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Sodium Valproate-induced hyperammonemia without clinical hepatic dysfunction

Departments of Neurology (Drs. Zaret. Wagle. and Passarelli) Clinical pharmacy (Dr. Beckner) and Medicine (Dr. Marini (University of Massachusetts Medical Center, Worcester. MA.

Three adults on unrestricted protein diets receiving valproic acid (VPA) developed gastrointestinal symptoms with enceph- alopathy and/or deteriorating seizure control associated with arterial hyperammonemia and normal liver function tests. The signs and symptoms did not directly correlate with VPA dosage and the arterial ammonium levels did not correlate with serum VPA concentrations. Two of the three patients had phenobarbital concentrations above the therapeutic range, but remission of neurologic or gastrointestinal symptoms was dependent on a reduction of the VPA concentration. In one case, rechallenge with VPA reproduced hyperammonemia.

Address correspondence and reprint requests to Dr. Zaret, Department of Neurology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester. MA 01605.

Accepted for publication July 8, 1981.

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