Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward
Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward
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DOI：
10.1097/wco.0000000000000067
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发表时间：
2014-04-01
影响因子：
4.8
通讯作者：
Brigo, Francesco
中科院分区：
文献类型：
--
作者：
Trinka, Eugen;Brigo, Francesco
综述目的癫痫学的临床前研究在开发抗癫痫药物(ASD)方面取得了非常成功的进展。一些临床前的概念验证研究也为一些抗癫痫药物预防癫痫发展的积极治疗效果提供了证据。令人失望的是，由于几个原因，所有预防大脑侮辱后癫痫的人类抗癫痫试验都失败了。最近的发现目前可用的ASD中没有一种被证明可以预防中风后癫痫、创伤性脑损伤或脑肿瘤。对接受联合放化疗治疗恶性胶质母细胞瘤的患者的随机对照试验的回顾性系列和事后分析发现，丙戊酸盐患者的存活率增加，因此提示可能对这些患者与癫痫共病相关的症状起到作用。雷帕霉素和伊波利莫斯等靶向治疗目前正在进行临床研究，以预防结节性硬化症患者的癫痫。摘要基础和临床科学家需要协调努力，开发合适的抗癫痫药物、强大的生物标志物和有效的临床试验设计，以将成功预防癫痫的新疗法推向市场。
Purpose of reviewPreclinical research in epileptology has been very successful in developing antiseizure drugs (ASDs). Several preclinical proof-of-concept studies have also provided evidence for positive treatment effects of some antiepileptogenic drugs to prevent the development of epilepsy. Disappointingly, all human antiepileptogenesis trials to prevent epilepsy after brain insults have failed, because of several reasons.Recent findingsNone of the currently available ASDs have been shown to prevent epilepsy after stroke, traumatic brain injury, or in brain tumours. Retrospective series and post-hoc analyses of randomized controlled trials of patients undergoing combined radiochemotherapy for malignant glioblastoma found an increased survival of patients with valproate, thus suggesting a possible role against the symptoms related to the comorbidity of epilepsy in these patients. Target-oriented treatments such as rapamycin and everolimus are currently under clinical investigation to prevent epilepsy in patients with tuberous sclerosis.SummaryAn orchestrated effort among basic and clinical scientists is needed to develop proper antiepileptogenic drugs, powerful biomarkers, and valid clinical trial designs to bring new treatments on the market that can successfully prevent epilepsy.