Wang Zhuo, Xu Xia, Jia Fei, Ren Wenjing, Wang Jun, Liu Yang, Jiang Jingqi, Zhou Liang, Ai Kai, Zhang Jing
Department of Magnetic Resonance, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou, China; Gansu Medical MRI Equipment Application Industry Technology Center, Lanzhou, China.
Department of Magnetic Resonance, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Mult Scler Relat Disord. 2025 Aug;100:106531. doi: 10.1016/j.msard.2025.106531. Epub 2025 May 14.
To explore the glymphatic dysfunction in relapsing-remitting multiple sclerosis (RRMS) and its potential associations with brain structural damage, clinical disability, and cognitive impairment (Co-I).
The study involved 70 patients with RRMS and 44 healthy controls. Neurological and MRI assessments were performed, and cognitive performance was assessed via the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). To assess the glymphatic function, we calculated the choroid plexus volume (CPV) and diffusion tensor imaging along perivascular spaces (DTI-ALPS) index. Multivariable linear regression analyses were used to examine correlations between glymphatic dysfunction and MRI-derived brain damage metrics. Additionally, we utilised random forest analysis to identify predictors of Co-I and assessed the mediating role of DTI-ALPS.
Patients with RRMS, particularly those with Co-I, exhibited a low DTI-ALPS index and large CPV. A lower DTI-ALPS index was associated with longer disease duration, greater disability, larger lesion volume (LV), mean diffusivity (MD), and CPV, as well as lower fractional anisotropy (FA) (all FDR-p < 0.05). Moreover, DTI-ALPS mediated 27.21 % and 43.75 % of CPV effects on information processing speed and visuospatial memory, respectively. Random forest analysis indicated that lower education (relative importance [RI] = 100 %), higher CPV (RI = 95.8 %), lower DTI-ALPS index (RI = 80.7 %), higher MD (RI = 61.3 %), lower FA (RI = 60.5 %), older age (RI = 54.6 %), and higher EDSS score (RI = 45.4 %) are predictors of Co-I.
The study implied that glymphatic dysfunction may contribute to brain structural damage, clinical disability, and cognitive impairment in RRMS, indicating that glymphatic dysfunction may play a key role in the pathogenesis of RRMS.
探讨复发缓解型多发性硬化症（RRMS）中的类淋巴系统功能障碍及其与脑结构损伤、临床残疾和认知障碍（Co-I）的潜在关联。
该研究纳入了70例RRMS患者和44名健康对照者。进行了神经学和MRI评估，并通过简短可重复神经心理测验电池（BRB-N）评估认知表现。为评估类淋巴系统功能，我们计算了脉络丛体积（CPV）和沿血管周围间隙的扩散张量成像（DTI-ALPS）指数。采用多变量线性回归分析来检验类淋巴系统功能障碍与MRI衍生的脑损伤指标之间的相关性。此外，我们利用随机森林分析来确定Co-I的预测因素，并评估DTI-ALPS的中介作用。
RRMS患者，尤其是伴有Co-I的患者，表现出较低的DTI-ALPS指数和较大的CPV。较低的DTI-ALPS指数与疾病持续时间较长、残疾程度较高、病变体积（LV）、平均扩散率（MD）和CPV较大以及分数各向异性（FA）较低相关（所有FDR-p<0.05）。此外，DTI-ALPS分别介导了CPV对信息处理速度和视觉空间记忆影响的27.21%和43.75%。随机森林分析表明，较低的教育程度（相对重要性[RI]=100%）、较高的CPV（RI=95.8%）、较低的DTI-ALPS指数（RI=80.7%）、较高的MD（RI=61.3%）、较低的FA（RI=60.5%）、较高的年龄（RI=54.6%）和较高的扩展残疾状态量表（EDSS）评分（RI=45.4%）是Co-I的预测因素。
该研究表明，类淋巴系统功能障碍可能导致RRMS中的脑结构损伤、临床残疾和认知障碍，表明类淋巴系统功能障碍可能在RRMS的发病机制中起关键作用。
