1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-8-95-a 10.15844/pedneurbriefs-8-12-11 Antiepileptic Drugs Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Valproate-Associated Hepatotoxicity Update http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 12 1994 01 06 2016 8 12 95 95 Copyright: © 1994 The Author(s) 1994 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities

Eight new fatalities from valproate (VPA)-related hepatotoxicity, 6 reversible cases, and a review of 132 fatal cases Worldwide are reported from various Universities in Germany.

 VPA-Related Hepatotoxicity Febrile Infections Metabolic Disorders

Eight new fatalities from valproate (VPA)-related hepatotoxicity, 6 reversible cases, and a review of 132 fatal cases Worldwide are reported from various Universities in Germany. In fatal cases, 65% were developmentally delayed, 75% were taking additional AEDs, and 65% were >2 years old. Early symptoms were nausea, vomiting, apathy, coma, exacerbation of seizures, and febrile infections. Two thirds of fatalities occurred within 6 months of introducing VPA. In reversible cases, VPA had been withdrawn promptly. In addition to Alper’s disease, a variety of underlying metabolic defects, especially acyl CoA-dehydrogenase deficiency, has been recognized in some cases of VPA-related hepatotoxicity. [1]

COMMENT. Metabolic testing is indicated in children <2 years old with developmental abnormalities when considering VPA therapy. Those patients with recognized metabolic disorders should not receive VPA. Further, VPA should be discontinued promptly and alternative AEDs substituted at the earliest sign of liver failure, if seizures are suddenly exacerbated, and particularly with status epilepticus and febrile infections.

 Konig SA Scheffner D Siemes H Blaker F Boenigk E Gross-Selbeck G Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities Epilepsia 1994 Sep-Oct 35 5 1005 1015 10.1111/j.1528-1157.1994.tb02546.x 7925143