From the Division of Neurology (S.K.), Department of Medicine, Neuroscience and Mental Health Institute (S.K., A.I.), and Department of Biomedical Engineering (C.B.), University of Alberta, Edmonton, Canada; Department of Neurology (H.-P.M., J.K.), University of Ulm, Germany; Sunnybrook Health Sciences Centre (L.Z., S.J.G.), University of Toronto, Ontario; Departments of Clinical Neurosciences (L.K., R.F.) and Radiology (R.F.), Hotchkiss Brain Institute, University of Calgary, Alberta; Montreal Neurological Institute and Hospital (A.G.), McGill University, Quebec; and Seaman Family MR Research Centre (R.F.), Foothills Medical Centre, Calgary, Alberta, Canada.
Neurology. 2020 Aug 25;95(8):e943-e952. doi: 10.1212/WNL.0000000000010235. Epub 2020 Jul 9.
To evaluate progressive white matter (WM) degeneration in amyotrophic lateral sclerosis (ALS).
Sixty-six patients with ALS and 43 healthy controls were enrolled in a prospective, longitudinal, multicenter study in the Canadian ALS Neuroimaging Consortium (CALSNIC). Participants underwent a harmonized neuroimaging protocol across 4 centers that included diffusion tensor imaging (DTI) for assessment of WM integrity. Three visits were accompanied by clinical assessments of disability (ALS Functional Rating Scale-Revised [ALSFRS-R]) and upper motor neuron (UMN) function. Voxel-wise whole-brain and quantitative tract-wise DTI assessments were done at baseline and longitudinally. Correction for site variance incorporated data from healthy controls and from healthy volunteers who underwent the DTI protocol at each center.
Patients with ALS had a mean progressive decline in fractional anisotropy (FA) of the corticospinal tract (CST) and frontal lobes. Tract-wise analysis revealed reduced FA in the CST, corticopontine/corticorubral tract, and corticostriatal tract. CST FA correlated with UMN function, and frontal lobe FA correlated with the ALSFRS-R score. A progressive decline in CST FA correlated with a decline in the ALSFRS-R score and worsening UMN signs. Patients with fast vs slow progression had a greater reduction in FA of the CST and upper frontal lobe.
Progressive WM degeneration in ALS is most prominent in the CST and frontal lobes and, to a lesser degree, in the corticopontine/corticorubral tracts and corticostriatal pathways. With the use of a harmonized imaging protocol and incorporation of analytic methods to address site-related variances, this study is an important milestone toward developing DTI biomarkers for cerebral degeneration in ALS.
NCT02405182.
评估肌萎缩侧索硬化症（ALS）中的进行性白质（WM）退化。
66 例 ALS 患者和 43 例健康对照者参加了加拿大 ALS 神经影像学联合会（CALSNIC）的一项前瞻性、纵向、多中心研究。参与者在 4 个中心接受了一项协调的神经影像学方案，包括扩散张量成像（DTI）以评估 WM 完整性。3 次就诊时都进行了残疾（修订后的肌萎缩侧索硬化功能评定量表 [ALSFRS-R]）和上运动神经元（UMN）功能的临床评估。在基线和纵向进行了全脑体素和定量束DTI 评估。对站点方差进行校正，纳入了来自健康对照者和每个中心接受 DTI 方案的健康志愿者的数据。
ALS 患者的皮质脊髓束（CST）和额叶的各向异性分数（FA）呈进行性下降。束状分析显示 CST、皮质桥脑/皮质红核束和皮质纹状体束的 FA 降低。CST FA 与 UMN 功能相关，额叶 FA 与 ALSFRS-R 评分相关。CST FA 的进行性下降与 ALSFRS-R 评分的下降和 UMN 体征的恶化相关。快速进展与缓慢进展的患者 CST 和上额叶的 FA 降低更为明显。
ALS 中的进行性 WM 退化最明显的是 CST 和额叶，其次是皮质桥脑/皮质红核束和皮质纹状体通路。使用协调的成像方案和采用分析方法解决与站点相关的变异性，本研究是朝着开发 ALS 大脑退化的 DTI 生物标志物迈出的重要一步。
临床试验.gov 标识符：NCT02405182。
