Frank J. Ritter

A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome

Objective: To evaluate the efficacy and safety of topiramate as adjunctive therapy for Lennox–Gastaut syndrome in a multicenter, double-blind, placebo-controlled trial. Background: Conventional antiepileptic drugs are frequently ineffective against multiple-seizure types of Lennox–Gastaut syndrome. Methods: Ninety-eight patients >1 year to <30 years of age, with slow spike-and-wave patterns on EEG, seizure types including drop attacks, and either a history of or active atypical absence seizures, were assigned to an 11-week, double-blind treatment phase with either topiramate or placebo. Topiramate was titrated to target doses of approximately 6 mg/kg/d. Results: For drop attacks, the most severe seizures associated with this syndrome, the median percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and −5.1% (an increase) for the placebo group (p = 0.041). Topiramate-treated patients demonstrated greater improvement in seizure severity than did placebo-treated patients based on parental global evaluations (p = 0.037). The percentage of patients with a ≥50% reduction from baseline in major seizures (drop attacks and tonic-clonic seizures) was greater in the topiramate group (15/46 or 33%) than in the control group (4/50 or 8%; p = 0.002). The most common adverse events in both groups were CNS related; there were no discontinuations from topiramate therapy due to adverse events. Conclusions: Topiramate adjunctive therapy was effective in reducing the number of drop attacks and major motor seizures and in improving seizure severity as determined by parental global evaluation.

A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures

Background and Objective: Topiramate is effective as adjunctive treatment of partial-onset seizures in adults. The efficacy and safety of topiramate as adjunctive therapy for the treatment of primary generalized tonic-clonic (PGTC) seizures were investigated in a randomized, double-blind, placebo-controlled study. Methods: Eighty patients, 3 to 59 years old, who experienced three or more PGTC seizures during an 8-week baseline phase were randomly assigned to treatment with either topiramate (n = 39) or placebo (n = 41). Topiramate was titrated to target doses of approximately 6 mg/kg/day over 8 weeks and maintained for another 12 weeks. Results: The median percentage reduction from baseline in PGTC seizure rate was 56.7% for topiramate patients and 9.0% for placebo patients (p = 0.019). The proportion of patients with 50% or higher reduction in PGTC seizure rate was 22/39 (56%) and 8/40 (20%) for the topiramate and placebo groups, respectively (p = 0.001). The median percentage reduction in the rate of all generalized seizures was 42.1% for topiramate patients and 0.9% for placebo patients (p = 0.003). The proportions of patients with 50% or higher reductions in generalized seizure rate were 18/39 (46%) and 7/41 (17%) for the topiramate and placebo groups, respectively (p = 0.003). The most common adverse events were somnolence, fatigue, weight loss, difficulty with memory, and nervousness. Treatment-limiting adverse events occurred in one patient in the topiramate group (anorexia and weight loss) and one in the placebo group (granulocytopenia and thrombocytopenia). Conclusion: Topiramate is well-tolerated and effective for the adjunctive treatment of PGTC seizures.

Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label Trial

Summary:  Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment‐resistant partial‐onset seizures.

Pharmacokinetic Study of Levetiracetam in Children

Summary:  Purpose: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open‐label, single‐dose study.

Topiramate in Lennox–Gastaut Syndrome: Open-Label Treatment of Patients Completing a Randomized Controlled Trial

Purpose: The response to topiramate (TPM) as long‐term adjunctive therapy was evaluated in patients with Lennox‐Gastaut syndrome (LGS) in a long‐term, open‐label extension to a double‐blind, placebo‐controlled trial.

Nonepileptic Events in Childhood

Summary: The medical records of 27 children admitted to the MINCEP Epilepsy Program for evaluation of intractable epilepsy but later shown to have nonepileptic events by EEG with simultaneous video monitoring were reviewed. Four groups were identified: pure psychogenic events (5 patients), psychogenic events plus epileptic seizures (3 patients), pure nonepileptic physiologic events (5 patients), and nonepileptic physiologic events plus seizures (14 patients). Historical data, physical examinations, and neurodiagnostic evaluations (including previous EEGs, neuroradiologic evaluations, and neuropsychologic testing) were reviewed. Children in all groups, except for those with pure psychogenic seizures, had a history of multiple seizure types identified by parents or caretakers. A history of status epilepticus was obtained in 64% (of 22 patients), including 11 of 14 patients with physiologic events plus seizures. Abnormal findings on neurologic examination were common, especially in children with nonepileptic physiologic events. AH but two patients had a history of interictal epileptiform abnormalities on previous routine EEGs. Based on identification of nonepileptic events, antiepileptic drugs (AEDs) were discontinued completely in eight patients (30%) and the total number of AEDs was reduced in nine others (33%). A diagnosis of nonepileptic events should be considered in all children with refractory seizures or multiple seizure types. Abnormal findings on routine (interictal) EEG may actually confound the diagnosis. Intensive neurodiagnostic EEG‐video recording is the preferred method for distinguishing nonepileptic from epileptic seizures.

Effectiveness, Tolerability, and Safety of Topiramate in Children with Partial‐Onset Seizures

Purpose: Children with partial‐onset seizures, with or without secondary generalization, participating in a double‐blind, placebo‐controlled trial of topiramate (TPM) as adjunctive therapy were eligible to participate in an open‐label, long‐term extension study.

Clobazam in the treatment of Lennox-Gastaut syndrome

Purpose:  This randomized, double‐blind, dose‐ranging study evaluated safety and efficacy of clobazam (CLB) as adjunctive therapy for drop seizures in patients with Lennox‐Gastaut syndrome (LGS).

Diverse seizure presentation of acute Mycoplasma pneumoniae encephalitis resolving with immunotherapy.

We report 3 previously normal children that presented for evaluation of new onset seizures. Case 1, a 7-year-old female, presented with refractory left frontal lobe seizures associated with right arm simple motor seizures refractory to 6 antiepileptic medications at sufficient doses and levels. Case 2, a 15-year-old female, presented with left frontotemporal lobe seizures and nonconvulsive seizures, associated with neuropsychiatric symptoms refractory to 5 antiepileptic medications. Both patients received intravenous steroids and intravenous immunoglobulin. Case 3, an 11-year-old male, presented with a generalized tonic clonic seizure and worsening hallucinations responding to intravenous corticosteroids and 1 antiepileptic medication. All 3 patients had extensive infectious and metabolic evaluation and were found to be serum immunoglobulin M positive for mycoplasma pneumoniae. Despite their prolonged severe symptoms, all patients had virtually complete recovery with excellent seizure control after aggressive seizure management with immunotherapy and antiepileptic medication.

Adjunctive Therapy for Intractable Epilepsy with Ethotoin

Summary: In a retrospective study, records of 46 patients (24 women and 22 men aged 17–51 years; mean 29.2 years), who had been treated with ethotoin (EHN) as adjunctive therapy for control of intractable seizures were reviewed. Overall, ∽51% of this highly selected patient population had a reduction >50% in overall seizure frequency 1 month after initiation of treatment. This was reduced to ∽25% for the last 3 months of follow‐up (mean follow‐up period 10.6 months). Tonic seizure frequency was reduced most dramatically, by >50%, in 60% of patients at 1 month and in 35% of patients for the last 3 months of follow‐up. This study suggests that prospective controlled trials of EHN, especially for tonic seizures, are needed.