Kakita Akiyoshi, Kameyama Shigeki, Hayashi Shintaro, Masuda Hiroshi, Takahashi Hitoshi
Department of Pathological Neuroscience, Brain Research Institute, University of Niigata, Japan.
J Child Neurol. 2005 Apr;20(4):341-50. doi: 10.1177/08830738050200041301.
Malformations caused by abnormalities of cortical development, or cortical dysplasias, were examined in surgical specimens from 108 patients with medically intractable epilepsy to determine the scope of histopathologic changes. The relevance of the clinical findings was also evaluated. Various types and degrees of dysplastic features were observed in various combinations, including architectural abnormalities, an increased number of neurons in the molecular layer and/or cortical layer II, neuronal clustering, an increased number of satellite oligodendrocytes, abnormal gyration, single and/or aggregates of heterotopic neurons in the white matter, and the appearance of cytologically abnormal cells, such as giant or dysmorphic neurons and balloon cells. In the temporal lobe specimens, microdysgenesis (corresponding to mild malformations caused by abnormalities of cortical development and type IA/B focal cortical dysplasias) was more frequently observed than Taylor-type focal cortical dysplasia (type IIA/B), whereas in the frontal lobe specimens, the frequency of occurrence of both types was even. The ages at seizure onset and surgery of patients with the latter type were significantly lower than those of patients with the former. On the other hand, prominent astrocytosis in the cortex and white matter was evident in all cases, and many corpora amylacea and neurofibrillary tangle-like inclusions were observed in a subset of cases. An ultrastructural investigation revealed dilatation of the postsynaptic dendritic spines and shafts in the cortex and features indicating the occurrence in the white matter of demyelination followed by remyelination. Thus, with regard to the epileptogenic lesions, although dysplastic changes constitute the pathogenetic basis, the overlapping subsequent degenerative processes involving synapses, dendrites, and axons might contribute to the development of epileptogenic processes. Astrocytes might also actively participate in the development of the pathogenesis of epilepsy.
对108例药物难治性癫痫患者手术切除标本中的皮质发育异常所致畸形，即皮质发育异常进行检查，以确定组织病理学改变的范围。还评估了临床发现的相关性。观察到各种类型和程度的发育异常特征以各种组合形式出现，包括结构异常、分子层和/或皮质第II层神经元数量增加、神经元聚集、卫星少突胶质细胞数量增加、脑回异常、白质中异位神经元单个和/或聚集以及出现细胞学异常的细胞，如巨大或异形神经元和气球样细胞。在颞叶标本中，微发育异常（对应于皮质发育异常和IA/B型局灶性皮质发育异常所致轻度畸形）比泰勒型局灶性皮质发育异常（IIA/B型）更常见，而在额叶标本中，两种类型的发生率相当。后一种类型患者的癫痫发作起始年龄和手术年龄明显低于前一种类型患者。另一方面，所有病例中皮质和白质均有明显的星形细胞增生，部分病例中观察到许多淀粉样体和神经原纤维缠结样包涵体。超微结构研究显示皮质中突触后树突棘和树突干扩张，白质中有脱髓鞘后再髓鞘化的特征。因此，关于致痫性病变，虽然发育异常改变构成发病机制基础，但随后涉及突触、树突和轴突的重叠退行性过程可能有助于致痫过程的发展。星形细胞也可能积极参与癫痫发病机制的发展。
