{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:23:41Z","timestamp":1791433421286,"version":"4.3.3"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"French-Italian university","award":["ANR MNP2008-007125"],"award-info":[{"award-number":["ANR MNP2008-007125"]}]},{"DOI":"10.13039\/100007379","name":"Fondation pour l'aide \u00e0 la recherche sur la scl\u00e9rose en plaques","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARSEP Foundation"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale. Assistance Publique des H\u00f4pitaux de Paris","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed up for 5\u2005years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex.<\/jats:p>\n               <jats:p>We investigated 140 people with MS (37 clinically isolated syndrome, 71 relapsing-MS, 32 progressive-MS), who were clinically assessed at baseline and after 5\u2005years and, along with 84 healthy controls, underwent a 3\u2005T-MRI protocol including MTI at baseline and after 1\u2005year. Changes in cortical volume over the radiological follow-up were computed with a Jacobian integration method. Magnetization transfer ratio was employed to calculate for each patient an index of cortical demyelination at baseline and of dynamic cortical demyelination and remyelination over the follow-up period.<\/jats:p>\n               <jats:p>The three indices of cortical myelin content change were heterogeneous across patients but did not significantly differ across clinical phenotypes or treatment groups. Cortical remyelination, which tended to fail in the regions closer to CSF (\u221211%, P &amp;lt; 0.001), was extensive in half of the cohort and occurred independently of age, disease duration and clinical phenotype. Higher indices of cortical dynamic demyelination (\u03b2 = 0.23, P = 0.024) and lower indices of cortical remyelination (\u03b2 = \u22120.18, P = 0.03) were significantly associated with greater cortical atrophy after 1\u2005year, independently of age and MS phenotype. While the extent of cortical demyelination predicted a higher probability of clinical progression after 5\u2005years in the entire cohort [odds ratio (OR) = 1.2; P = 0.043], the impact of cortical remyelination in reducing the risk of accumulating clinical disability after 5\u2005years was significant only in the subgroup of patients with shorter disease duration and limited extent of demyelination in cortical regions (OR = 0.86, P = 0.015, area under the curve = 0.93). In this subgroup, a 30% increase in cortical remyelination nearly halved the risk of clinical progression at 5\u2005years, independently of clinical relapses.<\/jats:p>\n               <jats:p>Overall, our results highlight the critical role of cortical myelin dynamics in the cascade of events leading to neurodegeneration and to the subsequent accumulation of irreversible disability in MS. Our findings suggest that early-stage myelin repair compensating for cortical myelin loss has the potential to prevent neuro-axonal loss and its long-term irreversible clinical consequences in people with MS.<\/jats:p>","DOI":"10.1093\/brain\/awae024","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T04:11:51Z","timestamp":1706155911000},"page":"1331-1343","source":"Crossref","is-referenced-by-count":35,"title":["Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5109-8533","authenticated-orcid":false,"given":"Andrea","family":"Lazzarotto","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Sorbonne Universit\u00e9, Paris Brain Institute, CNRS, Inserm , 75013 Paris , France"},{"name":"AP-HP, H\u00f4pital Universitaire Piti\u00e9-Salp\u00eatri\u00e8re , 75013 Paris , France"},{"name":"Padova Neuroscience Center, University of Padua , 35122 Padua , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariem","family":"Hamzaoui","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Sorbonne Universit\u00e9, Paris Brain Institute, CNRS, Inserm , 75013 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-5710","authenticated-orcid":false,"given":"Matteo","family":"Tonietto","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Fr\u00e9d\u00e9ric Joliot , 91400 Orsay , France"},{"name":"Roche Pharma Research & Early Development, F. Hoffmann-La Roche Ltd. , CH-4070 Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laure","family":"Dubessy","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Universitaire Piti\u00e9-Salp\u00eatri\u00e8re , 75013 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Khalil","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz , 8036 Graz , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4390-9703","authenticated-orcid":false,"given":"Lukas","family":"Pirpamer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz , 8036 Graz , Austria"},{"name":"Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel , CH-4051 Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ropele","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz , 8036 Graz , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz , 8036 Graz , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena , 53100 Siena , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Stromillo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena , 53100 Siena , 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Assunta","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Neurology Unit, IRCCS San Raffaele Scientific Institute , 20132 Milan , Italy"},{"name":"Vita-Salute San Raffaele University , 20132 Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gallo","sequence":"additional","affiliation":[{"name":"Padova Neuroscience Center, University of Padua , 35122 Padua , Italy"},{"name":"Multiple Sclerosis Centre of Veneto Region , 35128 Padua , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Gasperini","sequence":"additional","affiliation":[{"name":"San Camillo-Forlanini Hospital , 00152 Rome , 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