A Case of Hyperammonemic Encephalopathy Secondary to a Combination of Valproic Acid and Topiramate

Abstract

Purpose To report a case of hyperammonemic encephalopathy induced by a combination of valproic acid and topiramate. Case Summary A 30-year-old male was admitted to our institution after experiencing headaches, decreasing mental capacity and increasing somnolence over the previous 3 days. Past medical history was significant for generalized tonic-clonic seizure disorder and mild mental retardation for which he had been regularly taking valproic acid, topiramate, and lorazepam. The patient was seizure free for the past 9 months prior to his seizure 2 weeks prior to admission. Upon presentation, an electroencephalogram revealed excessive slowing in the left more than right, with a differential consistent with a metabolic encephalopathy, head injury, or postictal state. Laboratory workup revealed a valproic acid level that was slightly elevated, but still within normal limits, at 92.5 mcg/mL (normal = 50 to 100 mcg/mL). Furthermore, the patient's ammonia level was found to be elevated at 72 mcg/dL (normal = 14.7 to 55.3 mcg/dL). On hospital day 3, after discovering these findings, valproic acid was discontinued and lactulose 20 g three times daily was started. Five days after admission, the patient's mental status changes were resolved, and he was discharged with an ammonia level of 57 mcg/dL. Conclusion Hyperammonemic encephalopathy is rare, but a serious and sometimes fatal disorder can occur in patients receiving valproic acid therapy. The incidence of hyperammonemia may be increased in patients receiving concomitant valproic acid and topiramate therapy. In patients on valproic acid and topiramate who present with altered mental status, an ammonia level in addition to a serum valproate level should be ascertained to rule out this potentially serious adverse drug reaction.