Valproate-induced hyperammonemic encephalopathy enhanced by topiramate and phenobarbitone: a case report and an update.
Although sodium valproate (VPA)-induced hepatic encephalopathy is a well-recognized entity, VPA can occasionally produce encephalopathy secondary to hyperammonemia in the presence of normal hepatic function, namely valproate-induced non-hepatic hyperammonemic encephalopathy (VNHE). Known risk factors include therapy with multiple antiepileptic drugs, especially when topiramate is one of the drugs; presence of underlying inborn errors of metabolism; febrile states; and insufficient nutritional intake. We describe a 5-year-old male child who developed VNHE while on polypharmacy with topiramate and phenobarbitone; the child also had poor nutritional intake. The encephalopathy reversed with withdrawal of VPA and treatment with L-carnitine. We emphasize the need for early recognition, investigation, and treatment of this potentially life-threatening condition. We also recommend that VPA, topiramate, and phenobarbitone should not be given in combination.
Vivekanandan
S
S
Department of Clinical Biochemistry, Global Hospitals and Health City, Chennai - 600100, India.
Nayak
S Dinesh
SD
J Neurol Neurosurg Psychiatry. 1996 Aug;61(2):211
8708702
Ann Pharmacother. 1993 May;27(5):582-3
8347908
J Assoc Physicians India. 2004 Sep;52:746-8
15839456
J Neurol Neurosurg Psychiatry. 1998 May;64(5):680-2
9598692
Acta Neurol Scand. 2004 Apr;109(4):297-301
15016014
J Child Neurol. 2005 Feb;20(2):157-60
15794187
J Neurol. 1982;228(2):133-41
6185649
Neurology. 2000 Jan 11;54(1):230-2
10636156
Am J Physiol. 1986 Feb;250(2 Pt 2):F181-8
3511732
Lancet. 2007 Mar 24;369(9566):1016-26
17382828
Epilepsy Res. 2009 Jul;85(1):65-71
19299111
Neurol India. 2005 Jun;53(2):226-8
16010067
J Pak Med Assoc. 2008 Nov;58(11):627-31
19024136
Epilepsy Behav. 2007 Jun;10(4):583-7
17412645
Epilepsia. 1998 Nov;39(11):1216-25
9821988
Arch Fr Pediatr. 1993 Dec;50(10):875-8
8053766
Ther Drug Monit. 1985;7(2):185-90
3927530