{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:46:31Z","timestamp":1793724391466,"version":"4.6.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"United Kingdom MS Society","award":["995"],"award-info":[{"award-number":["995"]}],"id":[{"id":"https:\/\/ror.org\/043fwdk81","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","award":["1207-CF"],"award-info":[{"award-number":["1207-CF"]}],"id":[{"id":"10.13039\/501100001543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NMR"},{"name":"University College London Hospitals NIHR Biomedical Research Centre"},{"DOI":"10.13039\/501100000627","name":"Guarantors of Brain","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after \u223c15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0\u201310); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P &lt; 0.01) and spinal cord lesions (odds ratio 4.71, P &lt; 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (\u03b2 = 1.32, P &lt; 0.01) and spinal cord lesions (\u03b2 = 1.53, P &lt; 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (\u03b2 = \u2212 0.79, P &lt; 0.01) and Symbol Digit Modalities Test (\u03b2 = \u22120.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.<\/jats:p>","DOI":"10.1093\/brain\/awz156","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T07:08:10Z","timestamp":1559200090000},"page":"2276-2287","source":"Crossref","is-referenced-by-count":186,"title":["Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis"],"prefix":"10.1093","volume":"142","author":[{"given":"Wallace J","family":"Brownlee","sequence":"first","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan R","family":"Altmann","sequence":"additional","affiliation":[{"name":"Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, UK"}],"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 MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"},{"name":"Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, UK"},{"name":"Universitat Oberta de Catalunya, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Miszkiel","sequence":"additional","affiliation":[{"name":"Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Eshaghi","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A M","family":"Gandini Wheeler-Kingshott","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"},{"name":"Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy"},{"name":"Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"},{"name":"Centre for Medical Image Computing (CMIC), Department of Medical Physics and Bioengineering, University College London, London, UK"},{"name":"Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands"},{"name":"National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ciccarelli","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK"},{"name":"National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,25]]},"reference":[{"key":"2019072604004376600_awz156-B1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1177\/1352458517697830","article-title":"Spinal cord lesions: a modest contributor to diagnosis in clinically isolated syndromes but a relevant prognostic factor","volume":"24","author":"Arrambide","year":"2018","journal-title":"Mult Scler"},{"key":"2019072604004376600_awz156-B2","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1136\/jnnp-2014-308675","article-title":"Earlier and more frequent diagnosis of multiple sclerosis using the McDonald criteria","volume":"86","author":"Brownlee","year":"2015","journal-title":"J Neurol Neurosurg 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