levetiracetam and Epilepsy--Absence

To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).. Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.. We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.. This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Topics: Adolescent; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Ethosuximide; Hormones; Humans; Infant; Lamotrigine; Levetiracetam; Network Meta-Analysis; Nitriles; Odds Ratio; Piracetam; Pyridones; Spasms, Infantile; Treatment Outcome; Triazines; Valproic Acid

To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.. A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003.. Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Topics: Acetates; Adolescent; Adult; Age Factors; Amines; Antipsychotic Agents; Carbamazepine; Child; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Drug Approval; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Tiagabine; Topiramate; Triazines; United States; United States Food and Drug Administration; Zonisamide

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

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

To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy.. Patients were randomized in a 2:1 ratio to receive de novo monotherapy with levetiracetam (up to 30 mg/kg/day) or placebo for 2 weeks under double-blind conditions. Responder status (primary end point) was defined as freedom from clinical seizures on days 13 and 14 and from electroencephalographic (EEG) seizures during a standard EEG recording with hyperventilation and intermittent photic stimulation on day 14. The double-blind phase was followed by an open-label follow-up.. Nine of 38 patients (23.7%) were responders in the levetiracetam group, compared with one of 21 (4.8%) in the placebo group (p = 0.08). Seven of 38 patients (18.4%) were free from clinical and EEG seizures during the last 4 days of the trial (including 24-h EEG monitoring on day 14) compared with none of the patients treated with placebo (p = 0.04). Seventeen patients remained seizure-free on levetiracetam after 1 year follow-up. Of the 41 patients who discontinued levetiracetam due to lack of efficacy (n = 39) or adverse events (n = 2), 34 became seizure-free on other treatments.. Although superiority to placebo just failed to reach statistical significance for the primary end point, the overall findings are consistent with levetiracetam having modest efficacy against absence seizures. Further controlled trials exploring larger doses and an active comparator are required to determine the role of levetiracetam in the treatment of absence epilepsy.

Topics: Adolescent; Age Factors; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Drug Resistance; Epilepsy, Absence; Female; Humans; Levetiracetam; Male; Outcome Assessment, Health Care; Piracetam

To assess the efficacy and tolerability of adjunctive levetiracetam in idiopathic generalized epilepsy (IGE) syndromes with onset during adolescence: juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and generalized tonic-clonic seizures on awakening (GTCSA).. Supplementary analysis of two double-blind, placebo-controlled trials. Patients received levetiracetam (target dose: adults 3000 mg/day; children 60 mg/kg/day; n=15 JAE, 78 JME, and 22 GTCSA) or placebo (n=12 JAE, 89 JME, and 27 GTCSA) for 16-24 weeks (including 4-week uptitration) in addition to 1-2 antiepileptic drugs.. Responder rates (> or =50%) were significantly higher for levetiracetam versus placebo for JAE (53.3% vs. 25.0%; p=0.004), JME (61.0% vs. 24.7%; p<0.001), and GTCSA (61.9% vs. 29.6%; p=0.024). Seizure freedom rates were significantly higher for levetiracetam versus placebo for JME (20.8% vs. 3.4%; p=0.002); differences between treatment groups for JAE (33.3% vs. 8.3%; p=0.15) and GTCSA (23.8% vs. 11.1%; p=0.45) appeared to be clinically relevant, but did not reach statistical significance. The most frequent adverse events on levetiracetam were headache (levetiracetam 16.8% and placebo 14.8%) and somnolence (levetiracetam 9.7% and placebo 3.9%).. Adjunctive levetiracetam was well tolerated and provided effective seizure control over 16-24 weeks in patients with insufficiently controlled IGE syndromes with onset during adolescence (JAE, JME, and GTCSA), supporting levetiracetam's broad spectrum of efficacy.

Topics: Adolescent; Adult; Age Factors; Aged; Anticonvulsants; Dose-Response Relationship, Drug; Double-Blind Method; Epilepsy, Absence; Epilepsy, Generalized; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Piracetam; Young Adult

The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty-one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrollment into the study were 8 years 9 months (SD 0.9) and 5 years 1 month to 13 years respectively. All patients were carefully evaluated at 6 months from baseline, and 12 patients were also re-evaluated at 12 months after the beginning of therapy with levetiracetam. At the 6-month evaluation, out of 21 patients studied, 11 were seizure free and one showed 'decreased' seizures (more than 50% reduction in seizures). A less than 50% reduction in seizures was observed in nine patients. At the 12-month evaluation, 10 patients were completely seizure free and two were seizure free with some anomalies in electroencephalograms. Two patients who had shown no improvement at 6 months had decreased seizures at the second follow-up. Our results suggest that monotherapy with levetiracetam could be effective and well tolerated in patients with childhood absence epilepsy and juvenile absence epilepsy. Prospective, large, long-term double-blind studies are needed to confirm these findings.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Double-Blind Method; Electrocardiography; Electroencephalography; Epilepsy, Absence; Female; Humans; Levetiracetam; Male; Piracetam; Prospective Studies

Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA.. Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50-60 mg/kg/day in two doses. Treatment period included a 5-6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic-clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests.. Thirty-five patients (23 F) with a mean age of 19 +/- 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 +/- 8.2. Twenty-one patients experienced GTCS (median number/month: 1 +/- 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had > or =75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 +/- 18.5 months.. Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings.

Topics: Adolescent; Adult; Anticonvulsants; Child; Comorbidity; Drug Therapy, Combination; Epilepsies, Myoclonic; Epilepsy, Absence; Epilepsy, Reflex; Eyelids; Female; Follow-Up Studies; Humans; Levetiracetam; Male; Myoclonus; Pilot Projects; Piracetam; Syndrome; Treatment Outcome

Clinical experience in open-label studies and anectodal reports suggest that levetiracetam is effective in generalized epilepsy. In this open-label prospective study, 19 patients (3 men, 16 women) affected by idiopathic generalized epilepsy were followed for at least 6 months following the introduction of levetiracetam. Patients were categorized according to syndrome subtype: juvenile myoclonic epilepsy (8), juvenile absence epilepsy (5), childhood absence epilepsy (4), and eyelid myoclonia with absences (2). Eleven patients received levetiracetam as monotherapy, eight as add-on therapy. Effectiveness was demonstrated in 18 patients: 13 became seizure-free (five juvenile myoclonic epilepsy, five juvenile absence epilepsy, three childhood absence epilepsy), and five achieved significant reductions in seizure frequency (three juvenile myoclonic epilepsy, one childhood absence epilepsy, one eyelid myoclonia with absences). Only one patient experienced no change in seizure frequency (eyelid myoclonia with absences). Clinical improvement was accompanied by EEG abnormality suppression or reduction. Levetiracetam was well tolerated; no patient reported side-effects.

Topics: Anticonvulsants; Electroencephalography; Epilepsy, Absence; Female; Humans; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Piracetam; Prospective Studies; Treatment Outcome

The aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy.. A total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy.. Initial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice.. Most of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy.

Topics: Adult; Aged; Anticonvulsants; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Expert Testimony; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Oxcarbazepine; Republic of Korea; Surveys and Questionnaires; Treatment Outcome; Valproic Acid; Young Adult

Levetiracetam is prescribed for a broad spectrum of seizure types but does not have a specific indication for absence epilepsy. We hypothesized that levetiracetam is commonly prescribed for children with absence epilepsies and evaluated the efficacy of this medication for absence epilepsy treatment in clinical practice. We also hypothesized that electroencephalographic (EEG) findings could help predict levetiracetam efficacy.. We reviewed the charts of all patients treated for new-onset absence epilepsies at our pediatric neurology clinic between January 2011 and January 2016. Among 158 children diagnosed with absence epilepsies, 72 were treated with levetiracetam.. Levetiracetam was discontinued in 74% (n = 53/72) because of incomplete seizure control (59%, n = 35/72) and/or intolerable side effects (41%, n = 24/72) after a median 8.5 months (interquartile range 2, 17 months). Among patients for whom levetiracetam was effective, 44% (n = 8/18) had polyspikes on their initial EEG, versus 27% (n = 14/52) of patients for whom levetiracetam was discontinued ( P = .17). The maximal prescribed dose was lower for children in whom levetiracetam was effective (29 ± 13 mg/kg/d) than those for whom levetiracetam failed (42 ± 20 mg/kg/d; P = .005).. In routine clinical practice, levetiracetam is often chosen for patients with absence seizures. However, only about one-quarter of children with absence epilepsy in this study became seizure free with levetiracetam. When effective, levetiracetam can control absence epilepsy at a relatively low dose. Lack of seizure control requiring continued dose escalation should prompt early consideration of a therapeutic medication transition.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsy, Absence; Female; Humans; Infant; Levetiracetam; Male; Retrospective Studies; Treatment Outcome

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

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

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

We report on a 25 year old female patient who had a diagnosis of Jeavons syndrome since her childhood. Although valproate led to seizure freedom, she developed persistent reproductive endocrine disorders attributed to this drug. The withdrawal of valproate in parallel with an initiation of levetiracetam monotherapy resulted in a maintenance of clinical remission and a resolution of these abnormalities. This case together with relevant literature data supports the view that the use of levetiracetam might be of benefit for female patients with Jeavons syndrome.

Topics: Adult; Anticonvulsants; Epilepsy, Absence; Female; Humans; Levetiracetam; Myoclonus; Piracetam

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Topics: Age of Onset; Anticonvulsants; Child, Preschool; Electroencephalography; Epilepsy, Absence; Humans; Levetiracetam; Male; Piracetam; Seizures; Treatment Outcome; Valproic Acid

A combination of valproates in dose 15-25 mg per day and levetiracetam in dose 20-25 mg per day was used in the treatment of 23 patients with different forms of epilepsy (juvenile myoclonic epilepsy, juvenile absence epilepsy, convulsive idiopathic generalized epilepsy and children absence epilepsy). The use of these drugs was effective in all forms of epilepsy. There were positive changes in the frequency of seizures and epileptic activity in the EEG.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Therapy, Combination; Epilepsy, Absence; Epilepsy, Generalized; Female; Humans; Levetiracetam; Male; Myoclonic Epilepsy, Juvenile; Piracetam; Treatment Outcome; Valproic Acid; Young Adult

Depression is most commonly associated with epilepsy. Recent reports have suggested a putative relationship between seizure development and onset of depressive behavior, whereas others proposed that two clinical entities might represent different neuropathologic aspects of the same neurologic disorder. The WAG/Rij rat absence epilepsy model has also been proposed as a suitable model to test antidepressant drugs. We previously reported on a long-term study of two antiepileptic drugs (AEDs) to assess their protective role in absence epileptogenesis. Here, we examined the effects of long-term treatment with several AEDs on absence seizure development and onset of depressive-like behavior in WAG/Rij rats at different ages, using a forced swimming test (FST).. Animals were divided into one untreated control group and four test groups, given ethosuximide, levetiracetam, zonisamide, or carbamazepine. Electroencephalography (EEG) readings were recorded at 6.5 months of age.. Ethosuximide-treated animals showed significant reductions in recorded spike-wave discharges (SWDs), and FST immobility time (IT) compared with untreated same age controls. However, zonisamide- and carbamazepine-treated animals had IT values similar to those of controls, but only zonisamide significantly decreased absence seizure development. Carbamazepine increased SWD incidence. Levetiracetam also protected against seizure development, while augmenting IT, suggesting a prodepressive effect.. Although treatment with ethosuximide, levetiracetam, or zonisamide reduced appearance of SWDs in WAG/Rij rats, this was not generally linked to a reduced onset of depressive characteristics, as assessed by FST. Therefore, expression of depressive-like behavior seems unrelated to seizure control in this model. Some possible alternative explanations for the observed data are discussed.

Topics: Animals; Anticonvulsants; Brain; Carbamazepine; Depression; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Absence; Ethosuximide; Isoxazoles; Levetiracetam; Male; Piracetam; Rats; Rats, Wistar; Seizures; Zonisamide

Recent data have reported the effectiveness of levetiracetam (LVT) on generalized seizures. Among them, it seems that LVT can be successfully used to treat absence seizures. Many antiepileptic drugs (AEDs) have been occasionally reported to paradoxically aggravate some seizures. We retrospectively identified patients with aggravation of absence seizures using LVT from the databases of 2 pediatric neurology departments (Robert-Debré, Paris and Amiens; France). We also used the prospective data from an open-label clinical trial performed in a third pediatric neurology department (Necker, Paris; France). We included 6 patients: n = 2 childhood absence epilepsy, n = 3 juvenile absence epilepsy and n = 1 epilepsy with myoclonic absences. All of them have had an aggravation of the absences with a causal and temporal relationship between introduction of the drug and the detrimental effect. The aggravation disappeared when LVT was decreased or was withdrawn. This report highlights that LVT may aggravate epilepsy with absence seizures.

Topics: Anticonvulsants; Child; Child, Preschool; Electroencephalography; Epilepsy, Absence; Female; France; Humans; Levetiracetam; Male; Piracetam; Retrospective Studies

Perioral myoclonia with absences belongs to the "idiopathic generalised epilepsy syndromes in development", currently not yet cited in the ILAE classification. This epilepsy syndrome is associated with a seizure type that appears to be specific. Here, we report polygraphic recordings of this seizure type in a young boy, previously misdiagnosed with focal epilepsy. EEG and clinical features were useful to differentiate diagnosis of his seizures from other absence or myoclonic seizures. Interestingly, some seizures were associated with neck myoclonia. Home video recording of myoclonic status aggravated by inappropriate treatment is also presented. [Published with video sequences].

Topics: Anticonvulsants; Brain; Carbamazepine; Child; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Absence; Humans; Levetiracetam; Magnetic Resonance Imaging; Male; Oxcarbazepine; Piracetam

Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow-up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range: 11 months to two years; follow-up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure-free without AEDs, three were seizure-free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early-onset CAE is not a homogeneous condition. The debate as to whether early-onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early-onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.

Topics: Age Factors; Age of Onset; Anticonvulsants; Child; Child Development; Child, Preschool; Cohort Studies; Disease Progression; Drug Therapy, Combination; Electroencephalography; Epilepsy, Absence; Ethosuximide; Female; Follow-Up Studies; Humans; Lamotrigine; Language Development Disorders; Levetiracetam; Male; Piracetam; Prognosis; Prospective Studies; Sex Factors; Treatment Outcome; Triazines

Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long-term treatment with some established antiabsence drugs might prevent the development of seizures, and whether such an effect could be sustained.. WAG/Rij rats were treated for ∼3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad-spectrum AED with antiabsence and antiepileptogenic properties).. We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model.. These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.

Topics: Age Factors; Analysis of Variance; Animals; Anticonvulsants; Chromatography, High Pressure Liquid; Disease Models, Animal; Epilepsy, Absence; Ethosuximide; Levetiracetam; Male; Piracetam; Rats; Rats, Mutant Strains; Time Factors

Levetiracetam (LEV) is known to inhibit convulsive seizures and is clinically used for treating both partial and generalized seizures. The study was performed to determine whether LEV possesses an inhibitory effect on absence seizures in a novel genetic animal model of absence epilepsy, Groggy (GRY) rats. Single injections of LEV at doses ranging from 20 to 160 mg/kg i.p. markedly inhibited absence seizures in GRY rats. The anti-absence action of LEV was potent and the cumulative duration of spike and wave discharges (SWD) in GRY rats was almost completely suppressed even at 20 mg/kg (i.p.). When the time-course of the inhibitory action of LEV (80 mg/kg i.p.) was examined up to 24 h after the treatment, the appearance of SWD was suppressed for over 6 h after injection of LEV in contrast to the action of sodium valproate (200 mg/kg i.p.) which had a very short effect (< 2 h). The maximum level of blood concentration of LEV was attained within 2 h after administration, and the drug disappeared from the blood in 24 h with T(¹/₂) of 2.7 h. These results revealed that LEV displays potent and relatively long-lasting inhibitory effects on absence seizures in GRY rats.

Topics: Animals; Anticonvulsants; Disease Models, Animal; Electroencephalography; Epilepsy, Absence; Levetiracetam; Piracetam; Rats; Rats, Mutant Strains; Rats, Wistar

The authors report a patient with Lennox-Gastaut syndrome who was a fraternal twin. The twins encountered myoclonic seizures at the age of 4 years, but the seizures in the other patient were controlled very quickly without intellectual development damage. With the disease evolving, other characteristic seizures of Lennox-Gastaut syndrome appeared and failed to be controlled by multiple antiepileptic drugs, so levetiracetam was added on. At this time, frequent partial seizures from the left occipital and posterior temporal regions occurred, which always intermixed with atypical absence seizures in a single ictal event. To control the status epilepticus, levetiracetam was withdrawn immediately, and clonazepam, midazolam, and corticotropin in turn were used. The partial seizures were gradually alleviated. The results obtained in this study suggest that there might be some correlative mechanisms between partial seizures and atypical absence seizures in a single event. There is a temporal relationship between the occurrence of partial seizures and the introduction of levetiracetam.

Topics: Adolescent; Epilepsy; Epilepsy, Absence; Humans; Intellectual Disability; Levetiracetam; Male; Piracetam

Valproic acid is an effective anti-epileptic medication often used for long-term control of seizure disorders that has been implicated in hematological toxicities, including rare reports of myelodysplasia and acute leukemia. Here, we report a case of valproic acid-related leukemia-like syndrome with a t(8;16) chromosomal translocation. After discontinuing valproic acid, the hematological findings completely resolved.

Topics: Acute Disease; Anticonvulsants; Cell Differentiation; Cell Division; Child, Preschool; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 8; Clone Cells; Cocarcinogenesis; Drug Therapy, Combination; Epilepsy, Absence; Female; Humans; Isoxazoles; Lamotrigine; Leukemia, Myeloid; Levetiracetam; Neoplastic Stem Cells; Oncogene Proteins, Fusion; Phenobarbital; Piracetam; Translocation, Genetic; Triazines; Valproic Acid; Zonisamide

Recent evidence highlights levetiracetam (LEV) as an advantageous treatment of absence epilepsy (AE). Thus, we investigated the effects of this drug in DBA/2J mice, a murine model of AE. Similarly to ethosuximide (200 mg/kg, intraperitoneal, i.p.) and sodium valproate (250 mg/kg, i.p.), two classic antiabsence agents, LEV (50-200 mg/kg, i.p.) reduced the occurrence of spike-and-wave discharges, AE's typical electroencephalographic patterns. Our results confirm LEV's efficacy in AE treatment.

Topics: Animals; Anticonvulsants; Electroencephalography; Epilepsy, Absence; Ethosuximide; Injections, Intraperitoneal; Levetiracetam; Male; Mice; Mice, Inbred DBA; Piracetam; Valproic Acid

To study the effect of the antiepileptic drug levetiracetam (LEV) on the patterns of intrinsic optical signals (IOSs) generated by slices of the somatosensory cortex obtained from 3- and 6-month-old WAG/Rij and age-matched, nonepileptic control (NEC) rats.. WAG/Rij and NEC animals were anesthetized with enfluorane and decapitated. Brains were quickly removed, and neocortical slices were cut coronally with a vibratome, transferred to a submerged tissue chamber, and superfused with oxygenated artificial cerebrospinal fluid (aCSF). Slices were illuminated with a dark-field condensor and examined with a x2.5 objective; images were processed with a real time digital video image-enhancement system. Images were acquired before (background) and during electrical stimulation with a temporal resolution of 10 images/s and were displayed in pseudocolors. Extracellular stimuli (200 micros; <4 V) were delivered through bipolar stainless steel electrodes placed in the white matter.. IOSs recorded in NEC slices bathed in control aCSF became less intense and of reduced size with age (p < 0.05); this trend was not seen in WAG/Rij slices. Age-dependent decreases in IOS intensity and area size were also seen in NEC slices superfused with aCSF containing the convulsant 4-aminopyridine (4-AP, 5 microM); in contrast, significant increases in both parameters occurred with age in 4-AP-treated WAG/Rij slices (p < 0.05). Under any of these conditions, the IOS intensity and area size slices were larger in WAG/Rij than in NEC slices. LEV (50-500 microM) application to WAG/Rij slices caused dose-dependent IOS reductions that were evident both in control and in 4-AP-containing aCSF and were more pronounced in 6-month-old tissue.. These data demonstrate age-dependent IOS modifications in NEC and WAG/Rij rat slices and identify a clear pattern of hyperexcitability that occurs in 6-month-old WAG/Rij neocortical tissue, an age when absence seizures occur in all animals. The ability of LEV to reduce these patterns of network hyperexcitability supports the potential use of this new antiepileptic drug in primary generalized epileptic disorders.

Topics: 4-Aminopyridine; Age Factors; Animals; Anticonvulsants; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; Epilepsy, Absence; Image Enhancement; In Vitro Techniques; Levetiracetam; Models, Genetic; Neocortex; Oscillometry; Piracetam; Rats; Rats, Inbred Strains; Rats, Wistar; Signal Processing, Computer-Assisted; Somatosensory Cortex; Videotape Recording

We examined the efficacy, optimum dosage and adverse effects of levetiracetam in two prospective trials in children with epilepsy. In the add-on trial, 67 children between 6 months and 16 years were included. In the mono-therapy trial, 10 children between 4 years and 16 years were included. Levetiracetam was titrated up to an optimal dosage for every individual patient, depending on efficacy and tolerability, and reflecting clinical practice. The range of dosages used was between 12 and 62 mg/kg/day, with a median of 33 mg/kg/day. Overall, 20 weeks after the start of levetiracetam, there was a median seizure reduction of 60% (add-on trial 50%; mono-therapy trial 81%). Levetiracetam was equally effective for partial and generalized seizures. Side effects were less common in the mono-therapy trial. Tiredness (7.8%) and aggressiveness (5%) were the most common side effects, and were dose-related, but were no reason to discontinue levetiracetam. In 25% of the children, a positive effect was seen on behaviour and/or alertness. This could not be related directly to seizure control. Overall, these two clinical trials confirm that levetiracetam is a broad spectrum anti-epileptic drug with a favourable safety profile. The positive effect on behaviour needs further quantitative study.

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Electroencephalography; Epilepsies, Myoclonic; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Female; Humans; Infant; Levetiracetam; Male; Piracetam; Prospective Studies; Syndrome; Treatment Outcome

Some evidence suggests that levetiracetam (LEV) possesses antiepileptogenic characteristics. The purpose of this study was to investigate the time course of seizure protection by LEV compared with that of phenytoin (PHT), phenobarbital (PB), valproate (VPA), and carbamazepine (CBZ) in the spontaneously epileptic rat (SER). The SER is a double mutant (tm/tm, zi/zi) showing both tonic convulsions and absence-like seizures.. The effect of single (40, 80, and 160 mg/kg, i.p.) and 5-day (80 mg/kg/day, i.p.) administration of LEV on tonic convulsions and absence-like seizures in SERs were studied. Tonic convulsions induced by blowing air onto the animal's head at 5-min intervals for 30 min and spontaneous absence-like seizures characterized by 5- to 7-Hz spike-wave-like complexes in the cortical and hippocampal EEG were recorded for 30 min. In the single-administration study, observations for seizure activity were performed once before and 3 times (45, 75, and 135 min) after drug administration. In the 5-day administration study, seizure observation was performed 4 times for 30 min (once before and 3 times after drug administration) during the 5-day drug-administration period, and continued once a day until 8 days after the final administration. The antiepileptic effects of 5-day administration of conventional AEDs (PHT, PB, VPA, and CBZ) were examined by using similar methods.. Tonic convulsions and absence-like seizures were inhibited by a single administration of LEV at 80 and 160 mg/kg, i.p., but not significantly at 40 mg/kg, i.p. When LEV was repeatedly administered at 80 mg/kg/day, i.p., for 5 days to SERs, the inhibitory effects on seizures increased with administration time. The number of tonic convulsions and absence-like seizures were significantly reduced to 39.1% and 38.4% compared with previous values, respectively, after 5-day LEV administration. Furthermore, significant inhibition of tonic convulsions was detected

Topics: Animals; Anticonvulsants; Behavior, Animal; Cerebral Cortex; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Epilepsy, Absence; Epilepsy, Generalized; Female; Injections, Intraperitoneal; Levetiracetam; Male; Piracetam; Rats; Rats, Mutant Strains; Time Factors

Effects of the novel anti-epileptic drug levetiracetam (50 and 100 mg/kg) on spike and wave discharges (SWDs) of WAG/Rij rats were studied. Levetiracetam decreased the incidence, average duration, total duration and peak frequency of the SWDs. There was no difference between the two doses. These results agree with results obtained in Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Furthermore, the decrease of the SWD peak frequency might support the suggestions that levetiracetam might have a GABAergic mechanism of action.

Topics: Animals; Anticonvulsants; Electroencephalography; Epilepsy, Absence; Levetiracetam; Male; Piracetam; Rats

The anticonvulsant effects of levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.

Topics: Acoustic Stimulation; Animals; Anticonvulsants; Behavior, Animal; Electroencephalography; Epilepsies, Partial; Epilepsy; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Female; Levetiracetam; Male; Piracetam; Rats; Rats, Inbred Strains; Rats, Wistar