Finsterer Josef, Scorza Fulvio A
Krankenanstalt Rudolfstiftung, Vienna, Austria.
Disciplina de Neurociência, Escola Paulista de Medicina/Universidade Federal de São Paulo, (EPM/UNIFESP), São Paulo, Brazil.
Epilepsy Res. 2017 Oct;136:5-11. doi: 10.1016/j.eplepsyres.2017.07.003. Epub 2017 Jul 13.
Antiepileptic drugs (AEDs) exhibit adverse and beneficial effects on mitochondria, which have a strong impact on the treatment of patients with a mitochondrial disorder (MID) with epilepsy (mitochondrial epilepsy). This review aims at summarizing and discussing recent findings concerning the effect of AEDs on mitochondrial functions and the clinical consequences with regard to therapy of mitochondrial epilepsy and of MIDs in general.
Literature review.
AEDs may interfere with the respiratory chain, with non-respiratory chain enzymes, carrier proteins, or mitochondrial biogenesis, with carrier proteins, membrane-bound channels or receptors and the membrane potential, with anti-oxidative defense mechanisms, with morphology, dynamics and survival of mitochondria, and with the mtDNA. There are AEDs of which adverse effects outweigh beneficial effects, such as valproic acid, carbamazepine, phenytoin, or phenobarbital and there are AEDs in which beneficial effects dominate over mitochondrial toxic effects, such as lamotrigine, levetiracetam, gabapentin, or zonisamide. However, from most AEDs only little is known about their interference with mitochondria.
Mitochondrial epilepsy might be initially treated with AEDs with low mitochondrial toxic potential. Only in case mitochondrial epilepsy is refractory to these AEDs, AEDs with higher mitochondrial toxic potential might be tried. In patients carrying POLG1 mutations AEDs with high mitochondrial toxic potential are contraindicated.
抗癫痫药物（AEDs）对线粒体具有不良和有益影响，这对患有线粒体疾病（MID）合并癫痫（线粒体癫痫）的患者的治疗有重大影响。本综述旨在总结和讨论关于AEDs对线粒体功能的影响以及线粒体癫痫和一般MIDs治疗的临床后果的最新研究结果。
文献综述。
AEDs可能干扰呼吸链、非呼吸链酶、载体蛋白或线粒体生物发生，干扰载体蛋白、膜结合通道或受体以及膜电位，干扰抗氧化防御机制，干扰线粒体的形态、动力学和存活，以及干扰线粒体DNA。有些AEDs的不良反应超过有益作用，如丙戊酸、卡马西平、苯妥英或苯巴比妥，而有些AEDs的有益作用超过线粒体毒性作用，如拉莫三嗪、左乙拉西坦、加巴喷丁或唑尼沙胺。然而，对于大多数AEDs，人们对它们干扰线粒体的情况了解甚少。
线粒体癫痫最初可能用线粒体毒性低的AEDs治疗。只有在线粒体癫痫对这些AEDs难治时，才可以尝试线粒体毒性较高的AEDs。对于携带POLG1突变的患者，禁忌使用线粒体毒性高的AEDs。
