproate (29/35, 83%), and levetiracetam (30/32, 94%) (P=0.38) groups. There were no differences between the groups for secondary outcomes. One patient in the phenytoin group had a fluid-responsive shock, and one patient in the valproate group died due to encephalopathy and refractory shock.. Phenytoin, valproate, and levetiracetam were equally effective in controlling pediatric convulsive status epilepticus.

Topics: Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Intention to Treat Analysis; Levetiracetam; Male; Phenytoin; Status Epilepticus; Treatment Outcome; Valproic Acid

Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.. In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075.. Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group.. Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus.. National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infant; Levetiracetam; Male; Middle Aged; Phenytoin; Status Epilepticus; Valproic Acid; Young Adult

The Established Status Epilepticus Treatment Trial was a blinded, comparative-effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine-refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight-based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight-normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54-1.51) or >90 kg (OR = 0.85, 95% CI = 0.42-1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings.

Topics: Adolescent; Adult; Anticonvulsants; Body Weight; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Male; Phenytoin; Single-Blind Method; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

Convulsive status epilepticus is the most common neurological emergency in children. Its management is important to avoid or minimise neurological morbidity and death. The current first-choice second-line drug is phenytoin (Epanutin, Pfizer Inc., New York, NY, USA), for which there is no robust scientific evidence.. To determine whether phenytoin or levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) is the more clinically effective intravenous second-line treatment of paediatric convulsive status epilepticus and to help better inform its management.. A multicentre parallel-group randomised open-label superiority trial with a nested mixed-method study to assess recruitment and research without prior consent.. Participants were recruited from 30 paediatric emergency departments in the UK.. Participants aged 6 months to 17 years 11 months, who were presenting with convulsive status epilepticus and were failing to respond to first-line treatment.. Intravenous levetiracetam (40 mg/kg) or intravenous phenytoin (20 mg/kg).. Primary outcome - time from randomisation to cessation of all visible signs of convulsive status epilepticus. Secondary outcomes - further anticonvulsants to manage the convulsive status epilepticus after the initial agent, the need for rapid sequence induction owing to ongoing convulsive status epilepticus, admission to critical care and serious adverse reactions.. Between 17 July 2015 and 7 April 2018, 286 participants were randomised, treated and consented. A total of 152 participants were allocated to receive levetiracetam and 134 participants to receive phenytoin. Convulsive status epilepticus was terminated in 106 (70%) participants who were allocated to levetiracetam and 86 (64%) participants who were allocated to phenytoin. Median time from randomisation to convulsive status epilepticus cessation was 35 (interquartile range 20-not assessable) minutes in the levetiracetam group and 45 (interquartile range 24-not assessable) minutes in the phenytoin group (hazard ratio 1.20, 95% confidence interval 0.91 to 1.60;. First, this was an open-label trial. A blinded design was considered too complex, in part because of the markedly different infusion rates of the two drugs. Second, there was subjectivity in the assessment of 'cessation of all signs of continuous, rhythmic clonic activity' as the primary outcome, rather than fixed time points to assess convulsive status epilepticus termination. However, site training included simulated demonstration of seizure cessation. Third, the time point of randomisation resulted in convulsive status epilepticus termination prior to administration of trial treatment in some cases. This affected both treatment arms equally and had been prespecified at the design stage. Last, safety measures were a secondary outcome, but the trial was not powered to demonstrate difference in serious adverse reactions between treatment groups.. Levetiracetam was not statistically superior to phenytoin in convulsive status epilepticus termination rate, time taken to terminate convulsive status epilepticus or frequency of serious adverse reactions. The results suggest that it may be an alternative to phenytoin in the second-line management of paediatric convulsive status epilepticus. Simple trial design, bespoke site training and effective leadership were found to facilitate practitioner commitment to the trial and its success. We provide a framework to optimise recruitment discussions in paediatric emergency medicine trials.. Future work should include a meta-analysis of published studies and the possible sequential use of levetiracetam and phenytoin or sodium valproate in the second-line treatment of paediatric convulsive status epilepticus.. Current Controlled Trials ISRCTN22567894 and European Clinical Trials Database EudraCT number 2014-002188-13.. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in. Most epileptic tonic–clonic seizures, also called convulsions, last for < 4 minutes and stop spontaneously. A convulsion that lasts for > 5 minutes is called convulsive status epilepticus. This may cause neurological abnormalities or, rarely, death. There is good scientific evidence for the best first-line medicine, called a benzodiazepine, to stop convulsive status epilepticus. When a benzodiazepine has not stopped status, a second-line medicine is given. The usual second-line medicine, which has been used for > 50 years, is phenytoin (Epanutin, Pfizer Inc., New York, NY, USA). However, it stops status in only half of children. It must be given slowly because it can cause unpleasant and potentially serious side effects. A new medicine called levetiracetam (Keppra, UCB Pharma, Brussels, Belgium) may be more effective. It seems to have less serious side effects than phenytoin. However, there is no good scientific evidence as to whether phenytoin or levetiracetam is better. A randomised controlled trial is the best scientific way to decide which of these two medicines is better. The Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE) trial was a randomised controlled trial that compared levetiracetam with phenytoin. A total of 152 children were randomised to receive levetiracetam and a total of 134 children were randomised to receive phenytoin. Research without prior consent was shown to be acceptable to parents, doctors and nurses. Parents’ consent to use their child’s data and continue in the trial was provided after the emergency situation was resolved. Convulsive status epilepticus stopped in 70.4% of the levetiracetam-treated children and in 64% of the phenytoin-treated children. The median time to status stopping was 35 minutes in the levetiracetam-treated children and 45 minutes in the phenytoin-treated children. Only one participant on phenytoin (vs. none on levetiracetam) experienced serious side effects that were thought to be caused by their treatment. None of the results showed any statistically significant or meaningful difference between levetiracetam and phenytoin. However, the results suggest that levetiracetam might be an alternative choice to phenytoin.

Topics: Administration, Intravenous; Adolescent; Anticonvulsants; Child; Child, Preschool; Equivalence Trials as Topic; Female; Humans; Infant; Levetiracetam; Male; Phenytoin; Status Epilepticus; United Kingdom

Status epilepticus (SE) is a common neurological emergency condition that especially affects the elderly and old population. Older people with SE frequently have non-convulsive SE (NCSE) and are also at special risk of suffering a poor outcome. The application of benzodiazepines fails to control SE in about one third of the cases. For benzodiazepine refractory SE (BRSE) in elderly, there is little evidence that would justify the choice of one of the commonly used antiepileptic drugs. The present study aims to generate evidence for the treatment of BRSE in this age group.. We will conduct a prospective, randomized, double-blind comparative effectiveness study in more than twenty hospitals in Germany over a four-year period. Four hundred and seventy-seven elderly patients (≥ 65 years old) diagnosed with BRSE will be allocated by 1:1 randomization to receive either levetiracetam or valproate. All types of SE will be considered. For the diagnosis NCSE a verification by EEG is required. Levetiracetam or valproate will be administered in one single infusion. The primary endpoint is the stable cessation of ictal activity 15 min after the start of infusion persisting for the following 45 min of observation. EEG recording is maintained over the whole observation period, clinical examinations are conducted in predefined intervals. In case of treatment success patients and study staff remain blinded until 60 min after the start of the infusion. Adverse events will be recorded until the end of the study. EEG data will be reviewed by two external independent experts. To obtain data about the further treatment of SE, intrahospital complications and the functional outcome in the short term the study participants will be observed until the day of discharge or day 30 whichever is earliest.. ToSEE is the first study which shall deliver evidence for the SE-therapy in the elderly and old population in a controlled prospective comparator study. By design it also shall collect information about therapy regimes and outcome aspects of this disease.. The trial has been registered at the German Clinical Trials Register on 3 July, 2020 ( DRKS00022308 ,  https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022308 ).

Topics: Aged; Aged, 80 and over; Anticonvulsants; Double-Blind Method; Female; Germany; Humans; Levetiracetam; Male; Prospective Studies; Status Epilepticus; Valproic Acid

The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.. In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.. A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.. In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Double-Blind Method; Drug Resistance; Female; Humans; Hypotension; Infusions, Intravenous; Injections, Intramuscular; Levetiracetam; Male; Middle Aged; Phenytoin; Status Epilepticus; Valproic Acid; Young Adult

This randomized control study was conducted to compare the efficacy of sodium valproate (SVP) and levetiracetam (LEV) following initial intravenous lorazepam in elderly patients (age: >60years) with generalized convulsive status epilepticus (GCSE) and to identify predictors of poor seizure control.. A total of 118 patients (mean age: 67.5 ± 7.5 years, M:F = 1.6:1), who had presented with GCSE were randomized into the SVP or LEV treatment arms. All patients received initial intravenous lorazepam (0.1 mg/kg) followed by one of the two antiepileptic drugs (AEDs), parenteral SVP (20-25 mg/kg) or LEV (20-25 mg/kg). Those who failed to achieve control with the initial AED, were crossed over to receive the other AED. One-hundred patients (SVP = 50; LEV = 50) completed the study.. SE could be controlled with lorazepam and one of the AEDs (SVP or LEV) in 71.18% (84/118). Intention-to-treat analysis showed that the two groups did not differ significantly in terms of seizure control [SVP: 41/60 (68.3%); LEV: 43/58 (74.1%), p = 0.486]. Of 100 patients who completed the study, seizure control was achieved in 38/50(76%) in the SVP and 43/50(86%) in the LEV group (p = 0.202). After crossing over to the second AED, SE could be controlled in an additional in 50% (6/12) in SVP (+LEV) group and in 14.3% (1/7) in LEV (+SVP) group. Overall, after the second AED, seizure control was achieved in 77.1% (91/118). Higher STESS was associated with poor therapeutic response (p = 0.049).. The efficacy of SVP and LEV following initial lorazepam in controlling GCSE in elderly population was comparable, hence the choice of AED could be individualized.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Dose-Response Relationship, Drug; Electroencephalography; Female; Humans; Levetiracetam; Logistic Models; Lorazepam; Male; Middle Aged; Pilot Projects; Prospective Studies; Single-Blind Method; Status Epilepticus; Treatment Outcome; Valproic Acid

EcLiPSE (Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children) is a randomised controlled trial (RCT) in the United Kingdom. Challenges to success include the need to immediately administer an intervention without informed consent and changes in staffing during trial conduct, mainly due to physician rotations. Using literature on parents' perspectives and research without prior consent (RWPC) guidance, we developed an interactive training package (including videos, simulation and question and answer sessions) and evaluated its dissemination and impact upon on practitioners' confidence in recruitment and consent.. Questionnaires were administered before and immediately after training followed by telephone interviews (mean 11 months later), focus groups (mean 14 months later) and an online questionnaire (8 months before trial closure).. One hundred and twenty-five practitioners from 26/30 (87%) participating hospitals completed a questionnaire before and after training. We conducted 10 interviews and six focus groups (comprising 36 practitioners); 199 practitioners working in all recruiting hospitals completed the online questionnaire. Before training, practitioners were concerned about recruitment and consent. Confidence increased after training for explaining (all scale 0-5, 95% CIs above 0 and p values < 0.05): the study (66% improved mean score before 3.28 and after 4.52), randomisation (47% improvement, 3.86 to 4.63), RWPC (72% improvement, 2.98 to 4.39), and addressing parents' objections to randomisation (51% improvement, 3.37 to 4.25). Practitioners rated highly the content and clarity of the training, which was successfully disseminated. Some concerns about staff availability for training and consent discussions remained.. Training improved practitioners' confidence in recruitment and RWPC. Our findings highlight the value of using parents' perspectives to inform training and to engage practitioners in trials that are at high risk of being too challenging to conduct.

Topics: Emergencies; Humans; Informed Consent; Levetiracetam; Patient Selection; Phenytoin; Research Design; Status Epilepticus

Phenytoin is the current standard of care for second-line treatment of paediatric convulsive status epilepticus after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, can be given more quickly, is potentially more efficacious, and has a more tolerable adverse effect profile. We aimed to determine whether phenytoin or levetiracetam is the superior second-line treatment for paediatric convulsive status epilepticus.. ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand. Children aged between 3 months and 16 years, with convulsive status epilepticus that failed first-line benzodiazepine treatment, were randomly assigned (1:1) using a computer-generated permuted block (block sizes 2 and 4) randomisation sequence, stratified by site and age (≤5 years, >5 years), to receive 20 mg/kg phenytoin (intravenous or intraosseous infusion over 20 min) or 40 mg/kg levetiracetam (intravenous or intraosseous infusion over 5 min). The primary outcome was clinical cessation of seizure activity 5 min after the completion of infusion of the study drug. Analysis was by intention to treat. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12615000129583.. Between March 19, 2015, and Nov 29, 2017, 639 children presented to participating emergency departments with convulsive status epilepticus; 127 were missed, and 278 did not meet eligibility criteria. The parents of one child declined to give consent, leaving 233 children (114 assigned to phenytoin and 119 assigned to levetiracetam) in the intention-to-treat population. Clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). One participant in the phenytoin group died at 27 days because of haemorrhagic encephalitis; this death was not thought to be due to the study drug. There were no other serious adverse events.. Levetiracetam is not superior to phenytoin for second-line management of paediatric convulsive status epilepticus.. Health Research Council of New Zealand, A+ Trust, Emergency Medicine Foundation, Townsville Hospital Private Practice Fund, Eric Ormond Baker Charitable Fund, and Princess Margaret Hospital Foundation.

Topics: Adolescent; Aged; Anticonvulsants; Australia; Child; Child, Preschool; Drug Administration Schedule; Drug Resistant Epilepsy; Emergency Service, Hospital; Female; Humans; Infant; Levetiracetam; Male; New Zealand; Phenytoin; Status Epilepticus; Treatment Outcome

Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.. This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.. Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91-1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]).. Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus.. National Institute for Health Research Health Technology Assessment programme.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Administration Schedule; Drug Resistant Epilepsy; Emergency Service, Hospital; Female; Humans; Infant; Levetiracetam; Male; Phenytoin; Status Epilepticus; Treatment Outcome; United Kingdom

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

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

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

Convulsive status epilepticus (CSE) is the most common life-threatening neurological emergency in childhood. These children are also at risk of significant morbidity, with acute and chronic impact on the family and the health and social care systems. The current recommended first-choice, second-line treatment in children aged 6 months and above is intravenous phenytoin (fosphenytoin in the USA), although there is a lack of evidence for its use and it is associated with significant side effects. Emerging evidence suggests that intravenous levetiracetam may be effective as a second-line agent for CSE, and fewer adverse effects have been described. This trial therefore aims to determine whether intravenous phenytoin or levetiracetam is more effective, and safer, in treating childhood CSE.. This is a phase IV, multi-centre, parallel group, randomised controlled, open-label trial. Following treatment for CSE with first-line treatment, children with ongoing seizures are randomised to receive either phenytoin (20 mg/kg, maximum 2 g) or levetiracetam (40 mg/kg, maximum 2.5 g) intravenously. The primary outcome measure is the cessation of all visible signs of CSE as determined by the treating clinician. Secondary outcome measures include the need for further anti-seizure medications or rapid sequence induction for ongoing CSE, admission to critical care areas, and serious adverse reactions. Patients are recruited without prior consent, with deferred consent sought at an appropriate time for the family. The primary analysis will be by intention-to-treat. The primary outcome is a time to event outcome and a sample size of 140 participants in each group will have 80% power to detect an increase in CSE cessation rates from 60% to 75%. Our total sample size of 308 randomised and treated participants will allow for 10% loss to follow-up.. This clinical trial will determine whether phenytoin or levetiracetam is more effective as an intravenous second-line agent for CSE, and provide evidence for management recommendations. In addition, this trial will also provide data on which of these therapies is safer in this setting.. ISRCTN identifier, ISRCTN22567894 . Registered on 27 August 2015 EudraCT identifier, 2014-002188-13 . Registered on 21 May 2014 NIHR HTA Grant: 12/127/134.

Topics: Adolescent; Age Factors; Anticonvulsants; Child; Child, Preschool; Clinical Protocols; Emergencies; Female; Humans; Infant; Infusions, Intravenous; Intention to Treat Analysis; Ireland; Levetiracetam; Male; Phenytoin; Piracetam; Research Design; Status Epilepticus; Time Factors; Treatment Outcome; United Kingdom

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children.. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge.. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines.. Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Clinical Protocols; Emergencies; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Levetiracetam; Male; Phenytoin; Piracetam; Prospective Studies; Single-Blind Method; Status Epilepticus; Treatment Outcome

We report the efficacy and safety of lorazepam (LOR), phenytoin (PHT), valproate (VPA) and levetiracetam (LEV) as first and second choice antiepileptic drug (AED) in status epilepticus (SE) and their combinations in preventing refractory SE.. The results of our two earlier trials on SE were compared; one evaluated VPA versus PHT (group I) and the other LOR versus LEV (group II). In group I, additional patients were recruited in addition to published data. The primary outcome was cessation of SE after first and second AEDs and secondary outcome was mortality and side effects. The efficacy of these four drugs as first and second choice was compared. The frequency of refractory seizure in groups I and II and their contributing factors were analyzed.. One hundred and seventeen patients were in group I and 79 in group II. The baseline characteristics of the patients were similar in LOR, LEV, VPA and PHT groups. As a first choice, LOR controlled SE in 75.1%, LEV in 76.3%, VPA in 55.4% and PHT in 44.2% patients. As a second choice, LEV was effective in 88.9%, LOR in 70%, VPA in 74.1% and PHT in 25% patients. Refractory SE was more frequent in group I than group II (29.9% versus 10.5%), however, complications and mortality were higher in group II.. LOR and LEV combination was superior in reducing refractory SE but at the cost of higher complications and death.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Female; Humans; India; Infant; Levetiracetam; Lorazepam; Male; Middle Aged; Outcome Assessment, Health Care; Phenytoin; Piracetam; Status Epilepticus; Valproic Acid; Young Adult

Generalised convulsive status epilepticus (GCSE) should be treated quickly. Benzodiazepines are the only drug treatment available so far that is effective before admission to hospital. We assessed whether addition of the antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve prehospital treatment of GCSE.. We did a prehospital, randomised, double-blind, phase 3, placebo-controlled, superiority trial to determine the efficacy of adding intravenous levetiracetam (2.5 g) to clonazepam (1 mg) in treatment of GCSE in 13 emergency medical service centres and 26 hospital departments in France. Randomisation was done at the Paris Descartes Clinical Research Unit with a list of random numbers generated by computer. Adults with convulsions lasting longer than 5 min were randomly assigned (1:1) by prehospital physicians to receive levetiracetam or placebo in combination with clonazepam. All physicians and paramedics were masked to group assignments. If the status epilepticus lasted beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given. The primary outcome was cessation of convulsions within 15 min of drug injection. We analysed the modified intention-to-treat population that had received at least one injection of clonazepam and levetiracetam or placebo, excluding patients without valid consent and those randomised more than once. The trial is registered at EudraCT, number 2007-005782-35.. Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly assigned to receive placebo and 96 were assigned to receive levetiracetam. The trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence of a treatment difference, and 68 patients in each group were included in the modified intention-to-treat analysis. Convulsions stopped at 15 min of drug injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50 of 68 patients (74%) receiving clonazepam and levetiracetam (percentage difference -10.3%, 95% CI -24.0 to 3.4). Three deaths, 19 of 47 (40 %) serious adverse events, and 90 of 197 (46%) non-serious events were reported in the levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of 197 (54%) non-serious events were reported in the placebo group.. The addition of levetiracetam to clonazepam treatment presented no advantage over clonazepam treatment alone in the control of GCSE before admission to hospital. Future prehospital trials could assess the efficacy of clonazepam alone as a first-line treatment in status epilepticus and the efficacy of a second injection of clonazepam with another antiepileptic drug as second-line treatment.. UCB Pharma.

Topics: Adult; Aged; Anticonvulsants; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Emergency Medical Services; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Placebo Effect; Prospective Studies; Status Epilepticus; Treatment Outcome

The purpose of this study was to compare safety and efficacy of intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) in management of status epilepticus (SE). The second-line treatment of SE is limited to a few drugs available in an IV formulation such as PHT, fosphenytoin and valproate. The relative lack of serious side effects and favourable pharmacokinetics of LEV made it a promising option in management of SE. Randomized trials comparing relative efficacy of second-line agents are remarkably lacking. In this study, consecutive patients of SE (n=44) were randomized to receive either IV PHT (20mg/kg) or IV LEV (20mg/kg). The primary end point was successful clinical termination of seizure activity within 30min after the beginning of the drug infusion. Secondary end points included recurrence of seizures within 24 hours, drug related adverse effects, neurological outcome at discharge, need for ventilatory assistance, and mortality during hospitalization. Both LEV and PHT were equally effective with regard to primary and secondary outcome measures. PHT achieved control of SE in 15 (68.2%) patients compared to LEV in 13 (59.1%; p=0.53). Both the groups showed comparable results with respect to recurrence of seizures within 24 hours (p=0.34), outcome at discharge as assessed by functional independence measure (p=0.68), need of ventilatory assistance (p=0.47) and death (p=1). From this study it can be concluded that LEV may be an attractive and effective alternative to PHT in management of SE.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Anticonvulsants; Disease Management; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Patient Discharge; Phenytoin; Piracetam; Prospective Studies; Status Epilepticus; Young Adult

This study was conducted to compare the efficacy of phenytoin, valproate and levetiracetam in patients with GCSE.. This randomised controlled prospective study was conducted on 150 patients to compare the efficacy of phenytoin (n = 50), valproate (n = 50) and levetiracetam (n = 50) along with lorazepam in patients with GCSE. All recruited patients received i.v. lorazepam (0.1mg/kg) followed by one of the 3 AEDs viz. phenytoin (20 mg/kg), valproate (30 mg/kg), and levetiracetam (25 mg/kg). Those who remained uncontrolled with 1st AED, received the other two AEDs sequentially. Clinical, imaging, EEG, etiological factors were analysed. Predictors of poor seizure control and outcome at discharge and at one month follow-up were assessed.. In the phenytoin subgroup, the seizures could be controlled in 34 (68%) with lorazepam+phenytoin infusion. In the valproate subgroup (n = 50), seizures could be controlled in 34 (68%) with lorazepam+valproate infusion. In the levetiracetam subgroup (n = 50), seizures could be controlled in 39 (78%) with lorazepam+levetiracetam infusion. There was no statistically significant difference between the subgroups (p = 0.44). Overall, following lorazepam and 1st AED, 107/150 (71.3%) were controlled; with addition of 2nd AED, 130/150 (86.7%) and by adding 3rd AED, 138/150 (92%) were controlled. Fifteen out of 110 (13.6%) expired within 1 month of SE: phenytoin-6; valproate-4; and levetiracetam-5. Interestingly, 3 patients in the levetiracetam had post-ictal psychosis.. Phenytoin, valproate, and levetiracetam are safe and equally efficacious following lorazepam in GCSE. The choice of AEDs could be individualised based on co-morbidities. SE could be controlled in 92% of patients with AEDs only and anaesthetics were not required in them.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Drug Therapy, Combination; Electroencephalography; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Injections, Intravenous; Levetiracetam; Lorazepam; Male; Middle Aged; Phenytoin; Pilot Projects; Piracetam; Prognosis; Prospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

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

We present a novel Bayesian adaptive comparative effectiveness trial comparing three treatments for status epilepticus that uses adaptive randomization with potential early stopping.. The trial will enroll 720 unique patients in emergency departments and uses a Bayesian adaptive design.. The trial design is compared to a trial without adaptive randomization and produces an efficient trial in which a higher proportion of patients are likely to be randomized to the most effective treatment arm while generally using fewer total patients and offers higher power than an analogous trial with fixed randomization when identifying a superior treatment.. When one treatment is superior to the other two, the trial design provides better patient care, higher power, and a lower expected sample size.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Bayes Theorem; Child; Child, Preschool; Comparative Effectiveness Research; Early Termination of Clinical Trials; Emergency Service, Hospital; Humans; Intention to Treat Analysis; Levetiracetam; Middle Aged; Models, Statistical; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Research Design; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

Benzodiazepine-refractory status epilepticus (established status epilepticus, ESE) is a relatively common emergency condition with several widely used treatments. There are no controlled, randomized, blinded clinical trials to compare the efficacy and tolerability of currently available treatments for ESE. The ESE treatment trial is designed to determine the most effective and/or the least effective treatment of ESE among patients older than 2 years by comparing three arms: fosphenytoin (fPHT) levetiracetam (LVT), and valproic acid (VPA). This is a multicenter, randomized, double-blind, Bayesian adaptive, phase III comparative effectiveness trial. Up to 795 patients will be randomized initially 1:1:1, and response-adaptive randomization will occur after 300 patients have been recruited. Randomization will be stratified by three age groups, 2-18, 19-65, and 66 and older. The primary outcome measure is cessation of clinical seizure activity and improving mental status, without serious adverse effects or further intervention at 60 min after administration of study drug. Each subject will be followed until discharge or 30 days from enrollment. This trial will include interim analyses for early success and futility. This trial will be considered a success if the probability that a treatment is the most effective is >0.975 or the probability that a treatment is the least effective is >0.975 for any treatment. Proposed total sample size is 795, which provides 90% power to identify the most effective and/or the least effective treatment when one treatment arm has a true response rate of 65% and the true response rate is 50% in the other two arms.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Humans; Levetiracetam; Middle Aged; Phenytoin; Piracetam; Research Design; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

We performed a double-blind placebo-controlled crossover study of the effects of spike activity during sleep and when awake on learning, long-term memory, vigilance and behavior before and after treatment with levetiracetam in children with electrical status epilepticus during sleep. At baseline, verbal learning declined with increasing spike activity, but there were no relations between spike activity and memory, vigilance or behavior. Levetiracetam was effective in reducing sleep-related spike activity, but on a group level, this had no clear effects on behavior, vigilance or learning and memory. Our results do not allow firm conclusions whether to treat nocturnal epileptiform activity or not; larger samples and longer follow-up may be needed.

Topics: Action Potentials; Anticonvulsants; Child; Child Behavior; Child, Preschool; Cognition Disorders; Double-Blind Method; Electroencephalography; Female; Humans; Learning; Levetiracetam; Male; Memory; Neuropsychological Tests; Piracetam; Sleep; Status Epilepticus

For the management of status epilepticus (SE), lorazepam (LOR) is recommended as the first and phenytoin or fosphenytoin as the second choice. Both these drugs have significant toxicity. Intravenous levetiracetam (LEV) has become available, but its efficacy and safety has not been reported in comparison to LOR. We report a randomized, open labeled pilot study comparing the efficacy and safety of LEV and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min. Failure to control SE within 10 min of administration of one study drug was treated by the other study drug. The primary endpoint was clinical seizure cessation and secondary endpoints were 24 h freedom from seizure, hospital mortality, and adverse events. Our results are based on 79 patients. Both LEV and LOR were equally effective. In the first instance, the SE was controlled by LEV in 76.3% (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The 24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in 67.7% (21/31). LOR was associated with significantly higher need of artificial ventilation and insignificantly higher frequency of hypotension. For the treatment of SE, LEV is an alternative to LOR and may be preferred in patients with respiratory compromise and hypotension.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Levetiracetam; Lorazepam; Male; Middle Aged; Pilot Projects; Piracetam; Status Epilepticus; Young Adult

Current treatment of human status epilepticus (SE) relies on drugs developed for chronic treatment of epilepsy. Many potent compounds have been discovered in animal models of SE. But they may never be useful for chronic treatment of epilepsy and thus not available for human use. Naturally occurring canine SE may become a translational platform for evaluating these compounds for eventual use in human trials. A pilot study of levetiracetam in canine SE demonstrated a 56% response rate compared to 10% for placebo. Based on these results we have obtained an NIH R-21 to further evaluate canine SE as a translational platform for developing new approaches for treating human SE.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Levetiracetam; Phenytoin; Pilot Projects; Piracetam; Reproducibility of Results; Status Epilepticus

Therapeutic strategies for patients with generalized convulsive status epilepticus (GCSE) need to be improved. We present the design of an add-on, randomized, double-blind, placebo-controlled, phase III clinical trial, to compare the efficacy for GCSE of intravenous levetiracetam in association with clonazepam versus clonazepam alone. In the therapeutic arm, 1 mg clonazepam is injected together with 2500 mg levetiracetam over 5 min. In the control arm, 1 mg clonazepam is injected together with a placebo over 5 min. This ongoing study is managed by prehospital physicians within emergency mobile units (SAMU). Adult patients with GCSE lasting more than 5 minutes are included in the study. The primary outcome measure is the percentage of patients with cessation of convulsions within 15 minutes of the onset of initial injections. Emergency medical consent is obtained from family members. An informed consent for continued participation is also obtained from patients when they wake. The study is currently recruiting participants.

Topics: Adult; Anticonvulsants; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Emergency Medical Services; Female; Humans; Injections, Intravenous; Levetiracetam; Male; Piracetam; Status Epilepticus; Time Factors; Treatment Outcome

Refractory status epilepticus (RSE) is a common Neurological Emergency with increased mortality and morbidity in developing countries where facilities of intubation, adequate ventilation, Intensive Care Units (ICUs) and general anaesthesia are not ubiquitously available. Treatment protocols use antiepileptic drugs (AEDs) and need ICU facilities after failure of standard AEDs. Our aim was to see the response to two additional drugs in the armamentarium against refractory status, that is, valproate and levetiracetam.. Patients with generalized RSE admitted in neurology and neurosurgery services at AIIMS during December 2006 to June 2008 were included in the study. The patients were allotted to two groups based on certain criteria. Demographic details, reason for delay, etiology precipitating status, ongoing AEDs therapy, duration of status, the time taken for cessation along with clinical, EEG and MRI correlates were noted. Outcome parameters were analyzed by an independent blinded observer.. 82 patients with RSE were studied out of which 41 patients were given IV valproate (Group A) and 41 patients were given IV levetiracetam (Group B). Cessation of status failed in 13 patients in valproate group and 11 patients in levetiracetam group. Majority of the patients did not require ICU settings despite being classified as refractory.. RSE can be controlled with intravenous loading and maintenance of valproate or levetiracetam which do not cause respiratory depression, hypotension, need of intubation and ICU care. These must always be considered in a developing country scenario where ICU facilities are not always available or while transporting to centres where these facilities are available.

Topics: Adolescent; Adult; Anticonvulsants; Developing Countries; Electroencephalography; Female; Humans; India; Levetiracetam; Male; Piracetam; Status Epilepticus; Treatment Outcome; Valproic Acid; Young Adult

Status epilepticus is a condition of prolonged/repetitive seizures that often occurs in the elderly. Treatment in the elderly can be complicated by serious side effects associated with traditional drugs.. The aim of this pilot study was to evaluate the short-term efficacy/safety of intravenously administered LEV (IVLEV) as the treatment of choice for SE in the elderly.. We enrolled nine elderly patients (five female/four male; median age 78 years) with SE. Two patients had a previous diagnosis of epilepsy; in the remaining seven, SE was symptomatic. SE was convulsive in five and non-convulsive in four. All the patients presented concomitant medical conditions (arrhythmias/respiratory distress/hepatic diseases). As the traditional therapy for SE was considered unsafe, IVLEV was used as first-line therapy (loading dose of 1500 mg/100 ml/15 min, mean maintenance daily dose of 2500 mg/24 h) administered during video-EEG monitoring.. In all the patients but one, IVLEV was effective in the treatment of SE and determined either the disappearance of (7/8), or significant reduction in (1/8), epileptic activity; no patient relapsed in the subsequent 24 h. No adverse events or changes in the ECG/laboratory parameters were observed. These data suggest that IVLEV may be an effective/safe treatment for SE in the elderly.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Female; Geriatrics; Humans; Injections, Intravenous; Levetiracetam; Male; Pilot Projects; Piracetam; Status Epilepticus; Treatment Outcome

To evaluate the feasibility and safety of intravenous (iv) levetiracetam (LEV) added to the standard therapeutic regimen in adults with status epilepticus (SE), and as secondary objective to assess a population pharmacokinetic (PK) model for ivLEV in patients with SE.. In 12 adults presenting with SE, 2,500 mg ivLEV was added as soon as possible to standardized protocol, consisting of iv clonazepam and/or rectal diazepam, as needed followed by phenytoin or valproic acid. ivLEV was administered over approximately 5 min, in general after administration of clonazepam, regardless the need for further treatment. During 24-h follow-up, patients were observed for any clinically relevant side-effects. Blood samples for PK analysis were available in 10 patients. A population PK model was developed by iterative two-stage Bayesian analysis and compared to PK data of healthy volunteers.. Eleven patients with a median age of 60 years were included in the per protocol analysis. Five were diagnosed as generalized-convulsive SE, five as partial-convulsive SE, and one as a nonconvulsive SE. The median time from hospital admission to ivLEV was 36 min. No serious side effects could be related directly to the administration of ivLEV. During PK analysis, four patients showed a clear distribution phase, lacking in the others. The PK of the population was best described by a two-compartment population model. Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k(12)): 0.24 (0.12)/h, and peripheral to central (k(21)): 0.70 (0.22)/h. Mean maximal plasma concentration was 85 (19) mg/L.. The addition of ivLEV to the standard regimen for controlling SE seems feasible and safe. PK data of ivLEV in patients with SE correspond to earlier values derived from healthy volunteers, confirming a two-compartment population model.

Topics: Adult; Aged; Anticonvulsants; Bayes Theorem; Biological Availability; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Metabolic Clearance Rate; Middle Aged; Piracetam; Prospective Studies; Status Epilepticus

Topics: Adult; Anticonvulsants; Benzodiazepines; Humans; Levetiracetam; Retrospective Studies; Status Epilepticus

Convulsive status epilepticus (CSE) is the most common neurological emergency in children. It is a frequent cause of admission to pediatric intensive care units and is associated with significant short- and long-term morbidity. Management of CSE is a step-wise approach: first-line antiseizure agents (typically benzodiazepines) followed by a second-line agent before deeper anesthesia usually accompanied by intubation and ventilation. Current guidelines in the United Kingdom specify phenytoin as the second-line agent of choice for CSE. Two recent large international randomized controlled trials compared the efficacy of phenytoin with that of another second-line agent levetiracetam. Both studies found levetiracetam to be noninferior to phenytoin.. We conducted an online survey of clinicians across 67 emergency departments that treat children and 29 pediatric intensive care units in the United Kingdom and Ireland to assess their current and preferred second-line agents for treating pediatric CSE in light of recently published evidence. The survey was distributed via the Pediatric Emergency Research in United Kingdom and Ireland network and the Pediatric Critical Care Society.. We found that although most clinicians use phenytoin, as per current guidelines, they seek greater flexibility in choice of second-line agent, with levetiracetam being the preferred alternative to phenytoin.. To facilitate use of levetiracetam for treatment of CSE in pediatrics, it should be included as a second-line agent in addition to phenytoin in the next update of the National Institute for Health and Care Excellence and other United Kingdom clinical guidelines.

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

For an antiseizure medication (ASM) to be effective in status epilepticus (SE), the drug should be administered intravenously (i.v.) to provide quick access to the brain. However, poor aqueous solubility is a major problem in the development of parenteral drug solutions. Given its multiple mechanisms of action, topiramate (TPM) is a promising candidate for the treatment of established or refractory SE, as supported by clinical studies using nasogastric tube TPM administration. However, TPM is not clinically available as a solution for i.v. administration, which hampers its use in the treatment of SE. Here, we describe a novel easy-to-use and easy-to-prepare i.v. TPM formulation using the U.S. Food and Drug Administration (FDA)-approved excipient meglumine.. During formulation development, we compared the solubility of TPM in bi-distilled water with vs without a range of meglumine concentrations. Furthermore, the solubility of combinations of TPM and levetiracetam and TPM, levetiracetam, and atorvastatin in aqueous meglumine concentrations was determined. Subsequently, the pharmacokinetics and tolerability of meglumine-based solutions of TPM and TPM combinations were evaluated in rats, including animals following fluid percussion injury or pilocarpine-induced SE.. The amino sugar meglumine markedly enhances the aqueous solubility of TPM. A comparison with data on dissolving TPM using sulfobutylether-β-cyclodextrin (Captisol) demonstrates that meglumine is much more effective for dissolving TPM. Furthermore, meglumine can be used to prepare drug cocktails where TPM is co-administered with another ASM for SE treatment. The tolerability studies of the meglumine-based TPM solution and meglumine-based TPM combinations in normal rats and the rat fluid percussion injury and pilocarpine-induced SE models demonstrate excellent tolerability of the novel drug solutions. Preclinical studies on antiseizure efficacy in the SE model are underway.. In conclusion, the novel meglumine-based solution of TPM presented here may be well suited for clinical development.

Topics: Animals; Anticonvulsants; Fructose; Levetiracetam; Pilocarpine; Rats; Status Epilepticus; Topiramate

Status epilepticus (SE) is a frequent neurological emergency, derived from the failure of mechanisms responsible for seizure termination. The present study aims to compare the efficacy of the most common antiseizure medications (ASMs) employed for the treatment of benzodiazepine-refractory SE.. We performed a retrospective cohort study of all SE episodes treated in our hospital between January 2016 and December 2020. Inclusion criteria were: age ≥ 18 years; a diagnosis of status epilepticus. Exclusion criteria were: status epilepticus resolved by initial therapy with benzodiazepines; impossibility to retrieve medical records. We considered as effective the ASM that was the last drug introduced or increased in dose before termination of SE and without changes in the co-medication.. A total of 244 episodes in 219 patients were included in the study. The mean age of the final study cohort was 63.6 ± 19.2, with 108 (49%) men. In the total cohort, phenytoin (PHT) showed the highest response rate (57.6%), followed by lacosamide (LCM) (40.7%) and valproate (VPA) (39.8%). The comparative efficacy among the different drugs was significantly different (p < 0.001). In the pairwise comparisons, VPA was superior to levetiracetam (LEV) (response rate: 39.75% vs 24.71%; p = 0.004), but not to LCM. Phenytoin had a significantly higher resolution rate compared to VPA (response rate: 57.63% vs 39.75%; p = 0.02) and LEV (response rate: 57.63% vs 24.71; p < 0.001). The clinical predictors of anaesthetics administration were a disorder of consciousness upon clinical presentation, previous diagnosis of epilepsy, and younger age.. In our cohort of SE, PHT showed higher effectiveness in terminating established SE, as well as refractory SE in the subgroup of patients treated with anaesthetics.

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Cohort Studies; Female; Humans; Lacosamide; Levetiracetam; Male; Phenytoin; Retrospective Studies; Status Epilepticus; Treatment Outcome

Recommended loading doses of levetiracetam (LEV) for status epilepticus (SE) treatment have increased over time. However, this was not evidence-based, and the benefit of the increase remains unclear. The effect of different LEV loading doses on SE prognosis was explored.. This is a retrospective analysis of an SE adult registry (January 2016-December 2021), including patients receiving LEV as a second-line SE treatment. Patients were stratified according to LEV loading doses (threshold 35 mg/kg). Main outcomes were global mortality, LEV use as last SE treatment, and return to baseline conditions at discharge, exploring LEV as a dichotomized or continuous dose.. Among 202 patients, 44 received LEV at ≥35 mg/kg and 158 below it. Global mortality, adjusted for SE severity and potentially fatal aetiology, was more frequent in the high LEV dose group (27.2% vs. 17.1%, odds ratio 3.14, 95% confidence interval 1.23-8.06; p = 0.017), whilst LEV prescription as last treatment and return to baseline conditions were comparable. Considering continuous LEV dosages or mortality in ongoing SE, however, no outcome reached statistical significance.. Lower LEV loading doses do not seem to correlate with worse clinical outcome, challenging current guidelines. Further studies, ideally prospective, are needed on this topic.

Topics: Adult; Anticonvulsants; Humans; Levetiracetam; Piracetam; Prognosis; Prospective Studies; Retrospective Studies; Status Epilepticus

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

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

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

Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.. The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.. This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.. Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Child; Female; Hospitals, University; Humans; Lacosamide; Levetiracetam; Male; Medical Records; Midazolam; Middle Aged; Phenobarbital; Phenytoin; Propofol; Status Epilepticus; Valproic Acid

Prior to illustration of the causative genetic mutation responsible for Sotos syndrome, diagnosis was based on clinical criteria. They include characteristic facial gestalt, developmental delay, and evidence of overgrowth, in addition to other minor features as cardiac &genitourinary congenital malformation, seizures, scoliosis, among other features. Non-convulsive status epilepticus (NCSE) was not previously reported among Sotos patients.. An eleven-years old boy, with developmental delay, characteristic facial & skeletal features presented to the emergency department with a two-hour episode of lapse of consciousness. Electroencephalogram (EEG) showed fluctuating generalized spike-wave/poly-spike wave discharge <2.5 Hertz (Hz), lasting throughout the duration of recording. Intravenous (IV) levetiracetam was associated with clinical & EEG improvement & accordingly the patient was diagnosed as NCSE. The mother reported history of polyhydramnios, febrile seizure & developmental delay. Through clinical & radiological assessment revealed generalized hypotonia, low intelligence quotient (IQ), congenital ureteric stricture & pulmonary hypertension, prominent retro-cerebellar cistern, in addition to scoliosis & facial features suggestive of Sotos Syndrome. Six months after presentation, the patient remained seizure free on levetiracetam monotherapy.. NCSE could occur in Sotos syndrome. In our case, the first reported case of NCSE in Sotos syndrome, the characteristic facial & skeletal findings initiated further work up with fulfillment of the criteria required for the clinical diagnosis of Sotos syndrome.

Topics: Child; Electroencephalography; Humans; Levetiracetam; Male; Scoliosis; Sotos Syndrome; Status Epilepticus

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

A 75-year-old man with a history of temporal lobe epilepsy (treated with levetiracetam) was transferred to our hospital because of loss of consciousness. At admission, he was drowsy and exhibited myoclonus on the left side of face. We established a diagnosis of status epilepticus and started treatment with levetiracetam, fosphenytoin, and midazolam. FLAIR and DWI showed hyperintensity in the right cerebral cortex. Electroencephalography (EEG) showed lateralized periodic discharges (LPDs) at the right hemisphere, indicative of non-convulsive status epilepticus (NCSE). He regained consciousness after treatment with anti-epileptic drugs but showed persistent LPDs in EEG. MRI arterial spin labeling (ASL) showed normal perfusion in the right hemisphere; therefore, he was deemed to have recovered from status epilepticus and transferred to the rehabilitation hospital. MRI ASL is useful for diagnosing recovery from NCSE irrespective of sustained periodic discharges on EEG.

Topics: Aged; Electroencephalography; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Patient Discharge; Spin Labels; Status Epilepticus

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

Posterior Reversible Encephalopathy Syndrome (PRES) is characterized by acute neurological symptoms with typical imaging features, primarily in the territories of the brain supplied by the posterior circulation, probably due to vasogenic edema. Both clinical and imaging features are generally reversible. We report a 13-year-old girl affected by Nodular Sclerosis Classical Hodgkin Lymphoma stage IIIB into complete remission, with a recurrence and autologous bone-marrow transplantation, who has been treated with an anti-CD30 monoclonal antibody, brentuximab-vedotin. The girl has suddenly presented a convulsive status epilepticus, that needed intubation and sedation. Therefore, an IV therapy with levetiracetam was started. Furthermore, the girl has presented high blood pressure and reduced kidney function. Brain MRI demonstrated a diffuse PRES-like disease, that went into regression after the first week. After another week, the girl presented a new prolonged generalized tonic clonic convulsive episode, that needed intubation and sedation and an association of clobazam and levetiracetam: a new brain MRI showed a recurrence of PRES-like lesions in addition to some signs of leukoencephalopathy with brain lactate accumulation on 1H-MRS, due to cerebral energetic failure. The girl also presented a refractory arterial hypertension. After 45 days of ICU hospitalization the patient has been discharged and followed up with neurological examinations. Brain MRI and brain 1H-MRS, 5 months after patient's discharge, showed incomplete regression of cerebral white matter signal abnormalities with MRS normalization.

Topics: Adolescent; Brentuximab Vedotin; Female; Humans; Hypertension; Levetiracetam; Magnetic Resonance Imaging; Posterior Leukoencephalopathy Syndrome; Status Epilepticus

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

Topics: Aged; Anticonvulsants; Female; Humans; Levetiracetam; Myoclonus; Status Epilepticus

Levetiracetam (LEV) suppresses the upregulation of proinflammatory molecules that occurs during epileptogenesis after status epilepticus (SE). Based on previous studies, LEV likely helps prevent the onset of epilepsy after insults to the brain, unlike other conventional anti-epileptic drugs. Recently, we discovered that the increase in

Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Inflammation; Levetiracetam; Mice; Pilocarpine; Piracetam; Status Epilepticus

Acute brain inflammation after status epilepticus (SE) is involved in blood-brain barrier (BBB) dysfunction and brain edema, which cause the development of post-SE symptomatic epilepsy. Using pilocarpine-induced SE mice, we previously reported that treatment with levetiracetam (LEV) after SE suppresses increased expression levels of proinflammatory mediators during epileptogenesis and prevents the development of spontaneous recurrent seizures. However, it remains unclear how LEV suppresses neuroinflammation after SE. In this study, we demonstrated that LEV suppressed the infiltration of CD11b

Topics: Animals; Anticonvulsants; Cytokines; Disease Models, Animal; Encephalitis; Levetiracetam; Mice; Monocytes; Neutrophils; Pilocarpine; Proteome; Status Epilepticus

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

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

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

We previously showed that the antiepileptic drug levetiracetam (LEV) inhibits microglial activation, but the mechanism remains unclear. The purpose of this study was to identify the target of LEV in microglial activity suppression. The mouse microglial BV-2 cell line, cultured in a ramified form, was pretreated with LEV and then treated with lipopolysaccharide (LPS). A comprehensive analysis of LEV targets was performed by cap analysis gene expression sequencing using BV-2 cells, indicating the transcription factors BATF, Nrf-2, FosL1 (Fra1), MAFF, and Spic as candidates. LPS increased AP-1 and Spic transcriptional activity, and LEV only suppressed AP-1 activity. FosL1, MAFF, and Spic mRNA levels were increased by LPS, and LEV only attenuated FosL1 mRNA expression, suggesting FosL1 as an LEV target. FosL1 protein levels were increased by LPS treatment and decreased by LEV pretreatment, similar to FosL1 mRNA levels. The FosL1 siRNA clearly suppressed the expression of TNFα and IL-1β. Pilocarpine-induced status epilepticus increased hippocampus FosL1 expression, along with inflammation. LEV treatment significantly suppressed FosL1 expression. Together, LEV reduces FosL1 expression and AP-1 activity in activated microglia, thereby suppressing neuroinflammation. LEV might be a candidate for the treatment of several neurological diseases involving microglial activation.

Topics: Animals; Down-Regulation; Interleukin-1beta; Levetiracetam; Lipopolysaccharides; Mice; Mice, Inbred ICR; Microglia; Proto-Oncogene Proteins c-fos; RNA Interference; RNA, Small Interfering; Status Epilepticus; Transcription Factor AP-1; Transcription, Genetic; Tumor Necrosis Factor-alpha

Topics: Benzodiazepines; Humans; Levetiracetam; Phenytoin; Status Epilepticus; Treatment Outcome

Alternatives to prospective informed consent enable the conduct of paediatric emergency and critical care trials. Research without prior consent (RWPC) involves practitioners approaching parents after an intervention has been given and seeking consent for their child to continue in the trial. As part of an embedded study in the 'Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children' (EcLiPSE) trial, we explored how practitioners described the trial and RWPC during recruitment discussions, and how well this information was understood by parents. We aimed to develop a framework to assist trial conversations in future paediatric emergency and critical care trials using RWPC.. Qualitative methods embedded within the EcLiPSE trial processes, including audiorecorded practitioner-parent trial discussions and telephone interviews with parents. We analysed data using thematic analysis, drawing on the Realpe. We analysed 76 recorded trial discussions and conducted 30 parent telephone interviews. For 19 parents, we had recorded trial discussion and interview data, which were matched for analysis. Parental understanding of the EcLiPSE trial was enhanced when practitioners: provided a comprehensive description of trial aims; explained the reasons for RWPC; discussed uncertainty about which intervention was best; provided a balanced description of trial intervention; provided a clear explanation about randomisation and provided an opportunity for questions. We present a seven-step framework to assist recruitment practice in trials involving RWPC.. This study provides a framework to enhance recruitment practice and parental understanding in paediatric emergency and critical care trials involving RWPC. Further testing of this framework is required.

Topics: Anticonvulsants; Child; Critical Care; Data Collection; Emergency Service, Hospital; England; Female; Humans; Informed Consent; Levetiracetam; Male; Multicenter Studies as Topic; Parents; Phenytoin; Pragmatic Clinical Trials as Topic; Qualitative Research; Randomized Controlled Trials as Topic; Research Design; Status Epilepticus

Key challenges to the successful conduct of The Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE) trial were identified at the pre-trial stage. These included practitioner anxieties about conducting research without prior consent (RWPC), inexperience in conducting an ED-led trial and use of a medication that was not usual ED practice. As part of an embedded study, we explored parent and practitioner experiences of recruitment, RWPC and conduct of the trial to inform the design and conduct of future ED-led trials.. A mixed-methods study within a trial involving (1) questionnaires and interviews with parents of randomised children, (2) interviews and focus groups with EcLiPSE practitioners and (3) audio-recorded trial discussions. We analysed data using thematic analysis and descriptive statistics as appropriate.. A total of 143 parents (93 mothers, 39 fathers, 11 missing information) of randomised children completed a questionnaire and 30 (25 mothers, 5 fathers) were interviewed. We analysed 76 recorded trial recruitment discussions. Ten practitioners (4 medical, 6 nursing) were interviewed, 36 (16 medical, 20 nursing) participated in one of six focus groups. Challenges to the success of the trial were addressed by having a clinically relevant research question, pragmatic trial design, parent and practitioner support for EcLiPSE recruitment and research without prior consent processes, and practitioner motivation and strong leadership. Lack of leadership negatively affected practitioner engagement and recruitment. EcLiPSE completed on time, achieving its required sample size target.. Successful trial recruitment and conduct in a challenging ED-led trial was driven by trial design, recruitment experience, teamwork and leadership. Our study provides valuable insight from parents and practitioners to inform the design and conduct of future trials in this setting.

Topics: Anticonvulsants; Child; Data Collection; Emergency Service, Hospital; England; Female; Humans; Levetiracetam; Male; Multicenter Studies as Topic; Parents; Phenytoin; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design; Status Epilepticus

Although seizures are common in prehospital settings, standardized emergency medical services (EMS) treatment algorithms do not exist nationally. We examined nationwide variability in status epilepticus treatment by analyzing 33 publicly available statewide EMS protocols. All adult protocols recommend intravenous benzodiazepines (midazolam, n = 33; lorazepam, n = 23; diazepam, n = 24), 30 recommend intramuscular benzodiazepines (midazolam, n = 30; lorazepam, n = 8; diazepam, n = 3), and 27 recommend intranasal benzodiazepines (midazolam, n = 27; lorazepam, n = 3); pediatric protocols also frequently recommend rectal diazepam (n = 14). Recommended dosages vary widely, and first- and second-line agents are designated in only 18 and 2 states, respectively. Given this degree of variability, standardized national EMS guidelines are needed. ANN NEUROL 2021;89:604-609.

Topics: Administration, Intranasal; Administration, Rectal; Adult; Anticonvulsants; Benzodiazepines; Child; Cross-Sectional Studies; Diazepam; Emergency Medical Services; Humans; Injections, Intramuscular; Injections, Intravenous; Levetiracetam; Lorazepam; Midazolam; Phenobarbital; Practice Guidelines as Topic; Status Epilepticus; United States

Efficacy, safety and tolerability of lacosamide in the treatment of status epilepticus are well described. However, other evidence of its pharmacologic profile in elderly patients with other comorbidities seems warranted. We describe the case of an 80 year-old woman with an history of arterial hypertension, ischemic cardiomyopathy, COPD, CKD, previous laryngeal cancer, a stoma positioning for diverticular disease and previous surgery for a left frontal meningioma. Since then, the patient developed focal epilepsy and she was on levetiracetam and valproic acid therapy. The patient was admitted to our department for a focal status epilepticus characterized by non-fluent aphasia and right facio-brachial clonic movements. She also presented with aspiration pneumonia and started intravenous antibiotic treatment. After failure of a first-line antiepileptic drug, lacosamide intravenous treatment was started, with complete reversal of the clinical picture. EEG then showed focal slow waves mixed to interictal epileptiform discharges over the left fronto-temporal regions. The patient was then discharged home with an oral lacosamide treatment and at 3 months she was seizure-free. Our case report confirms the efficacy of lacosamide in status epilepticus, highlighting its safety and tolerability in an elderly and fragile patient with multiple comorbidities and drug therapy.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Comorbidity; Female; Humans; Lacosamide; Levetiracetam; Status Epilepticus

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

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

This study evaluated the anticonvulsant and neuroprotective effects of carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in convulsive status epilepticus (CSE) rat model. Twenty-five male Wistar rats were randomized into five groups (n = 5). Groups I and II received 0.2 ml of normal saline intraperitoneally (i.p), while groups III-V received CBZ (25 mg/kg i.p), LEV (50 mg/kg i.p) or combination of sub-therapeutic doses of CBZ (12.5 mg/kg i.p) and LEV (25 mg/kg i.p). Thirty minutes later, seizure was kindled with pilocarpine hydrochloride (350 mg/kg) in group II-V rats. Seizure indices, markers of excitotoxicity, and astroglioses were determined, while the hippocampal morphometry was also evaluated. The data was analysed using descriptive and inferential statistics, while the results were presented as mean ± SEM in graphs or tables, and the level of significance was taken at p < 0.05. The anticonvulsant treatments delayed the inception of seizure indices (p = 0.0006), while the percentage mortality decreased significantly (p = 0.0001) in all the treatment groups. The hippocampal concentrations of acetylcholine, malondialdehyde, and tissue necrotic factor-alpha decreased significantly (p = 0.0077) in all the treated group relative to the positive control. The reactive astrogliosis in the hippocampus (CA 1) increased significantly (p = 0.0001) compared with the control but abrogated in all the treatment groups relative to the positive control. The anticonvulsant and neuroprotective effects are in this order: LEV < CBZ + CBZ < CBZ. The drug efficacy is attributable to the inhibition of cholinergic transmission.

Topics: Acetylcholine; Animals; Anticonvulsants; Carbamazepine; Disease Models, Animal; Hippocampus; Levetiracetam; Male; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Status Epilepticus; Synaptic Transmission

New antiepileptic drugs (AEDs) are increasingly applied in second-line therapy of status epilepticus (SE). In our study, we analyzed the impact of the choice of second-line AEDs on the course and prognosis of SE.. This retrospective single- center study used data of an 8 year cohort of SE in adults from 2007 to 2014. Based on the year of market introduction with a cutoff at 1990, we classified AEDs as traditional or new. Prescription pattern associated differences in prognosis were measured through univariate and multivariable analysis of 3 endpoints: occurrence of refractory SE (RSE), functional outcome in survivors to discharge (good: mRS at discharge <3 or identical to admission mRS; otherwise poor), and in-hospital mortality.. From 362 SE episodes during the study period, 222 episodes were included into the study, among those 150 episodes treated with new and 72 with traditional AEDs. Use of new AEDs increased during the study period. After adjustment for confounders, treatment with new AEDs was on the one hand associated with higher rate of RSE occurrence (OR 1.95, 95 % CI 1.05-3.62, p = 0.03), but, on the other hand, also with better functional outcome at discharge (OR 2.64, 95 % CI 1.16-6.00, p = 0.02), while it was not an independent predictor of in- hospital mortality (OR 0.88, 95 % CI 0.33-2.33, p = 0.80).. Our observation that new AEDs may be associated with a higher rate of RSE development and relatively better functional outcome when adjusted for the premorbid mRS needs confirmation in prospective studies.

Topics: Aged; Anticonvulsants; Cohort Studies; Drug Prescriptions; Drug Resistant Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

Topics: Anticonvulsants; Child; Humans; Levetiracetam; Phenytoin; Research Design; Status Epilepticus

BACKGROUND Cefepime-induced neurotoxicity has been described in intensive care units (ICUs) and neuro ICU settings, occurring in patients started on cefepime for management of severe infections and sepsis. Most cases occur within 1 to 10 days after starting the drug. We publish a case that occurred on the general medical ward of a patient who had been on cefepime therapy for 4 weeks prior to admission. The aim of this study was to improve the knowledge of this serious condition to general internists as our patient was being managed on the general medical ward. CASE REPORT A 72-year-old female on prolonged intravenous antibiotics for sacral and pelvic osteomyelitis presented with acute encephalopathy and aphasia in the setting of an acute kidney injury. Due to the acute focal neurologic deficit, she was initially admitted as a stroke alert. After a negative magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG) was pursued and showed nonconvulsive status epilepticus (NCSE). NCSE was likely a result of cefepime therapy in the setting of an acute kidney injury. CONCLUSIONS Cefepime-induced neurotoxicity should be suspected in any patient on cefepime therapy who develops acute changes in mental status, myoclonus, or evidence of seizures. Risk factors for the disease include older age, renal dysfunction, critical illness, and inappropriate dosing based upon renal function. A high index of suspicion is required and delays in diagnosis are common as there are frequently multiple possible causes for altered mental status in systemically ill patients requiring treatment with broad-spectrum antibiotics.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticonvulsants; Aphasia; Brain Diseases; Cefepime; Female; Humans; Levetiracetam; Lorazepam; Osteomyelitis; Status Epilepticus

To develop and characterize a mouse model of spontaneous recurrent seizures following nerve agent-induced status epilepticus (SE) and test the efficacy of existing antiepileptic drugs.. SE was induced in telemeterized male C57Bl6/J mice by soman exposure, and electroencephalographic activity was recorded for 4-6 weeks. Mice were treated with antiepileptic drugs (levetiracetam, valproic acid, phenobarbital) or corresponding vehicles for 14 d after exposure, followed by 14 d of drug washout. Survival, body weight, seizure characteristics, and histopathology were used to characterize the acute and chronic effects of nerve agent exposure and to evaluate the efficacy of treatments in mitigating or preventing neurological effects.. Spontaneous recurrent seizures manifested in all survivors, but the number and frequency of seizures varied considerably among mice. In untreated mice, seizures became longer over time. Moderate to severe histopathology was observed in the amygdala, piriform cortex, and CA1. Levetiracetam provided modest improvements in neurological parameters such as reduced spike rate and improved histopathology scores, whereas valproic acid and phenobarbital were largely ineffective.. This model of post-SE spontaneous recurrent seizures differs from other experimental models in the brief latency to seizure development, the occurrence of seizures in 100 % of exposed animals, and the lack of damage to CA4/dentate gyrus. It may serve as a useful tool for rapidly and efficiently screening novel therapies that would be effective against severe epilepsy cases.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Levetiracetam; Mice; Nerve Agents; Phenobarbital; Soman; Status Epilepticus; Valproic Acid

Topics: Child; Double-Blind Method; Humans; Levetiracetam; Phenytoin; Status Epilepticus; Valproic Acid

Topics: Anticonvulsants; Child; Double-Blind Method; Humans; Levetiracetam; Phenytoin; Status Epilepticus; Valproic Acid

Multiple recent instances of nerve agent (NA) exposure in civilian populations have occurred, resulting in a variety of negative effects and lethality in both adult and pediatric populations. Seizures are a prominent effect of NAs that can result in neurological damage and contribute to their lethality. Current anticonvulsant treatments for NAs are approved for adults, but no approved pediatric treatments exist. Further, the vast majority of NA-related research in animals has been conducted in adult male subjects. There is a need for research that includes female and pediatric populations in testing. In this project, adult and pediatric male and female rats were challenged with sarin or VX and then treated with fosphenytoin, levetiracetam, or propofol. In this study, fosphenytoin and levetiracetam failed to terminate seizure activity when animals were treated 5 min after seizure onset. Propofol was effective, exhibiting high efficacy and potency for terminating seizure activity quickly in pediatric and adult animals, suggesting it may be an effective anticonvulsant for NA-induced seizures in pediatric populations.

Topics: Age Factors; Animals; Anticonvulsants; Brain; Disease Models, Animal; Female; Levetiracetam; Male; Organothiophosphorus Compounds; Phenytoin; Propofol; Rats, Sprague-Dawley; Sarin; Sex Factors; Status Epilepticus

Topics: Adolescent; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Emergency Treatment; Epilepsy; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Levetiracetam; Parents; Patient Care Planning; Phenytoin; Practice Guidelines as Topic; Status Epilepticus; Time Factors; Treatment Failure

Neurological complications are increasingly recognized with SARS-CoV-2, the causative pathogen for COVID-19. We present a single-center retrospective case series reporting the EEG and outcome of de novo status epilepticus (SE) in two African-American women with laboratory-confirmed SARS-CoV-2 virus. SE was the initial presentation in one asymptomatic individual. Patient 2 had COVID-19 pneumonia, and fluctuating mental status that raised the suspicion of subclinical SE. The patient with older age and higher comorbidities failed to recover from the viral illness that has no definitive treatment.

Topics: Aged; Anticonvulsants; Betacoronavirus; Black or African American; Coronavirus Infections; COVID-19; Electroencephalography; Female; Humans; Levetiracetam; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Status Epilepticus

Topics: Benzodiazepines; Humans; Levetiracetam; Phenytoin; Status Epilepticus; Treatment Outcome

Topics: Adult; Anticonvulsants; Disease Management; Drug Therapy, Combination; Epilepsy, Generalized; Female; Humans; Levetiracetam; Midazolam; Phenytoin; Status Epilepticus; Valproic Acid

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

To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation.. This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation.. We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49;. BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation.. This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.

Topics: Adolescent; Age Factors; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistant Epilepsy; Female; Guideline Adherence; Humans; Infant; Levetiracetam; Male; Multivariate Analysis; Phenobarbital; Phenytoin; Practice Guidelines as Topic; Proportional Hazards Models; Retrospective Studies; Sex Factors; Status Epilepticus; Time-to-Treatment

Organophosphorus (OP) compounds are chemical threat agents and are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that could include status epilepticus (SE). SE particularly targets the heart and brain and despite existing therapies, it is still associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular (i.m.) adjunct therapy consisting of atenolol (AT) and levetiracetam (LV) when administered after paraoxon (POX)-induced SE. The combination therapy was administered twice daily for 2, 7, or 14 days. POX exposure in rats produced rapid SE onset that was treated with atropine, pralidoxime chloride, and midazolam. Here, AT + LV therapy produced significant reductions in POX SE mortality assessed at 30 days post-SE. AT + LV therapy exhibited muscle pathology inflammation scores that were not significantly different from saline-treated controls. Pharmacokinetic analyses revealed that the i.m. route achieved faster and stabler plasma therapeutic levels for both AT and LV under OP SE conditions compared with oral administrations. Our data provide evidence of the safety and efficacy of i.m. AT + LV therapy for reducing mortality following POX SE.

Topics: Administration, Oral; Animals; Atenolol; Injections, Intramuscular; Levetiracetam; Male; Paraoxon; Rats; Rats, Sprague-Dawley; Status Epilepticus

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

Status epilepticus (SE) is a neurological emergency associated with significant morbidity and mortality. The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness.. A retrospective chart review of adult patients with SE admitted to the University of Alberta Hospital, Canada, was conducted.. Fifty-six admissions were included. Benzodiazepines (BDZs) were initially given in 89% of our patients. Following BDZs, PHT and levetiracetam were the most commonly initiated AEDs as first- and second-line agents and were deemed effective in 30/44 and 5/11 patients, respectively. Patients who received a PHT loading dose (LD) of 1000 mg were less likely to reach target levels compared with a weight-based LD ≥15 mg/kg (29% vs. 60%). Likewise, patients who received a maintenance dose (MD) of 300 mg/day were less likely to reach target compared with 400 mg/day or >5 mg/kg per day; however, this did not reach statistical significance. Three variables were found to be associated with PHT effectiveness: tonic-clonic SE (OR 5.01, 95% CI 1.02-24.7, p = 0.048), history of seizures and BMI <30 kg/m2 (OR 0.16, 95% CI 0.03-1.07, p = 0.059).. Further studies of the predictors of PHT effectiveness, specifically obesity, are necessary to help individualize care. Finally, we suggest that PHT should be loaded according to the guidelines as 20 mg/kg followed by an MD of at least 400 mg/day or >5 mg/kg per day.. Gérer les soins intensifs prodigués à des patients atteints de l’état de mal épileptique qui ont été admis dans un hôpital universitaire de niveau tertiaire Contexte: L’état de mal épileptique (status epilepticus) constitue une urgence neurologique associée à des taux notablement élevés de morbidité et de mortalité. L’objectif de cette étude a été d’examiner la gestion des soins intensifs prodigués à des patients atteints de cette complication en mettant l’accent sur des médicaments antiépileptiques. Nous avons aussi cherché à déterminer des stratégies optimales de posologie pour la phénytoïne et des indicateurs de son efficacité. Méthodes: Nous avons effectué un examen rétrospectif des dossiers de patients adultes atteints de l’état de mal épileptique qui ont été admis au University of Alberta Hospital (Canada). Résultats: Au total, cinquante-six patients admis ont été inclus dans cette étude. Soulignons que des benzodiazépines (BZD) ont été donnés à 89 % de ces patients dès leur admission. Une fois ces médicaments administrés, la phénytoïne et le lévétiracétam se sont avérés les antiépileptiques les plus couramment utilisés comme traitements de première intention et de seconde intention. À cet égard, la phénytoïne a été jugée efficace chez 30 patients sur 44 tandis que le lévétiracétam l’a été chez 5 patients sur 11. Les patients à qui l’on avait administré une dose d’attaque (loading dose) de 1000 mg de phénytoïne étaient moins susceptibles d’atteindre des cibles de traitement en comparaison avec une dose d’attaque fondée sur le poids (≥ 15 mg/kg ; 29 % contre 60 %). De même, les patients ayant reçu une dose de maintien de 300 mg par jour étaient moins susceptibles d’atteindre des cibles de traitement en comparaison avec une dose de 400 mg par jour ou > 5 mg/kg par jour. Cela dit, ces résultats n’ont pas revêtu de signification statistique valable. Il a été constaté par ailleurs que trois variables pouvaient être associées à l’efficacité de la phénytoïne: une manifestation tonico-clonique de l’état de mal épileptique (rapport des cotes 5,01; IC 95 % 1,02–24,7; p = 0,048), des antécédents de crises convulsives et un IMC < 30 kg/m2 (rapport de cotes 0,16; IC 95 % 0,03–1,07; p = 0,059). Conclusions: Des études plus poussées portant sur les prédicteurs de l’efficacité de la phénytoïne, l’obésité en particulier, demeurent nécessaires pour contribuer à individualiser les soins prodigués. Enfin, nous suggérons aussi que les doses d’attaque de phénytoïne devra

Topics: Aged; Anticonvulsants; Critical Care; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Retrospective Studies; Status Epilepticus; Tertiary Healthcare; Treatment Outcome

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

Status epilepticus (SE) is an important neurological emergency lacking adequate evidence for efficacy and safety of treatment beyond the application of benzodiazepines as first treatment step. To bridge the gap between the few pivotal trials and retrospective uncontrolled case series, we established a prospective multicenter registry recruiting patients in experienced centers in German-speaking countries. We could document 1179 episodes of 1049 patients over a period of 5 years. First data analysis showed that in the majority of the episodes, established treatment guidelines were not followed. Latency between status onset and different treatment steps were longer, and bolus doses lower than recommended. Moreover, a relevant proportion of the patients did not receive a benzodiazepine but levetiracetam as first treatment step. Although SE could be controlled in more than 90% of the episodes, lower bolus dose and longer treatment latency were associated with refractoriness of the SE in multivariate analysis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Austria; Benzodiazepines; Female; Germany; Humans; Levetiracetam; Male; Middle Aged; Prognosis; Prospective Studies; Registries; Status Epilepticus; Switzerland; Young Adult

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

To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables.. Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment.. Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups.. In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Austria; Benzodiazepines; Dose-Response Relationship, Drug; Female; Germany; Guideline Adherence; Humans; Levetiracetam; Male; Middle Aged; Multivariate Analysis; Practice Guidelines as Topic; Prognosis; Proportional Hazards Models; Prospective Studies; Registries; Status Epilepticus; Switzerland; Time Factors; Treatment Outcome; Young Adult

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

We previously reported that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam (DZP) prevents the development of spontaneous recurrent seizures. LEV suppresses increased expression levels of proinflammatory mediators during epileptogenesis after SE, but how LEV acts in neuroinflammatory processes is not yet known. In this study, we examined the effects of LEV on neuroinflammation and phagocytic microglia in vivo and in vitro and compared the effects of LEV with those of representative antiepileptic drugs valproate (VPA) and carbamazepine (CBZ). Repeated treatment with LEV for 30 days after the termination of pilocarpine-induced SE by DZP almost completely prevented the incidence of spontaneous recurrent seizures, while administration of VPA or CBZ showed no effect on the seizures. LEV clearly suppressed phagocytosis of mononuclear phagocytes, and cytokine expression was observed 2 days after SE. VPA attenuated neuroinflammation only, and CBZ showed no effect on changes after SE. Treatment with LEV significantly suppressed BV-2 microglial activation, which was defined by morphological changes, phagocytic activity and cytokine expression. By contrast, VPA and CBZ did not affect BV-2 microglial activity. In summary, LEV directly suppresses excess microglial phagocytosis during epileptogenesis, which might prevent the occurrence of spontaneous recurrent seizures after SE.

Topics: Animals; Anticonvulsants; Carbamazepine; Cells, Cultured; Cytokines; Inflammation; Levetiracetam; Male; Mice, Inbred ICR; Microglia; Phagocytes; Status Epilepticus; Valproic Acid

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

Postoperative blindness is a devastating surgical complication. Although usually associated with prolonged cardiac and prone spinal operations, it may follow other procedures as well. Postoperative blindness is most commonly caused by a vascular etiology, but it can more rarely be caused by status epilepticus. We have previously reported a case of this phenomenon following a staged spinal deformity surgery.. Here we report 2 additional cases following a skull base procedure and a single stage lumbar spine surgery. In all instances, rapid recognition that the patients' blindness was due to occipital seizures resulted in acute antiepileptiform treatment and full restoration of vision.. Although a rare phenomenon, this syndrome, first recognized and described by Tarik F. Ibrahim, should be considered in any patient with postoperative visual impairment.

Topics: Aged; Anticonvulsants; Blindness; Brain Neoplasms; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Lumbar Vertebrae; Occipital Lobe; Postoperative Complications; Skull Base; Spinal Stenosis; Status Epilepticus

The present study aims to determine qualitative outcomes of presentations with acute recurrent seizures or status epilepticus to the emergency department of our institution after the introduction of a new seizure management protocol.. We performed a retrospective analysis on two cohorts of patients for all presentations to the emergency department of our institution. Presentations were reviewed from January to July pre-protocol introduction and the same period post-protocol. Patients were included if they were treated for acute recurrent seizures or status epilepticus. The protocol applied a strict treatment regimen and used levetiracetam, valproate and phenobarbitone in place of phenytoin.. A total of 77 patients was included from the pre-protocol cohort and 72 from the post-protocol group. There was a significant reduction in intensive care unit (ICU) admission (seven patients in cohort 1 and 0 patients in cohort 2) and adverse drug reactions (18 patients in cohort 1 and four patients in cohort 2). There was a trend towards fewer deaths.. The introduction of the new seizure management protocol assessed in this study has resulted in fewer ICU admissions, adverse drug reactions and most importantly fewer patient deaths. This is likely attributable to a combination of improved efficacy of the newer antiepileptic agents and a clearly defined protocol directed therapy.

Topics: Adult; Anticonvulsants; Clinical Protocols; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Female; Humans; Levetiracetam; Male; Middle Aged; Phenobarbital; Phenytoin; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

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

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

Intravenous levetiracetam (LEV) is broadly used in the treatment of status epilepticus (SE). A loading dose is usually infused, aiming to reach quickly the range of plasma concentrations considered as therapeutic (12-46 mg/l). The aim of the study was to evaluate the response to LEV in SE, correlated exposure assessed by plasma concentration monitoring, as well as calculated exposure parameters.. We retrospectively analyzed a SE registry, including patients since 2015 with at least one available LEV plasma level measured less than 36 h after loading. A Bayesian maximum likelihood approach based on a population pharmacokinetic model was used to estimate LEV exposure parameters. We compared plasma levels and pharmacokinetics parameter estimates between responders and nonresponders. Therapeutic response was defined as SE cessation within 24 h following LEV introduction without a need for additional antiepileptic drug (AED).. We included 29 patients (45 plasma levels). Variability was salient in LEV loading doses (ranging between 17 and 38 mg/kg) and monitoring practice. There was no difference in median plasma concentrations (19.5 versus 21.5 mg/l; p = 0.71), median estimated LEV exposure (25.8 versus 37.0 mg/l; p = 0.61), peak (30.4 versus 41.5 mg/l; p = 0.36), or residual levels after loading dose (14.4 versus 20.5 mg/l; p = 0.07) between responders and nonresponders.. Levetiracetam exposure does not seem to differ significantly between responders and nonresponders; greater exposure was not associated with better outcome. Loading doses of 30 mg/kg seem, however, appropriate to quickly reach the target exposure level. The short LEV half-life makes standardized sampling measurement necessary to obtain directly interpretable LEV levels.

Topics: Administration, Intravenous; Aged; Aged, 80 and over; Anticonvulsants; Bayes Theorem; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Likelihood Functions; Male; Middle Aged; Retrospective Studies; Status Epilepticus

We explored the influence of four different efficacy criteria on the results of observational studies concerning the treatment of status epilepticus (SE) and its subtypes. We compared and contrasted the results of four different efficacy criteria for the effectiveness of phenytoin, valproate, levetiracetam, and lacosamide. Criterion 1=the last antiepileptic drug (AED) administered before SE termination. Criterion 2=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE and without changes in dosage or number of the co-medication. Criterion 3=the last drug introduced into the antiepileptic therapy or increased in dose within 24h before termination of the SE without changes in the co-medication. Criterion 4=the last drug introduced into the antiepileptic therapy within 72h before the cessation of SE even allowing changes in the co-medication. We used two-tailed χ

Topics: Acetamides; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Health Behavior; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

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

Levetiracetam has broad-spectrum activity in epilepsy. In contrast to phenytoin, levetiracetam has an ideal pharmacokinetic profile without any severe haemodynamic side effects and therefore intravenous loading of levetiracetam is commonly used in adult patients with status epilepticus, especially those who have medical problems. However, levetiracetam-induced serious adverse effects, such as thrombocytopenia and pancytopenia, have been reported in the literature. Here, we describe a case of status epilepticus after cardiac arrest treated with levetiracetam in which severe thrombocytopenia developed and was successfully managed by discontinuation of levetiracetam. Our report aims to increase awareness of this rare cause of thrombocytopenia among clinicians and provide a review of the literature.

Topics: Aged; Anticonvulsants; Female; Humans; Levetiracetam; Piracetam; Status Epilepticus; Thrombocytopenia

Topics: Adolescent; Age of Onset; Anticonvulsants; Electroencephalography; Epilepsy, Absence; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus; Valproic Acid

Topics: Acyclovir; Adrenal Cortex Hormones; Anti-Bacterial Agents; Antiviral Agents; Brain Neoplasms; Ceftriaxone; Dexamethasone; Diagnosis, Differential; Electroencephalography; Emergency Service, Hospital; Encephalitis, Herpes Simplex; Fever; Humans; Hypnotics and Sedatives; Infarction; Levetiracetam; Male; Massachusetts; Middle Aged; Phenytoin; Piracetam; Propofol; Status Epilepticus; Temporal Lobe; Tomography, X-Ray Computed; Unconsciousness; Vancomycin

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

Because of the lack of studies comparing the efficacy and safety of levetiracetam and valproate before the induction of general anesthesia in the treatment of convulsive refractory status epilepticus in children, we aimed to compare the effectiveness of these antiepileptic drugs in patients with convulsive status epilepticus admitted to the Pediatric Intensive Care Unit between 2011 and 2014. Forty-six (59%) of the 78 patients received levetiracetam, and 32 (41%) received valproate for the treatment of refractory status epilepticus. The response rate was not significantly different between the 2 groups. Although no adverse event was noted in patients who received levetiracetam, 4 (12.5%) patients in the valproate group experienced liver dysfunction (P = .025). According to our results, levetiracetam and valproate may be used in the treatment of refractory status epilepticus before the induction of general anesthesia. Levetiracetam appears as effective as valproate, and also safer.

Topics: Administration, Intravenous; Adolescent; Anticonvulsants; Child; Child, Preschool; Clinical Protocols; Critical Care; Female; Humans; Infant; Intensive Care Units, Pediatric; Levetiracetam; Male; Patient Safety; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome; Valproic Acid

Topics: Anticonvulsants; Benzodiazepines; Brain; Electroencephalography; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus; Substance-Related Disorders

Our previous study showed that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam might prevent the development of spontaneous recurrent seizures via the inhibition of neurotoxicity induced by brain edema events. In the present study, we determined the possible molecular and cellular mechanisms of LEV treatment after termination of SE. To assess the effect of LEV against the brain alterations after SE, we focused on blood-brain barrier (BBB) dysfunction associated with angiogenesis and brain inflammation. The consecutive treatment of LEV inhibited the temporarily increased BBB leakage in the hippocampus two days after SE. At the same time point, the LEV treatment significantly inhibited the increase in the number of CD31-positive endothelial immature cells and in the expression of angiogenic factors. These findings suggested that the increase in neovascularization led to an increase in BBB permeability by SE-induced BBB failure, and these brain alterations were prevented by LEV treatment. Furthermore, in the acute phase of the latent period, pro-inflammatory responses for epileptogenic targets in microglia and astrocytes of the hippocampus activated, and these upregulations of pro-inflammatory-related molecules were inhibited by LEV treatment. These findings suggest that LEV is likely involved in neuroprotection via anti-angiogenesis and anti-inflammatory activities against BBB dysfunction in the acute phase of epileptogenesis after SE.

Topics: Acute Disease; Animals; Anticonvulsants; Astrocytes; Blood-Brain Barrier; Brain Edema; Capillary Permeability; Cytokines; Disease Models, Animal; Endothelial Cells; Gliosis; Hippocampus; Levetiracetam; Male; Mice, Inbred ICR; Microglia; Neovascularization, Pathologic; Piracetam; Status Epilepticus

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

To investigate the antiepileptic and protective effects of intravenous levetiracetam (iv LEV) in the rhesus monkey model of acute status epilepticus (SE).. Thirty minutes before intraperitoneal induction of SE by Coriaria lactone (CL), rhesus monkeys were treated with LEV (15 or 150 mg/kg) delivered intravenously as a single bolus. CL dose and epileptic behavior were recorded. Electroencephalography (EEG) was performed before and during the experiment. All rhesus monkeys were killed after 1-month video monitoring and processed for pathological investigation of neuronal injury, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and glial fibrillary acidic protein (GFAP) staining.. No animal exhibited spontaneous seizures during 1-month video monitoring. Development of acute SE was significantly inhibited in the group given 150 mg/kg LEV, compared with controls and the 15 mg/kg LEV group. Delayed latency, reduction of SE duration, decreased cumulative time of tonic convulsions, slight severity of SE, and a high CL induction dose were observed in the high LEV dose group (p<0.05). The EEG showed less frequent epileptic discharges in the group administered with 150 mg/kg LEV. Hematoxylin and eosin (H&E) staining, ultrastructural examination, TUNEL and GFAP staining revealed serious damage, including neuron loss, swollen mitochondrion, and strong positivity for TUNEL in the hippocampus and thalamus of controls, whereas moderate damage in the group administered with 15 mg/kg LEV, and very mild damage in the 150 mg/kg LEV group. Gliosis was found in the hippocampus of controls, not in the LEV groups and normal rhesus monkey.. The study supports the antiepileptic and protective effect of pretreatment with intravenous LEV in rhesus monkey model with SE.

Topics: Administration, Intravenous; Animals; Anticonvulsants; Disease Models, Animal; Humans; Lactones; Levetiracetam; Macaca mulatta; Male; Neurons; Piracetam; Status Epilepticus

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

The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events.

Topics: Animals; Anticonvulsants; Brain Edema; Cell Death; Disease Models, Animal; Levetiracetam; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred ICR; Muscarinic Agonists; Neurons; Pilocarpine; Piracetam; Status Epilepticus; Time Factors

A 28 year-old man who had been diagnosed as having Dravet syndrome (DS) since his childhood by a pediatric hospital was referred to our department from the local pediatric clinic. Until then, his seizures were medically intractable, and generalized tonic-clonic convulsions had occurred monthly even when administered enough valproate, zonisamide and clorazepate. After adding levetiracetam (LEV) to his drug regimen at the age of 29, the seizures disappeared for more than one year. LEV was found to be effective in this adult patient as well as in a series of children affected with DS.

Topics: Adult; Drug Therapy, Combination; Epilepsies, Myoclonic; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus; Treatment Outcome; Valproic Acid

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

Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv).. In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale.. In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500 mg (range 110-6000 mg) per day. Median age was 66 years (range 0.7-90.3 years). The majority of patients (n=70, 75%) suffered from status epilepticus (SE, n=55, 59%) and acute seizure clusters (n=15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively.. In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Child; Child, Preschool; Female; Germany; Humans; Infant; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Registries; Status Epilepticus; Young Adult

To assess the efficacy of intravenous (IV) levetiracetam (LEV) in the treatment of status epilepticus (SE) and treatment outcomes.. This study was conducted on patients, who were classified according to the clinical characteristics of their seizures, in the emergency department, neurology, and other services of our hospital. Patients were administrated IV LEV for the treatment of their SE after failing to respond to IV diazepam.. We prospectively investigated 30 patients, 16 females and 14 males whose ages ranged between 17 and 90 years (55.6 ± 19.6). Fourteen patients had convulsive SE (CSE), 11 had nonconvulsive SE (NCSE), and 5 had epilepsia partialis continua (EPC). The patients were given IV LEV with dosages ranging between 1000 and 4000 mg/day. Twenty-nine of the patients continued to receive LEV orally as maintenance treatment. The most common etiologies were cerebrovascular diseases (n = 7) and brain tumors (n = 6). SE was terminated in 23 (76.6%) patients. In the 12 months that followed SE, 9 of our patients (30%) died and 4 patients could not be contacted. Fifteen patients reported having no adverse effects, whereas three had mild adverse effects. No major adverse effects or complications causing disability were observed in twelve patients who were unconscious.. Treatment with IV LEV is well-tolerated and effective both in focal and generalized SE. IV LEV has the combined advantage of efficacy, safety, and ease of use, which qualifies it to be the first choice after benzodiazepines (BZD) in the treatment of SE. This is the first prospective study of IV LEV treatment in status epilepticus and has the longest follow-up period, one year.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Diazepam; Drug Resistant Epilepsy; Electroencephalography; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Status Epilepticus; Treatment Failure; Treatment Outcome; Young Adult

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

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy. A male infant was born on pregnancy week 36, weighing 2.2kg. Both levetiracetam and and lacosamide were present in cord blood in levels similar to those in maternal blood. The infant was partially breast-fed and experienced poor feeding and sleepiness, starting to resolve after two first weeks. Milk samples were drawn 5 days after the delivery and a blood sample from the infant 3 days later. Lacosamide level in milk was low, resulting in an estimated relative infant dose of 1.8% of the maternal weight-adjusted daily dose in a fully breast-fed infant. This is the first case describing lacosamide use during pregnancy and lactation.

Topics: Acetamides; Adult; Anticonvulsants; Female; Fetal Blood; Humans; Infant, Newborn; Lacosamide; Levetiracetam; Male; Milk, Human; Piracetam; Pregnancy; Status Epilepticus; Venous Thrombosis

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 seizure-provoking effect of the tetracyclic antidepressant mirtazapine is not a well-known adverse effect of the drug. The authors report on a 39-year-old non-epileptic patient who had been treated for depression with the usual daily dose of mirtazapine. Having increased the daily dose of the drug from 30 to 45 milligrams he experienced a few clonic seizures of the right lower limb. This symptom and insomnia erroneously intended the patient to further increase the daily dose of mirtazapine, which immediately resulted in the evolution of focal clonic status epilepticus in the same limb. After admission, this condition was recorded by video-EEG and abolished by intravenous administration of levetiracetam after the intravenous clonazepam had been ineffective. Discontinuation of mirtazapine and administration of carbamazepine resulted in completely seizure-free state that persisted even after carbamazepine treatment was terminated. The clinical and laboratory data indicate the seizure-provoking effect of mirtazapine in the reported case.

Topics: Adult; Anticonvulsants; Antidepressive Agents, Tricyclic; Carbamazepine; Electroencephalography; Epilepsy, Partial, Motor; Humans; Levetiracetam; Male; Mianserin; Mirtazapine; Piracetam; Status Epilepticus; Video Recording

Authors assume that super-refractoriness is probably characterized by the specific pathophysiological mechanisms of status epilepticus development and can't be treated using standard treatment schemes. By the example of two clinical cases, we have analyzed the efficacy of complex treatment of super-refractory nonconvulsive and myoclonic status using intravenous valproate, central anesthetics (thiopental sodium, propofol), levetiracetam and cortexin. Preliminary results suggest that cortexin and levetiracetam as add-on to standard treatment may be vitally important drugs for the patients.. Авторы предполагают, что при суперрефрактерности, вероятно, существуют иные патофизиологические механизмы развития статуса, при которых недостаточно эффективны стандартные схемы терапии. На примере 2 клинических наблюдений проанализирована эффективность комплексной терапии суперрефрактерного бессудорожного и миоклонического статусов с использованием вальпроата для внутривенного введения, центрального анестетика (тиопентал натрия, пропофол), леветирацетама и кортексина. Предварительные результаты позволяют считать, что в этих случаях кортексин и леветирацетам в добавление к стандартной схеме терапии могут оказаться для больных жизненно важными препаратами.

Topics: Adult; Anesthetics, Intravenous; Anticonvulsants; Clinical Protocols; Drug Therapy, Combination; Electroencephalography; Female; Humans; Intercellular Signaling Peptides and Proteins; Levetiracetam; Peptides; Piracetam; Propofol; Status Epilepticus; Thiopental; Treatment Outcome; Valproic Acid; Young Adult

To compare intravenous phenytoin (PHT) and intravenous lacosamide (LCM) for treatment of status epilepticus after failure of the first and second drug.. We retrospectively identified patients from a large community hospital in northern Germany who had been diagnosed with SE between August 2008 and December 2010. Patients who had failed to respond to the first two drugs were selected for this analysis.. Forty-six patients (23 female, median age 68 years) were identified. LCM was used as third drug in 21 patients (median bolus 400 mg) and PHT in 15 patients (median bolus 1500 mg). Pretreatment was similar regarding substance groups (benzodiazepine as first line, levetiracetam as second line drug) and bolus doses. Status epilepticus was terminated in six patients (40%) of the PHT group and in seven patients (33%) of the LCM group. Four patients (27%) of the PHT group and no patient of the LCM group suffered from a relevant, treatment-related side effect during administration of the third drug.. Lacosamide and PHT showed similar success rates for treatment of SE when used after failure of benzodiazepines and levetiracetam. However, PHT was associated with relevant side effects that were not seen with LCM.

Topics: Acetamides; Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Female; Humans; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Retreatment; Retrospective Studies; Status Epilepticus; Treatment Outcome; Young Adult

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

Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE.. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration.. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions.. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Levetiracetam; Male; Piracetam; Status Epilepticus; Treatment Outcome

To study the efficacy of levetiracetam (LEV) combined with short-term clonazepam (CZP) in the treatment of electrical status epilepticus during sleep (ESES) in children with benign childhood epilepsy with centrotemporal spikes (BECCT).. Fifteen children (9 boys and 6 girls) diagnosed with BECCT with ESES, who had continuous spike-and-wave accounting for over 85% of the non-rapid eye movement sleep as monitored by 24-hours ambulatory EEG or 3-hours video EEG, were enrolled. The clinical manifestations and EEG characteristics of patients were retrospectively analyzed. These children received two months of CZP treatment in addition to oral LEV [20-40 mg/(kg·d)]. All patients were followed up for 6-18 months.. The 15 children were orally given LEV in the early stage, but showed no improvement when reexamined by EEG or had seizures during treatment. Then, they received LEV in combination with short-term CZP. Re-examinations at 1 and 6 months after treatment showed that 14 cases had significantly reduced discharge (only little discharge in the Rolandic area) or no discharge, as well as completely controlled seizure; one case had recurrent ESES and two epileptic seizures during follow-up. The recurrent case received the combination therapy again, and re-examinations 1 and 6 months later revealed normal EEG; no seizure occurred in the 8 months of follow-up.. LEV combined with short-term CZP is effective and has few side effects in treating ESES syndrome among children with BECCT.

Topics: Anticonvulsants; Child; Child, Preschool; Clonazepam; Drug Therapy, Combination; Electroencephalography; Epilepsy, Rolandic; Female; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies; Sleep; Status Epilepticus

Novel, chiral derivatives of pyrrolo[1,2-a]pyrazine with aromatic substituents at carbon C-4 were synthesized by a short synthetic sequence involving Ugi multicomponent reaction. The compounds were evaluated for their in vivo efficacy in animal models of epilepsy within the Anticonvulsant Screening Program (ASP). High activity in 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests was characteristic for meta-substituted analogs. On the other hand, efficacy of compounds in the 6 Hz model of pharmacoresistant limbic seizures was only marginally affected by the orientation of substituents in the phenyl moiety. The most active derivative, 5a, displayed an ED50 value of 32.24 mg/kg and a protective index of 6.6 (PI) in the 6 Hz test. It was also active in a pilocarpine-induced status prevention model of pharmacoresistant status epilepticus.

Topics: Animals; Anticonvulsants; Male; Mice; Pyrazines; Pyrroles; Rats; Rats, Sprague-Dawley; Status Epilepticus; Structure-Activity Relationship

Levetiracetam has been reported to be well tolerated and effective in status epilepticus (SE) refractory to benzodiazepine. Because of little preclinical or clinical data concerning the outcomes of LEV in SE-induced neuronal death and vasogenic edema, we investigated the effect of LEV on SE-induced injury in comparison to diazepam (DZP), and valproate (VPA).. Two hours after pilocarpine-induced SE, rats were given one of the following drugs; (1) DZP, (2) LEV, (3) VPA, (4) DZP+LEV, (5) DZP+VPA, and (6) DZP+oxiracetam. Three-four days after SE, neuronal damage and vasogenic edema were evaluated by Fluoro-Jade B (FJB) staining and serum-protein extravasation, respectively.. LEV (≥50 mg/kg) was effective to protect neuronal damage from SE in comparison to DZP and VPA. LEV as an add-on drug with DZP could not alleviate neuronal damage as compared to LEV alone. VPA (≥100 mg/kg) was effective to protect neuronal damage from SE, as compared to DZP. VPA as an add-on drug with DZP reduced neuronal damage, as compared to DZP alone.. These findings suggest that LEV may negatively interact with DZP, and be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment.

Topics: Animals; Behavior, Animal; Cell Death; Diazepam; Disease Models, Animal; Drug Therapy, Combination; Fluoresceins; Hippocampus; Levetiracetam; Neurons; Pilocarpine; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus; Valproic Acid

A 67-year-old woman was brought to our institution because of unconsciousness. Clinical and electrophysiological findings lead us to diagnose her with nonconvulsive status epilepticus. Initial magnetic resonance imaging revealed hyperintensity in the left cerebral cortex and the right cerebellum on diffusion-weighted image and fluid-attenuated inversion recovery (FLAIR). Single-photon emission computed tomography showed increased blood flow in the left frontal cerebrum but not in the right cerebellum. The hyperintensity in the left cerebrum on the follow-up FLAIR was still present. The contralateral cerebellum remained undamaged even though the blood flow was not increased in this region because the excitotoxicity there was far lesser than that in the cerebrum.

Topics: Aged; Anticonvulsants; Brain Waves; Cerebellum; Cerebrovascular Circulation; Diffusion Magnetic Resonance Imaging; Electroencephalography; Female; Humans; Levetiracetam; Perfusion Imaging; Piracetam; Predictive Value of Tests; Status Epilepticus; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

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

Sturge-Weber syndrome is a rare, sporadic, congenital neurocutaneous syndrome characterized by facial cutaneous vascular malformation, leptomeningeal angioma and eye abnormalities. Seizures develop during the first year of life, may become refractory to multiple anticonvulsants and status epilepticus may develop. A rare subtype of Sturge-Weber syndrome with bilateral facial vascular malformation, unilateral cerebral involvement and neonatal status epilepticus is reported here. Neonatal status epilepticus was successfully controlled with intravenous levetiracetam infusion.

Topics: Anticonvulsants; Electroencephalography; Female; Humans; Infant, Newborn; Levetiracetam; Magnetic Resonance Angiography; Piracetam; Status Epilepticus; Sturge-Weber Syndrome

As part of the development of the Neurocritical Care Society (NCS) Status Epilepticus (SE) Guidelines, the NCS SE Writing Committee conducted an international survey of SE experts.. The survey consisted of three patient vignettes (case 1, an adult; case 2, an adolescent; case 3, a child) and questions regarding treatment. The questions for each case focused on initial and sequential therapy as well as when to use continuous intravenous (cIV) therapy and for what duration. Responses were obtained from 60/120 (50%) of those surveyed.. This survey reveals that there is expert consensus for using intravenous lorazepam for the emergent (first-line) therapy of SE in children and adults. For urgent (second-line) therapy, the most common agents chosen were phenytoin/fosphenytoin, valproate sodium, and levetiracetam; these choices varied by the patient age in the case scenarios. Physicians who care for adult patients chose cIV therapy for RSE, especially midazolam and propofol, rather than a standard AED sooner than those who care for children; and in children, there is a reluctance to choose propofol. Pentobarbital was chosen later in the therapy for all ages.. There is close agreement between the recently published NCS guideline for SE and this survey of experts in the treatment of SE.

Topics: Administration, Intravenous; Adult; Anticonvulsants; Child; Consensus; Expert Testimony; Humans; Hypnotics and Sedatives; Levetiracetam; Lorazepam; Midazolam; Pentobarbital; Phenytoin; Piracetam; Propofol; Societies, Medical; Status Epilepticus; Surveys and Questionnaires; Valproic Acid

There were nearly 700,000 patients in the United States in 2010 living with brain tumor diagnoses. The incidence of seizures in this population is as high as 70% and is historically difficult to control. Approximately 30-40% of brain tumors patients who present with status epilepticus (SE) will not respond to typical therapy consisting of benzodiazepines and phenytoin (PHT), resulting in patients with refractory status epilepticus (RSE). RSE is usually treated with anesthetic doses of propofol or midazolam infusions. This therapy can have significant risk, particularly in patients with cancer.. A retrospective chart review was performed on 23 patients with primary or metastatic brain tumors whose SE was treated with intravenous PHT, levetiracetam (LEV), and oral pregabalin (PGB).. In all the patients under study, PHT or LEV was used as first-line therapy. PGB was typically used as third-line treatment. The median daily dose of PGB was 375 mg (usually divided BID or TID), and the median daily dose of LEV 3000 mg (usually divided BID). Cessation of SE was seen in 16/23 (70%) after administration of PHT, LEV, and PGB. SE was aborted, on average, 24 h after addition of the third antiepileptic drug. Only one patient in the responder group required intubation. Mortality rate was zero in the responder group. No adverse reactions to this medication regimen were observed.. Our study suggests that the administration of PHT, LEV, and PGB in brain tumor patients with RSE is safe and highly effective.

Topics: Acute Disease; Aged; Anticonvulsants; Brain Neoplasms; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pregabalin; Retrospective Studies; Status Epilepticus; Treatment Outcome

Numerous anticonvulsant agents are now available for treating status epilepticus (SE). However, a paucity of data is available to guide clinicians in the initial treatment of seizures or SE. This study describes the current strategies being employed to treat SE in the U.S.A.. Fifteen American academic medical centers completed a retrospective, multicenter, observational study by reviewing 10-20 of the most recent cases of SE at their institution prior to December 31, 2009. A multivariate analysis was performed to determine factors associated with cessation of seizures.. A total of 150 patients were included. Most patients with SE had a seizure disorder (58%). SE patients required a median of 3 AEDs for treatment. Three quarters of patients received a benzodiazepine as first-line therapy (74.7%). Phenytoin (33.3%) and levetiracetam (10%) were commonly used as the second AED. Continuous infusions of propofol, barbiturate, or benzodiazepine were used in 36% of patients. Median time to resolution of SE was 1 day and was positively associated with presence of a complex partial seizure, AED non-compliance prior to admission, and lorazepam plus another AED as initial therapy. Prolonged ICU length of stay and topiramate therapy prior to admission were negatively associated with SE resolution. Mortality was higher in patients without a history of seizure (22.2 vs. 6.9%, p = 0.006).. The use of a benzodiazepine followed by an AED, such as phenytoin or levetiracetam, is common as first and second-line therapy for SE and appears to be associated with a shorter time to SE resolution. AED selection thereafter is highly variable. Patients without a history of seizure who develop SE had a higher mortality rate.

Topics: Adult; Aged; Anticonvulsants; Benzodiazepines; Critical Care; Female; Humans; Levetiracetam; Male; Middle Aged; Multivariate Analysis; Phenytoin; Piracetam; Retrospective Studies; Risk Factors; Status Epilepticus; Treatment Outcome; United States

We present the first reported case of a rapid clinical and electroencephalographic response to intravenous levetiracetam infusion of myoclonic status epilepticus in a patient with progressive myoclonus epilepsy due to Gaucher disease. Under continuous video-EEG monitoring, the clinical myoclonic status and the electrographic ictal discharges resolved within 10 minutes after the infusion was initiated. The patient tolerated the treatment well without any reported side effects. This case suggests that levetiracetam may be a safe, effective, and well tolerated intravenous drug in patients with metabolic myoclonic status epilepticus such as Gaucher disease.

Topics: Adolescent; Anticonvulsants; Electroencephalography; Epilepsies, Myoclonic; Gaucher Disease; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus

To study the efficacy of levetiracetam (LEV) in the treatment of electrical status epilepticus during sleep (ESES) in children.. The clinical data of 27 children who were newly diagnosed with ESES and treated with LEV between August 2009 and March 2011 and who were followed up for at least 6 months were retrospectively studied.. The onset age of the 27 children ranged from 9 months to 9 years and 7 months. Partial motion seizures were found in 81% of the children in the early stage. Twenty-three children received LEV treatment after ESES was definitely diagnosed. Of the 23 children, 19 were diagnosed as epilepsy syndrome of benign childhood epilepsy with centrotemporal spikes (BECT). The age of the patients at the beginning of LEV treatment ranged from 1 year and 8 months to 11 years and 9 months. The follow- up duration was 7 to 19 months. The effective rate of LEV for seizure control was 82% and for EEG recovery it was 78% (P<0.05). The other 4 children received LEV treatment before the occurrence of ESES. Seizure control and EEG recovery were noted in two of the 4 children.. LEV treatment is efficacious, to some extent, for both seizure control and EEG recovery in children with ESES.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Electroencephalography; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Retrospective Studies; Status Epilepticus

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; Carbamazepine; Choristoma; Consciousness Disorders; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Electroencephalography; Epilepsy; Female; Fluorodeoxyglucose F18; Frontal Lobe; Headache; Humans; Levetiracetam; Middle Aged; Oxcarbazepine; Piracetam; Positron-Emission Tomography; Radiopharmaceuticals; Status Epilepticus

Topics: Anticonvulsants; Bacteriuria; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Electroencephalography; Epilepsies, Partial; Facial Paralysis; Hemiplegia; Humans; Hydrocephalus; Levetiracetam; Male; Meningitis, Listeria; Middle Aged; Piracetam; Postoperative Complications; Status Epilepticus; Stroke; Ventriculoperitoneal Shunt

Topics: Anticonvulsants; Child; Humans; Intellectual Disability; Lennox Gastaut Syndrome; Levetiracetam; Male; Piracetam; Spasms, Infantile; Status Epilepticus

Systemic injection of high doses of 11-deoxycortisol succinate had been reported to induce status epilepticus in rats and cats that was associated with paroxysmal epileptiform activity refractory to first generation antiepileptic drugs (AEDs). Using patch clamp recordings we have investigated the mechanisms of 11-deoxycortisol-induced excitability and we have discovered that this molecule accelerates the decay time of the inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors, both in neuronal cultures and in hippocampal slices. In addition, it reduces the amplitude and frequency of IPSCs. Thus, 11-deoxycortisol action on GABAergic neurotransmission may be one of the underlying causes of convulsive seizures that had been observed in rats. In the present study, we have reproduced the ability of 11-deoxycortisol to induce convulsive seizures after intravenous infusion in mice. The threshold dose of 11-deoxycortisol necessary for seizure induction was also determined (0.95 mmol/kg). Furthermore, we have established that these seizures are completely refractory to several AEDs such as phenytoin (up to 100 mg/kg), carbamazepine (up to 56 mg/kg), and valproate (up to 300 mg/kg). Levetiracetam and diazepam afforded only limited protection at high doses, 540 and 3-10 mg/kg, respectively. Interestingly, long-lasting seizures induced by 11-deoxycortisol in mice were not associated with typical neuropathological changes observed in other models of status epilepticus. We propose that 11-deoxycortisol-induced seizures may be an advantageous experimental model of drug-resistant epilepsy. Finally, better understanding of the pro-epileptic properties of 11-deoxycortisol is very important, because this endogenous steroid precursor may play a role in the pathophysiology of epilepsy. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

Topics: Animals; Anticonvulsants; Cerebellum; Cortodoxone; Dose-Response Relationship, Drug; Drug Resistance; Electroencephalography; Epilepsy; Hippocampus; Inhibitory Postsynaptic Potentials; Levetiracetam; Male; Mice; Mice, Inbred C57BL; Piracetam; Receptors, GABA-A; Status Epilepticus

Non-convulsive status epilepticus (NCSE) is an underdiagnosed clinical entity in which electrical seizures occur with subtle or no overt clinical manifestations. It can cause delayed recovery from anesthesia and constitutes an important differential diagnosis for prolonged postoperative unconsciousness. This condition can be diagnosed only by electroencephalogram (EEG), and the institution of early treatment is associated with better prognosis. This case is presented to illustrate the occurrence of this rare clinical entity in a patient who had undergone extradural surgery.. An elderly female with no history of seizures or predisposing factors for convulsions underwent an uncomplicated left frontotemporal craniotomy for excision of an extradural meningioma. She was unresponsive following surgery, which could not be explained by the imaging and laboratory investigations. A subsequent EEG demonstrated periodic epileptiform discharges in lateralized left hemispheric distribution characteristic of seizures. The seizures were not effectively prevented by prophylactic fosphenytoin; however, the patient responded slowly to intravenous levetiracetam, which is known to be a more effective treatment for NCSE. The patient had no predisposing factors for the development of seizures and was undergoing an extradural surgery.. This case illustrates NCSE and emphasizes the importance of obtaining an electro-encephalogram early following craniotomy to diagnose any changes in the patient's mental status. This case also emphasizes that institution of early treatment is important to assure better prognosis.

Topics: Aged, 80 and over; Anticonvulsants; Craniotomy; Electroencephalography; Female; Humans; Levetiracetam; Meningeal Neoplasms; Meningioma; Piracetam; Postoperative Complications; Recovery Room; Status Epilepticus

Lacosamide has been reported to have been successfully used for non-convulsive status epilepticus after benzodiazepine failure, and convulsive status epilepticus after benzodiazepine and levetiracetam failure. We report a case of simple motor status epilepticus refractory to benzodiazepines and multiple anti-epileptic medications (AEDs) over 4 days. The addition of lacosamide in combination with existing levetiracetam aborted the continuous seizure with maintenance of seizure freedom through the most recent follow-up at 4 weeks.

Topics: Acetamides; Anticonvulsants; Humans; Lacosamide; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Piracetam; Status Epilepticus

Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin being the most common first line treatment. Intravenous levetiracetam (ivLEV) is a new antiepileptic drug with interesting properties for SE.. Efficacy and effectiveness of ivLEV in SE were assessed in an observational, multicentric and retrospective study. Efficacy was defined as cessation of seizures in the 24h subsequent to starting ivLEV, with no need of any further antiepileptic drug. All patients were treated following the standard protocol (benzodiazepines plus phenytoin or valproate). ivLEV was used as add-on therapy, except in those cases with contraindication for the standard protocol, when it was administered earlier.. 40 patients were included, 57% men, with a mean age of 63 years. The most common type of SE was partial convulsive (90%). ivLEV was effective in approximately half of the patients (57.5%), in a mean time of 14.4h. ivLEV was used as add-on treatment in 26 patients (after benzodiazepines plus phenytoin, valproate or both) with an efficacy of 46.1%, and as early treatment (pretreatment with benzodiazepines or nothing) in 14 patients with an efficacy of 78.5% (p 0.048). Adverse events were observed in 15% of patients.. ivLEV was an effective antiepileptic drug for SE, but its efficacy depends on the timing of its administration, being more effective when used as early treatment, and less effective as add-on treatment.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus; Time Factors; Treatment Outcome; Young Adult

Status epilepticus is a common neurological emergency in childhood and associated with significant morbidity and mortality. Status epilepticus (SE) has been defined as continuous seizure activity lasting more than 30 min or 2 or more seizures in this duration without gaining consciousness between them. However, the operational definition has brought the time down to 5 min. Management can be broadly divided into initial stabilization, seizure termination, and evaluation and treatment of the underlying cause. Diagnostic evaluation and seizure control should be achieved simultaneously to improve outcome. Seizure termination is achieved by pharmacotherapy. Benzodiazepines are the first line drugs for SE. Commonly used drugs include lorazepam, diazepam, and midazolam. In children without an IV access, buccal or nasal midazolam or rectal diazepam can be used. Phenytoin as a second line agent is usually indicated when seizure is not controlled after one or more doses of benzodiazepines. If the seizures continue to persist, valproate, phenobarbitone or levetiracetam is indicated. Midazolam infusion is useful in refractory status epilepticus. Thiopentone, propofol or high dose phenobarbitone are considered for treatment of refractory status epilepticus. Prolonged SE is associated with higher morbidity and mortality. Long term neurological sequelae include epilepsy, behavioural problems, cognitive decline, and focal neurologic deficits.

Topics: Anticonvulsants; Benzodiazepines; Child; Clinical Protocols; Fructose; GABA Modulators; Humans; Ketamine; Levetiracetam; Midazolam; Pentobarbital; Phenobarbital; Phenytoin; Piracetam; Propofol; Status Epilepticus; Thiopental; Topiramate; Valproic Acid

Case reports suggest lacosamide may have a role in status epilepticus (SE). The purpose of this case series is to describe the use of lacosamide in refractory SE (RSE) at our institution.. Observational study of all patients admitted to the neurosciences intensive care unit with RSE who received at least one dose of lacosamide from October 2009 to September 2010.. Nine patients received lacosamide after failure of at least two other agents. Lacosamide was started a median of 2 days (range: 0-14 days) after the onset of SE. The most frequently used dosing regimen was an initial intravenous dose of 200 mg followed by 200 mg every 12 h. Most patients had received 3 (range: 2-5) AEDs prior to lacosamide. Levetiracetam was used prior to lacosamide in all cases. No patients evaluated responded to lacosamide according to our predefined criteria. One patient developed angioedema after receiving two doses; another patient developed angioedema where timing in relation to the lacosamide was unclear. Care was withdrawn in three of the nine patients for reasons unrelated to lacosamide. Lacosamide was continued at discharge on all surviving patients except in one case of angioedema.. This is the largest case series to date describing the use of lacosamide in patients with RSE. Despite the novel mechanism of action, we observed no evidence that lacosamide is effective in RSE; however, our sample size was small. Further study is needed to determine the role of lacosamide in SE, especially early in the treatment course.

Topics: Acetamides; Aged; Aged, 80 and over; Angioedema; Anticonvulsants; Drug Administration Schedule; Drug Eruptions; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Intensive Care Units; Lacosamide; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus

Phenytoin (PHT), valproic acid (VPA), or levetiracetam (LEV) are commonly used as second-line treatment of status epilepticus (SE), but comparative studies are not available.. Among 279 adult SE episodes identified prospectively in our tertiary care hospital over 4 years, we retrospectively identified 187 episodes in which PHT, VPA, or LEV were given after benzodiazepines. Patients with postanoxic SE were not included. Demographics, clinical SE features, failure of second-line treatment to control SE, new handicap, and mortality at hospital discharge were assessed. Uni- and multivariable statistical analyses were applied to compare the three agents.. Each compound was used in about one third of SE episodes. VPA failed to control SE in 25.4%, PHT in 41.4%, and LEV in 48.3% of episodes in which these were prescribed. A deadly etiology was more frequent in the VPA group, whereas SE episodes tended to be more severe in the PHT group. After adjustment for these known SE outcome predictors, LEV failed more often than VPA [odds ratio (OR) 2.69; 95% confidence interval (CI) 1.19-6.08]; 16.8% (95% CI: 6.0-31.4%) of second-line treatment failures could be attributed to LEV. PHT was not statistically different from the other two compounds. Second-line treatment did not seem to influence new handicap and mortality, whereas etiology and the SE Severity Score (STESS) were robust independent predictors.. Even without significant differences on outcome at discharge, LEV seems less efficient than VPA to control SE after benzodiazepines. A prospective comparative trial is needed to address this potentially concerning finding.

Topics: Aged; Analysis of Variance; Anticonvulsants; Chi-Square Distribution; Female; Humans; Levetiracetam; Logistic Models; Male; Middle Aged; Multivariate Analysis; Phenytoin; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Failure; Valproic Acid

To report changes of cerebral blood flow and metabolism associated with status epilepticus after cardiac arrest.. Case report.. Neurological intensive care unit in a university hospital.. An 85-year-old man resuscitated from out-of-hospital cardiac arrest underwent brain multimodality monitoring and treatment with therapeutic hypothermia.. Changes of cerebral blood flow and metabolism.. Repetitive electrographic seizure activity detected at the start of monitoring was associated with dramatic reductions in brain tissue oxygen tension and striking surges in cerebral blood flow and brain temperature. Intravenous lorazepam and levetiracetam administration resulted in immediate cessation of the seizures and these associated derangements. The lactate to pyruvate ratio was initially elevated and trended down after administration of anticonvulsants.. Brain multimodality monitoring is a feasible method for evaluating secondary brain injury associated with seizure activity after cardiac arrest.

Topics: Aged, 80 and over; Body Temperature; Brain; Cerebrovascular Circulation; Electroencephalography; Humans; Hyperemia; Hypothermia, Induced; Hypoxia, Brain; Injections, Intravenous; Intracranial Pressure; Levetiracetam; Lorazepam; Male; Out-of-Hospital Cardiac Arrest; Piracetam; Status Epilepticus

We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistance; Electricity; Electroencephalography; Ethosuximide; Female; Humans; Levetiracetam; Male; Piracetam; Sleep Stages; Sleep Wake Disorders; Status Epilepticus; Syndrome; Valproic Acid

Children with Angelman syndrome have an increased risk of developing a nonconvulsive status epilepticus. Although the urgency to treat nonconvulsive status epilepticus depends on the underlying illness, most clinicians and authors agree that treatment should be focused to rapidly terminate this condition. Until now, the use of levetiracetam to treat nonconvulsive status epilepticus in children is based only on some case reports. Our case further supports this treatment regime for a subgroup of children with a special risk of nonconvulsive status epilepticus and developmental delay.

Topics: Angelman Syndrome; Anticonvulsants; Brain; Child; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus; Treatment Outcome

Tolerance to drug treatment is a serious problem in the treatment of epilepsy. We previously showed that tolerance to levetiracetam (LEV) developed within 4 days after the start of the treatment in a rat model for spontaneous seizures after electrically induced status epilepticus. In the current study we tested whether the development of tolerance to LEV could be prevented by alternating between LEV and valproate (VPA) treatment.. Before starting the alternating therapy with LEV and VPA (3 day LEV-3 day VPA, two cycles), we assessed the efficacy of VPA monotherapy by administering VPA to chronic epileptic rats via osmotic minipumps during 7 days. The anticonvulsive effects were determined by continuous video-EEG (electroencephalography) monitoring, and the concentration of VPA and LEV was measured in plasma using gas chromatography.. VPA significantly suppressed spontaneous seizures in chronic epileptic rats for 5 days. Hereafter, seizure frequency increased to pretreatment values despite adequate VPA blood levels. Seizure duration was reduced for 6 days during treatment. Seizure severity was reduced throughout the 7-day treatment period. Alternating treatment of LEV and VPA did not prevent development of tolerance; however, seizures were suppressed significantly longer compared to VPA and LEV monotherapy.. Because alternating treatment with LEV and VPA led to a prolonged effective seizure control in the animal model, it would be worthwhile to explore the possibilities of using an alternating treatment protocol in pharmacoresistant patients in whom an effective treatment is hampered by tolerance to antiepileptic drugs.

Topics: Animals; Anticonvulsants; Dentate Gyrus; Disease Models, Animal; Drug Administration Schedule; Drug Resistance; Drug Tolerance; Electric Stimulation; Electroencephalography; Epilepsy; Epilepsy, Temporal Lobe; Humans; Levetiracetam; Male; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus; Treatment Outcome; Valproic Acid

Lacosamide (Vimpat) is a newly licensed novel antiepileptic drug. We report a case of refractory convulsive status epilepticus (CSE) that was successfully controlled with lacosamide. The 38-year-old male patient was admitted for a series of complex partial seizures with secondary generalization leading to refractory CSE. During the transport to the hospital the patient was given 22.5 mg diazepam, 12.5 mg etomidate, and 5 mg midazolam without success. An additional dose of 4 mg lorazepam and a dose of 1,500 mg levetiracetam after admission were yet without clinical effect. A further treatment with lacosamide (300 mg via percutaneous gastric fistula) resulted in complete clinical remission of the epileptic activity within 30 min. The application of lacosamide resulted in cessation of CSE and was well tolerated. To our knowledge, this is the first case of successful treatment of refractory CSE with lacosamide. Further studies are needed to evaluate the safety and efficacy of lacosamide in treatment of SE.

Topics: Acetamides; Adult; Anticonvulsants; Diazepam; Drug Resistance; Drug Therapy, Combination; Epilepsy; Etomidate; Humans; Lacosamide; Levetiracetam; Male; Midazolam; Piracetam; Practice Guidelines as Topic; Status Epilepticus; Treatment Outcome

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

We previously showed that gene expression of synaptic vesicle protein 2A (SV2A), the binding site for the antiepileptic drug levetiracetam, is reduced during epileptogenesis in the rat. Since absence of SV2A has been associated with increased epileptogenicity, changes in expression of SV2A could have consequences for the progression of epilepsy. Therefore we investigated hippocampal SV2A protein expression of temporal lobe epilepsy (TLE) patients and in rats during epileptogenesis and in the chronic epileptic phase.. SV2A immunocytochemistry and Western blot analysis were performed on the hippocampus of autopsy controls, patients that died from status epilepticus (SE), and pharmacoresistant TLE patients. In addition, in epileptic rats, SV2A expression was determined after SE during the acute, latent, and chronic epileptic phase.. In control tissue, presynaptic SV2A was expressed in all hippocampal subfields, with strongest expression in mossy fiber terminals. SV2A positive puncta were distributed in a patchy pattern over the somata and dendrites of neurons. SV2A decreased throughout the hippocampus of TLE patients with hippocampal sclerosis (HS), compared to autopsy control, SE, and non-HS tissue. In most rats, SV2A was already decreased in the latent period especially in the inner molecular layer and stratum lucidum. Similarly as in humans, SV2A was also decreased throughout the hippocampus of chronic epileptic rats, specifically in rats with a progressive form of epilepsy.. These data support previous findings that reduced expression of SV2A could contribute to the increased epileptogenicity. Whether this affects the effectiveness of levetiracetam needs to be further investigated.

Topics: Adolescent; Adult; Animals; Anticonvulsants; Blotting, Western; Child; Disease Models, Animal; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Infant; Levetiracetam; Male; Membrane Glycoproteins; Microscopy, Confocal; Middle Aged; Nerve Tissue Proteins; Piracetam; Rats; Sclerosis; Status Epilepticus; Young Adult

The objective of this study was to investigate the utility of levetiracetam (LEV) in children with refractory status epilepticus (RSE). Records of children with RSE who received LEV as adjunctive therapy were reviewed. Over a 7-year period, 11 children had received LEV for RSE. Age ranged from 2 days to 9 years (median = 2.5 months). Prior to administration of LEV, the number of anticonvulsants used to treat RSE ranged from 2 to 7 (median = 3). Starting doses of LEV ranged from 15 to 70 mg/kg (median = 30 mg/kg). LEV was felt to be of benefit in 45% (5/11) of cases, resulting in either resolution of RSE or successful weaning of patients off continuous infusions of other anticonvulsants. In 27% (3/11), response to LEV was unclear as other medications were either added or increased concomitantly with LEV use. The median latency to cessation of RSE following LEV initiation was 1.5 days (range = 1-8 days). All responding patients were on LEV doses >or= 30 mg/kg/day (median 40 mg/kg/day). No significant adverse effects of LEV were reported. LEV may be an effective and safe adjuvant therapy in children with RSE.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Resistance; Electroencephalography; Female; Humans; Infant; Injections, Intravenous; Intubation, Gastrointestinal; Levetiracetam; Male; Piracetam; Status Epilepticus

Clinical experience with intravenous levetiracetam (LEV IV) is still very limited, especially in elderly subjects. The primary objective of this retrospective observational study was to describe the efficacy and tolerability of LEV IV in older patients presenting with epileptic seizure emergencies.. Medical records of 14 older people treated with LEV IV were analysed retrospectively. All patients suffered from series of complex partial seizures or convulsive or non-convulsive status epilepticus needing emergent intravenous (IV) antiepileptic drug (AED) treatment. Nine patients were taking AED therapy when LEV IV was administered.. Mean age was 73.9 years (range 61-97). Mean dosage was 1,643 mg/day (range 500-4,000). Seizure control could be achieved in 11/14 patients (78.6%). No significant adverse events were noted besides sedation.. LEV IV was effective and well tolerated in these critically ill older patients. LEV IV seems to be a reasonable practical alternative in multimorbid older patients who need IV treatment with an AED.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Drug Tolerance; Emergencies; Epilepsy; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Levetiracetam (LEV) is approved as second line treatment for partial onset seizures in adults and children older than four years of age. Recently, an intravenous formulation was developed as an alternative to standard oral medication. We report the successful treatment of two children suffering from myoclonic status epilepticus with intravenous LEV. Intravenous application of LEV was safe and not associated with significant side effects. In conclusion, intravenous application of LEV appears to be a further option in treatment of children with myoclonic status epilepticus.

Topics: Anticonvulsants; Child; Electroencephalography; Humans; Infant; Levetiracetam; Male; Piracetam; Status Epilepticus

Utilization behavior (UB) consists of reaching out and using objects in the environment in an automatic manner and out of context. This behavior has been correlated to frontal lobe dysfunction, especially of the right hemisphere. We describe a 60-year-old woman, affected by a glioblastoma located in the right frontal region, who presented with intermittent UB of the mobile phone as the main clinical manifestation of partial complex status epilepticus. Video/EEG studies showed a striking correlation between mobile phone utilization and ictal epileptic activity. Clinical and EEG findings were markedly reduced after the introduction of antiepileptic drugs. This case study suggests that UB may be added to the symptoms described for partial seizures originating from frontal areas.

Topics: Anticonvulsants; Benzodiazepines; Brain Neoplasms; Cell Phone; Clobazam; Electroencephalography; Epilepsy, Complex Partial; Female; Frontal Lobe; Glioblastoma; Humans; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Piracetam; Status Epilepticus; Tomography, X-Ray Computed

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: Aged; Anticonvulsants; Female; Humans; Levetiracetam; Pancytopenia; Piracetam; Status Epilepticus

Panayiotopoulos syndrome (PS) represents the second commonest benign partial epilepsy of childhood. This study evaluated the effects of levetiracetam (LEV) in three children with this syndrome. All three children (aged 8, 12 and 10 years) had episodic autonomic symptoms for 4, 6 and 2 years, respectively. Symptoms duration varied between a few minutes and 5-7 days, reflecting an autonomic status epilepticus. Children previously controlled on valproate (VPA) but with recurring seizures, were given LEV (1000-2000 mg/day) initially as add-on therapy, and after as monotherapy. All three children received LEV monotherapy and remained seizure-free after 3, 3 and 2 years of treatment, respectively. One child, after 2 years seizure free, stopped LEV treatment. Now, he is asymptomatic for 2 years. LEV has shown efficacy on autonomic seizure control in three patients with PS where VPA was ineffective.

Topics: Anticonvulsants; Child; Drug Therapy, Combination; Electroencephalography; Epilepsies, Partial; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Piracetam; Status Epilepticus; Syndrome; Valproic Acid

The purpose of this study was to investigate the safety and efficacy of intravenous levetiracetam (LEV-iv) in refractory status epilepticus (SE). A retrospective chart review was performed on patients who received LEV-iv for treatment of SE (n = 36) and had failed at least one other antiepileptic drug. LEV-iv (median 3000 mg/day; range 1000-9000) was administered as a bolus loading (500-2000 mg per 30-60 min, n = 30) or as a continuous pump infusion (n = 6). SE was terminated in 69% ("responders"); 31% ("non-responders") remained in SE. Factors associated with failure were: dose escalation over 3000 mg/day, lack of bolus loading, treatment latency over 48 h, age over 80 years, non-convulsive SE with coma ("subtle SE"), periodic lateralised epileptiform discharges (PLEDs) on EEG, acute cerebral lesion and intubation narcosis. SE was terminated in all eight patients without brain lesion (p = 0.033), and in all seven patients with complex partial SE (p = 0.051). Outcome was favourable (ambulatory patients) in 48% (responders) compared with 0% (non-responders), and "adverse" (death or continuing coma/stupor) in 24% (responders) compared with 100% (non-responders). Mortality was 17% (responders 4%, non-responders 45%). No patient had cardiocirculatory side effects or worsening of SE. Two patients experienced nausea and vomiting during LEV-iv loading, leading to aspiration pneumonia in one. This study suggests that LEV-iv may be a safe and efficacious treatment of SE. Prospective and controlled trials are imperative to confirm these preliminary findings.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus; Survival Rate; Treatment Outcome

There are established drugs for the treatment of status epilepticus (SE) but their potentially hazardous side-effects are well known. Levetiracetam (LEV) is a novel anticonvulsant available for intravenous (i.v.) application. It could be an alternative when standard drugs fail or should be avoided. We retrospectively identified patients from two German teaching hospitals who were treated with LEV i.v. for SE. Their charts were reviewed regarding sociodemographic data, type, etiology, onset and duration of SE, dose of LEV, concurrent antiepileptic drugs (AED) treatment, tolerability, and outcome. Thirty-two patients (15 female) were found who were treated with i.v. LEV for SE (median age 71 years). Two patients were exclusively treated with LEV. Eight received a low and further 20 patients a high dose of benzodiazepines before LEV. Two patients were treated with LEV to enable discontinuation of narcosis. SE was generalized convulsive in five, nonconvulsive in 20, and simple focal in seven patients. Etiology was acute 13 times and remote symptomatic 16 times; three SE were of unknown etiology. Therapy was initiated within a median time of 3 h and LEV i.v. was applied within a median time of 6 h. Median LEV bolus was 2,000 mg; median total dose on day 1 was 3,500 mg. Benzodiazepines plus i.v. LEV terminated SE in 23 patients without application of additional anticonvulsants, 10 within 30 min. LEV could not terminate SE in seven patients. We documented nausea and emesis in one and elevation of liver enzymes in another patient that were likely to be attributed to LEV. LEV i.v. seems to be safe with relevant efficiency for the treatment of SE in elderly and multimorbid patients when comorbidity and respiratory insufficiency precludes high doses of benzodiazepines or phenytoin.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus; Time Factors; Treatment Outcome; Young Adult

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

To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI).. IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months.. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up.. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

Topics: Ammonia; Anticonvulsants; Blood Cell Count; Creatine; Drug Administration Schedule; Electroencephalography; Epilepsy, Partial, Sensory; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Lactic Acid; Levetiracetam; Liver; Male; Piracetam; Status Epilepticus

Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Cerebrovascular Disorders; Epilepsies, Myoclonic; Epilepsies, Partial; Female; Germany; Humans; Injections, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus

Status epilepticus is a medical emergency associated with significant morbidity and mortality.. To report our experience with the use of intravenous (IV) levetiracetam in patients with status epilepticus who had not responded to IV benzodiazepines.. A retrospective review of the clinical charts of patients with status epilepticus who were treated with IV levetiracetam from July 2007 to July 2008 in our department was performed. Data on demographics, epileptic syndrome, aetiology, treatment dosage and adverse effects were analysed. IV levetiracetam was administered over a period of 15-30 minutes; each 500 mg of levetiracetam was diluted in 100 mL of normal saline.. Thirty-four patients (19 men and 15 women, 11-90 years old) with status epilepticus were treated with IV levetiracetam. Six patients (18%) had primarily generalized status epilepticus and 28 (82%) had focal status epilepticus. The aetiologies were: vascular (47%), cryptogenic (24%), tumours (12%), metabolic (12%) and brain anoxia (6%). The indications for administering IV levetiracetam were: no response to IV phenytoin and/or IV valproic acid (53% of patients) or to avoid adverse effects, contraindications or potential interactions (47% of patients). The median loading dose of IV levetiracetam was 1000 mg and the maintenance dosage ranged from 500 to 1500 mg/12 hours (median 1000 mg/12 hours). Status epilepticus stopped in a clear temporal relationship with IV levetiracetam in 71% of patients. IV levetiracetam was especially effective in older patients with vascular status epilepticus, while cryptogenic status epilepticus, primarily generalized status epilepticus, previous therapy with IV phenytoin and/or valproic acid and status epilepticus due to brain anoxia were associated with a poor response. There were no serious adverse events documented in the patients' charts.. While waiting for large, controlled studies, our data suggest that IV levetiracetam might be an alternative for the treatment of status epilepticus, especially in elderly patients with vascular status epilepticus and concomitant medical conditions.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anticonvulsants; Child; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome; Young Adult

Topics: Adult; Anticonvulsants; Electroencephalography; Female; Humans; Infusions, Intravenous; Levetiracetam; Phenytoin; Piracetam; Status Epilepticus

We report a 23-year-old with complex partial status epilepticus, possibly related to underlying stroke-like migraine attacks after radiation therapy syndrome, that was refractory to benzodiazepines and phenytoin but was terminated by administration of intravenous levetiracetam.

Topics: Anticonvulsants; Humans; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Status Epilepticus; Young Adult

Topics: Adult; Anticonvulsants; Drug Administration Schedule; Electroencephalography; Humans; Injections, Intravenous; Levetiracetam; Male; Piracetam; Status Epilepticus

Levetiracetam (Keppra) is a new generation antiepileptic drug characterized by a unique profile of activity in experimental models of epilepsy. It also has a distinct binding site in the brain, i.e. the synaptic vesicle protein type 2 (SV2A). Levetiracetam has been reported to have antiepileptogenic and disease-modifying properties. In the present study the effects of chronic treatment with levetiracetam were assessed in rats that sustained pilocarpine-induced status epilepticus (SE). Hippocampal field potentials were recorded in vivo in anesthetized animals after 3-day washout period that followed 21-day treatment with different doses of levetiracetam (50, 150 or 300 mg/kg/day) administered via ALZET osmotic mini-pumps. Vehicle treated rats together with naive animals (not subjected to SE) were used as control groups. Chronic treatment with levetiracetam yielded clinically relevant plasma concentrations throughout the experiment with complete washout of the drug 3 days after treatment cessation. At this point in time post-SE rats chronically treated with vehicle developed clear signs of hippocampal hyperexcitability, i.e. increased amplitude of population spike (PS) recorded in the dentate gyrus and reduced paired-pulse inhibition in the CA1 area. Levetiracetam treatment dose-dependently counteracted these long-term effects of pilocarpine-induced SE. Furthermore, at the dose of 300 mg/kg/day levetiracetam restored these parameters back to control level. The present results indicate that chronic treatment with levetiracetam completely inhibits the development of hippocampal hyperexcitability following pilocarpine-induced SE.

Topics: Animals; Anticonvulsants; Dose-Response Relationship, Drug; Hippocampus; Humans; Levetiracetam; Male; Membrane Potentials; Muscarinic Agonists; Pilocarpine; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus

The emergency treatment of seizures is an important practical issue, especially the treatment of generalized convulsive status epilepticus (GCSE). Benzodiazepines or older standard antiepileptic drugs (phenobarbital, phenytoin) have typically been used as initial intravenous treatment of GCSE. As new parenteral antiepileptic drugs are developed, and more are on the horizon, questions are raised regarding their role in the treatment of status epilepticus (SE). This review discusses the evidence for the treatment of GCSE, including the newer agents (valproate, levetiracetam). We correlate the treatment of SE with our modern understanding of the underlying neurophysiology and seizure duration.

Topics: Anticonvulsants; Humans; Levetiracetam; Piracetam; Status Epilepticus; Valproic Acid

In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticonvulsants; Benzodiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Electroencephalography; Epilepsy, Complex Partial; Female; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Levetiracetam is an antiepileptic drug that was shown to be effective in various seizure types. Experience with this agent for treating status epilepticus is just emerging. To the best of our knowledge, there is no report in the literature regarding its use in children with nonconvulsive status epilepticus. We here report a liver-transplanted child with nonconvulsive status epilepticus who responded well to oral levetiracetam treatment.

Topics: Anticonvulsants; Child; Female; Humans; Immunosuppressive Agents; Levetiracetam; Liver Transplantation; Piracetam; Status Epilepticus; Tacrolimus; Treatment Outcome

Topics: Adult; Anticonvulsants; Electroencephalography; Epilepsy, Complex Partial; Humans; Infusions, Intravenous; Levetiracetam; Lorazepam; Piracetam; Retrospective Studies; Status Epilepticus; Treatment Outcome

Topics: Amines; Anesthetics, Intravenous; Anticonvulsants; Child; Comorbidity; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Male; Piracetam; Porphyria, Acute Intermittent; Propofol; Status Epilepticus

Topics: Adult; Anticonvulsants; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Refractory Period, Electrophysiological; Status Epilepticus

Status epilepticus (SE) is often followed by severe cognitive impairment, including memory impairment. Previous studies have shown that SE is associated with impairment of single cells in the hippocampus that fire action potentials when the animal is in a specific location in space, the so-called place cells, and that place cell function correlates well with performance in tasks of visual-spatial memory. Place cell patterns therefore appear to be an excellent measure of spatial memory and may serve as a tool to assess seizure-induced impairment in memory. In this study we determined the relationship between visual-spatial memory and place cell function following SE. In addition, we determined if levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can improve cognitive function and place cell firing patterns when administered following SE. SE was induced in adult male rats which were then randomized to post-SE treatment with LEV or normal saline (NS) treatment for 14 days. Non-SE control rats also were randomized to LEV or NS. Following discontinuation of LEV rats were tested for visual-spatial memory in the Morris water-maze and then underwent unit recording in the CA1 region of the hippocampus. Brains were then evaluated for cell loss and mossy fiber sprouting. SE was associated with severely impaired performance in the water-maze with SE rats demonstrating no learning over four days of testing. Paralleling this memory deficit was a marked disturbance in firing patterns of pyramidal neurons in CA1. Non-SE rats learned quickly over four days of water-maze testing and had normal pyramidal cell firing patterns. LEV had no major effects on water-maze performance or place cell function. Histopathological examination of the brains showed severe cell loss in CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV treatment resulted in less histological damage in the hippocampus but had no effect on visual-spatial function or place cell physiology in either control or SE rats.

Topics: Animals; Anticonvulsants; Behavior, Animal; Cell Death; Disease Models, Animal; Electroencephalography; Hippocampus; Levetiracetam; Male; Maze Learning; Memory Disorders; Pilocarpine; Piracetam; Random Allocation; Rats; Rats, Sprague-Dawley; Status Epilepticus; Swimming; Water

Neuronal death and dysfunction occur after status epilepticus (SE), and is associated with mitochondrial enzyme damage. We previously showed, using the rat perforant pathway stimulation model, that levetiracetam administration (LEV; 1000 mg/kg intraperitoneal) during established SE reduces seizure severity and prevents mitochondrial dysfunction. We now show that administration of the same dose of LEV after 5h SE, does not protect from mitochondrial dysfunction.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electric Stimulation; Electroencephalography; Levetiracetam; Mitochondria; Neuroprotective Agents; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus; Time Factors

Non-convulsive status epilepticus (NCSE) is characterized by continuous or recurrent, generalized or focal epileptiform activity on the electroencephalogram and diverse clinical symptoms with alterations of mental state and vigilance. NCSE is not rare but certainly under diagnosed. There is some debate about how aggressive NCSE should be treated, as high dose anticonvulsants maybe partially responsible for the morbidity and mortality of patients with NCSE. We hypothesized that levetiracetam (LEV) as a well tolerated, highly effective new anticonvulsant, may be a safe treatment option. We retrospectively analyzed all (8) patients with NCSE who received levetiracetam from our database, compared with 11 patients with NCSE treated with conventional intravenous status medication as controls. These eight patients showed a marked clinical improvement with final cessation of ictal EEG-activity and clinical symptoms of NCSE after initiation of LEV within 3 days (mean 1.5 days). The response to conventional treatment was similarly effective but there were severe side effects whereas no relevant side effects in the LEV-treated group were noticed. A long-term follow up (6-36 months from discharge) revealed six patients with a persisting reduction in seizure frequency on medication with LEV. One patient changed the anticonvulsive medication because of inefficacy and one died from other causes than epilepsy 2 months after discharge from hospital. We found no significant differences in hospitalisation time, time in intensive care unit and outcome between the LEV group and the control group. This retrospectively acquired data suggests that LEV may be a well tolerated, effective treatment option in NCSE. This highlights the need for a prospective controlled study to further elucidate the utility of LEV in the treatment of NCSE, particularly as an intravenous formulation is now available.

Topics: Aged; Aged, 80 and over; Anticonvulsants; Electroencephalography; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Levetiracetam; Middle Aged; Piracetam; Retrospective Studies; Status Epilepticus

Levetiracetam (LEV) is a structurally novel antiepileptic drug (AED) which has demonstrated a broad spectrum of anticonvulsant activities both in experimental and clinical studies. Previous experiments in the kindling model suggested that LEV, in addition to its seizure-suppressing activity, may possess antiepileptogenic or disease-modifying activity. In the present study, we evaluated this possibility by using a rat model in which epilepsy with spontaneous recurrent seizures (SRS), behavioral alterations, and hippocampal damages develop after a status epilepticus (SE) induced by sustained electrical stimulation of the basal amygdala. Two experimental protocols were used. In the first protocol, LEV treatment was started 24h after onset of electrical amygdala stimulation without prior termination of the SE. In the second protocol, the SE was interrupted after 4h by diazepam, immediately followed by onset of treatment with LEV. Treatment with LEV was continued for 8 weeks (experiment #1) or 5 weeks (experiment #2) after SE, using continuous drug administration via osmotic minipumps. The occurrence of SRS was recorded during and after treatment. In addition, the rats were tested in a battery of behavioral tests, including the elevated-plus maze and the Morris water maze. Finally, the brains of the animals were analyzed for histological lesions in the hippocampal formation. With the experimental protocols chosen for these experiments, LEV did not exert antiepileptogenic or neuroprotective activity. Furthermore, the behavioral alterations, e.g., behavioral hyperexcitability and learning deficits, in epileptic rats were not affected by treatment with LEV after SE. These data do not support the idea that administration of LEV after SE prevents or reduces the long-term alterations developing after such brain insult in rats.

Topics: Amygdala; Analysis of Variance; Animals; Anticonvulsants; Behavior, Animal; Brain Damage, Chronic; Diazepam; Disease Models, Animal; Drug Administration Schedule; Electric Stimulation; Exploratory Behavior; Female; Hippocampus; Hyperkinesis; Levetiracetam; Maze Learning; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus; Swimming; Time Factors

Status epilepticus (SE) is a medical emergency requiring prompt treatment to try to limit mortality and improve outcome. So far, newer antiepileptic drugs (AED) have not assumed a noticeable role in the treatment of SE. This may be in part due to the lack of IV forms for the newer AEDs. The IV form of Levetiracetam (IV-LEV) has recently become available and has a potential role in the treatment of SE.. We report two cases of non-convulsive SE that responded favorably to IV-LEV. The first patient is an 83-year-old male with a history of complex partial seizure disorder who presented with impaired consciousness. The second patient is an 82-year-old male with history of old left middle cerebral artery ischemic infarction, who presented with confusion. Both patients were found to have a non-convulsive status epilepticus on electroencephalography (EEG) and treated with IV-LEV. In both cases, electrographic SE stopped with marked clinical improvement. Both patients tolerated the medication well and no significant side effects occurred.. IV-LEV may have a potential role in the treatment of non-convulsive status epileptics.

Topics: Aged, 80 and over; Anticonvulsants; Electroencephalography; Humans; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Status Epilepticus

The authors report the case of a child with cerebral palsy and refractory epilepsy who developed nonconvulsive status epilepticus without acute medical cause treated successfully with levetiracetam. In accordance with other studies whose authors hypothesized that aggressive treatment may worsen the prognosis in elderly patients with nonconvulsive status epilepticus, the present authors successfully used a more conservative approach to the treatment of nonconvulsive status epilepticus in their patient. This case suggests that levetiracetam is a useful option for the treatment of nonconvulsive status epilepticus in childhood, in accordance with some authors who have described the anticonvulsant effects of levetiracetam in experimental status epilepticus and in status epilepticus in adults and in children with continuous spike waves during slow sleep.

Topics: Anticonvulsants; Child; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus

Cortical laminar necrosis (CLN) is radiologically defined as high intensity cortical lesions on T1 weighted MRI images following a gyral distribution. Histopathologically, CLN is characterised by pannecrosis of the cortex involving neurones, glial cells, and blood vessels. It has been reported to be associated with hypoxia, metabolic disturbances, drugs, and infections. We present two patients who developed CLN and permanent neurological deficits after prolonged and repeated focal status epilepticus. The possible mechanisms leading to CLN in these patients are discussed, together with the implications of prompt and aggressive treatment in similar cases.

Topics: Adult; Anticonvulsants; Aphasia, Wernicke; Brain Diseases; Cerebral Cortex; Functional Laterality; Hemianopsia; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Middle Aged; Necrosis; Paresis; Phenytoin; Piracetam; Status Epilepticus; Tomography, Emission-Computed, Single-Photon

Six patients with status epilepticus (SE) of various etiologies refractory to at least two antiepileptic drugs (AEDs) had complete cessation of their seizures following administration of oral levetiracetam (LEV). Seizure types included convulsive, focal, and nonconvulsive status epilepticus. Effective doses of levetiracetam ranged from 500 to 3000 mg/day, achieving seizure control within 12-96 h. No significant adverse events were noted. Adjunctive levetiracetam should be considered for patients with status epilepticus unresponsive to initial therapy.

Topics: Adolescent; Adult; Aged, 80 and over; Anticonvulsants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus

To report 2 cases of nonconvulsive status epilepticus (NCSE) following infusion of ifosfamide.. Two patients who received ifosfamide-containing chemotherapy developed NCSE. One woman received ifosfamide 1000 mg/m2 (1 h infusion on days 1-5); confusion, lethargy, and speech deterioration developed on day 3. The second patient developed similar symptoms on day 3 of treatment with 2500 mg/m2. Both patients responded to intravenous administration of diazepam 10 mg and were given levetiracetam as maintenance therapy.. The severity and presentation of central nervous system toxicity due to ifosfamide varies greatly and involves a spectrum ranging from subclinical electroencephalogram changes to coma. NCSE, an epileptic disorder in which typical convulsive activity is absent, has previously been reported in only 4 patients receiving ifosfamide. Levetiracetam may be used for maintenance antiepileptic therapy after diazepam administration.. Among the many presentations of ifosfamide neurotoxicity, clinicians should consider NCSE as a possible explanation for changes in consciousness in a patient receiving this agent. An objective causality assessment by use of the Naranjo probability scale revealed that NCSE due to ifosfamide was probable.

Topics: Anticonvulsants; Antineoplastic Agents, Alkylating; Diazepam; Female; Humans; Ifosfamide; Levetiracetam; Middle Aged; Neoplasms; Piracetam; Status Epilepticus

The use of new antiepileptic drugs for treatment of status epilepticus (SE) has not been studied systematically, particularly with respect to response predictors, the possibility of a dose-response relationship, and the efficacy of administration through a nasogastric tube. We analyzed 23 patients with SE treated with levetiracetam (LEV). The median daily dose of LEV was 2000 mg (range: 750-9000 mg). Ten patients (43%) responded; all had received LEV within 4 days after the beginning of their SE episode (P=0.019 vs nonresponders), and were administered less than 3000 mg LEV/day (P=0.046). No demographic or etiological variable was predictive. Among 16 patients given LEV through a nasogastric tube, administration was successful in 5; blood levels in 2 nonresponders were within or above the range 5-30 microg/mL. These data suggest that LEV may be a useful alternative in SE if administered early, even in intubated patients, and that escalating the dosage beyond 3000 mg/day will unlikely provide additional benefit.

Topics: Administration, Oral; Anticonvulsants; Dose-Response Relationship, Drug; Female; Humans; Intubation, Gastrointestinal; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Retrospective Studies; Status Epilepticus; Treatment Outcome

To assess the anticonvulsant activity of the novel antiepileptic drug, levetiracetam (LEV) in a model of self-sustaining limbic status epilepticus, and to measure the consequence of LEV treatment on the pattern of mitochondrial dysfunction known to occur after status epilepticus (SE).. The rat perforant pathway was stimulated for 2 h to induce self-sustaining status epilepticus (SSSE). Stimulated rats were assigned to one of three treatment groups, receiving intraperitoneal injections of saline, 200 mg/kg LEV, or 1,000 mg/kg LEV, 15 min into SSSE and at 3 times over the next 44-h period. All animals received diazepam after 3-h SSSE to terminate seizures. Forty-four hours later, the hippocampi were extracted and prepared for electrochemical high-performance liquid chromatography (HPLC), to measure reduced glutathione levels, and for spectrophotometric assays to measure activities of mitochondrial enzymes (aconitase, alpha-ketoglutarate dehydrogenase, citrate synthase, complex I, and complex II/III). These parameters were compared between treatment groups and with sham-operated rats.. LEV administration did not terminate seizures or have any significant effect on spike frequency, although rats that received 1,000 mg/kg LEV did exhibit improved behavioral seizure parameters. Significant biochemical changes occurred in saline-treated stimulated rats compared with shams: with reductions in glutathione, alpha-ketoglutarate dehydrogenase, aconitase, citrate synthase, and complex I activities. Complex II/III activities were unchanged throughout. Rats that received 1,000 mg/kg LEV had significantly improved biochemical parameters, in many instances, comparable to sham control levels.. Despite continuing seizures, administration of LEV (1,000 mg/kg) protects against mitochondrial dysfunction, indicating that in addition to its antiepileptic actions, LEV may have neuroprotective effects.

Topics: Aconitate Hydratase; Animals; Anticonvulsants; Chromatography, High Pressure Liquid; Citrate (si)-Synthase; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Electroencephalography; Epilepsy; Glutathione; Hippocampus; Levetiracetam; Male; Mitochondria; Mitochondrial Diseases; Neurons; Neuroprotective Agents; Perforant Pathway; Piracetam; Rats; Rats, Sprague-Dawley; Status Epilepticus

We report on a 3-year-old boy with myoclonic-astatic epilepsy who developed myoclonic status epilepticus with continuous twitching of the face and unresponsiveness under monotherapy with levetiracetam. Recently, a nonconvulsive status epilepticus in an adult epilepsy patient has also been described. Our observation points to the possibility of a causal relationship between the induction of myoclonic status by levetiracetam in certain patients with Doose's syndrome. However, a spontaneous evolution cannot be excluded. Levetiracetam is a well-known drug for the control of myoclonic seizures. A controlled study would provide a better understanding of any possible aggravating role in certain forms of myoclonic-astatic epilepsy.

Topics: Anticonvulsants; Behavior; Child, Preschool; Electroencephalography; Electromyography; Epilepsies, Myoclonic; Ethosuximide; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus

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

In several studies the efficacy and tolerability of levetiracetam (LEV) have been demonstrated. We report two patients who developed nonconvulsive status epilepticus on treatment with LEV. Both patients never experienced status epilepticus before. One patient had a symptomatic epilepsy with complex partial seizures following radiotherapy of astrocytoma in 1985; the second patient had complex partial seizures due to mesial temporal sclerosis. Both patients received LEV 2000 mg/day. We postulate a correlation between occurrence of nonconvulsive status and treatment with LEV. This has not been described before apart from a single report of mentally retarded patients with status epilepticus on high dosages of LEV.

Topics: Adult; Aged; Anticonvulsants; Electroencephalography; Humans; Levetiracetam; Male; Piracetam; Status Epilepticus; Treatment Outcome

Treatment of status epilepticus (SE) has changed little over the last two decades, but the burden of this condition remains important. There is thus a need for alternative pharmacological therapies. Levetiracetam (LEV) has a wide spectrum of action and a favorable pharmacokinetic profile; however, little data exist regarding its use in SE. We identified patients with SE who received LEV, in a database comprising 127 SE episodes. Demographic, clinical and pharmacological data were analyzed, and compared to a control group consisting of 2 subjects from the database for each LEV patient, matched for age and sex. We identified 13 SE episodes occurring in 12 patients (10% of the database). Demographic, etiologic and clinical characteristics and outcome did not differ between the groups. Daily LEV dose ranged between 1,000-6,000 mg. Three patients were probable responders (23%), 1 responded to the treatment but subsequently died (8%), 4 were non-responders (31%, 1 died), and 5 had an undetermined response (38%). LEV may represent a useful alternative in the treatment of SE, particularly if a parenteral form of administration becomes available; to better define its role in this setting, prospective studies are needed.

Topics: Adult; Aged; Aged, 80 and over; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Status Epilepticus; Treatment Outcome

Status epilepticus (SE) is a neurological emergency, with high mortality and high morbidity among survivors, and novel therapeutic agents are needed to improve this picture. We examined the effects of the antiepileptic drug levetiracetam (LEV) in an experimental model of self-sustaining status epilepticus (SSSE), induced in rats by electrical stimulation of the perforant path. LEV's unique spectrum of anticonvulsant activity, very high therapeutic index, and neuroprotective properties, make it a potentially interesting agent in the treatment of SE. Pretreatment with LEV intravenously reduced (30 mg/kg) or prevented (50-1000 mg/kg) the development of self-sustaining seizures. Treatment during the maintenance phase of SSSE diminished (at 200 mg/kg) or aborted seizures (in doses of 500 or 1000 mg/kg). Addition of LEV significantly enhanced the anticonvulsant effects of diazepam (DZP), even when both drugs where given in doses far below their therapeutic level. We conclude that LEV deserves further evaluation in the treatment of status epilepticus.

Topics: Action Potentials; Animals; Anticonvulsants; Diazepam; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electric Stimulation; Levetiracetam; Male; Piracetam; Rats; Status Epilepticus