A hypothesis regarding the pathogenesis and epileptogenesis of pediatric cortical dysplasia and hemimegalencephaly based on MRI cerebral volumes and NeuN cortical cell densities
A hypothesis regarding the pathogenesis and epileptogenesis of pediatric cortical dysplasia and hemimegalencephaly based on MRI cerebral volumes and NeuN cortical cell densities
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DOI：
10.1111/j.1528-1167.2007.01292.x
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发表时间：
2007-01-01
期刊：
影响因子：
5.6
通讯作者：
Vinters, Harry V.
中科院分区：
文献类型：
--
作者：
Mathern, Gary W.;Andres, Marissa;Vinters, Harry V.
本研究比较了皮质发育不良（CD; n = 25）和半侧巨脑畸形（HME; n = 14）的小儿癫痫手术患者的MRI脑体积和神经元核（NeuN）细胞密度。我们的目的是推断可能的发病机制和癫痫的基础上正常发育皮质神经元的理解。我们使用MRI测量大脑半球体积，并使用NeuN染色确定分子层、灰质和白色物质中的灰质和白色物质细胞密度和细胞大小。将CD和HME手术病例与尸检或非CD病例进行比较（n = 20）。非CD、CD和HME病例之间的总MRI脑体积相似。然而，在HME患者中，与非CD病例相比，患侧大脑半球较大，而非患侧较小。与尸检病例相比，CD和HME患者的分子层、上灰质和白色物质中NeuN细胞密度和细胞大小增加。在CD和HME病例中，大脑半球总体积大小正常，上层皮质神经元比预期的多。皮质神经元密度的增加与CD和HME发病机制涉及皮质形成晚期（而非早期）神经发生增加的假设一致。此外，更多的神经元在分子层和白色物质支持的概念，CD和HME发病机制也涉及不完全的程序性细胞死亡的残余细胞占据前板和subplate区域。基于我们的解剖学和以前的电生理研究结果，我们提出，在CD和HME癫痫发作的产生是不完全的大脑发育与不成熟和成熟的细胞和细胞网络之间的异常相互作用的结果。
This study compared MRI cerebral volumes and Neuronal-Nuclei (NeuN) cell densities in pediatric epilepsy surgery patients with cortical dysplasia (CD; n = 25) and hemimegalencephaly (HME; n = 14). Our purpose was to deduce possible mechanisms of pathogenesis and epileptogenesis based on an understanding of normal developmental corticoneurogenesis. We used MRI to measured cerebral hemisphere volumes, and NeuN staining to determine grey and white matter cell densities and cell sizes in the molecular layer, grey, and white matter. CD and HME surgical cases were compared with autopsy or non-CD cases (n = 20). Total MRI brain volumes were similar between non-CD, CD, and HME cases. However, in HME patients, the affected cerebral hemisphere was larger and the nonaffected side smaller than non-CD cases. Compared with autopsy cases, NeuN cell densities and cell sizes in CD and HME patients were increased in the molecular layer, upper grey matter, and white matter. In CD and HME cases, total cerebral hemisphere volumes were normal in size and there were more cortical neurons in upper layers than expected. The increase in cortical neuronal densities is consistent with the hypothesis that CD and HME pathogenesis involves increased neurogenesis in the late (not early) phases of cortical formation. In addition, more neurons in the molecular layer and white matter supports the concept that CD and HME pathogenesis also involves incomplete programmed cell death in the remnant cells occupying the preplate and subplate regions. Based on our anatomical and previous electrophysiological findings, we propose that in CD and HME seizure generation is the consequence of incomplete cerebral development with abnormal interactions between immature and mature cells and cellular networks.