Turner Martin R, Hammers Alexander, Allsop Joanna, Al-Chalabi Ammar, Shaw Christopher E, Brooks David J, Leigh P Nigel, Andersen Peter M
Department of Neurology, John Radcliffe Hospital, Oxford, UK.
Amyotroph Lateral Scler. 2007 Dec;8(6):343-7. doi: 10.1080/17482960701538734.
Patients homozygous for the D90A mutation of the SOD1 gene (homD90A) demonstrate markedly slower progression of disease than those patients with sporadic ALS (SALS). PET studies have demonstrated a different cortical vulnerability in the two groups, reflected also in neurophysiological studies showing reduced cortical excitability in homD90A. Voxel-based morphometric analysis of magnetic resonance images (MRIs) enables the detection of regional differences in grey matter volume, and can be used to localize cortical atrophy in vivo. In this study, segmented, spatially normalized, modulated and smoothed grey matter portions of the MRIs from 23 SALS and seven homD90A patients with similar disability, were compared with those from 28 healthy control subjects. The SALS group showed bilateral areas of atrophy mainly confined to motor and pre-motor cortices. Cortical changes in the homD90A group were more pronounced within the frontal lobes when both were compared with healthy controls. This study provides further evidence for a different pattern of cortical neuronal vulnerability in homD90A versus SALS patients that may provide insight as to their slower rate of disease progression.
超氧化物歧化酶1（SOD1）基因D90A突变的纯合患者（homD90A）与散发性肌萎缩侧索硬化症（SALS）患者相比，疾病进展明显较慢。正电子发射断层扫描（PET）研究表明，两组患者的皮质易损性不同，神经生理学研究也反映了这一点，即homD90A患者的皮质兴奋性降低。基于体素的磁共振成像（MRI）形态学分析能够检测灰质体积的区域差异，并可用于在体内定位皮质萎缩。在本研究中，将23例SALS患者和7例残疾程度相似的homD90A患者的MRI图像经分割、空间归一化、调制和平滑处理后的灰质部分，与28例健康对照者的灰质部分进行比较。SALS组双侧萎缩区域主要局限于运动和运动前皮质。与健康对照相比，homD90A组的额叶皮质变化更为明显。这项研究为homD90A患者与SALS患者皮质神经元易损性的不同模式提供了进一步的证据，这可能有助于解释他们疾病进展较慢的原因。
