Preventing and treating posttraumatic seizures: The human experience
Preventing and treating posttraumatic seizures: The human experience
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DOI：
10.1111/j.1528-1167.2008.02005.x
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发表时间：
2009-01-01
期刊：
影响因子：
5.6
通讯作者：
Temkin, Nancy R.
中科院分区：
文献类型：
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作者：
Temkin, Nancy R.
创伤后癫痫是预防工作的理想目标。创伤性脑损伤（TBI）是常见的，使人们处于高风险的特征，如穿透性损伤或硬膜下血肿或诱发癫痫发作很容易识别，并且损伤和癫痫发作之间的潜伏期通常很短。已经测试了几种药物预防TBI后诱发癫痫发作和癫痫的能力。我们描述了这些研究的设计和结果。苯妥英钠和卡马西平显著降低诱发癫痫发作的发生率。苯巴比妥和苯巴比妥与苯妥英的组合也看起来有希望减少诱发癫痫发作，但在评估这些药物的研究中，样本量小，无法得出明确的结论。所研究的药物（苯妥英、苯巴比妥、其组合、卡马西平、丙戊酸盐或镁）均未显示出预防或甚至抑制TBI后癫痫发作的可靠证据。对于大多数测试的方案（苯妥英/苯巴比妥组合是例外），效果的最佳估计是减少25%以下的创伤后癫痫发作，远低于大多数研究设计检测的50%减少。然而，对测试药物的评估存在严重的局限性，自1980年以来开发的抗癫痫药物（AED）和其他化合物几乎没有进行过测试。更好地了解癫痫发生的过程，在实验室中测试证明抗癫痫作用的治疗方法，并在尝试确定性试验之前进行彻底的临床前和II期评估，这将大大提高确定预防创伤后癫痫的方法的机会，为这种情况提供最终的治愈方法。
Posttraumatic epilepsy presents an ideal target for prevention efforts. Traumatic brain injury (TBI) is common, characteristics that put people at high risk such as penetrating injury or subdural hematoma or provoked seizures are easily identified, and the latency between the injury and the onset of epileptic seizures is frequently short. Several drugs have been tested for their ability to prevent provoked seizures and epilepsy after TBI. We describe the design of those studies and their results. Phenytoin and carbamazepine significantly reduce the incidence of provoked seizures. Phenobarbital and the combination of phenobarbital and phenytoin also look promising for reducing provoked seizures, but small sample sizes in the studies evaluating these drugs do not allow definitive conclusions. None of the drugs studied (phenytoin, phenobarbital, their combination, carbamazepine, valproate, or magnesium) have shown reliable evidence that they prevent, or even suppress, epileptic seizures after TBI. For most of the regimens tested (the phenytoin/phenobarbital combination being the exception), the best estimate of effect is under a 25% reduction in posttraumatic seizures, well less than the 50% reduction most studies were designed to detect. The evaluation of the tested drugs has serious limitations, however, and antiepileptic drugs (AEDs) developed since 1980 and other compounds have barely been tested at all. Better understanding the process of epileptogenesis, testing treatments that demonstrate antiepileptogenic effects in the laboratory, and performing thorough preclinical and phase II evaluations before attempting definitive trials should greatly improve the chance of identifying ways to prevent posttraumatic epilepsy, providing the ultimate cure for this condition.