Different clinical manifestations of hyperammonemic encephalopathy

Valproate is an effective anticonvulsant. Although it is usually well tolerated, it has been associated with many neurological, hematopoietic, hepatic, and digestive system side effects. Among these side effects, hyperammonemia without clinical or laboratory evidence of hepatotoxicity is rare and is an important clinical consideration. The aim of this article was to evaluate the reasons for the unexpected symptoms observed in seven patients with epilepsy patients during valproate treatment. We evaluated seven adult patients with localization-related epilepsy who presented with different acute or subacute neurological symptoms related to valproate-induced hyperammonemic encephalopathy. Four of the seven patients had acute onset of confusion, decline in cognitive abilities, and ataxia. Two had subacute clinical symptoms, and the other patient had symptoms similar to those of acute toxicity. These unusual clinical symptoms and similar cases had not been reported in the literature before. Serum ammonia levels were elevated in all seven patients. After discontinuation of valproate, complete clinical improvement was observed within 5-10 days. On the basis of our work, we suggest that the ammonia levels of a patient who has new neurological symptoms and has been taking valproate must be checked. Clinicians should be aware that these clinical symptoms may be related to valproate-induced hyperammonemic encephalopathy. The symptoms have been observed to resolve dramatically after withdrawal of the drug.