A case of valproate-induced hyperammonemic encephalopathy: look beyond the liver

The article by Alqahtani et al is a welcome reminder that hyperammonemia is a common side effect of valproate therapy. I am not, however, convinced that hyperammonemia is a benign asymptomatic condition. I wonder whether the sedation often accepted as a side effect of valproate is indeed a symptom of low-grade encephalopathy. I have had two patients with bipolar disorder taking valproate in the past year complain of foul smelling urine. The odour was described by both as “strong,” and, on smelling it myself, I was at loss to come up with a better descriptor. Blood ammonia levels were elevated in both patients, and, since mood stabilization was sub optimal on an already optimal dose, I decided to discontinue the valproate. Both patients noted that the smell disappeared upon discontinuation of the medication and has since not returned. As well, mental clarity was subjectively felt to be improved as well. Of note, both patients were placed on oxcarbazepine instead of valproate with significant improvement in mood stability. If strong smelling urine is indeed a sign of valproate related hyperammonemia, it is simple enough to question patients as to whether they are experiencing this side effect. If they are, I would then suggest that a blood ammonia level be drawn and, if elevated, the need for this medication be reassessed. In family practice, this odour may be mistaken for a urinary tract infection. Should a negative culture come back in the absence of other clinical signs such as urgency and dysuria in a patient taking valproate, I would suspect the medication as the culprit. The authors recommendations for managing valproate related hyperammonemic encephalopathy are prudent, but I wonder if they are missing half the picture. Does valproate unmask underlying conditions such as urea cycle disorders or fatty acid oxidation defects? Were these disorders looked for in this patient, and, if not, why not? More importantly, how does the average family doctor begin investigating for these problems? What tests should the physician in the trenches be ordering to screen for these conditions once suspicions are raised? Perhaps the CMAJ could more thoroughly address this issue in a future edition. Harold Pupko M.D. Private practice Toronto

Conflict of Interest:

None declared