{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:03:58Z","timestamp":1789707838949,"version":"4.0.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"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>Glymphatic dysfunction has been reported in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), yet disease-specific patterns of glymphatic-related impairment and their structural and cognitive consequences remain poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 196 MS patients, 88 NMOSD patients, and 108 healthy controls (HC). Glymphatic-related function was assessed using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and periventricular diffusivity (PVeD). Between-group differences, partial correlations with structural and clinical outcomes, AQP4 subgroup comparisons, mediation analyses, and subcortical atrophy-based subgroup analyses were performed to characterize disease-specific glymphatic-related impairment patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MS showed more extensive glymphatic-related impairment than NMOSD, with significant reductions in both DTI-ALPS and PVeD compared to HC (all p&amp;lt;0.001). PVeD was significantly reduced in NMOSD compared to HC in both cohorts (p \u2264 0.008), whereas DTI-ALPS differences in NMOSD relative to HC were inconsistent across cohorts, reaching significance only in the GE replication cohort. In MS, PVeD showed widespread structural and cognitive associations; in NMOSD, associations were restricted to ventricular and choroid plexus volumes. A parallel multiple mediation model showed that subcortical gray matter atrophy, but not lesion volume, independently mediated the association between PVeD and Symbol Digit Modalities Test performance in MS, a pattern absent in NMOSD. Stratified subgroup analysis showed a pattern consistent with a glymphatic-cognitive association specific to patients with greater subcortical atrophy in MS, although formal interaction tests did not reach statistical significance; no such association was observed in either atrophy subgroup in NMOSD. AQP4-seropositive, but not seronegative, NMOSD patients showed significantly lower glymphatic-related metrics than HC (p&amp;lt;0.001); direct comparison between the two subgroups was not significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glymphatic-related dysfunction exhibits distinct disease-specific patterns in MS and NMOSD, with PVeD showing broader sensitivity across both cohorts. These findings support PVeD as a promising complementary glymphatic-related diffusion marker in inflammatory demyelinating disease, though causal and disease-mechanistic interpretations await validation in longitudinal and mechanistic studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1917373","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:36:05Z","timestamp":1789706165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease-specific patterns of glymphatic-related dysfunction between multiple sclerosis and neuromyelitis optica spectrum disorder"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoya","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuowei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichun","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.216","article-title":"Neuroimmunology: towards more-accurate diagnosis in neuromyelitis optica","volume":"10","author":"Fujihara","year":"2014","journal-title":"Nat Rev Neurol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70133-3","article-title":"Aquaporin 4 and neuromyelitis optica","volume":"11","author":"Papadopoulos","year":"2012","journal-title":"Lancet Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3348\/kjr.2023.0360","article-title":"Understanding the pathophysiology and magnetic resonance imaging of multiple sclerosis and neuromyelitis optica spectrum disorders","volume":"24","author":"Cacciaguerra","year":"2023","journal-title":"Korean J Radiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1581-6","article-title":"The glymphatic system: A beginner's guide","volume":"40","author":"Jessen","year":"2015","journal-title":"Neurochem Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci Transl Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2025.110484","article-title":"Glymphatic system dysfunction in multiple sclerosis: A systematic review and meta-analysis","volume":"123","author":"Mahmoudi","year":"2025","journal-title":"Magn Reson Imaging"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241280842","article-title":"Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability","volume":"30","author":"Bayoumi","year":"2024","journal-title":"Mult Scler"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.966781","article-title":"Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients","volume":"13","author":"Yao","year":"2022","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1698986","article-title":"Glymphatic dysfunction in neuromyelitis optica spectrum disorder","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer's disease cases","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn J Radiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.parkreldis.2020.11.009","article-title":"Altered glymphatic system in idiopathic normal pressure hydrocephalus","volume":"82","author":"Bae","year":"2021","journal-title":"Parkinsonism Relat Disord"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2504","article-title":"Glymphatic system function in patients with newly diagnosed focal epilepsy","volume":"12","author":"Lee","year":"2022","journal-title":"Brain Behav"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2021.12.013","article-title":"Glymphatic system dysfunction in obstructive sleep apnea evidenced by DTI-ALPS","volume":"89","author":"Lee","year":"2022","journal-title":"Sleep Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201300","article-title":"Association of MRI indices of glymphatic system with amyloid deposition and cognition in mild cognitive impairment and Alzheimer disease","volume":"99","author":"Kamagata","year":"2022","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26680","article-title":"Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using mri indices from diffusion tensor imaging","volume":"45","author":"Kim","year":"2024","journal-title":"Hum Brain Mapp"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.rev.2023-0175","article-title":"Diffusion tensor image analysis along the perivascular space (dti-alps): revisiting the meaning and significance of the method","volume":"23","author":"Taoka","year":"2024","journal-title":"Magn Reson Med Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.70282","article-title":"White matter geometry confounds diffusion tensor imaging along perivascular space (Dti-Alps) measures","volume":"46","author":"Schilling","year":"2025","journal-title":"Hum Brain Mapp"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70659","article-title":"Periventricular diffusivity reflects apoe epsilon4-modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum","volume":"21","author":"Chen","year":"2025","journal-title":"Alzheimers Dement"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.101849","article-title":"Automated segmentation of changes in FLAIR-hyperintense white matter lesions in multiple sclerosis on serial magnetic resonance imaging","volume":"23","author":"Schmidt","year":"2019","journal-title":"NeuroImage Clin"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/jon.70086","article-title":"Reliability and spatial consistency of MR diffusion tensor imaging measures along the cerebral perivascular space","volume":"35","author":"Qiu","year":"2025","journal-title":"J Neuroimaging"},{"key":"B24","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s11604-022-01370-2","article-title":"Improved reproducibility of diffusion tensor image analysis along the perivascular space (DTI-ALPS) index: an analysis of reorientation technique of the OASIS-3 dataset","volume":"41","author":"Tatekawa","year":"2023","journal-title":"Jpn J Radiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0321-2","article-title":"Cross-vendor test-retest validation of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function","volume":"15","author":"Liu","year":"2024","journal-title":"Aging Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab454","article-title":"Glymphatic system impairment in multiple sclerosis: relation with brain damage and disability","volume":"145","author":"Carotenuto","year":"2022","journal-title":"Brain"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200414","article-title":"Glymphatic system may mediate the relation between choroid plexus and brain damage in multiple sclerosis","volume":"12","author":"Preziosa","year":"2025","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1758859","article-title":"Deep gray matter atrophy mediates the associations between glymphatic dysfunction and clinical disability in relapsing-remitting multiple sclerosis: a neuroimaging subgroup study","volume":"17","author":"Zhang","year":"2026","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26911","article-title":"Cognitive impairment is related to glymphatic system dysfunction in pediatric multiple sclerosis","volume":"95","author":"Margoni","year":"2024","journal-title":"Ann Neurol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105456","article-title":"The glymphatic system and multiple sclerosis: An evolving connection","volume":"83","author":"Alghanimy","year":"2024","journal-title":"Mult Scler Relat Disord"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1917373\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:36:07Z","timestamp":1789706167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1917373\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,18]]},"references-count":30,"alternative-id":["10.3389\/fimmu.2026.1917373"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1917373","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,18]]},"article-number":"1917373"}}