{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:49:53Z","timestamp":1776916193926,"version":"3.51.2"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":239,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007601","name":"European Union\u2019s Horizon 2020 Research and Innovation Program","doi-asserted-by":"publisher","award":["EU RIA 733161"],"award-info":[{"award-number":["EU RIA 733161"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"European Union\u2019s Horizon 2020 Research and Innovation Program","doi-asserted-by":"publisher","award":["WISDOM EU RIA 101137154"],"award-info":[{"award-number":["WISDOM EU RIA 101137154"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["390857198"],"award-info":[{"award-number":["390857198"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Radiologically isolated syndrome (RIS) represents a pivotal stage for identifying individuals at high risk of transitioning into multiple sclerosis (MS). Early therapy initiation reduces the risk of conversion. The 2023-RIS criteria were proposed to identify presymptomatic individuals earlier. We aimed to replicate the diagnostic value of the 2023-RIS criteria in an independent cohort. In this retrospective cohort study, individuals diagnosed with RIS and longitudinally followed in three centres were stratified by the 2009- and 2023-RIS criteria. We conducted comparative analyses, including survival, hazard ratio and performance evaluations. Among n = 136 individuals, 27.2% converted to MS between 2009 and 2024 (observation time 55.4 months). We confirmed improved identification of individuals at risk using the 2023-RIS criteria (HR 4.30, P &amp;lt; 0.05; HR 4.71, P &amp;lt; 0.05) compared to 2009-RIS criteria (HR 1.32, P = 0.4; HR 1.43; P = 0.3) in 5- and 10-year intervals, respectively. 2023-RIS criteria demonstrated high sensitivity (94%) and negative predictive value (94%) but low specificity (29%). Adding CSF immunoglobulin G and M indices as an additional parameter following RIS diagnosis enhanced risk prediction specificity. We confirm the high sensitivity and predictive value of the 2023-RIS criteria for identifying individuals at risk of conversion to MS and suggest adding immunoglobulin indices to further improve specificity.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf323","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T11:23:03Z","timestamp":1756120983000},"source":"Crossref","is-referenced-by-count":1,"title":["Replication of the 2023 radiologically isolated syndrome criteria in a multi-centre cohort"],"prefix":"10.1093","volume":"7","author":[{"given":"Friederike","family":"Held","sequence":"first","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Uibel","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelius","family":"Berberich","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neuroradiology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Schaller-Nagengast","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm , 89081 Ulm ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasil","family":"Mitrevski","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-University, Institute of Clinical Neuroimmunology, LMU Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Hutter","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-University, Institute of Clinical Neuroimmunology, LMU Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayrettin","family":"Tumani","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm , 89081 Ulm ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Havla","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-University, Institute of Clinical Neuroimmunology, LMU Hospital , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Gasperi","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-2709","authenticated-orcid":false,"given":"Mark","family":"M\u00fchlau","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achim","family":"Berthele","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan S","family":"Kirschke","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neuroradiology, TUM University Hospital , 81675 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-6784","authenticated-orcid":false,"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[{"name":"Technical University of Munich, School of Medicine and Health, Department of Neurology, TUM University Hospital , 81675 Munich ,","place":["Germany"]},{"name":"Munich Cluster for Systems Neurology (SyNergy) , 81377 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"issue":"11","key":"2025103013410988400_fcaf323-B1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S1474-4422(23)00281-8","article-title":"Radiologically isolated syndrome","volume":"22","author":"Lebrun-Frenay","year":"2023","journal-title":"Lancet Neurol"},{"issue":"3","key":"2025103013410988400_fcaf323-B2","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/ana.26555","article-title":"Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome","volume":"93","author":"Okuda","year":"2023","journal-title":"Ann Neurol"},{"issue":"10","key":"2025103013410988400_fcaf323-B3","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1001\/jamaneurol.2023.2815","article-title":"Teriflunomide and time to clinical multiple sclerosis in patients with radiologically isolated syndrome: The TERIS randomized clinical trial","volume":"80","author":"Lebrun-Frenay","year":"2023","journal-title":"JAMA Neurol"},{"issue":"2","key":"2025103013410988400_fcaf323-B4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/ana.25799","article-title":"Radiologically isolated syndrome: 10-year risk estimate of a clinical event","volume":"88","author":"Lebrun-Frenay","year":"2020","journal-title":"Ann Neurol"},{"issue":"9","key":"2025103013410988400_fcaf323-B5","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1212\/01.wnl.0000335764.14513.1a","article-title":"Incidental MRI anomalies suggestive of multiple sclerosis: The radiologically isolated syndrome","volume":"72","author":"Okuda","year":"2009","journal-title":"Neurology"},{"issue":"1","key":"2025103013410988400_fcaf323-B6","doi-asserted-by":"crossref","first-page":"e200044","DOI":"10.1212\/NXI.0000000000200044","article-title":"Neurofilament light chain levels are predictive of clinical conversion in radiologically isolated syndrome","volume":"10","author":"Rival","year":"2023","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"4","key":"2025103013410988400_fcaf323-B7","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/brain\/awy021","article-title":"Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome","volume":"141","author":"Matute-Blanch","year":"2018","journal-title":"Brain"},{"issue":"3","key":"2025103013410988400_fcaf323-B8","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/jnc.15500","article-title":"Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: A real-world investigation","volume":"159","author":"Rosenstein","year":"2021","journal-title":"J Neurochem"},{"issue":"8","key":"2025103013410988400_fcaf323-B9","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.1093\/brain\/awad073","article-title":"The radiologically isolated syndrome: Revised diagnostic criteria","volume":"146","author":"Lebrun-Frenay","year":"2023","journal-title":"Brain"},{"issue":"2","key":"2025103013410988400_fcaf323-B10","doi-asserted-by":"crossref","first-page":"162","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"},{"issue":"8","key":"2025103013410988400_fcaf323-B11","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1136\/jnnp.57.8.897","article-title":"Cerebrospinal fluid in the diagnosis of multiple sclerosis: A consensus report","volume":"57","author":"Andersson","year":"1994","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"2025103013410988400_fcaf323-B12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ncl.2017.08.006","article-title":"Progressive forms of multiple sclerosis: Distinct entity or age-dependent phenomena","volume":"36","author":"Zeydan","year":"2018","journal-title":"Neurol Clin"},{"issue":"8","key":"2025103013410988400_fcaf323-B13","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1136\/jnnp-2012-304695","article-title":"Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: A meta-analysis of prevalence, prognosis and effect of latitude","volume":"84","author":"Dobson","year":"2013","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"Pt 7","key":"2025103013410988400_fcaf323-B14","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/brain\/awv105","article-title":"Defining high, medium and low impact prognostic factors for developing multiple sclerosis","volume":"138","author":"Tintore","year":"2015","journal-title":"Brain"},{"issue":"10","key":"2025103013410988400_fcaf323-B15","doi-asserted-by":"crossref","first-page":"e2128271","DOI":"10.1001\/jamanetworkopen.2021.28271","article-title":"Risk factors and time to clinical symptoms of multiple sclerosis among patients with radiologically isolated syndrome","volume":"4","author":"Lebrun-Frenay","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"8","key":"2025103013410988400_fcaf323-B16","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1212\/WNL.0b013e31820d8b1d","article-title":"Asymptomatic spinal cord lesions predict disease progression in radiologically isolated syndrome","volume":"76","author":"Okuda","year":"2011","journal-title":"Neurology"},{"issue":"11","key":"2025103013410988400_fcaf323-B17","first-page":"1379","article-title":"Conversion from radiologically isolated syndrome to multiple sclerosis","volume":"5","author":"Etemadifar","year":"2014","journal-title":"Int J Prev Med"},{"issue":"2","key":"2025103013410988400_fcaf323-B18","doi-asserted-by":"crossref","first-page":"e436","DOI":"10.1212\/NXI.0000000000000436","article-title":"Quantitative spinal cord MRI in radiologically isolated syndrome","volume":"5","author":"Alcaide-Leon","year":"2018","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2025103013410988400_fcaf323-B19","doi-asserted-by":"crossref","first-page":"726","DOI":"10.3389\/fimmu.2019.00726","article-title":"The cerebrospinal fluid in multiple sclerosis","volume":"10","author":"Deisenhammer","year":"2019","journal-title":"Front Immunol"},{"issue":"1-2","key":"2025103013410988400_fcaf323-B20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2013.06.014","article-title":"Intrathecal oligoclonal IgG synthesis in multiple sclerosis","volume":"262","author":"Petzold","year":"2013","journal-title":"J Neuroimmunol"},{"issue":"8","key":"2025103013410988400_fcaf323-B21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1177\/1352458514568827","article-title":"Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study","volume":"21","author":"Kuhle","year":"2015","journal-title":"Mult Scler"},{"key":"2025103013410988400_fcaf323-B22","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.3389\/fimmu.2020.01799","article-title":"Igg index revisited: Diagnostic utility and prognostic value in multiple sclerosis","volume":"11","author":"Zheng","year":"2020","journal-title":"Front Immunol"},{"issue":"4","key":"2025103013410988400_fcaf323-B23","doi-asserted-by":"crossref","first-page":"e1005","DOI":"10.1212\/NXI.0000000000001005","article-title":"Kappa-free light chains in CSF predict early multiple sclerosis disease activity","volume":"8","author":"Berek","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"2025103013410988400_fcaf323-B24","doi-asserted-by":"crossref","first-page":"e200156","DOI":"10.1212\/NXI.0000000000200156","article-title":"Kappa free light chain index predicts disease course in clinically and radiologically isolated syndromes","volume":"10","author":"Levraut","year":"2023","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2025103013410988400_fcaf323-B25","doi-asserted-by":"crossref","first-page":"1172807","DOI":"10.3389\/fneur.2023.1172807","article-title":"Advanced central nervous system imaging biomarkers in radiologically isolated syndrome: A mini review","volume":"14","author":"Collorone","year":"2023","journal-title":"Front Neurol"},{"issue":"11","key":"2025103013410988400_fcaf323-B26","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1111\/ene.14416","article-title":"Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis","volume":"27","author":"Aly","year":"2020","journal-title":"Eur J Neurol"},{"key":"2025103013410988400_fcaf323-B27","doi-asserted-by":"crossref","first-page":"1385231","DOI":"10.3389\/fimmu.2024.1385231","article-title":"Inter-assay diagnostic accuracy of cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis","volume":"15","author":"Dekeyser","year":"2024","journal-title":"Front Immunol"},{"issue":"1","key":"2025103013410988400_fcaf323-B28","doi-asserted-by":"crossref","first-page":"e200049","DOI":"10.1212\/NXI.0000000000200049","article-title":"Kappa free light chain biomarkers are efficient for the diagnosis of multiple sclerosis: A large multicenter cohort study","volume":"10","author":"Levraut","year":"2023","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2025103013410988400_fcaf323-B29","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1001\/jamaneurol.2025.1481","article-title":"Prognostic factors for multiple sclerosis symptoms in radiologically isolated syndrome","author":"Fissolo","year":"2025","journal-title":"JAMA Neurol"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaf323\/64150392\/fcaf323.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf323\/64150392\/fcaf323.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/5\/fcaf323\/64150392\/fcaf323.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:41:22Z","timestamp":1761846082000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf323\/8242846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf323","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf323"}}