Abstracts

RATIONALE: Zonisamide (ZNS, Zonegran[reg]) is a novel antiepilepsy drug (AED) approved in the United States for adjunctive treatment of partial seizures in adults with epilepsy. The objective of this report is to present information regarding clinical and electroencephalogram (EEG) improvements in 2 pediatric patients treated with ZNS.
METHODS: Patient 1 (9-year-old male) displayed intractable partial and secondarily generalized tonic-clonic seizures of left frontal lobe origin secondary to a low-grade astrocytoma. EEG showed bifrontal spikes (left[gt]right) and secondarily generalized spike and polyspike and wave discharges. A partial left frontal lobectomy was performed (October 2000) with removal of the astrocytoma. Despite initial improvement, 4 weeks after surgery he presented with multiple seizures per hour, characterized by staring, automatisms, and head and body drops. EEG confirmed numerous seizures of left frontal lobe origin, as well as interictal bifrontal spikes and secondarily generalized spike-wave bursts. His AEDs included divalproex sodium (DVPX), topiramate, levetiracetam, and phenytoin. ZNS was added (100 mg/d). All other AEDs were discontinued, except DVPX (1500 mg/d). Patient 2 (10-year-old boy) was followed for Landau-Keffner syndrome (onset at age 2 years). He had previously been treated with steroids and DVPX, with good clinical and EEG response. At age 8.5 years when on DVPX alone, he developed relatively rapid language and behavioral regression. A 24-hour EEG showed a recurrence of epileptiform abnormalities characterized by almost continuous left temporal and central spikes. Magnetoencephalography (MEG) showed additional right-sided epileptiform discharges, ruling out surgical treatment with subpial transection. He also developed episodes of staring and confusion suspicious for complex partial seizures. ZNS was initiated at 100 mg/d and titrated to 300 mg/d. Topiramate was rapidly weaned, and DVPX therapy continued (375 mg/d).
RESULTS: Patient 1 had complete cessation of seizures 2 days after starting ZNS and has remained seizure free on the combination of ZNS (100 mg/d) and DVPX (500 mg BID). Repeat EEG after 8 months showed mid bifrontal slowing (left[gt]right), with no epileptiform activity. Patient 2 had marked improvement in speech and language within 1 month of being on ZNS and DVPX. Episodes suspicious for complex partial seizures subsided. EEG after 4 months of ZNS and DVPX therapy was normal, with no epileptiform activity. No adverse events associated with ZNS were reported by either patient.
CONCLUSIONS: Experience in these patients suggests that ZNS may be useful in some difficult-to-treat pediatric patients. The patients demonstrated marked improvement, both clinically and electroencephalographically, with the addition of ZNS to their therapeutic regimen, and no adverse events were reported.
(Disclosure: Consulting - Elan Pharmaceuticals, Honoraria - Elan Pharmaceuticals)