Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus.

We report on a 33-year-old female suffering from frequent complex-partial seizures who developed a non-convulsive status epilepticus after one week of antiepileptic therapy with valproate (VPA) which had been added to a basic medication with barbexaclone (BBC) in rapidly increasing dosage. The electroencephalogram (EEG) showed continuous rhythmic generalized sharp and slow wave activity with a frontal maximum. Intravenous administration of 3.0 mg of the benzodiazepine (BZ) receptor antagonist flumazenil under monitoring with video-EEG led to an immediate and marked electroclinical improvement, whereas 6.0 mg of the BZ receptor agonist midazolam was followed by a deterioration both clinically and in the EEG. We discuss the concept of VPA-encephalopathy and the possible mechanisms of the action of flumazenil on VPA-induced as well as on other toxic and metabolic encephalopathies. Flumazenil might antagonize increased benzodiazepine receptor activity with agonistic and even convulsive properties in these encephalopathic syndromes. Further investigations are needed concerning the relation of drug-induced or metabolic encephalopathies and central benzodiazepine receptor activity. We recommend a therapeutic trial with flumazenil, if stupor or decreased seizure control develop in patients treated with valproate.