Mahmoudi Farhad, Mirmosayyeb Omid, Yazdan Panah Mohammad, Vaheb Saeed, Shaygannejad Vahid, Salan Teddy, Nelson Flavia
Department of Neurology, University of Miami, Miami, FL 33136, USA.
Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
Magn Reson Imaging. 2025 Nov;123:110484. doi: 10.1016/j.mri.2025.110484. Epub 2025 Aug 6.
The glymphatic system (GS) facilitates cerebral waste elimination through the exchange of cerebrospinal and interstitial fluid along perivascular pathways, serving a crucial role in neural homeostasis. GS dysfunction has been implicated in various neurological diseases, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This review aimed to assess glymphatic dysfunction in people with MS (PwMS), NMOSD, and MOGAD using diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS).
PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched up to March 10, 2025. We reviewed studies comparing ALPS index values between patient groups and healthy controls (HC). We further analyzed the relationships between glymphatic function and clinical characteristics, as well as MRI indices.
The meta-analysis revealed significantly lower ALPS index values in PwMS compared to HC (SMD = -0.91, p < 0.01), suggesting impaired glymphatic function. A significant inverse correlation was found between the ALPS index and disease duration (r = -0.26, p < 0.01), Expanded Disability Status Scale (EDSS) (r = -0.32, p < 0.01), and white matter lesion volume (r = -0.42, p < 0.01). Lower ALPS values, or reduced glymphatic function, were associated with more advanced disease, greater disability, and a higher lesion burden in MS. Preliminary findings for NMOSD and MOGAD also showed reduced glymphatic function; however, due to the limited and heterogeneous data available, these conditions were not included in the meta-analytic synthesis. Their results are discussed narratively and should be interpreted cautiously.
Evidence for glymphatic dysfunction in PwMS is supported by a small body of research, correlating with disease activity measures. DTI-ALPS offers a non-invasive technique to evaluate glymphatic activity and holds promise as a potential biomarker for monitoring disease progression. Further studies with larger sample sizes and standardized protocols are needed to confirm these findings.
类淋巴系统（GS）通过沿血管周围途径交换脑脊液和组织间液促进脑内废物清除，在神经内环境稳态中起关键作用。GS功能障碍与多种神经系统疾病有关，包括多发性硬化症（MS）、视神经脊髓炎谱系障碍（NMOSD）和髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）。本综述旨在使用基于扩散张量成像的血管周围间隙分析（DTI-ALPS）评估MS患者（PwMS）、NMOSD和MOGAD患者的类淋巴功能障碍。
检索截至2025年3月10日的PubMed/MEDLINE、Embase、Scopus和Web of Science数据库。我们回顾了比较患者组和健康对照（HC）之间ALPS指数值的研究。我们进一步分析了类淋巴功能与临床特征以及MRI指标之间的关系。
荟萃分析显示，与HC相比，PwMS的ALPS指数值显著更低（标准化均值差= -0.91，p < 0.01），表明类淋巴功能受损。发现ALPS指数与疾病持续时间（r = -0.26，p < 0.01）、扩展残疾状态量表（EDSS）（r = -0.32，p < 0.01）和白质病变体积（r = -0.42，p < 0.01）之间存在显著负相关。在MS中，较低的ALPS值或类淋巴功能降低与疾病进展更严重、残疾程度更高和病变负担更大相关。NMOSD和MOGAD的初步研究结果也显示类淋巴功能降低；然而，由于可用数据有限且异质性较大，这些情况未纳入荟萃分析综合。对其结果进行了叙述性讨论，应谨慎解释。
一小部分研究支持PwMS中类淋巴功能障碍的证据，与疾病活动度测量相关。DTI-ALPS提供了一种评估类淋巴活动的非侵入性技术，有望作为监测疾病进展的潜在生物标志物。需要进一步进行更大样本量和标准化方案的研究来证实这些发现。
