{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:55:26Z","timestamp":1790801726132,"version":"4.1.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100008731","name":"European Leukodystrophy Association","doi-asserted-by":"crossref","award":["2007-0481"],"award-info":[{"award-number":["2007-0481"]}],"id":[{"id":"10.13039\/501100008731","id-type":"DOI","asserted-by":"crossref"}]},{"name":"INSERM-DHOS"},{"name":"Programme Hospitalier de Recherche Clinique"},{"name":"Agence nationale de la Recherche","award":["MNP2008-007125"],"award-info":[{"award-number":["MNP2008-007125"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la recherche m\u00e9dicale","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Commissariat aux energies atomique"},{"DOI":"10.13039\/100007379","name":"ARSEP","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008659","name":"ECTRIMS","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Assistance Publique des H\u00f4pitaux de Paris"},{"name":"Investissements d\u2019avenir","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In multiple sclerosis, spontaneous remyelination is generally incomplete and heterogeneous across patients. A high heterogeneity in remyelination may also exist across lesions within the same individual, suggesting the presence of local factors interfering with myelin regeneration. In this study we explored in vivo the regional distribution of myelin repair and investigated its relationship with neurodegeneration. We first took advantage of the myelin binding property of the amyloid radiotracer 11C-PiB to conduct a longitudinal 11C-PiB PET study in an original cohort of 19 participants with a relapsing\u2013remitting form of multiple sclerosis, followed-up over a period of 1\u20134 months. We then replicated our results on an independent cohort of 40 people with multiple sclerosis followed-up over 1 year with magnetization transfer imaging, an MRI metrics sensitive to myelin content. For each imaging method, voxel-wise maps of myelin content changes were generated according to modality-specific thresholds.<\/jats:p>\n               <jats:p>We demonstrated a selective failure of remyelination in periventricular white matter lesions of people with multiple sclerosis in both cohorts. In both the original and the replication cohort, we estimated that the probability of demyelinated voxels to remyelinate over the follow-up increased significantly as a function of the distance from ventricular CSF. Enlarged choroid plexus, a recently discovered biomarker linked to neuroinflammation, was found to be associated with the periventricular failure of remyelination in the two cohorts (r = \u22120.79, P = 0.0018; r = \u22120.40, P = 0.045, respectively), suggesting a role of the brain\u2013CSF barrier in affecting myelin repair in surrounding tissues. In both cohorts, the failure of remyelination in periventricular white matter lesions was associated with lower thalamic volume (r = 0.86, P &amp;lt; 0.0001; r = 0.33; P = 0.069, respectively), an imaging marker of neurodegeneration. Interestingly, we also showed an association between the periventricular failure of remyelination and regional cortical atrophy that was mediated by the number of cortex-derived tracts passing through periventricular white matter lesions, especially in patients at the relapsing\u2013remitting stage.<\/jats:p>\n               <jats:p>Our findings demonstrate that lesion proximity to ventricles is associated with a failure of myelin repair and support the hypothesis that a selective periventricular remyelination failure in combination with the large number of tracts connecting periventricular lesions with cortical areas is a key mechanism contributing to cortical damage in multiple sclerosis.<\/jats:p>","DOI":"10.1093\/brain\/awac334","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T04:16:45Z","timestamp":1663042605000},"page":"182-194","source":"Crossref","is-referenced-by-count":64,"title":["Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9591-5710","authenticated-orcid":false,"given":"Matteo","family":"Tonietto","sequence":"first","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Service Hospitalier Fr\u00e9d\u00e9ric Joliot, Universit\u00e9 Paris-Saclay, CEA, CNRS, Inserm, BioMaps , Orsay , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Poirion","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lazzarotto","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Neurology Department, St Antoine Hospital, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Ricigliano","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Neurology Department, St Antoine Hospital, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Papeix","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Neurology Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Bottlaender","sequence":"additional","affiliation":[{"name":"Service Hospitalier Fr\u00e9d\u00e9ric Joliot, Universit\u00e9 Paris-Saclay, CEA, CNRS, Inserm, BioMaps , Orsay , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Bodini","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Neurology Department, St Antoine Hospital, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9631-4674","authenticated-orcid":false,"given":"Bruno","family":"Stankoff","sequence":"additional","affiliation":[{"name":"Paris Brain Institute, Sorbonne Universit\u00e9, ICM, CNRS, Inserm , Paris , France"},{"name":"Neurology Department, St Antoine Hospital, APHP , Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,13]]},"reference":[{"key":"2023010803512009500_awac334-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1101\/cshperspect.a028936","article-title":"Multiple sclerosis 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