Salamon Noriko, Andres Marissa, Chute Dennis J, Nguyen Snow T, Chang Julia W, Huynh My N, Chandra P Sarat, Andre Veronique M, Cepeda Carlos, Levine Michael S, Leite Joao P, Neder Luciano, Vinters Harry V, Mathern Gary W
Division of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Brain. 2006 Feb;129(Pt 2):352-65. doi: 10.1093/brain/awh681. Epub 2005 Nov 16.
In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23), this study compared clinical, neuroimaging and pathologic features to discern potential mechanisms for suboptimal post-hemispherectomy developmental outcomes and structural pathogenesis. MRI measured affected and non-affected cerebral hemisphere volumes for HME and non-HME cases, including monozygotic twins where one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and white matter cell densities and sizes in HME and autopsy cases, including the non-affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was larger and the non-affected side smaller in HME compared with non-HME children. The affected HME side showed enlarged abnormal deep grey and white matter structures and/or T2-weighted hypointensity in the subcortical white matter in 75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias. Histopathological examination of the affected HME side revealed immature-appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of cases. Compared with autopsy cases, in HME children NeuN cell densities on the affected side were increased in the molecular layer and upper cortex (+244 to +18%), decreased in lower cortical layers (-35%) and increased in the white matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted white matter hypointensity correlated with the presence of immature-appearing neurons and PMG on histopathology, decreased NeuN cell densities in lower cortical layers and a positive history of infantile spasms. Post-surgery seizure control was associated with decreased NeuN densities in the molecular layer. In young children with HME and epilepsy, these findings indicate that there are bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly is a likely explanation for poorer post-surgery seizure control and cognitive outcomes. In addition, our findings support the hypothesis that HME pathogenesis probably involves somatic mutations that affect each developing cerebral hemisphere differently with more neurons than expected on the HME side.
在患有半侧巨脑症（HME；n = 23）的小儿癫痫手术患者中，本研究比较了临床、神经影像学和病理特征，以辨别半球切除术后发育结果欠佳和结构发病机制的潜在机制。MRI测量了HME和非HME病例中受影响和未受影响的脑半球体积，包括其中一个同胞患有HME的单卵双胞胎。针对神经元细胞核（NeuN）的染色确定了HME和尸检病例中的灰质和白质细胞密度及大小，包括HME手术/尸检病例的未受影响侧。通过MRI，与非HME儿童相比，HME患者的患侧半球更大，对侧半球更小。75%的HME患侧显示深部灰质和白质结构异常增大和/或皮质下白质T2加权低信号，提示产前神经发生过多和异位。对HME患侧的组织病理学检查显示，70%的病例中有不成熟外观的神经元，61%有多小脑回（PMG），45%有气球样细胞。与尸检病例相比，HME儿童患侧的NeuN细胞密度在分子层和上层皮质增加（+244至+18%），在下层皮质减少（-35%），在白质增加（+139至+149%）。深部灰质MRI异常和/或T2加权白质低信号与组织病理学上不成熟外观的神经元和PMG的存在、下层皮质NeuN细胞密度降低以及婴儿痉挛的阳性病史相关。术后癫痫控制与分子层NeuN密度降低有关。在患有HME和癫痫的幼儿中，这些发现表明存在双侧大脑半球异常，对侧半侧微脑回可能是术后癫痫控制和认知结果较差的原因。此外，我们的发现支持这样的假设，即HME的发病机制可能涉及体细胞突变，这些突变对每个发育中的大脑半球的影响不同，HME侧的神经元比预期的更多。
