Huang Nao-Xin, Zeng Jing-Yi, Huang Hui-Wei, Fang Si-Yuan, Chen Sheng, Li Jian-Qi, Chen Hua-Jun, Zou Zhang-Yu
Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China.
Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, China.
Quant Imaging Med Surg. 2025 Apr 1;15(4):3445-3457. doi: 10.21037/qims-24-1297. Epub 2025 Mar 28.
Formation and aggregation of pathological proteins in the brain constitutes a critical hallmark of amyotrophic lateral sclerosis (ALS). However, the role of the glymphatic system in the clearance of pathological proteins in ALS remains unclear. The purpose of this cross-sectional study was to evaluate glymphatic system disturbance in ALS and its relation to neural function.
This study included 38 healthy controls (HCs) and 30 patients with ALS who underwent diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI). The disease severity, duration, and progression rate of ALS were recorded. Glymphatic system function was indirectly evaluated by DTI analysis along the perivascular space (ALPS) surrounding the deep medullary vein. Neural activity was examined in sensorimotor-related brain areas by measuring amplitude of low-frequency fluctuation (ALFF) based on rs-fMRI. A two-sample -test or Mann-Whitney test was used to examine between-group differences in ALPS, diffusivities measured along the x-, y-, and z-axis in the association (Dxx_association, Dyy_association, Dzz_association) and projection (Dxx_projection, Dyy_projection, Dzz_projection) fiber areas, and ALFF indices. The associations between ALPS, diffusivities, ALFF, and clinical assessments were determined via Spearman correlation analysis, and diagnostic performance was evaluated with receiver operating characteristic curve analysis.
Patients with ALS exhibited significantly decreased ALPS and increased diffusivities (Dyy_association and Dyy_projection) as compared to HCs (all P values <0.05). Patients with ALS showed decreased ALFF in sensorimotor-related regions, including the bilateral primary motor and somatosensory areas (all P values <0.001) and left supplementary motor area (P=0.031). ALPS and diffusivities were correlated with ALFF in the sensorimotor-motor regions (all P values <0.05), and ALPS and ALFF correlated with disease severity and duration (all P values <0.05). ALPS, diffusivities, and ALFF showed moderate ability to diagnose ALS.
The glymphatic system function was impaired in ALS. This may contribute to spontaneous neural activity disturbance and could represent a mechanism for the development of sensorimotor deficits frequently observed in patients with ALS.
大脑中病理性蛋白质的形成和聚集是肌萎缩侧索硬化症（ALS）的一个关键标志。然而，类淋巴系统在ALS中病理性蛋白质清除过程中的作用仍不清楚。这项横断面研究的目的是评估ALS中类淋巴系统的紊乱及其与神经功能的关系。
本研究纳入了38名健康对照者（HCs）和30名ALS患者，他们均接受了扩散张量成像（DTI）和静息态功能磁共振成像（rs-fMRI）检查。记录了ALS患者的疾病严重程度、病程和进展速度。通过沿深髓静脉周围的血管周围间隙（ALPS）进行DTI分析间接评估类淋巴系统功能。基于rs-fMRI，通过测量低频振幅（ALFF）来检查感觉运动相关脑区的神经活动。采用两样本t检验或曼-惠特尼检验来检查ALPS、在联合纤维区（Dxx_association、Dyy_association、Dzz_association）和投射纤维区（Dxx_projection、Dyy_projection、Dzz_projection）沿x、y和z轴测量的扩散率以及ALFF指数的组间差异。通过Spearman相关分析确定ALPS、扩散率、ALFF与临床评估之间的关联，并通过受试者工作特征曲线分析评估诊断性能。
与HCs相比，ALS患者的ALPS显著降低，扩散率（Dyy_association和Dyy_projection）增加（所有P值<0.05）。ALS患者在感觉运动相关区域，包括双侧初级运动区和躯体感觉区（所有P值<0.001）以及左侧辅助运动区（P=0.031）的ALFF降低。在感觉运动区域，ALPS和扩散率与ALFF相关（所有P值<0.05），并且ALPS和ALFF与疾病严重程度和病程相关（所有P值<0.05）。ALPS、扩散率和ALFF显示出中等的ALS诊断能力。
ALS患者的类淋巴系统功能受损。这可能导致自发神经活动紊乱，并可能代表ALS患者中经常观察到的感觉运动缺陷发生发展的一种机制。
