title: Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both?
abstract: Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.
authors.affiliation: Department of Neurology, Hospital Cavale Blanche, Boulevard Tanguy Prigent, 29200 Brest, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Latour
authors.forename: Arnaud
authors.initials: A
authors.lastname: Biraben
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Polard
authors.forename: Danièle
authors.initials: D
authors.lastname: Bentué-Ferrer
authors.forename: Anne
authors.initials: A
authors.lastname: Beauplet
authors.forename: Olivier
authors.initials: O
authors.lastname: Tribut
authors.forename: Hervé
authors.initials: H
authors.lastname: Allain
mesh_terms: D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D000641:Ammonia