Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Amsterdam.
Brain Pathol. 2012 May;22(3):380-401. doi: 10.1111/j.1750-3639.2012.00581.x.
Structural abnormalities of the brain are increasingly recognized in patients that suffer from pharmacoresistant focal epilepsies by applying high-resolution imaging techniques. In many of these patients, epilepsy surgery results in control of seizures. Neuropathologically, a broad spectrum of malformations of cortical development (MCD) is observed in respective surgical brain samples. These samples provide a unique basis to further understand underlying pathomechanisms by molecular approaches and develop improved diagnostics and entirely new therapeutic perspectives. Here we provide a comprehensive description of neuropathological findings, available classification systems as well as molecular mechanisms of MCDs. We emphasize the recently published ILEA classification system for focal cortical dysplasias (FCDs), which are now histopathologically distinguished as types I to III. However, this revised classification system represents a major challenge for molecular neuropathologists, as the underlying pathomechanisms in virtually all FCD entities will need to be specified in detail. The fact that only recently, the mammalian target of rapamycin (mTOR)-antagonist Everolimus has been introduced as a treatment of epilepsies in the context of tuberous sclerosis-associated brain lesions is a striking example of a successful translational "bedside to bench and back" approach. Hopefully, the exciting clinico-pathological developments in the field of MCDs will in short term foster further therapeutic breakthroughs for the frequently associated medically refractory epilepsies.
应用高分辨率成像技术，越来越多的药物难治性局灶性癫痫患者出现大脑结构异常。在这些患者中，许多癫痫手术可控制癫痫发作。神经病理学上，在相应的手术脑样本中观察到广泛的皮质发育畸形（MCD）。这些样本通过分子方法提供了进一步了解潜在病理机制的独特基础，并开发了改进的诊断方法和全新的治疗方法。在这里，我们全面描述了神经病理学发现、现有的分类系统以及 MCD 的分子机制。我们强调了最近发布的局灶性皮质发育不良（FCD）ILEA 分类系统，该系统现在在组织病理学上分为 I 型至 III 型。然而，这个修订的分类系统对分子神经病理学家来说是一个重大挑战，因为实际上所有 FCD 实体的潜在病理机制都需要详细说明。直到最近，雷帕霉素靶蛋白（mTOR）拮抗剂依维莫司才被引入作为治疗结节性硬化症相关脑病变相关癫痫的一种方法，这是一个成功的转化“从床边到实验室再回到床边”方法的显著例子。希望 MCD 领域令人兴奋的临床病理发展将在短期内为经常与药物难治性相关的癫痫带来更多的治疗突破。
