Department of Pathology and Laboratory Medicine.
Department of Pathology and Laboratory Medicine Residency Program, Medical University of South Carolina, Charleston, South Carolina.
J Neuropathol Exp Neurol. 2019 Apr 1;78(4):365-372. doi: 10.1093/jnen/nlz009.
Focal cortical dysplasia (FCD) is a common histopathologic finding in cortical specimens resected for refractory epilepsy. GABAergic neuronal abnormalities and K-Cl cotransporter type 2 (KCC2) immaturity may be contributing factors for FCD-related epilepsy. We examined surgical specimens from 12 cases diagnosed with FCD, and brain tissues without developmental abnormality obtained from 6 autopsy cases. We found that GABAergic neuronal density was abnormal in FCD with 2 distinct patterns. In 7 of 12 (58%) FCD subjects, the GABAergic neuron density in dysplastic regions and in neighboring nondysplastic regions was equally reduced, hence we call this a "broad pattern." In the remaining cases, GABAergic neuron density was decreased in dysplastic regions but not in the neighboring nondysplastic regions; we designate this "restricted pattern." The different patterns are not associated with pathologic subtypes of FCD. Intracytoplasmic retention of KCC2 is evident in dysmorphic neurons in the majority of FCD type II subjects (5/7) but not in FCD type I. Our study suggests that (1) "broad" GABAergic deficiency may reflect epileptic vulnerability outside the dysplastic area; and (2) abnormal distribution of KCC2 may contribute to seizure generation in patients with FCD type II but not in type I.
局灶性皮质发育不良（FCD）是切除难治性癫痫皮质标本中常见的组织病理学发现。GABA 能神经元异常和 K-Cl 共转运蛋白 2（KCC2）不成熟可能是 FCD 相关癫痫的促成因素。我们检查了 12 例诊断为 FCD 的手术标本，以及 6 例尸检无发育异常的脑组织。我们发现 FCD 中 GABA 能神经元密度存在 2 种不同的异常模式。在 12 例 FCD 患者中，有 7 例（58%）异常区域和邻近非异常区域的 GABA 能神经元密度同样降低，因此我们称之为“广泛模式”。在其余病例中，异常区域的 GABA 能神经元密度降低，但邻近的非异常区域没有；我们将其指定为“局限模式”。不同的模式与 FCD 的病理亚型无关。在大多数 FCD II 型患者（5/7）而非 FCD I 型患者中，KCC2 的细胞质内滞留是明显的。我们的研究表明：（1）“广泛”的 GABA 能缺乏可能反映了异常区域外的癫痫易感性；（2）KCC2 的异常分布可能导致 FCD II 型患者而非 I 型患者的癫痫发作。
