Abstracts

RATIONALE: To assess in an open pilot study the efficacy of ZNS in the treatment of MAE, a syndrome that is relatively refractory to antiepileptic drugs (AEDs).
METHODS: Four consecutive patients were enrolled who met criteria for MAE and were treated with ZNS because they had not become seizure free with 3-9 previous AEDs.
RESULTS: Age at onset of afebrile seizures 5 [onehalf] years. Persistent myoclonic and astatic seizures despite treatment with valproate (VPA), clonazepam, and ethosuximide. VPA caused encephalopathy with generalized delta slowing on EEG. Lamotrigine (LTG) markedly reduced generalized tonic-clonic (GTC) seizures. Age at introduction of ZNS 6 1/12 years. ZNS ineffective. Subsequently no response to topiramate (TPM). Levetiracetam (LEV) reduced myoclonic and astatic seizures by about 50%. No astatic seizure for 2 months since vagus nerve stimulator (VNS) implant. Age at onset of afebrile seizures 4 years. Persistent GTC seizures despite treatment with 9 AEDs including VPA, LTG, TPM, and LEV. Methsuximide markedly reduced myoclonic and astatic seizures. Age at introduction of ZNS 10 4/12 years. ZNS reduced GTC seizures by [gt]50%. Patient scheduled for VNS implant. Age at onset of afebrile seizures 2 5/12 years. Persistent GTC and astatic seizures despite treatment with VPA, TPM and LTG. VPA caused encephalopathy with generalized delta slowing on EEG. Age at introduction of ZNS 3 7/12 years. After introduction of ZNS, astatic seizures subsided within one day, GTC seizures within 12 days. Patient now seizure free for 15 months. Age at onset of afebrile seizures 3 [onehalf] years. Persistent daily astatic seizures despite treatment with valproate PHT, VPA, lorazepam, and TPM. VPA caused encephalopathy with generalized delta slowing on EEG. TPM controlled the GTC seizures. Age at introduction of ZNS 4 years. After the introduction of ZNS, gradual reduction then cessation of astatic seizures after 2 [onehalf] months. Patient now free of astatic seizures for 11 months. On monotherapy with ZNS for past 5 months. Two GTC seizures during a febrile episode.
CONCLUSIONS: Two of 4 consecutive patients with MAE and persistent myoclonic astatic and/or GTC seizures refractory to 3-9 AED trials became seizure free soon after the introduction of ZNS, and the most refractory of the 4 patients (9 AEDs) had a [gt]50% reduction in GTC seizures. The two patients who became seizure free were younger at the time of seizure onset (2 5/12 and 3 [onehalf] vs. 4 and 5 [onehalf] years) and of ZNS treatment (3 7/12 and 4 vs. 6 1/12 and 10 4/12 years). These results suggest selective efficacy of ZNS in this generally refractory syndrome. These results warrant further study of ZNS in the treatment of MAE. Three of these 4 patients with MAE developed an encephalopathic reaction to valproate.
(Disclosure: Grant - Elan, Novartis, Ortho McNeil, Pfizer, UCB Pharma, Consulting - Abbott, Elan, Glaxo Wellcome, Novartis, Ortho McNeil, Pfiaer, Schwarz Pharma, Shire, UCB Pharma, Honoraria - Elan, Glaxo, Novartis, Ortho McNeil, Pfizer, UCB Pharma)