From the Neuroimaging Research Unit (F.A., E.G.S., E.P., P.V., M.F.) and Department of Neurology (M.F.), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; and Clinic of Neurology (I.V.M., Z.S., B.S.-D., M.J., D.L., V.S.K.), Faculty of Medicine, University of Belgrade, Serbia.
Neurology. 2018 Feb 20;90(8):e707-e716. doi: 10.1212/WNL.0000000000005002. Epub 2018 Jan 24.
To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase () gene compared with sporadic ALS.
Twenty patients with ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR).
Patients with ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls ( = 0.001-0.02) and SOD1-related ALS ( = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS ( < 0.001). No cord MTR differences were found between patient groups.
Patients with ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive ALS therapies.
与散发性肌萎缩侧索硬化症（ALS）相比，探究超氧化物歧化酶 1（SOD1）基因突变所致 ALS 患者的大脑和颈髓的结构与功能变化。
20 例 ALS 患者（11 例散发性 ALS，9 例 SOD1 相关性 ALS）和 33 例健康对照者接受临床评估和脑 MRI 检查。进行皮质厚度分析、皮质脊髓束（CST）和胼胝体弥散张量 MRI 及静息状态功能连通性分析。ALS 患者还接受颈髓 MRI 以评估脊髓横截面积和磁化传递率（MTR）。
与散发性 ALS 患者相比，SOD1 相关性 ALS 患者的疾病病程更长，功能下降速度更慢。与对照组相比，ALS 患者的皮质厚度无异常。各向异性分数显示，与对照组（ = 0.001-0.02）和 SOD1 相关性 ALS（ = 0.05）相比，散发性 ALS 患者 CST 损伤显著，而后者 CST 改变处于对照组和散发性 ALS 之间。与对照组相比，散发性 ALS 患者感觉运动网络中的运动皮质功能连通性增强。相反，SOD1 相关性 ALS 患者的整个颈髓脊髓横截面积均小于散发性 ALS 患者（ < 0.001）。各组患者的脊髓 MTR 无差异。
与散发性 ALS 患者相比，SOD1 相关性 ALS 患者的颈髓萎缩，大脑运动结构和功能网络相对保留。SOD1 相关性 ALS 的神经退行性变可能主要发生在脊髓。对脊髓损伤进行客观、准确的评估可能有助于未来对 ALS 预防性治疗的评估。
