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Psych Congress  

Valproate Induced Hyperammonemic Encephalopathy: Diagnosis and Management

Daniel Matthews, M.D. – Universal Health Services, Inc; Glenda Matthews, M.D. – Neuropsychiatric Associates

BACKGROUND:Hyperammonemia and a carnitine deficiency with concomitant encephalopathy have been reported to result from valproate administration. The reported incidence of hyperammonemia in children treated with valproate is 19%.
OBJECTIVE: This study explores the feasibility of reversing Valproate Induced Hyperammonemic Encephalopathy (VHE) by discontinuing valproate and normalizing the carnitine level via L-carnitine supplementation.
METHODS:Three males (ages 10-16 years), are reported with 12 – 24 months histories of cognitive decline during treatment for "Bipolar Disorder of Childhood" with valproate. The subjects received neuropsychological testing, complex EEG, valproate, carnitine, and ammonia blood levels. Oxcarbazepine was substituted for valproate. Reference laboratory levels were as follows: (1) ammonia (15-45 mcg/dl), (2) total carnitine (34-77 nmol/ml), and (3) valproate (50-125 mcg/ml).
RESULTS:Patient 1:  Male, 10 years old, ammonia 78 mcg/dl; carnitine 17 nmol/ml; valproic acid 92 mcg/ml. IQ 79 (previously105); EEG, left temporal aberrancies.
Patient 2: Male, 12 years old, ammonia 92 mcg/dL; carnitine 14 nmol/ml; valproic acid 104 mcg/ml. IQ 89 (previously109); EEG, left temporal aberrancies.
Patient 3: Male, 16 years old, ammonia 84 mcg/dl; carnitine 24 nmol/ml; valproic acid 125 mcg/ml. IQ 45 (previously 65); EEG, left temporal aberrancies.
After valproate was removed and L-carnitine added, ammonia and carnitine levels normalized. IQ's returned to previous baselines, EEG aberrancies were unchanged. Patients were mood and behaviorally stable on oxcarbazepine.
CONCLUSION:Evidence of cognitive decline while on valproate warrants ammonia and carnitine level testing. If these are abnormal, VHE should be diagnosed. Valproate should be removed. L-carnitine supplementation should be implemented

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