{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:42:32Z","timestamp":1788838952177,"version":"build-2803163510"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Multiple Sclerosis Society of Great Britain"},{"DOI":"10.13039\/501100012317","name":"NIHR University College London Hospitals Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Society of Neuroradiology"},{"DOI":"10.13039\/100008659","name":"ECTRIMS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MAGNIMS Research Fellowships"},{"name":"Guarantors of Brain fellowship"},{"DOI":"10.13039\/501100012317","name":"NIHR University College London Hospitals Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012317","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alzheimer\u2019s Society Junior Fellowship","award":["AS-JF-17-001"],"award-info":[{"award-number":["AS-JF-17-001"]}]},{"name":"NIHR Research Professor","award":["RP-2017-08-ST2-004"],"award-info":[{"award-number":["RP-2017-08-ST2-004"]}]},{"name":"MRC Research","award":["MR\/S026088\/1"],"award-info":[{"award-number":["MR\/S026088\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30\u2009years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30\u2009years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3\u2009T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30\u2009years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.<\/jats:p>","DOI":"10.1093\/brain\/awab033","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T03:27:12Z","timestamp":1612927632000},"page":"1384-1395","source":"Crossref","is-referenced-by-count":52,"title":["Cortical involvement determines impairment 30 years after a clinically isolated syndrome"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1556-1770","authenticated-orcid":false,"given":"Lukas","family":"Haider","sequence":"first","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"Department of Biomedical Imaging and Image Guided Therapy, Medical University Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-0142","authenticated-orcid":false,"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK"},{"name":"Universitat Oberta de Catalunya, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chung","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-9716","authenticated-orcid":false,"given":"Olivia","family":"Goodkin","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-8800","authenticated-orcid":false,"given":"Baris","family":"Kanber","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"Centre for Medical Image Computing (CMIC), Department of Medical Physics and Biomedical Engineering, University College London, London, UK"},{"name":"Department of Clinical and Experimental Epilepsy, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5753-428X","authenticated-orcid":false,"given":"Carole","family":"Sudre","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"School of Biomedical Engineering and Imaging Sciences, King\u2019s College London, London, UK"},{"name":"Dementia Research Centre, Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-446X","authenticated-orcid":false,"given":"Marios","family":"Yiannakas","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0197-702X","authenticated-orcid":false,"given":"Rebecca S","family":"Samson","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-2724","authenticated-orcid":false,"given":"Stephanie","family":"Mangesius","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, Austria"},{"name":"Neuroimaging Core Facility, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-8496","authenticated-orcid":false,"given":"Alan J","family":"Thompson","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4832-1300","authenticated-orcid":false,"given":"Claudia A M","family":"Gandini Wheeler-Kingshott","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy"},{"name":"Brain MRI 3T Research Centre, IRCCS Mondino Foundation, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7485-1367","authenticated-orcid":false,"given":"Olga","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-2682","authenticated-orcid":false,"given":"Declan T","family":"Chard","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, UK"},{"name":"National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-3706","authenticated-orcid":false,"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, Queen Square Institute of Neurology, University College London, London, 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