title: Neuropathology of a human hippocampus following long-term treatment with vigabatrin: lack of microvacuoles.
abstract: Vigabatrin (gamma-vinyl-GABA), an irreversible inhibitor of gamma-aminobutyric acid transaminase, has been reported to be effective in the treatment of refractory epilepsies. Animal toxicology studies have shown that long-term application of vigabatrin induces intramyelinic edema and microvacuolation of the white matter in non-primate species. However, clinical and neuropathological studies of patients exposed to long-term vigabatrin treatment have, so far, provided no evidence for microvacuolation in the human brain. We report on the histopathological findings of selective amygdalohippocampectomy specimens from a 36-year-old female patient treated with vigabatrin for a period of 11.5 months, and from 2 control patients with chronic refractory temporal lobe seizures. All specimens showed changes associated with chronic epileptic seizures including focal neuronal loss and hippocampal gliosis. Microvacuoles, intramyelinic edema or other manifestations of neurotoxic damage were not observed in vigabatrin exposed tissue, supporting the view that this compound may not exert hippocampal neurotoxicity in humans.
authors.affiliation: Department of Neurology, University Hospital, Zurich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Agosti
authors.forename: G
authors.initials: G
authors.lastname: Yasargil
authors.forename: M
authors.initials: M
authors.lastname: Egli
authors.forename: H G
authors.initials: HG
authors.lastname: Wieser
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
mesh_terms: D000328:Adult; D000614:Aminocaproates / Q000009:adverse effects / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000627:therapeutic use*; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D014617:Vacuoles / Q000473:pathology*; D020888:Vigabatrin
chemical_list: D000614:Aminocaproates; D000927:Anticonvulsants; D020888:Vigabatrin