Abdijadid Sara, Mathern Gary W, Levine Michael S, Cepeda Carlos
Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
CNS Neurosci Ther. 2015 Feb;21(2):92-103. doi: 10.1111/cns.12345. Epub 2014 Nov 18.
Cortical dysplasia (CD) is a neurodevelopmental disorder due to aberrant cell proliferation and differentiation. Advances in neuroimaging have proven effective in early identification of the more severe lesions and timely surgical removal to treat epilepsy. However, the exact mechanisms of epileptogenesis are not well understood. This review examines possible mechanisms based on anatomical and electrophysiological studies. CD can be classified as CD type I consisting of architectural abnormalities, CD type II with the presence of dysmorphic cytomegalic neurons and balloon cells, and CD type III which occurs in association with other pathologies. Use of freshly resected brain tissue has allowed a better understanding of basic mechanisms of epileptogenesis and has delineated the role of abnormal cells and synaptic activity. In CD type II, it was demonstrated that balloon cells do not initiate epileptic activity, whereas dysmorphic cytomegalic and immature neurons play an important role in generation and propagation of epileptic discharges. An unexpected finding in pediatric CD was that GABA synaptic activity is not reduced, and in fact, it may facilitate the occurrence of epileptic activity. This could be because neuronal circuits display morphological and functional signs of dysmaturity. In consequence, drugs that increase GABA function may prove ineffective in pediatric CD. In contrast, drugs that counteract depolarizing actions of GABA or drugs that inhibit the mammalian target of rapamycin (mTOR) pathway could be more effective.
皮质发育异常（CD）是一种由于细胞异常增殖和分化导致的神经发育障碍。神经影像学的进展已被证明在早期识别更严重的病变以及及时手术切除以治疗癫痫方面是有效的。然而，癫痫发生的确切机制尚未完全明确。本综述基于解剖学和电生理学研究探讨了可能的机制。CD可分为I型，其具有结构异常；II型，存在异形巨细胞神经元和气球样细胞；III型，与其他病理情况相关。使用新鲜切除的脑组织有助于更好地理解癫痫发生的基本机制，并明确异常细胞和突触活动的作用。在II型CD中，已证明气球样细胞不会引发癫痫活动，而异形巨细胞和未成熟神经元在癫痫放电的产生和传播中起重要作用。小儿CD中一个意外的发现是γ-氨基丁酸（GABA）突触活动并未降低，实际上，它可能促进癫痫活动的发生。这可能是因为神经回路显示出发育不成熟的形态和功能特征。因此，增加GABA功能的药物在小儿CD中可能无效。相比之下，对抗GABA去极化作用的药物或抑制雷帕霉素哺乳动物靶点（mTOR）途径的药物可能更有效。
