Abstracts

Rationale: Zonisamide (ZNS) is a broad-spectrum antiepileptic drug, whose antiepileptic activity is thought to arise from sodium and T-type calcium channel blockade. This also has free-radical scavenging effect. Oxidative stress is very important for pathogenesis of mitochondrial dysfunction. We reviewed the efficacy and safety of ZNS as long-term adjunctive therapy in childhood epilepsy patients with mitochondrial respiratory chain complexes (MRC) defects. Methods: We evaluated the seizure frequency and side effects of 31 epileptic patients with MRC defects maintained on ZNS for at least 12 months. MRC defects were confirmed by biochemical assays using muscle biopsies. Results: 1) For epileptic classification, there were 5 cases (16.1%) of West syndrome, 8 cases (25.8%) of Lennox-Gastaut syndrome, 6 cases (19.4%) of generalized epilepsy, and 12 cases (38.7%) of partial epilepsy. 2) In our clinical diagnosis, there were 10 cases (32.3%) with Leigh syndrome and the remaining 21 cases (67.7%) had uncategorized mitochondrial cytopathy with nonspecific encephalopathy. 3) Twenty-three cases (74.2%) were MRC I deficient and 8 cases (25.8%) were MRC IV deficient. 4) Of the 31 patients 3 (9.7%) had 100% seizure control; 11 (35.5%) had >75% to <100% reduction in seizure frequency; 7 (22.6%) had >50% to <75% reduction in seizure frequency; 4 (12.9%) had >0% to <50% reduction in seizure frequency, and 6 (19.4%) had no seizure reduction. 5) Adverse events included somnolence and irritability, but all were transient and successfully managed by careful follow-up. Conclusions: ZNS was effective and safe as adjunctive therapy in childhood epilepsy patients with MRC defects. The broad efficacy of ZNS can provide considerable benefit in epilepsy with energy metabolic problems.