ObjectiveThe aim of this study was to investigate whether, compared to pediatric healthy controls (HCs), the glymphatic system is impaired in pediatric multiple sclerosis (MS) patients according to their cognitive status, and to assess its association with clinical disability and MRI measures of brain structural damage.MethodsSixty‐five pediatric MS patients (females = 62%; median age = 15.5 [interquartile range, IQR = 14.5;17.0] years) and 23 age‐ and sex‐matched HCs (females = 44%; median age = 14.1 [IQR = 11.8;16.2] years) underwent neurological, neuropsychological and 3.0 Tesla MRI assessment, including conventional and diffusion tensor imaging (DTI). We calculated the diffusion along the perivascular space (DTI‐ALPS) index, a proxy of glymphatic function. Cognitive impairment (Co‐I) was defined as impairment in at least 2 cognitive domains.ResultsNo significant differences in DTI‐ALPS index were found between HCs and cognitively preserved (Co‐P) pediatric MS patients (estimated mean difference [EMD] = −0.002 [95% confidence interval = −0.069; 0.065], FDR‐p = 0.956). Compared to HCs and Co‐P patients, Co‐I pediatric MS patients (n = 20) showed significantly lower DTI‐ALPS index (EMD = −0.136 [95% confidence interval = −0.214; −0.058], FDR‐p ≤ 0.004). In HCs, no associations were observed between DTI‐ALPS index and normalized brain, cortical and thalamic volumes, and normal‐appearing white matter (NAWM) fractional anisotropy (FA) and mean diffusivity (MD) (FDR‐p ≥ 0.348). In pediatric MS patients, higher brain WM lesion volume (LV), higher NAWM MD, lower normalized thalamic volume, and lower NAWM FA were associated with lower DTI‐ALPS index (FDR‐p ≤ 0.016). Random Forest selected lower DTI‐ALPS index (relative importance [RI] = 100%), higher brain WM LV (RI = 59.5%) NAWM MD (RI = 57.1%) and intelligence quotient (RI = 51.3%) as informative predictors of cognitive impairment (out‐of‐bag area under the curve = 0.762).InterpretationGlymphatic system dysfunction occurs in pediatric MS, is associated with brain focal lesions, irreversible tissue loss accumulation and cognitive impairment. ANN NEUROL 2024

中文翻译：

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认知障碍与小儿多发性硬化症的类淋巴系统功能障碍有关

目的：本研究的目的是调查与儿科健康对照 (HC) 相比，儿科多发性硬化症 (MS) 患者的类淋巴系统是否因认知状态而受损，并评估其与临床残疾和 MRI 测量的相关性。方法 65 名儿科多发性硬化症患者（女性 = 62%；中位年龄 = 15.5 [四分位距，IQR = 14.5;17.0] 岁）和 23 名年龄和性别匹配的 HC（女性 = 44%；中位年龄 = 14.1 [IQR = 11.8;16.2] 岁）接受了神经学、神经心理学和 3.0 Tesla MRI 评估，包括常规和扩散张量成像 (DTI)。我们计算了沿血管周围空间的扩散（DTI-ALPS）指数，这是类淋巴功能的代表。认知障碍 (Co-I) 被定义为至少 2 个认知领域的障碍。 结果 HC 和认知保留 (Co-P) 儿童 MS 患者之间 DTI-ALPS 指数没有发现显着差异（估计平均差 [EMD] = − 0.002 [95% 置信区间 = −0.069; 0.065]，FDR-p = 0.956）。与 HC 和 Co-P 患者相比，Co-I 儿科 MS 患者 (n = 20) 显示出显着较低的 DTI-ALPS 指数 (EMD = -0.136 [95% 置信区间 = -0.214; -0.058]，FDR-p ≤ 0.004 ）。在 HC 中，未观察到 DTI-ALPS 指数与标准化大脑、皮质和丘脑体积以及正常白质 (NAWM) 分数各向异性 (FA) 和平均扩散率 (MD) 之间的关联 (FDR-p ≥ 0.348)。在儿科 MS 患者中，较高的脑 WM 病变体积 (LV)、较高的 NAWM MD、较低的标准化丘脑体积和较低的 NAWM FA 与较低的 DTI-ALPS 指数相关 (FDR-p ≤ 0.016)。随机森林选择较低的 DTI‐ALPS 指数（相对重要性 [RI] = 100%）、较高的大脑 WM LV（RI = 59.5%）、NAWM MD（RI = 57.1%）和智商（RI = 51.3%）作为信息预测因子认知障碍（袋外曲线下面积 = 0.762）。解释儿童多发性硬化症中会发生类淋巴系统功能障碍，与脑局灶性病变、不可逆组织丢失积累和认知障碍有关。安神经学 2024