Abstract: Objective To compare the differences between the gray matter structures of amyotrophic lateral sclerosis (ALS) patients with limb-onset and bulbar-onset. Methods A total of 35 ALS patients with normal cognitive function were enrolled in Peking Union Medical College Hospital ALS Registry Platform from September 2013 to March 2018, and 20 healthy controls with matched age and education were included in the study. ALS patients were divided into limb-onset group (ALS-L group, n=20) and bulbar-onset group (ALS-B group, n=15) according to their clinical onset sites. Three-dimensional T₁-fast spoiled gradient-recalled (3D-T₁-FSPGR) of all subjects was collected. Gray matter volume of each group were compared using voxel-based morphometry (VBM). Within the compound region of interest (ROI) consisting of bilateral primary motor cortex, premotor cortex and supplementary motor area, the atrophy patterns of the motor cortex were compared between ALS-L group and ALS-B group. Results Compared with the control group, the ALS-L group had decreased gray matter volume in the left superior temporal gyrus-temporal pole (t=3.932, uncorrected P<0.001), left middle temporal gyrus (t=3.836, uncorrected P<0.001), right insula (t=3.992, uncorrected P<0.001). Compared with the ALS-B group, the ALS-L group had decreased gray matter volume in the right superior frontal gyrus (t=-3.158, uncorrected P<0.001), left cingulate gyrus (t=-3.002, uncorrected P<0.001). In the analysis of the motor cortex as ROI, the gray matter volume of the segments representing hand (t=2.237, uncorrected P<0.001) and lower limb (t=2.728, uncorrected P<0.001) of the left motor cortex in the ALS-L group was reduced significantly than that of ALS-B group. Conclusions ALS-L has more significant gray matter atrophy than ALS-B, and the local atrophy pattern of motor cortex in ALS patients corresponds to its functional disability.

Key words: Amyotrophic lateral sclerosis, Gray matter, Magnetic resonance imaging

摘要： 目的 探讨肢体发病与延髓发病的肌萎缩侧索硬化症（ALS）患者脑灰质结构差异。方法 纳入2013年9月至2018年3月中国医学科学院北京协和医院肌萎缩侧索硬化症注册系统中认知功能正常的35例患者，根据发病部位分为肢体发病组（ALS-L组，20例）和延髓发病组（ALS-B组，15例），并同期招募20例社区健康对照者，所有受试者均行三维T₁-快速扰相梯度回波序列，采用基于体素的形态学分析方法比较各组受试者灰质体积；以双侧初级运动皮质、前运动皮质及辅助运动区的复合区作为兴趣区，比较ALS-L与ALS-B患者运动皮质萎缩模式。结果 与对照组相比，ALS-L组左侧颞上回-颞极（t=3.932，未校正P<0.001）、左侧颞中回（t=3.836，未校正P<0.001）、右侧岛叶（t=3.992，未校正P <0.001）存在小簇灰质体积减少区域；与ALS-B组相比，ALS-L组右侧额上回（t=-3.158，未校正P <0.001）、左侧扣带回（t=-3.002，未校正P<0.001）存在灰质体积减少区域，且兴趣区内左侧运动皮质拓扑地形图手部（t=2.237，未校正P<0.001）及下肢（t=2.728，未校正P<0.001）定位区灰质体积减少。结论 ALS-L患者较ALS-B患者具有更显著的灰质体积减少，且肌萎缩侧索硬化症患者运动皮质局部萎缩模式与其功能致残性相对应。

关键词: 肌萎缩侧索硬化, 灰质, 磁共振成像