Agosti R, Yasargil G, Egli M, Wieser H G, Wiestler O D
Department of Neurology, University Hospital, Zurich, Switzerland.
Epilepsy Res. 1990 Jul;6(2):166-70. doi: 10.1016/0920-1211(90)90092-a.
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.
氨己烯酸（γ-乙烯基-GABA）是γ-氨基丁酸转氨酶的不可逆抑制剂，据报道对难治性癫痫有效。动物毒理学研究表明，长期应用氨己烯酸会在非灵长类动物中引起髓鞘内水肿和白质微空泡形成。然而，迄今为止，对接受长期氨己烯酸治疗的患者进行的临床和神经病理学研究并未提供人脑存在微空泡形成的证据。我们报告了一名36岁女性患者经氨己烯酸治疗11.5个月后选择性杏仁核海马切除术标本的组织病理学结果，以及2名慢性难治性颞叶癫痫对照患者的标本结果。所有标本均显示出与慢性癫痫发作相关的变化，包括局灶性神经元丢失和海马胶质增生。在暴露于氨己烯酸的组织中未观察到微空泡、髓鞘内水肿或神经毒性损伤的其他表现，这支持了该化合物可能不会对人类海马体产生神经毒性的观点。
