Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Brain and Mind Research Center, Nagoya University, Nagoya, Japan.
Eur J Neurol. 2022 Feb;29(2):432-440. doi: 10.1111/ene.15136. Epub 2021 Oct 31.
To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis.
We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables.
The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p < 0.05, familywise error-corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel-based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho = -0.530, p < 0.001; central motor conduction time [CMCT] in the upper limb: rho = -0.474, p = 0.008; disease duration: rho = -0.383, p = 0.007; ALS Functional Rating Scale-Revised: rho = 0.340, p = 0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs.
Our findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments.
为了阐明肌萎缩侧索硬化症（ALS）中纤维特异性白质变化与上运动神经元（UMN）受累的临床征象之间的关系，我们进行了基于纤维束的分析（FBA），这是一种新的弥散加权成像分析框架。
我们在这项研究中纳入了 96 名参与者，包括 48 名非家族性 ALS 患者和 48 名年龄和性别匹配的健康对照者（HCs），并进行了全脑 FBA 和基于体素的形态计量学分析。我们比较了 ALS 组和 HCs 组之间的纤维密度（FD）、纤维形态（纤维横截面积 [FC]）和 FD 和 FC 的综合指数（FDC）。我们进行了感兴趣区域分析，以提取全脑分析中显著区域的 FD 值。然后，我们评估了 FD 值与临床变量之间的关联。
与 HCs 相比，ALS 患者双侧皮质脊髓束（CSTs）和胼胝体（CC）的 FD 和 FDC 降低（p < 0.05，经家族性错误校正），而 FC 比较则未发现任何区域与其他区域有显著差异。基于体素的形态计量学显示，包括初级运动区在内的区域皮质体积减少。临床评分与 CSTs 中的 FD 值相关（UMN 评分：rho = -0.530，p < 0.001；上肢中央运动传导时间 [CMCT]：rho = -0.474，p = 0.008；疾病持续时间：rho = -0.383，p = 0.007；肌萎缩侧索硬化功能评定量表修订版：rho = 0.340，p = 0.018）。此外，由于未引出波而无法计算 CMCT 的患者 CSTs 中的 FD 值也降低。
我们的研究结果表明，通过 FBA 估计的 CSTs 的 FD 值可用于评估 UMN 损伤。
