Cohen J A, Fisher R S, Brigell M G, Peyster R G, Sze G
Mellen Center for Multiple Sclerosis Treatment and Research, Department of Neurology, Cleveland Clinic Foundation, Ohio 44195, USA.
Epilepsia. 2000 Feb;41(2):148-57. doi: 10.1111/j.1528-1157.2000.tb00134.x.
Vigabatrin (Sabril, Hoechst Marion Roussel) is an antiepilepsy drug (AED) presently marketed in 64 countries for the treatment of partial and secondarily generalized seizures. Vigabatrin (VGB) is marketed in a subset of these countries for the treatment of infantile spasms. Clinical experience in humans has shown that VGB provides effective seizure control with a wide margin of safety. However, animal toxicity studies raised concern when prolonged administration of VGB was shown to induce intramyelinic edema (IME) in some laboratory animal species.
Animal and human data were reviewed with respect to the potential for VGB-induced IME. Surveillance of patients receiving VGB in clinical trials or by prescription has been conducted for >15 years to identify patients developing clinical abnormalities that might be IME related.
The histologic lesions of VGB-induced IME in animals are reliably reproduced and correlate with changes in multimodality evoked potentials (EPs) and magnetic resonance imaging (MRI). Numerous studies of the effects of VGB on EP and MRI in epilepsy patients have demonstrated no clear-cut IME-related changes in these modalities. Additionally, autopsy and surgical brain samples from VGB-treated patients have been scrutinized for potential IME histopathology. In an estimated 350,000 patient-years of VGB exposure (approximately 175,000 patients exposed for 2 years at an average dose of 2 g/day), no definite case of VGB-induced IME has been identified.
Comprehensive review of a variety of sources of data failed to identify any definite case of IME in humans treated with VGB.
氨己烯酸（喜保宁，赫斯特·马里恩·罗塞尔公司）是一种抗癫痫药物（AED），目前在64个国家上市，用于治疗部分性发作和继发性全身性发作。在其中一些国家，氨己烯酸（VGB）被用于治疗婴儿痉挛症。人体临床经验表明，VGB能有效控制癫痫发作，且安全性高。然而，动物毒性研究显示，长期给予VGB会在一些实验动物物种中诱发髓鞘内水肿（IME），这引发了人们的担忧。
回顾了关于VGB诱发IME可能性的动物和人体数据。对在临床试验中或通过处方接受VGB治疗的患者进行了超过15年的监测，以确定出现可能与IME相关的临床异常的患者。
动物中VGB诱发IME的组织学损伤能够可靠重现，且与多模态诱发电位（EPs）和磁共振成像（MRI）的变化相关。众多关于VGB对癫痫患者EPs和MRI影响的研究表明，这些检查中没有明显与IME相关的变化。此外，对VGB治疗患者的尸检和手术脑样本进行了潜在IME组织病理学检查。在估计350,000患者年的VGB暴露量（约175,000名患者，平均剂量2 g/天，暴露2年）中，未发现明确的VGB诱发IME病例。
对各种数据来源的全面审查未能在接受VGB治疗的人类中发现任何明确的IME病例。
