We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.

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SUMMARY Vigabatrin (y-vinyl GABA) is a new anticonvulsive drug that irreversibly inhibits the activity ofGABA transaminase. The effect ofvigabatrin on neurotransmission-related amino acids in CSF of 28 epileptic patients was studied and the relationship between the amino acid pattern and clinical response during 7 months of administration ofvigabatrin. Of this study population, 46% had more than 50% decrease in seizure frequency (responders). In 54% the seizures decreased less than 50% (nonresponders). In the whole study group, the levels of total GABA during vigabatrin treatment were 283%, free GABA 197%, homocarnosine 310% and glycine 128% that ofthe levels at baseline in the same patients. Glutamate, glutamine, aspartate, asparagine, and taurine concentrations did not change. The amino acid pattern in CSF during administration of vigabatrin did not differ significantly in responders and nonresponders. The study suggests that both GABAergic and glycinergic neurotransmission are affected by vigabatrin. The changes in CSF levels of neurotransmitter amino acids are, however, not necessarily related to the clinical response.Vigabatrin (y-vinyl GABA, 5-amino-4-hex-enoic acid), is an anticonvulsive drug that inhibits GABA transaminase (GABA-T, EC 2.6.1.19) activity by an irreversible mechanism.' Levels of GABA and homocarnosine (HC) in the brain and cerebrospinal fluid (CSF) of animals as well as CSF levels of GABA and HC in humans are elevated up to 2-4 fold during vigabatrin administration at doses that have anticonvulsive efficacy.'2 Previous data about the unchanged levels of markers of cholinergic, dopaminergic, serotonergic and peptidergic systems3 4 and the relatively few side effects observed in patients during vigabatrin administration suggest that the mechanism of action is quite specifip. However, the elevation of GABA levels alone seems not to explain all the effects ofvigabatrin. First, studies of the rat brain suggest that other amino acids, such as fi-alanine and hypotaurine, are also affected by vigabatrin.5 Second, the maximal elevations of GABA levels in the brain and CSF are not always correlated with maximal anticonvulsive efficacy.6 Third, elevation of CSF levels of GABA seems to be a constant finding in patients receiving vigabatrin, but the anticonvulsive effect is found only in 40-60% of these Address for reprint requests: Asla Pitkinen, MD,

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