Abstracts

Progressive myoclonus epilepsies (PME) are a group of rare, severe, hereditary conditions, that includes many specific, mainly metabolic disorders. Pharmacoresistant myoclonus and generalized seizures, neurological deterioration, cognitive decline, overall unfavorable clinical course and poor prognosis are the main characteristics of PME. A group of 19 patients, children and adolescents with PME was studied for the efficacy and safety of antiepileptic treatment. The specific diagnosis included neuronal ceroid lipofuscinosis-NCL (4), Lafora disease (8), Unverriht-Lundborg disease (1), MERRF (3) and sialidosis type I-cherry red spot[ndash]myoclonus (2). Underlying pathology remained unknown in one child. Clinical follow-up lasted from 11 to 68 months. Conventional AEDs were mainly ineffective for myoclonus and generalized seizures. Carbamazepine (10-18 mg/kg) and vigabatrin (20-30 mg/kg) aggravated myoclonias in early, still unrecognized stages of PME in four patients. Valproate was partially effective in PME seizure control (seizure reduction for [lt]=50%). Piracetam (7.2-14.4 g/daily) or L-tryptophan (0.5-2 g/daily) was given in patients with Lafora disease with no stable and long-term therapeutic effect. High-dose imunoglobulins i.v. administered in two boys with Jansky-Bielschowsky disease and one girl with syalidosis had no influence on myoclonus. Polyvitamine cocktail and diet with polyunsaturated fatty acids for patients with NCL were not helpful. No therapeutic response on N-acethylcistein (2g/daily) in two patients with Lafora disease was noted. Ketogenic diet was cancelled because of complications or inefficacy in two adolescents with Lafora disease in one boy with NCL. Pulses of methyl-prednosolon induced dramatic but short-term cessation of myoclonus in two PME adolescents. Lamotrigine, topiramate or zonisamide as new add-on AEDs were administered. All patients were comedicated with valproic acid and clonazepam / clobazame. Lamotrigine (4-8 mg/kg) was given in 9 patients. Five children (NCL-3, MERRF-2) experienced favorable control of GTCS and reduction of stimulus sensitivity, with no significant LTG effect on myoclonus. Moderate efficacy for generalized seizures was noted in four (Lafora-3, sialidosis-1) of 8 patients treated with topiramate (8-11 mg/kg). Zonisamide given in a daily dose of 400 mg significantly reduced both myoclonias and generalized seizures in four of 8 patients with Lafora disease for [gt]6 months. Two patients showed stable, long-term favorable seizure control for 18 months. No actually effective antiepileptic treatment for seizures in PME was available. Neither conventional or new AEDs nor alternative therapy are recommended. The need for new treatment strategies in PME was imperative. It is hoped that new antiepileptic agents, other neuroactive molecules and molecular genetic approach will provide a rational therapy for both underlying pathology and seizures.