Abstracts

RATIONALE: Baltic myoclonic epilepsy is a familial disorder resulting in progressive motor and cognitive impairment and myoclonic seizures which respond poorly to conventional antiepileptic drugs(AED). Zonisamide (ZNS), a sulfonamide derivative, is a broad-spectrum AED, which has recently been approved for adjunctive therapy of partial seizures in the United States. However, ZNS has been used in Japan since 1989 and has demonstrated efficacy against both partial and generalized seizures, including myoclonic seizures
METHODS: We studied 3 brothers (ages 29, 32, and 39 years) diagnosed with familial progressive Baltic myoclonic epilepsy. In all cases, the condition began in childhood and has slowly deteriorated over time. Seizure control has been insufficient with current AEDs (including valproate and clonazepam). Case histories and physical and neurological exams were obtained at study initiation. The oldest and most affected brother had nearly continuous myoclonus, which was considered too numerous to quantitate. He was treated with (ZNS), 25 mg, titrating to the highest nonsedating dose of 100mg TID. For the two younger sibs, occurrences of myoclonic seizure episodes were recorded in a seizure diary (half-hour periods, 3 times/day) during both a 2-week baseline period and 16-week ZNS treatment period. ZNS was added to the patient[ssquote]s current treatment regimens, titrating the daily does of ZNS was from 25 to 300 mg during weeks 1-7 to a maximal dose of 400 mg during weeks 8-16.
RESULTS: ZNS produced substantial reductions in both the severity and frequency of myoclonic seizures for each patient. In the younger two, mean daily seizure frequency decreased from 2.57 and 3.57 during baseline to 0.46 and 0.03 for the 2 patients, respectively, during weeks 9-16 with ZNS treatment. In addition, all three patients reported greatly improved coordination, motivation, and energy level. The oldest had a noticeable decrease in myoclonus, and improved functionally from , inability to speak, bed and wheel chair bound, and complete dependence for all activities including feeding before treatment, propelling his own wheel chair, assist with feeding, effectively communicate clearly, and perform independent transfers to bed and chair. The middle, intermediately affected brother went from generally wheelchair-bound at baseline to mostly unassisted walking at termination. No adverse events related to ZNS treatment were noted.
CONCLUSIONS: These positive findings suggest that ZNS offers a highly effective option as adjunctive therapy for treating progressive myoclonic epilepsy. Additional placebo-controlled clinical trials are warranted.
Support: Elan Pharmaceuticals and Marshfield Medical Research Foundation