{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:00:37Z","timestamp":1791104437940,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008375","name":"University of Basel","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008375","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Susceptibility-based MRI biomarkers, including paramagnetic rim lesions (PRLs) and central vein sign (CVS), were incorporated into the 2024 McDonald criteria because they improve diagnostic specificity in adult-onset MS; however, their role in pediatric-onset MS (POMS) remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To synthesize current evidence on the prevalence and diagnostic value of PRLs and CVS in POMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a PRISMA-compliant systematic review and random-effects meta-analysis of studies reporting PRLs and\/or CVS in POMS. Outcomes included the proportion of patients with \u22651 PRL, the mean proportion of CVS-positive lesions, and fulfillment of CVS-based thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven studies were included. Across seven studies, the pooled proportion of POMS patients with \u22651 PRL was 71.6% (95%\u00a0CI 61.1\u201380.2;\n                      <jats:italic>n<\/jats:italic>\n                      =149), with low between-study heterogeneity. Across six studies, the pooled mean proportion of CVS-positive lesions was 57.9% (95%\u00a0CI 39.7\u201376.2;\n                      <jats:italic>n<\/jats:italic>\n                      =99), and 66.2% (95%\u00a0CI 10.5\u201397.0;\n                      <jats:italic>n<\/jats:italic>\n                      =219) of patients fulfilled the 40%-CVS rule, with substantial variability across studies. In comparative analyses, PRLs showed high specificity for POMS, while CVS was more prevalent than in mimics; however, limited data precluded quantitative evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PRLs are frequent in POMS. Limited comparative data suggest that PRLs may have high diagnostic specificity, whereas CVS appears more variable; however, pediatric diagnostic accuracy evidence remains scarce. Further pediatric-specific studies are needed to define the optimal diagnostic use of these biomarkers in POMS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14084-6","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T15:48:13Z","timestamp":1787413693000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Central vein sign and paramagnetic rim lesions in pediatric-onset multiple sclerosis: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"273","author":[{"given":"Anna","family":"de Mauro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Cortese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fadda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"De Stefano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Sormani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Banwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-8761","authenticated-orcid":false,"given":"Cristina","family":"Granziera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cagol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"14084_CR1","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMOA067597\/ASSET\/D5314296-5590-4BC1-B2EB-82590B6E534C\/ASSETS\/IMAGES\/LARGE\/NEJMOA067597_T2.JPG","volume":"356","author":"C Renoux","year":"2007","unstructured":"Renoux C, Vukusic S, Mikaeloff Y et al (2007) Natural history of multiple sclerosis with childhood onset. 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R.C. received speaker honoraria\/travel support from Roche, Merck Serono, UCB, Sanofi-Genzyme, Alexion, Novartis, and Janssen, and received a research grant from the Italian Ministry of University and Research. G.F. received honoraria for lectures\/advisory boards from Horizon Therapeutics\/Amgen, Novartis and Roche; she received travel support from Roche and research support from Brain Canada, Future Leaders in Brain Research. She holds a Canada Research Chair in Inflammation, Infection and Immunity and an Early Investigator Chair from the Department of Medicine, University of Ottawa. N.D.S. has received honoraria from Biogen-Idec, Bristol Myers Squibb, Celgene, Genzyme, Immunic, Merck, Novartis, Roche and Teva for consulting services, speaking, and travel support. He serves on advisory boards for Immunic, Merck, Novartis, Biogen-Idec, Roche, and Sanofi. He has received research support from the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. He is Associate Editor of Neurological Sciences and co-founder of Siena-Imaging s.r.l. L.K. received no personal compensation; his institutions (University Hospital Basel\/Stiftung Neuroimmunology and Neuroscience Basel) received payments for steering committee, advisory and data safety monitoring board participation, consultancy services and educational activities from Bayer, Biogen, Bristol Myers Squibb, Celltrion Inc, Clene Nanomedicine Inc., EMD Serono Research and Development, Galapagos NV, Genentech, Immunic AG, Janssen, Kiniksa Pharmaceuticals, Laboratoires Juvise Pharmaceuticals, Merck Healthcare AG, MSD Merck Sharp and Dohme AG, Minoryx Therapeutics S.L., Neurostatus UHB AG, Novartis, Roche, Sanofi, Shionogi BV, Wellmera AG, Zai Lab; research support from Novartis, Roche and Innosuisse. M.P.S. received consulting fees from Biogen, Merck, Novartis, Roche, Sanofi, Immunic, Alexion. B.B. serves as a consultant for Novartis, Roche, UCB and Sanofi. She has received grant funding from the NIH, and from the National MS Society and Canadian MS Society. C.G. The University Hospital Basel (USB) and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), as the employers of Cristina Granziera, have received the following fees which were used exclusively for research support from Siemens, GeNeuro, Genzyme-Sanofi, Biogen, Hoffmann La Roche. They also have received advisory board and consultancy fees from Actelion, Genzyme-Sanofi, Novartis, GeNeuro, Merck, Biogen and Hoffmann La Roche; as well as speaker fees from Genzyme-Sanofi, Novartis, GeNeuro, Merck, Biogen and Hoffmann La Roche. A.C. has received personal fees from Merck, Novartis, and Roche (speaker honoraria) and serves on the editorial board of Neurology. He has received grant funding from the Swiss MS Society.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"540"}}