{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:15:48Z","timestamp":1788171348645,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"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>Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis typically presents with acute neuroinflammation, and many patients often experience persistent cognitive impairment during the post-acute\/recovery phase. While impaired cerebrospinal fluid (CSF)-related markers\u2014including glymphatic function and choroid plexus (CP) structural remodeling\u2014are well documented in neurodegenerative diseases, their role in acute autoimmune brain injury remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate a glymphatic surrogate (diffusion tensor image analysis along the perivascular space (DTI-ALPS) index), choroid plexus structural remodeling (CP\/intracranial volume (ICV) ratio), white matter microstructural integrity (global fractional anisotropy (FA) using tract-based spatial statistics (TBSS)), and structural covariance network (SCN) topology in anti-NMDAR encephalitis using multimodal MRI, and to investigate their associations with cognition, with an exploratory mediation analysis examining whether white matter microstructure mediates these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 103 anti-NMDAR encephalitis patients and 97 healthy controls (HCs) with comparable sex distribution were enrolled. The glymphatic surrogate was evaluated by DTI-ALPS and CP structural remodeling was quantified by CP. White matter microstructural differences were analyzed using TBSS; mean FA values were extracted from all statistically significant clusters within the white matter skeleton (FA threshold = 0.2) after TFCE correction (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05), and the mean FA across these clusters was used as a global measure. Group-level SCNs were constructed based on 68 cortical regions, and graph theory metrics were compared. Partial correlation and bootstrap mediation analysis (5, 000 resamples) examined relationships among CSF markers, FA, and cognitive scores (MoCA, MMSE). A Monte Carlo sensitivity analysis was performed to determine the minimum indirect effect detectable at the achieved sample size (n = 103).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to HCs, patients with anti-NMDAR encephalitis showed significantly decreased bilateral DTI-ALPS indices (left: 1.361 \u00b1 0.196 vs. 1.489 \u00b1 0.178; right: 1.335 \u00b1 0.183 vs. 1.483 \u00b1 0.174;\n                      <jats:italic>q =<\/jats:italic>\n                      0.0001), increased CP\/ICV ratio (0.080 \u00b1 0.026 vs. 0.071 \u00b1 0.019,\n                      <jats:italic>q =<\/jats:italic>\n                      0.0135), and reduced global FA (0.506 \u00b1 0.052 vs. 0.597 \u00b1 0.099,\n                      <jats:italic>q&amp;lt;<\/jats:italic>\n                      0.0001). In covariate-adjusted analyses within the patient group (n=103), the CP\/ICV ratio showed strong negative correlations with MoCA (partial\n                      <jats:italic>r<\/jats:italic>\n                      = \u22120.463,\n                      <jats:italic>q&amp;lt;<\/jats:italic>\n                      0.001) and MMSE (partial\n                      <jats:italic>r =<\/jats:italic>\n                      \u22120.317,\n                      <jats:italic>q =<\/jats:italic>\n                      0.0078), while the left DTI-ALPS index showed a significant positive correlation with MoCA (partial\n                      <jats:italic>r =<\/jats:italic>\n                      0.310,\n                      <jats:italic>q =<\/jats:italic>\n                      0.0078). Global FA was strongly correlated with the DTI-ALPS index (partial\n                      <jats:italic>r =<\/jats:italic>\n                      0.394,\n                      <jats:italic>q&amp;lt;<\/jats:italic>\n                      0.001). However, exploratory bootstrap mediation analysis revealed that global FA significantly mediated the DTI-ALPS-MoCA association (indirect effect = 0.075, 95% CI [0.011, 0.152]; proportion mediated = 70.57%), but did not mediate the CP\/ICV-cognition associations (all 95% CIs included zero). Sensitivity analysis indicated adequate power to detect indirect effects \u2265 0.13; the observed effect (0.075) fell below this threshold, warranting caution in interpretation. Exploratory group-level structural covariance network analysis revealed topological changes in patients, including increased clustering coefficient and modularity and decreased global efficiency; however, these network metrics could not be linked to individual cognitive or CSF measures due to the group-level nature of network construction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with anti-NMDAR encephalitis exhibit concurrent glymphatic function, CP structural remodeling, widespread white matter microstructural damage, and topological reorganization. The CP\/ICV ratio emerged as the primary imaging correlate of cognitive dysfunction. Although exploratory mediation suggested that FA partially accounted for the ALPS-cognition association, this likely reflects shared methodological collinearity rather than a distinct biological pathway, reinforcing CP\/ICV as the more robust clinically relevant marker.These findings extend the concept of glymphatic-choroid plexus pathology from neurodegenerative diseases to post-acute autoimmune brain injury, providing a framework for non-invasive biomarkers in anti-NMDAR encephalitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1918658","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:27:40Z","timestamp":1788168460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Glymphatic surrogate, choroid plexus remodeling, and exploratory brain network analysis in the post-acute phase of anti-NMDAR encephalitis: multimodal MRI evidence for cognitive associations and differential white matter mediation"],"prefix":"10.3389","volume":"17","author":[{"given":"Run","family":"Du","sequence":"first","affiliation":[{"name":"Department of Radiology, the First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Radiology, the First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Banan Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Xiang","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":"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":"Wenwen","family":"Wang","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"}]},{"given":"Chun","family":"Zeng","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":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200255","article-title":"Racial and ethnic disparities in the incidence of Anti-NMDA receptor encephalitis","volume":"11","author":"Alsalek","year":"2024","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.4154","article-title":"Autoimmune encephalitis-misdiagnosis, misconceptions, and how to avoid them","volume":"80","author":"Dalmau","year":"2023","journal-title":"JAMA Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12974-023-02841-7","article-title":"Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood\u2013brain barrier disruption in anti-NMDA receptor encephalitis","volume":"20","author":"Chang","year":"2023","journal-title":"J Neuroinflamm"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210109","article-title":"Long-term cognitive, functional, and patient-reported outcomes in patients with anti-NMDAR encephalitis","volume":"103","author":"Brenner","year":"2024","journal-title":"Neurology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.12.006","article-title":"Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets","volume":"113","author":"Segal","year":"2025","journal-title":"Neuron"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2021.101572","article-title":"Sleep, cerebrospinal fluid, and the glymphatic system: A systematic review","volume":"61","author":"Chong","year":"2022","journal-title":"Sleep Med Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr4606","article-title":"Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations","volume":"11","author":"Ran","year":"2025","journal-title":"Sci Adv"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2025.10.036","article-title":"Resolving the mysteries of brain clearance and immune surveillance","volume":"113","author":"Kipnis","year":"2025","journal-title":"Neuron"},{"key":"B9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1146\/annurev-physiol-043024-120520","article-title":"Cerebrospinal fluid-mediated brain clearance: Insights from human studies","volume":"88","author":"Eide","year":"2026","journal-title":"Annu Rev Physiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2021204426","article-title":"Choroid plexus enlargement in inflammatory multiple sclerosis: 3.0-T MRI and translocator protein PET evaluation","volume":"301","author":"Ricigliano","year":"2021","journal-title":"Radiology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12970","article-title":"Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus","volume":"19","author":"\u010carna","year":"2023","journal-title":"Alzheimers Dement"},{"key":"B12","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1186\/s40001-025-03026-z","article-title":"Choroid plexus volume in multiple sclerosis: A systematic review and meta-analysis of an emerging imaging biomarker","volume":"30","author":"Moases Ghaffary","year":"2025","journal-title":"Eur J Med Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12987-025-00702-4","article-title":"Choroid plexus volume in brain disorders: A systematic review","volume":"22","author":"Tireli","year":"2025","journal-title":"Fluids Barriers CNS"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70699","article-title":"MRI markers of cerebrospinal fluid dynamics predict dementia and mediate the impact of cardiovascular risk","volume":"21","author":"Hong","year":"2025","journal-title":"Alzheimers Dement"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102995","article-title":"Glymphatic dysfunction in Parkinson's disease: Aging-associated impairments, imaging biomarkers, and therapeutic strategies","volume":"114","author":"Lv","year":"2026","journal-title":"Ageing Res Rev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-024-00852-3","article-title":"Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis","volume":"18","author":"Yang","year":"2024","journal-title":"Brain Imaging Behav"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s44319-024-00056-2","article-title":"Converging synaptic and network dysfunctions in distinct autoimmune encephalitis","volume":"25","author":"Hunter","year":"2024","journal-title":"EMBO Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102189","article-title":"Cerebral functional activity and connectivity changes in anti-N-methyl-D-aspartate receptor encephalitis: A resting-state fMRI study","volume":"25","author":"Cai","year":"2020","journal-title":"NeuroImage Clin"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-019-02321-x","article-title":"Voxel-based analysis and multivariate pattern analysis of diffusion tensor imaging study in anti-NMDA receptor encephalitis","volume":"62","author":"Liang","year":"2020","journal-title":"Neuroradiology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-022-06574-y","article-title":"The alterations of spontaneous neural activities and white matter microstructures in anti-N-methyl-D-aspartate receptor encephalitis: A resting-state fMRI and DTI study","volume":"44","author":"Wei","year":"2023","journal-title":"Neurol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232899","article-title":"Evaluation of diffusion tensor imaging analysis along the perivascular space as a marker of the glymphatic system","volume":"310","author":"Haller","year":"2024","journal-title":"Radiology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001147","article-title":"Choroid plexus volume in multiple sclerosis vs neuromyelitis optica spectrum disorder: A retrospective, cross-sectional analysis","volume":"9","author":"M\u00fcller","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B23","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/s41583-024-00882-2","article-title":"Structural MRI of brain similarity networks","volume":"26","author":"Sebenius","year":"2025","journal-title":"Nat Rev Neurosci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf151","article-title":"Structural covariance analysis for neurodegenerative and neuroinflammatory brain disorders","volume":"148","author":"Mongay-Ochoa","year":"2025","journal-title":"Brain"},{"key":"B25","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-025-02762-8","article-title":"DSI Studio: an integrated tractography platform and fiber data hub for accelerating brain research","volume":"22","author":"Yeh","year":"2025","journal-title":"Nat Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021","article-title":"FreeSurfer","volume":"62","author":"Fischl","year":"2012","journal-title":"Neuroimage"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.09.015","article-title":"FSL","volume":"62","author":"Jenkinson","year":"2012","journal-title":"Neuroimage"},{"key":"B29","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41531-025-01139-0","article-title":"The effects of aquaporin-4 polymorphisms on glymphatic function and motor symptoms in Parkinson's disease","volume":"11","author":"Qin","year":"2025","journal-title":"NPJ Parkinsons Dis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1030230","article-title":"Diffusion kurtosis imaging and diffusion tensor imaging parameters applied to white matter and gray matter of patients with anti-N-methyl-D-aspartate receptor encephalitis","volume":"16","author":"Liu","year":"2022","journal-title":"Front Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108624","article-title":"The diverse and complex modes of action of anti-NMDA receptor autoantibodies","volume":"194","author":"Wollmuth","year":"2021","journal-title":"Neuropharmacology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12974-025-03642-w","article-title":"Characterizing CSF inflammatory proteomics in pediatric post-hemorrhagic hydrocephalus and anti-NMDAR encephalitis","volume":"23","author":"Broudy","year":"2025","journal-title":"J Neuroinflamm"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106632","article-title":"Lymphocytes in autoimmune encephalitis: Pathogenesis and therapeutic target","volume":"200","author":"Chen","year":"2024","journal-title":"Neurobiol Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s00415-024-12869-1","article-title":"Brain tissue integrity in neuromyelitis optica spectrum disorder through T1-w\/T2-w ratio, MTR and DTI","volume":"272","author":"Boaventura","year":"2025","journal-title":"J Neurol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.07.007","article-title":"Epitope landscape in autoimmune neurological disease and beyond","volume":"45","author":"Talucci","year":"2024","journal-title":"Trends Pharmacol Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2021.11.036","article-title":"Structural covariance networks in schizophrenia: A systematic review part II","volume":"239","author":"Prasad","year":"2022","journal-title":"Schizophr Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200343","article-title":"Patient-reported outcome measures in NMDA receptor encephalitis","volume":"12","author":"Heine","year":"2025","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.680424","article-title":"High level of soluble CD146 in cerebrospinal fluid might be a biomarker of severity of anti-N-methyl-D-aspartate receptor encephalitis","volume":"12","author":"Li","year":"2021","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.971659","article-title":"Identification of cerebrospinal fluid biomarker candidates for anti-N-methyl-D-aspartate receptor encephalitis: High-throughput proteomic investigation","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1918658\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:27:42Z","timestamp":1788168462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1918658\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2026.1918658"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1918658","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"article-number":"1918658"}}