title: Pronounced reversible hyperammonemic encephalopathy associated with combined valproate-topiramate therapy in a 7-year-old girl.
abstract: Valproate is one of the most frequently used anticonvulsive drugs in children and adults. Valproate is a generally well tolerated medication. However, encephalopathy with or without hyperammonemia is one of its rare adverse events. We present a 7-year-old girl who suffered from epilepsy with generalized tonic-clonic seizures and absence epilepsy. She was initially treated with topiramate. Methylprednisolone pulse therapy and long-term therapy with valproate were initiated due to an increase of seizure frequency. At day 5 of therapy, a further increase of seizure frequency was observed followed by lethargy and somnolence. Liver enzymes remained within normal range, but ammonia serum levels increased to a maximum of 544 mmol/l. Discontinuing valproate and starting potassium-benzoate and sodium-phenylbutyrate improved the clinical condition and ammonia serum levels. Haemodialysis was not required. Cranial magnetic resonance imaging ruled out brain edema. The patient was further on successfully treated with a combination of both, topiramate and levetiracetam. Seizures did not recur and development was normal until now (3 years later). To the best of our knowledge, we observed the highest ammonia serum levels ever reported in valproate-induced hyperammonemia with a complete remission of the subsequent encephalopathy. Topiramate might increase the risk of valproate-induced encephalopathy by carbonic anhydrase inhibition.
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weise
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Syrbe
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany ; Department of Neurosurgery, Pediatric Neurosurgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preuss
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Bertsche
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Merkenschlager
authors.affiliation: Department of Women and Child Health, University Hospital for Children and Adolescents, Liebigstr. 20a, 04103 Leipzig, Germany.
authors.forename: Matthias K
authors.initials: MK
authors.lastname: Bernhard
keywords: Encephalopathy; Glutamine; Hyperammonemia; Topiramate; Valproate