{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:38:19Z","timestamp":1791837499256,"version":"4.3.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Impaired glymphatic function is linked to cerebral atrophy and contributes to clinical disability in patients with relapsing-remitting multiple sclerosis (RRMS). Deep gray matter volume (DGMV) loss is associated with disability; however, its mediating effect in MS-related disability and glymphatic function changes remains underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One hundred and thirty-one RRMS patients and 50 healthy controls (HC) underwent MRI scans. The DTI-ALPS index was used to evaluate glymphatic function. Z-scores of cortical and deep gray matter volumes (CGMV and DGMV) and WM-FA in RRMS patients were determined based on the mean and standard deviation of HC. RRMS patients were divided into two subgroups: the \u201cMS-DGM-preserved\u201d subgroup (z-scores of both CGMV, DGMV, and WM-FA &amp;gt; -2) and the \u201cMS-DGM-atrophied\u201d subgroup (z-scores of DGMV &amp;lt; -2) according to combinations of z-scores compared to HC. The mediating effect of DGMV in the relationship between the DTI-ALPS index and the clinical disability was further explored. Patients were followed up and had longitudinal outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among all participants, 79 cases (60.3%) were classified as the MS-DGM-preserved subgroup, and 52 cases (39.7%) as the MS-DGM-atrophied subgroup. The MS-DGM-atrophied subgroup exhibited lower DTI-ALPS index (d=1.42, p-FDR&amp;lt; 0.001), higher T2-hyperintense white matter lesion volume (d=0.98, p-FDR&amp;lt; 0.001) and EDSS scores (d=0.49, p-FDR&amp;lt; 0.001), and longer disease duration (d=0.33, p-FDR=0.005) compared to the MS-DGM-preserved subgroup. Additionally, in the MS-DGM-atrophied subgroup, the DTI-ALPS index was significantly positively correlated with DGMV (r=0.59, p-FDR&amp;lt;0.001), and negatively correlated with EDSS scores and disease duration (r=-0.59, r=-0.56, p-FDR&amp;lt;0.001). Mediation analysis revealed that DGMV partially mediated the relationship between the DTI-ALPS index and clinical disability (EDSS and disease duration). In the longitudinal cohort, 18 MS patients were followed for a median time of 14 months (12.75, 14.00 months; range: 8\u201318 months). Compared to baseline, the DTI-ALPS index significantly decreased during follow-up (d=0.92, p-FDR=0.009).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The RRMS subgroups based on the gradient classification of DGMV using structural MRI effectively distinguishes differences in glymphatic function and clinical disability. When DGM atrophy reaches a certain threshold, it partially mediates the relationship between glymphatic function and clinical disability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1758859","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:23:23Z","timestamp":1772515403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Deep gray matter atrophy mediates the associations between glymphatic dysfunction and clinical disability in relapsing-remitting multiple sclerosis: a neuroimaging subgroup study"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology, The First Hospital of China Medical University","place":["Shenyang, Liaoning, 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