{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:43:32Z","timestamp":1788335012449,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008659","name":"European Committee for Treatment and Research in Multiple Sclerosis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017147","name":"International Progressive MS Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000381","name":"Multiple Sclerosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Newly appearing lesions in multiple sclerosis (MS) may evolve into chronically active, slowly expanding lesions (SELs), leading to sustained disability progression. The aim of this study was to evaluate the incidence of newly appearing lesions developing into SELs, and their correlation to clinical evolution and treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective analysis of a fingolimod trial in primary progressive MS (PPMS; INFORMS, NCT 00731692) was undertaken. Data were available from 324 patients with magnetic resonance imaging scans up to 3\u2009years after screening. New lesions at year 1 were identified with convolutional neural networks, and SELs obtained through a deformation\u2010based method. Clinical disability was assessed annually by Expanded Disability Status Scale (EDSS), Nine\u2010Hole Peg Test, Timed 25\u2010Foot Walk, and Paced Auditory Serial Addition Test. Linear, logistic, and mixed\u2010effect models were used to assess the relationship between the Jacobian expansion in new lesions and SELs, disability scores, and treatment status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One hundred seventy patients had \u22651 new lesions at year 1 and had a higher lesion count at screening compared to patients with no new lesions (median\u2009=\u200927 vs. 22, <jats:italic>p<\/jats:italic>\u2009=\u20090.007). Among the new lesions (median\u2009=\u20092 per patient), 37% evolved into definite or possible SELs. Higher SEL volume and count were associated with EDSS worsening and confirmed disability progression. Treated patients had lower volume and count of definite SELs (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.04, 95% confidence interval [CI] = \u22120.07 to \u22120.01, <jats:italic>p<\/jats:italic>\u2009=\u20090.015; <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.36, 95% CI = \u22120.67 to \u22120.06, <jats:italic>p<\/jats:italic>\u2009=\u20090.019, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Incident chronic active lesions are common in PPMS, and fingolimod treatment can reduce their number.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16092","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T13:09:05Z","timestamp":1697116145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1953-2803","authenticated-orcid":false,"given":"Alberto","family":"Calvi","sequence":"first","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Laboratory of Advanced Imaging in Neuroimmunological Diseases, Hospital Clinic Barcelona, Fundaci\u00f3 Clinic per a la Recerca Biom\u00e8dica  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Department of Radiology Charit\u00e9 School of Medicine and University Hospital Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weaam","family":"Hamed","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Department of Radiology Mansoura University Hospital  Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan","family":"Chard","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"National Institute for Health Research, Biomedical Research Centre University College London Hospitals  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Tur","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Neurology\u2010Neuroimmunology Department Multiple Sclerosis Centre of Catalonia, Vall d'Hebron Barcelona Hospital Campus  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-0844","authenticated-orcid":false,"given":"Jon","family":"Stutters","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"MacManus","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Kanber","sequence":"additional","affiliation":[{"name":"National Institute for Health Research, Biomedical Research Centre University College London Hospitals  London UK"},{"name":"Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A. M. Gandini","family":"Wheeler\u2010Kingshott","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing University College London  London UK"},{"name":"Radiology and Nuclear Medicine, Amsterdam University Medical Centers (UMC) Vrije Universiteit  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[{"name":"NMR Research Unit, Institute of Neurology University College London  London UK"},{"name":"Department of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing University College London  London UK"},{"name":"e\u2010Health Centre Universitat Oberta de Catalunya  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2020.1568"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70103-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/135245859900500415"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.52.4.839"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24497"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1818-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520958589"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1636-z"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458518814117"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3174\/AJNR.A6742"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200144"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103048"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000001139"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211033464"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NICL.2020.102411"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585221141964"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585231162262"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01314-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30475-6"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.04.034"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2015.2418298"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.06.053"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1040"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00031-9"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1255"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e24136"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab088"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2022.1025"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMANEUROL.2022.4655"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.4.731"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz212"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ANA.21867"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2012.09.004"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.16092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T10:18:52Z","timestamp":1710929932000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.16092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,12]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/ene.16092"],"URL":"https:\/\/doi.org\/10.1111\/ene.16092","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,12]]},"assertion":[{"value":"2023-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16092"}}