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We aimed to use such patterns to identify patient subgroups. MS patients of all classical disease phenotypes underwent annual clinical, blood, and MRI examinations over 6\u2009years. Spinal, striatal, pallidal, thalamic, cortical, white matter, and T2\u2010weighted lesion volumes as well as serum neurofilament light chain (sNfL) were quantified. CNS VLOT patterns were identified using principal component analysis and patients were classified using hierarchical cluster analysis. 225 MS patients were classified into four distinct Groups A, B, C, and D including 14, 59, 141, and 11 patients, respectively). These groups did not differ in baseline demographics, disease duration, disease phenotype distribution, and lesion\u2010load expansion. Interestingly, Group A showed pronounced spinothalamic VLOT, Group B marked pallidal VLOT, Group C small between\u2010structure VLOT differences, and Group D myelocortical volume increase and pronounced white matter VLOT. Neurologic deficits were more severe and progressed faster in Group A that also had higher mean sNfL levels than all other groups. Group B experienced more frequent relapses than Group C. In conclusion, there are distinct patterns of VLOT across the CNS in MS patients, which do not overlap with clinical MS subtypes and are independent of disease duration and lesion\u2010load but are partially associated to sNfL levels, relapse rates, and clinical worsening. Our findings support the need for a more biologic classification of MS subtypes including volumetric and body\u2010fluid markers.<\/jats:p>","DOI":"10.1002\/hbm.25375","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T08:30:17Z","timestamp":1614155417000},"page":"2399-2415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Classification of multiple sclerosis based on patterns of<scp>CNS<\/scp>regional atrophy covariance"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-6316","authenticated-orcid":false,"given":"Charidimos","family":"Tsagkas","sequence":"first","affiliation":[{"name":"Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering University Hospital Basel and University of Basel Basel Switzerland"},{"name":"Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering University Hospital Basel and University of Basel Basel Switzerland"},{"name":"Medical Image Analysis Center AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Parmar","sequence":"additional","affiliation":[{"name":"Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering University Hospital Basel and University of Basel Basel Switzerland"},{"name":"Translational Imaging in Neurology (ThINK) Basel, Department of Medicine and Biomedical Engineering University Hospital Basel and University of Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Pezold","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Basel Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Barro","sequence":"additional","affiliation":[{"name":"Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering University Hospital Basel and University of Basel Basel Switzerland"},{"name":"Ann Romney Center for Neurologic Diseases, Department of Neurology Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mallar M.","family":"Chakravarty","sequence":"additional","affiliation":[{"name":"Department of Psychiatry McGill University Montreal QC Canada"},{"name":"Cerebral Imaging Centre\u2014Douglas Mental Health University Institute Verdun QC Canada"},{"name":"Department of Biomedical Engineering McGill University Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Gaetano","sequence":"additional","affiliation":[{"name":"F. 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