{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T16:39:32Z","timestamp":1776703172673,"version":"3.51.2"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T00:00:00Z","timestamp":1522713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008084","name":"Swedish State Support for Clinical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008084","name":"Neurof\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Frimurarestiftelsen"},{"name":"Swedish State Support for Clinical Research"},{"name":"Swedish State Support for Clinical Research"},{"DOI":"10.13039\/501100008084","name":"Neurof\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Edith Jacobsons Foundation"},{"name":"Edith Jacobsons Foundation"},{"name":"Helena Ahlin's Foundation"},{"name":"Biogen unconditional grant"},{"name":"Biogen unconditional grant"},{"name":"Teva unconditional grant"},{"name":"Novartis unconditional grant"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0194828","type":"journal-article","created":{"date-parts":[[2018,4,3]],"date-time":"2018-04-03T14:13:30Z","timestamp":1522764810000},"page":"e0194828","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":46,"title":["Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-6395","authenticated-orcid":true,"given":"Lenka","family":"Novakova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Axelsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-0088","authenticated-orcid":true,"given":"Clas","family":"Malmestr\u00f6m","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-663X","authenticated-orcid":true,"given":"Henrik","family":"Imberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olle","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olle","family":"Nerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Lycke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,4,3]]},"reference":[{"issue":"4","key":"ref1","first-page":"901","article-title":"Pathology of multiple sclerosis: where do we stand?","volume":"19","author":"BF Popescu","year":"2013","journal-title":"Continuum (Minneap Minn)"},{"issue":"1\u20132","key":"ref2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jns.2006.08.017","article-title":"Inflammatory demyelination and neurodegeneration in early multiple sclerosis","volume":"259","author":"A Charil","year":"2007","journal-title":"J Neurol Sci"},{"issue":"9","key":"ref3","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S1474-4422(10)70168-X","article-title":"Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis","volume":"9","author":"A Petzold","year":"2010","journal-title":"Lancet Neurol"},{"issue":"16","key":"ref4","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1212\/01.wnl.0000295995.46586.ae","article-title":"Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis","volume":"69","author":"E Gordon-Lipkin","year":"2007","journal-title":"Neurology"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"e18132","DOI":"10.1371\/journal.pone.0018132","article-title":"Association of retinal and macular damage with brain atrophy in multiple sclerosis","volume":"6","author":"J Dorr","year":"2011","journal-title":"PLoS One"},{"issue":"Pt 1","key":"ref6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/brain\/awu335","article-title":"Vision and vision-related outcome measures in multiple sclerosis","volume":"138","author":"LJ Balcer","year":"2015","journal-title":"Brain"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S1474-4422(17)30278-8","article-title":"Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis","volume":"16","author":"A Petzold","year":"2017","journal-title":"Lancet Neurol"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1177\/1352458509359725","article-title":"Neurofilament light as a prognostic marker in multiple sclerosis","volume":"16","author":"J Salzer","year":"2010","journal-title":"Mult Scler"},{"issue":"5","key":"ref9","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1007\/s00415-010-5863-2","article-title":"Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis","volume":"258","author":"M Axelsson","year":"2011","journal-title":"J Neurol"},{"issue":"10","key":"ref10","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1136\/jnnp-2013-306906","article-title":"Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study","volume":"85","author":"C Jacobsen","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1\u20132","key":"ref11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jns.2015.11.017","article-title":"Retinal nerve fiber layer thickness and neurologic disability in relapsing-remitting multiple sclerosis","volume":"359","author":"R Behbehani","year":"2015","journal-title":"J Neurol Sci"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.msard.2015.04.006","article-title":"Is it time to target no evident disease activity (NEDA) in multiple sclerosis?","volume":"4","author":"G Giovannoni","year":"2015","journal-title":"Mult Scler Relat Disord"},{"issue":"2","key":"ref13","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/ana.22366","article-title":"Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria","volume":"69","author":"CH Polman","year":"2011","journal-title":"Annals of neurology"},{"issue":"11","key":"ref14","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1212\/WNL.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)","volume":"33","author":"JF Kurtzke","year":"1983","journal-title":"Neurology"},{"issue":"1","key":"ref15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/ane.12667","article-title":"Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society","volume":"135","author":"M Vagberg","year":"2017","journal-title":"Acta neurologica Scandinavica"},{"issue":"22","key":"ref16","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1212\/WNL.0b013e3181c47cc2","article-title":"A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking","volume":"73","author":"CE Teunissen","year":"2009","journal-title":"Neurology"},{"issue":"2","key":"ref17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0165-0270(94)90011-6","article-title":"A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults","volume":"51","author":"LE Rosengren","year":"1994","journal-title":"Journal of neuroscience methods"},{"issue":"3","key":"ref18","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3174\/ajnr.A3262","article-title":"Automated determination of brain parenchymal fraction in multiple sclerosis","volume":"34","author":"M Vagberg","year":"2013","journal-title":"AJNR American journal of neuroradiology"},{"issue":"4","key":"ref19","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1177\/1352458512457844","article-title":"Optic neuritis interferes with optical coherence tomography and magnetic resonance imaging correlations","volume":"19","author":"H Zimmermann","year":"2013","journal-title":"Mult Scler"},{"key":"ref20","article-title":"R: A language and environment for statistical computing","year":"2017"},{"key":"ref21","unstructured":"Terry Therneau BAaBR. rpart: Recursive Partitioning and Regression Trees. R package version 4.1\u201311. 2017."},{"issue":"11","key":"ref22","doi-asserted-by":"crossref","first-page":"e50101","DOI":"10.1371\/journal.pone.0050101","article-title":"Volumetric MRI markers and predictors of disease activity in early multiple sclerosis: a longitudinal cohort study","volume":"7","author":"T Kalincik","year":"2012","journal-title":"PLoS One"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.3174\/ajnr.A3503","article-title":"Evolution of cortical and thalamus atrophy and disability progression in early relapsing-remitting MS during 5 years","volume":"34","author":"R Zivadinov","year":"2013","journal-title":"AJNR American journal of neuroradiology"},{"issue":"11","key":"ref24","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1212\/WNL.0000000000004354","article-title":"Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings","volume":"89","author":"AJ Coles","year":"2017","journal-title":"Neurology"},{"issue":"11","key":"ref25","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1212\/WNL.0000000000004313","article-title":"Alemtuzumab CARE-MS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy","volume":"89","author":"E Havrdova","year":"2017","journal-title":"Neurology"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ana.1032","article-title":"Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis","volume":"50","author":"WI McDonald","year":"2001","journal-title":"Annals of neurology"},{"issue":"2","key":"ref27","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"AJ Thompson","year":"2018","journal-title":"Lancet Neurol"},{"issue":"1\u20132","key":"ref28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jneuroim.2006.07.006","article-title":"Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness","volume":"180","author":"H Link","year":"2006","journal-title":"Journal of neuroimmunology"},{"issue":"5","key":"ref29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1177\/1352458512459684","article-title":"Oligoclonal bands and cerebrospinal fluid markers in multiple sclerosis: associations with disease course and progression","volume":"19","author":"P Lourenco","year":"2013","journal-title":"Mult Scler"},{"issue":"5","key":"ref30","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1177\/1352458514549397","article-title":"Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis","volume":"21","author":"MA Martinez","year":"2015","journal-title":"Mult Scler"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1212\/WNL.0000000000003653","article-title":"Serum neurofilament is associated with progression of brain atrophy and disability in early MS","volume":"88","author":"J Kuhle","year":"2017","journal-title":"Neurology"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S1474-4422(06)70349-0","article-title":"The measurement and clinical relevance of brain atrophy in multiple sclerosis","volume":"5","author":"RA Bermel","year":"2006","journal-title":"Lancet Neurol"},{"issue":"Pt 2","key":"ref33","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/brain\/awf025","article-title":"Brain atrophy in clinically early relapsing-remitting multiple sclerosis","volume":"125","author":"DT Chard","year":"2002","journal-title":"Brain"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0022-510X(00)00259-8","article-title":"Brain atrophy in relapsing-remitting multiple sclerosis: relationship with 'black holes', disease duration and clinical disability","volume":"174","author":"A Paolillo","year":"2000","journal-title":"J Neurol Sci"},{"issue":"14","key":"ref35","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1177\/1352458513488231","article-title":"Clinical impact of early brain atrophy in clinically isolated syndromes","volume":"19","author":"F Perez-Miralles","year":"2013","journal-title":"Mult Scler"},{"issue":"8","key":"ref36","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.3174\/ajnr.A3086","article-title":"Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis","volume":"33","author":"N Bergsland","year":"2012","journal-title":"AJNR American journal of neuroradiology"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.neurad.2016.08.002","article-title":"Brain parenchymal fraction in an age-stratified healthy population\u2014determined by MRI using manual segmentation and three automated segmentation methods","volume":"43","author":"M Vagberg","year":"2016","journal-title":"J Neuroradiol"},{"issue":"6","key":"ref38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.3174\/ajnr.A4665","article-title":"Clinical Feasibility of Synthetic MRI in Multiple Sclerosis: A Diagnostic and Volumetric Validation Study","volume":"37","author":"T Granberg","year":"2016","journal-title":"AJNR American journal of neuroradiology"},{"issue":"11","key":"ref39","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1136\/jnnp.2007.134825","article-title":"Regional grey matter atrophy in clinically isolated syndromes at presentation","volume":"79","author":"RG Henry","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref40","first-page":"1352458517740214","article-title":"The loss of macular ganglion cells begins from the early stages of disease and correlates with brain atrophy in multiple sclerosis patients","author":"AM Pietroboni","year":"2017","journal-title":"Mult Scler"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0194828","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T04:22:57Z","timestamp":1540268577000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0194828"}},"subtitle":[],"editor":[{"given":"Omid","family":"Beiki","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,4,3]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0194828","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,3]]}}}