Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly.
Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly.
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半巨脑畸形儿童的对侧半脑畸形和临床病理相关性。
DOI：
10.1093/brain/awh681
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Mathern,GaryW
中科院分区：
文献类型：
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作者：
Salamon,Noriko;Andres,Marissa;Chute,DennisJ;Nguyen,SnowT;Chang,JuliaW;Huynh,MyN;Chandra,PSarat;Andre,VeroniqueM;Cepeda,Carlos;Levine,MichaelS;Leite,JoaoP;Neder,Luciano;Vinters,HarryV;Mathern,GaryW
在患有半脑畸形的小儿癫痫手术患者 (HME;n= 23) 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 病例的受影响和未受影响的大脑半球体积，包括其中一个兄弟姐妹患有 HME 的同卵双胞胎。神经元核 (NeuN) 染色确定了 HME 和尸检病例中的灰质和白质细胞密度和大小，包括 HME 手术/尸检病例的未受影响的一侧。通过 MRI 发现，与非 HME 儿童相比，HME 受影响的半球较大，未受影响的半球较小。 75% 的病例中，受影响的 HME 侧显示增大的异常深部灰质和白质结构和/或皮质下白质 T2 加权低信号，提示过度的产前神经发生和异位。对受影响的 HME 侧进行组织病理学检查，发现 70% 的病例出现未成熟的神经元，61% 的病例出现多小脑回 (PMG)，45% 的病例出现气球细胞。与尸检病例相比，HME儿童患侧NeuN细胞密度在分子层和上皮层增加（+244%至+18%），在下皮层减少（−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未成熟神经元和 PMG 的存在、下皮质层 NeuN 细胞密度降低以及婴儿痉挛症阳性病史相关。术后癫痫发作控制与分子层 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，而对侧半脑畸形可能是术后癫痫控制和认知结果较差的解释。此外，我们的研究结果支持这样的假设：HME 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 一侧的神经元数量比预期的要多。
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.