DRUG-REFRACTORY EPILEPSY IN BRAIN-DAMAGE - EFFECT OF DEXTROMETHORPHANON EEG IN 4 PATIENTS

High doses of dextromethorphan (20-42 mg/kg/day) were given to four cr itically ill children with seizures and frequent epileptiform abnormal ities in the EEG that were refractory to antiepileptic drugs. Their ac ute diseases (hypoxia, head trauma and hypoxia, neurodegenerative dise ase, hypoglycaemia) were thought to be due in part to N-methyl-D-aspar tate (NMDA) receptor mediated processes. Treatment with dextromethorph an, an NMDA receptor antagonist, was started between 48 hours and 14 d ays after the critical incident. In three patients the EEG improved co nsiderably within 48 hours and seizures ceased within 72 hours. In the patient with neurodegenerative disease the effect on the EEG was impr essive, but the seizures were not controlled. Despite the improvement of the EEG the clinical outcome was poor in all children: three died i n the critical period or due to the progressing disease; the patient w ith hypoglycaemia survived with severe neurological sequelae. Plasma c oncentrations of dextromethorphan varied between 74-1730 ng/ml and its metabolite dextrorphan varied between 349-3790 ng/ml. In one patient corresponding concentrations in CSF were lower than those in plasma. T he suppression of epileptic discharges by the doses of dextromethorpha n given suggests that such doses are sufficient to block NMDA receptor s.