1Department of Pathology, Istanbul University.
2Department of Neurology and Clinical Neurophysiology, Istanbul University.
Neurosurg Focus. 2022 Oct;53(4):E6. doi: 10.3171/2022.7.FOCUS21731.
In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies.
Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation.
In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases.
Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.
在治疗抵抗性癫痫的组织病理学检查中，局灶性皮质发育不良（FCD）是儿科中最常见的诊断。FCD 根据国际抗癫痫联盟（ILAE）分类进行组织病理学分类。在 ILAE 分类发布后的过去十年中，分子遗传学研究揭示了 mTOR 通路相关突变是主要病因。本研究的目的是确定治疗抵抗性癫痫患者中 FCD 的发生率，探索组织形态学和免疫组织化学特征，检查临床病理相关性，使用 pS6 抗体进行免疫组织化学检测以显示 mTOR 通路激活，并尝试引入可能的靶向治疗的候选物。
回顾性重新检查治疗抵抗性癫痫患者的石蜡块和组织切片。根据 ILAE 分类确定 FCD 的组织病理学亚型。进行 NeuN 和神经丝 H（NF-H）染色，并另外使用 pS6 抗体显示 mTOR 通路激活。
在 32 例诊断为 FCD 的病例中（183 例手术性癫痫组织中的 17.5%），ILAE FCD 亚型的临床变量的统计分析中没有显著差异。推荐抗体 NeuN 在 FCD 型 Ia 和 IIIa 组中显示微柱状排列，在 Ib 型组中显示分层丢失。另一种推荐的抗体 NF-H 被发现无法用于区分正常和畸形神经元。在所有 FCD 型 II 病例中，均观察到显示 mTOR 通路激活的 pS6 表达。
FCD 型 II 中的显著 pS6 表达代表了文献中提到的疾病的基因组性质。然而，已知的 MTOR 基因和 mTOR 通路相关突变在所有 FCD 型 II 病例中仍然相对较少，无法解释 mTOR 通路的激活。预计随着最近的发展，将进行临床病理和遗传综合分类，并将 mTOR 通路抑制剂用于治疗。
