VALPROATE-INDUCED COMA - CASE-REPORT AND LITERATURE-REVIEW

OBJECTIVE: To report a case of hyperammonemia without hepatic dysfunct ion as a possible cause of lethargy, stupor, and coma in a woman after valproic acid (VPA) administration, and discuss the possible differen t mechanisms of ammonia elevation and coma. CASE SUMMARY: A woman diag nosed with complex partial seizures that secondarily generalize was tr eated with phenytoin (PHT) 250 mg/d for 18 years. Three months before admission, this dosage was increased to 300 mg/d and phenobarbital (PB ) 100 mg/d was added because the seizures were incompletely controlled . The patient developed a progressive inability to walk. She was diagn osed as having PHT intoxication. VPA therapy was begun while PHT was b eing tapered and progressive impairment of consciousness occurred. Thi s evolved into a coma without focal neurologic signs, and was accompan ied by isolated hyperammonemia without hepatic failure. DISCUSSION: Ad verse effects attributable to VPA were reviewed in the literature. Occ asionally, VPA may lead to severe secondary effects such as hepatic fa ilure and coma. In these cases increased blood concentrations of trans aminases, bilirubin, and ammonia have been found. Several reports have stressed the existence of hyperammonemic coma without biochemical evi dence of hepatic failure, which is what occurred in our patient. This suggests that isolated hyperammonemia and hepatic failure after VPA tr eatment may have a different biochemical basis. CONCLUSIONs: VPA-induc ed coma with hyperammonemia and without evidence of hepatic failure sh ould be considered in patients being treated with PHT or PB when VPA i s administered concomitantly. This case report shows the importance of clinical monitoring and immediate drug discontinuation when drowsines s, gastrointestinal symptoms, or lethargy occur.