Department of Anatomic Pathology, Centro Hospitalar Universitário São João; Department of Pathology, Faculdade de Medicina da Universidade do Porto (FMUP), Alameda Prof. Hernâni Monteiro, Porto, Portugal.
Department of Anatomic Pathology, Centro Hospitalar Universitário São João, Porto; Department of Anatomic Pathology, Hospital Pedro Hispano, Matosinhos, Portugal.
Indian J Pathol Microbiol. 2022 May;65(Supplement):S189-S197. doi: 10.4103/ijpm.ijpm_1226_21.
Focal cortical dysplasias (FCDs) represent the third most frequent cause of drug-resistant focal epilepsy in adults (after hippocampal sclerosis and tumours) submitted to surgery, and the most common in the pediatric age group. The International League Against Epilepsy (ILAE) classification of focal cortical dysplasia is still a reference and consists of a three-tiered system: FCD type I refers to isolated abnormalities in cortical layering; FCD type II refers to cases with abnormalities in cortical architecture and dysmorphic neurons with or without balloon cells; and FCD type III refers to abnormalities in cortical layering associated with other lesions. Recent studies have demonstrated that somatic mutations occurring post-zygotically during embryonal development and leading to mosaicism, underlie most brain malformations. The molecular pathogenesis of FCD type II is associated with activation of the mTOR pathway. Pathogenic variants in this pathway are recognized in up to 63% of cases and may occur both through single activating variants in activators of the mTOR signaling pathway or double-hit inactivating variants in repressors of the signaling pathway. The newly described mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy, has been found to show recurrent pathogenic variants in SLC35A2 with mosaicism. The present review describes the lesions of FCD and discusses the molecular pathogenesis and proposal for a revised classification.
局灶性皮质发育不良（FCD）是成人手术治疗耐药性局灶性癫痫的第三大常见病因（仅次于海马硬化和肿瘤），也是儿童时期最常见的病因。国际抗癫痫联盟（ILAE）的局灶性皮质发育不良分类仍然是一个参考标准，包括一个三级系统：FCD Ⅰ型是指皮质分层的孤立异常；FCD Ⅱ型是指皮质结构异常和形态异常神经元，伴有或不伴有气球细胞；FCD Ⅲ型是指与其他病变相关的皮质分层异常。最近的研究表明，胚胎发育过程中合子后发生的体细胞突变导致镶嵌性，是大多数脑畸形的基础。FCD Ⅱ型的分子发病机制与 mTOR 通路的激活有关。在多达 63%的病例中识别到该通路的致病性变异，可能通过 mTOR 信号通路的激活变体或信号通路的抑制物的双打击失活变体发生。新近描述的伴有癫痫的少突胶质细胞增生的皮质发育轻度畸形，已发现 SLC35A2 中存在镶嵌性的复发性致病性变异。本文综述了 FCD 的病变，并讨论了其分子发病机制和修订分类的建议。
