Spreafico R, Pasquier B, Minotti L, Garbelli R, Kahane P, Grand S, Benabid A L, Tassi L, Avanzini G, Battaglia G, Munari C
Department of Neurophysiology, National Neurological Institute C. Besta, Milano, Italy.
Epilepsy Res. 1998 Sep;32(1-2):34-48. doi: 10.1016/s0920-1211(98)00038-2.
In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.
在本报告中，我们描述了三名患有发育性皮质异常（通常称为皮质发育异常）的患者，这些异常通过磁共振成像（MRI）显示，并因难治性癫痫接受了手术。出于严格的治疗原因切除的组织，根据电临床数据和立体脑电图（SEEG）记录被定义为致痫区。组织样本最初进行组织学处理，选择的切片进一步进行免疫细胞化学研究，以确定皮质发育异常区域是否与致痫区范围一致。在两名患有结节性异位的患者中，在结节内发现了神经元的无序聚集（通过神经元细胞骨架标记物显示）。结节内既有锥体细胞也有局部回路神经元，但没有反应性胶质增生。当结节到达皮质时，皮质层被破坏。在患有局限性皮质发育异常的患者中，发现皮质分层完全紊乱，白质中也有大量神经元。还存在用细胞骨架神经元标记物弱标记的方向紊乱的锥体细胞，但未发现巨细胞。一名患有结节性异位的患者仅对“致痫区”和病变进行了部分切除；该患者仍有癫痫发作。另一名患有结节性异位的患者在完全切除病变和致痫区后无癫痫发作。第三名患有局灶性皮质发育异常的患者接受了两次手术；仅在切除SEEG记录检测到的致痫区后她才无癫痫发作。目前的数据表明，MRI识别出的发育异常区域不应被视为癫痫放电的唯一起源部位。从神经病理学角度来看，局灶性皮质发育异常可被视为一种纯粹的迁移障碍形式。然而，在皮质下结节性异位中，白质中散布着大量神经元聚集，这表明神经元迁移缺陷可能与神经母细胞的过度产生和/或自然发生的细胞死亡机制的破坏有关。
