Abstracts

RATIONALE: Decreased levels of gamma-aminobutyric acid (GABA) in the brain have been linked to the occurence of epileptic seizures. In the wake of this theory, two antiepileptic drugs (AEDs)have been formulated : vigabatrin (VGB) which is a suicide inhibitor of GABA-transaminase, and tiagabine(TGB), a potent inhibitor of GABA.Increased GABA levels can induce diffuse hypersynchonous slow waves on EEG recordings, resembling either deep sleep waves or generalized absence seizures, and that most GABA mimetic drugs aggravate absence epilepsy in human as well in animal models. Whe here report two patients with "non convulsive status epilepticus" corresponding to a metabolic encephalopathy induced by increased GABA in the brain, caused by the synergetic effects of TGB and VGB. METHODS: Two patient treated with VGB with temporal lobe epilepsy presented recurrent episodes of drowsiness and mental confusion shortly after an add-on treatment with TGB was initiated. Drowsiness, disorientation, aphasia and reduced visual field (one case) appeared when TGB was increased for a daily intake of 15-30 mg/day. The confusionnal episodes repeated themselves over several days, occurring about one hour after the patients had taken his AEDs and lasting over a period of 6-8 hours. RESULTS: EEG before medication was normal. Parallel to the appearance of clinical symptoms and about one hour after AED intake, there was a diffuse generalised rhythmic bilateral high amplitude slow activity at 3 cycles/second which persisted also for 6-8 hours. TGB was withdrawn for three days, VGB unchanged. A single dose of TGB (15mg) was reintroduced, at which point the same phenomena reoccurred over an identical time lapse. TGB was definitively discontinued. There has been no new confusionnal episode since. CONCLUSIONS: Imputability of TGB was tested in those cases following all official criteria (clinical, chronological, bibliographical. We suggest that those cases corresponds to a metabolic encephalopathy induced by vastly increased synaptic levels of GABA in the brain, caused by the synergetic effects of two very specific AEDs. We therefore warn against such associations.