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-6-22 10.15844/pedneurbriefs-6-3-8 Antiepileptic Drugs Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Valproate for Intractable Epilepsy 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 03 1992 01 07 2016 6 3 22 23 Copyright: © 1992 The Author(s) 1992 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. Treatment of intractable childhood epilepsy with high-dose valproate

The efficacy and side effects of high dose valproic acid (VPA) therapy in 46 children with refractory epilepsy were studied at the Department of Child Neurology, Okayama University Medical School, Okayama, Japan.

 Valproic Acid Therapy Symptomatic Partial Epilepsy West Syndrome

The efficacy and side effects of high dose valproic acid (VPA) therapy in 46 children with refractory epilepsy were studied at the Department of Child Neurology, Okayama University Medical School, Okayama, Japan. Serum VPA concentrations ranged from 105.1 to 198.4 mcg/ml. Seizures were completely controlled in 15 (32.6%) and improved in 12 (26.1%). This degree of control was sustained at 6 months or more follow-up. VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike waves during slow wave sleep. Symptomatic generalized epilepsy and symptomatic partial epilepsy were benefitted equally. No significant difference in efficacy was noted between the monotherapy and bipharmacy groups, but adverse side effects appeared more frequently and higher serum levels of VPA were difficult to obtain in the bipharmacy group. Liver enzymes were transiently increased in 50% of the patients and elevated serum amylase occurred in 10% of patients. Hyperammonemia in 6.5% of patients necessitated withdrawal of the drug. Thrombocytopenia less than 100,000/mm3 occurred in 21.7% and hypofibrinogenemia was detected in 65% of patients. These side effects were reversible with reduction of dosage. [1]

COMMENT. The authors recommend high dose VPA therapy for intractable childhood epilepsy of generalized and partial types and particularly for patients with West syndrome. The monitoring of platelet counts and fibrinogen levels in addition to liver function tests is advised.

Kreuz W et al. from Frankfort, Germany report the induction of von Willebrand disease type I in 67% of 30 children receiving VPA therapy [2]. The decrease in coagulation parameters were not dependent on either VPA dose or the period of drug administration. This increased tendency to hemorrhage in patients receiving VPA must be considered, especially during surgical intervention and after traumatic events.

Kondo T et al. from Hirosaki University, Japan, report that 3 risk factors (young age, polypharmacy, and high VPA serum level) enhance the susceptibility to VPA hepatotoxicity by altering the metabolism of VPA and by increasing the conversion of VPA to 4-en, the most toxic VPA metabolite. [3]

 Ohtsuka Y Ohtahara S Amano R Mizukawa M Oka E Treatment of intractable childhood epilepsy with high-dose valproate Epilepsia 1992 Jan-Feb 33 1 158 164 10.1111/j.1528-1157.1992.tb02300.x 1733751 Kreuz W Linde R Funk M Meyer-Schrod R Foll E Nowak-Gottl U Valproate therapy induces von Willebrand disease type I Epilepsia 1991 Jan-Feb 33 1 178 184 10.1111/j.1528-1157.1992.tb02303.x 1733754 Kondo T Kaneko S Otani K Ishida M Hirano T Fukushima Y Associations between risk factors for valproate hepatotoxicity and altered valproate metabolism Epilepsia 1992 Jan-Feb 33 1 172 177 10.1111/j.1528-1157.1992.tb02302.x 1733753