Epilepsy Research Group, Berlin, Germany.
Epileptic Disord. 2012 Jun;14(2):105-13. doi: 10.1684/epd.2012.0512.
Any attempt to make antiepileptogenesis a realistic goal in clinical trials should be based on the experience of failures of the past. A wide variety of experimental studies and clinical trials using chronic antiseizure drug therapy during the extended post-injury period have had minimal success. The disappointing results of these studies may be due to several factors including the possibility that antiseizure drugs, despite the fact they suppress seizure activity, do not interfere in any substantial way with the “epileptogenic” process of focal epilepsies. Although the reasons for the failure are not entirely clear, it may be that the antiseizure drugs may have been tested at the wrong doses, for the wrong duration, or at the wrong time after brain injury. Surprisingly, the anti-absence drug ethosuximide has also been shown to be antiepileptogenic in several experimental models of absence epilepsy. In addition, clinical trials aimed at preventing focal post-injury epilepsy have suffered from poor enrolment and other issues related to the comorbidity of severe epilepsies that follow overt brain injury. Testing specific anti-inflammatory and immunological antiepileptogenic agents to prevent focal epilepsies, as well as prevention trials for genetic epilepsies, possibly with anti-absence drugs, may be a way to resolve the dilemma. Although more evidence is needed, there is hope on the horizon for antiepileptogenic therapy that works.
任何将抗癫痫发生作为临床试验中一个现实目标的尝试都应基于过去失败的经验。大量使用慢性抗癫痫药物治疗在创伤后延长期间的实验研究和临床试验仅取得了最小的成功。这些研究令人失望的结果可能归因于多种因素，包括抗癫痫药物尽管抑制了癫痫发作活动，但实际上并没有以任何实质性方式干扰局灶性癫痫的“致痫”过程的可能性。尽管失败的原因尚不完全清楚，但抗癫痫药物可能在脑损伤后以错误的剂量、错误的持续时间或错误的时间进行了测试。令人惊讶的是，抗失神发作药物乙琥胺在几种失神性癫痫的实验模型中也被证明有致癫痫发生作用。此外，旨在预防创伤后局灶性癫痫的临床试验因严重癫痫的共病相关的入组率低和其他问题而受到影响。测试特定的抗炎和免疫性抗癫痫发生药物以预防局灶性癫痫，以及针对遗传性癫痫的预防试验，可能是解决这一困境的一种方法。尽管还需要更多的证据，但有希望出现有效的抗癫痫发生治疗方法。
