Becker Albert J, Blümcke Ingmar, Urbach Horst, Hans Volkmar, Majores Michael
Department of Neuropathology, Bonn University Medical Center, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany.
J Neuropathol Exp Neurol. 2006 Feb;65(2):99-108. doi: 10.1097/01.jnen.0000199570.19344.33.
Glioneuronal malformations (malformations of cortical development [MCD]) include focal cortical dysplasias (FCD) as well as highly differentiated glioneuronal tumors (i.e. gangliogliomas) and constitute frequent findings in patients with pharmacoresistent focal epilepsies. Tailored resection strategies evolved as promising treatment options and allow a systematic neuropathologic and molecular biologic examination of the epileptogenic area in these patients. The histopathologic appearance and immunophenotype of glioneuronal lesions are, however, characterized by numerous similarities and suggest impaired proliferation, migration, and differentiation of neural precursor cells to play a pathogenetic role. Recent studies point toward molecular alterations within a variety of genes and pathways involved in development of the central nervous system, neuronal growth, and maturation. Compromised signaling within insulin- or reelin-transduction cascades are common findings and were associated with specific MCD entities. Unraveling pathogenic mechanisms may advance refined classification systems for epilepsy-associated malformations and open new avenues for the development of targeted treatment strategies in pharmacoresistent focal epilepsies associated with cortical malformations.
神经胶质神经元畸形（皮质发育畸形[MCD]）包括局灶性皮质发育异常（FCD）以及高度分化的神经胶质神经元肿瘤（即节细胞胶质瘤），是药物难治性局灶性癫痫患者的常见表现。量身定制的切除策略已成为有前景的治疗选择，并允许对这些患者的致痫区域进行系统的神经病理学和分子生物学检查。然而，神经胶质神经元病变的组织病理学表现和免疫表型具有许多相似之处，提示神经前体细胞的增殖、迁移和分化受损发挥了致病作用。最近的研究指向了参与中枢神经系统发育、神经元生长和成熟的多种基因和信号通路中的分子改变。胰岛素或Reelin转导级联中的信号受损是常见发现，并与特定的MCD实体相关。阐明致病机制可能会推动癫痫相关畸形的精细分类系统的发展，并为与皮质畸形相关的药物难治性局灶性癫痫的靶向治疗策略的开发开辟新途径。
