{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:22:59Z","timestamp":1791433379880,"version":"4.3.3"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The growing demand for personalized treatment in multiple sclerosis (MS) highlights the need for more precise biomarkers that can outperform magnetic resonance imaging and clinical assessment in patient stratification. Advances in multiplex proteomic technologies suggest that cerebrospinal fluid (CSF) analysis at MS onset may not only improve diagnostic accuracy, but also offer prognostic and staging information, as well as insight into molecular therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter study retrospectively analyzed cryopreserved CSF samples from 160 individuals undergoing diagnostic evaluation for possible neuroimmunological disorder, and among these, followed a cohort of 96 people with confirmed MS for at least 3\u2009years. The goal was to externally validate previously published CSF\u2010based diagnostic and prognostic classifiers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Upon unblinding, the CSF\u2010based molecular diagnostic test distinguished 96 people with confirmed MS from 30 individuals with other inflammatory neurological diseases, and 34 individuals with non\u2010inflammatory neurological diseases, achieving an area under the receiver operating characteristic curve of 0.94 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.7\u2009\u00d7\u200910\n                      <jats:sup>\u221221<\/jats:sup>\n                      ). The test also differentiated 65 individuals with relapsing\u2013remitting MS from 31 individuals with progressive MS, with an area under the receiver operating characteristic curve of 0.76 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.4\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ). The prognostic classifier predicted prospectively measured Expanded Disability Status Scale scores at follow up (rho\u2009=\u20090.43,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092.54\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This multicenter external validation study demonstrates that CSF\u2010based molecular tests can robustly distinguish MS from other neurological conditions, stratify MS subtypes, and predict future disability progression in real\u2010world settings. These results lay the groundwork for development of next\u2010generation molecular tools to personalize care in MS. ANN NEUROL 2026;99:328\u2013340<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78047","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T10:27:22Z","timestamp":1759487242000},"page":"328-340","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["From Diagnosis to Disease Staging: Multisite Validation of Cerebrospinal Fluid Molecular Tests in Multiple Sclerosis"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-9730","authenticated-orcid":false,"given":"Laura","family":"Ghezzi","sequence":"first","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences University of Milan  Milan Italy"},{"name":"IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1392-0629","authenticated-orcid":false,"given":"Peter","family":"Kosa","sequence":"additional","affiliation":[{"name":"Neuroimmunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-1201","authenticated-orcid":false,"given":"Mark","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Department of Mathematical Sciences Montana State University  Bozeman MT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5854-9643","authenticated-orcid":false,"given":"Enrique","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rocky Mountain Multiple Sclerosis Center at the University of Colorado  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. L.","family":"Freedman","sequence":"additional","affiliation":[{"name":"University of Ottawa Department of Medicine and the Ottawa Hospital Research Institute  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-7569","authenticated-orcid":false,"given":"Anne H.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St Louis MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pace","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St Louis MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-9701","authenticated-orcid":false,"given":"Mark S.","family":"Freedman","sequence":"additional","affiliation":[{"name":"University of Ottawa Department of Medicine and the Ottawa Hospital Research 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