{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:32:25Z","timestamp":1791804745603,"version":"4.3.4"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008486","name":"Schweizerische Multiple Sklerose Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008486","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Multiple sclerosis (MS) symptoms are expected to aggregate in specific patterns across different stages of the disease. Here, we studied the clustering of onset symptoms and examined their characteristics, comorbidity patterns and associations with potential risk factors.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Data stem from the Swiss Multiple Sclerosis Registry, a prospective study including 2,063 participants by November 2019. MS onset symptoms were clustered using latent class analysis (LCA). The latent classes were further examined using information on socio-demographic characteristics, MS-related features, potential risk factors, and comorbid diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The LCA model with six classes (frequencies ranging from 12 to 24%) was selected for further analyses. The latent classes comprised a multiple symptoms class with high probabilities across several symptoms, contrasting with two classes with solitary onset symptoms: vision problems and paresthesia. Two gait classes emerged between these extremes: the gait-balance class and the gait-paralysis class. The last class was the fatigue-weakness-class, also accompanied by depression symptoms, memory, and gastro-intestinal problems. There was a moderate variation by sex and by MS types. The multiple symptoms class yielded increased comorbidity with other autoimmune disorders. Similar to the fatigue-weakness class, the multiple symptoms class showed associations with angina, skin diseases, migraine, and lifetime prevalence of smoking. Mononucleosis was more frequently reported in the fatigue-weakness and the paresthesia class. Familial aggregation did not differ among the classes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Clustering of MS onset symptoms provides new perspectives on the heterogeneity of MS. The clusters comprise different potential risk factors and comorbidities. They point toward different risk mechanisms.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2021.693440","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T02:52:59Z","timestamp":1625539979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Onset Symptom Clusters in Multiple Sclerosis: Characteristics, Comorbidities, and Risk Factors"],"prefix":"10.3389","volume":"12","author":[{"given":"Vladeta","family":"Ajdacic-Gross","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Steinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Horv\u00e1th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Rodgers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Kamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg","family":"Kesselring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zina-Mary","family":"Manjaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zecca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Calabrese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo A.","family":"Puhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor von","family":"Wyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.3389\/fimmu.2018.03116","article-title":"Pathogenic mechanisms associated with different clinical courses of multiple sclerosis","volume":"9","author":"Lassmann","year":"2018","journal-title":"Front Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/j.1750-3639.1996.tb00854.x","article-title":"Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis","volume":"6","author":"Lucchinetti","year":"1996","journal-title":"Brain Pathol."},{"key":"B3","volume-title":"Zur Problematik der Multiplen Sklerose [Research problems in multiple sclerosis]","author":"Georgi","year":"1961"},{"key":"B4","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/BF00313635","article-title":"Past infectious events and disease evolution in multiple sclerosis","volume":"230","author":"Lamoureux","year":"1983","journal-title":"J Neurol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.msard.2018.12.007","article-title":"Multiple sclerosis risk factors contribute to onset heterogeneity","volume":"28","author":"Briggs","year":"2019","journal-title":"Mult Scler Relat Disord."},{"key":"B6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3390\/brainsci7070078","article-title":"Multiple sclerosis: immunopathology and treatment update","volume":"7","author":"Dargahi","year":"2017","journal-title":"Brain Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bionps.2019.100001","article-title":"Biomarkers in neuropsychiatric disorders: translating research toclinical applications","volume":"1","author":"Nasrallah","year":"2019","journal-title":"Biomarkers Neuropsychiatric Disord."},{"key":"B8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fneur.2014.00102","article-title":"How implementation of systems biology into clinical trials accelerates understanding of diseases","volume":"5","author":"Bielekova","year":"2014","journal-title":"Front Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1097\/JNN.0b013e3181e26c5f","article-title":"Symptom cluster and quality of life: preliminary evidence in multiple sclerosis","volume":"42","author":"Motl","year":"2010","journal-title":"J Neurosci Nurs."},{"key":"B10","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1097\/JNN.0b013e3182478cba","article-title":"Symptom clusters in women with relapsing-remitting multiple sclerosis","volume":"44","author":"Newland","year":"2012","journal-title":"J Neurosci Nurs."},{"key":"B11","doi-asserted-by":"publisher","first-page":"203183","DOI":"10.1155\/2014\/203183","article-title":"Symptoms and association with health outcomes in relapsing-remitting multiple sclerosis: results of a US patient survey","volume":"2014","author":"Williams","year":"2014","journal-title":"Mult Scler Int."},{"key":"B12","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1177\/1352458506070759","article-title":"Classification of multiple sclerosis patients by latent class analysis of magnetic resonance imaging characteristics","volume":"12","author":"Zwemmer","year":"2006","journal-title":"Mult Scler."},{"key":"B13","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1177\/1352458520914844","article-title":"The multiple sclerosis prodrome: emerging evidence, challenges, and opportunities","volume":"27","author":"Tremlett","year":"2020","journal-title":"Mult Scler."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1111\/ene.13925","article-title":"Prodrome in relapsing-remitting and primary progressive multiple sclerosis","volume":"26","author":"Wijnands","year":"2019","journal-title":"Eur J Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/ana.24769","article-title":"Preclinical disease activity in multiple sclerosis: a prospective study of cognitive performance prior to first symptom","volume":"80","author":"Cortese","year":"2016","journal-title":"Ann Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1016\/j.jocn.2014.02.026","article-title":"Clinically isolated syndromes and the relationship to multiple sclerosis","volume":"21","author":"Brownlee","year":"2014","journal-title":"J Clin Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.nic.2016.12.008","article-title":"Radiologically isolated syndrome: MR imaging features suggestive of multiple sclerosis prior to first symptom onset","volume":"27","author":"Okuda","year":"2017","journal-title":"Neuroimaging Clin N Am."},{"key":"B18","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.24564","article-title":"Primary progressive multiple sclerosis evolving from radiologically isolated syndrome","volume":"79","author":"Kantarci","year":"2016","journal-title":"Ann Neurol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12883-018-1118-0","article-title":"The Swiss Multiple Sclerosis Registry (SMSR): study protocol of a participatory, nationwide registry to promote epidemiological and patient-centered MS research","volume":"18","author":"Steinemann","year":"2018","journal-title":"BMC Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"w14623","DOI":"10.4414\/smw.2018.14623","article-title":"A digitally facilitated citizen-science driven approach accelerates participant recruitment and increases study population diversity","volume":"148","author":"Puhan","year":"2018","journal-title":"Swiss Med Wkly."},{"key":"B21","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1177\/1352458518823955","article-title":"How do patients enter the healthcare system after the first onset of multiple sclerosis symptoms? The influence of setting and physician specialty on speed of diagnosis","volume":"26","author":"Barin","year":"2019","journal-title":"Mult Scler."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2055217318814562","DOI":"10.1177\/2055217318814562","article-title":"Factors associated with time from first-symptoms to diagnosis and treatment initiation of Multiple Sclerosis in Switzerland","volume":"4","author":"Kaufmann","year":"2018","journal-title":"Mult Scler J Exp Transl Clin."},{"key":"B23","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00415-019-09563-y","article-title":"Factors influencing patient satisfaction with the first diagnostic consultation in multiple sclerosis: a Swiss Multiple Sclerosis Registry (SMSR) study","volume":"267","author":"Kamm","year":"2020","journal-title":"J Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"102148","DOI":"10.1016\/j.msard.2020.102148","article-title":"Development and validation of the self-reported disability status scale (SRDSS) to estimate EDSS-categories","volume":"42","author":"Kaufmann","year":"2020","journal-title":"Mult Scler Relat Disord."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s11136-011-9903-x","article-title":"Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)","volume":"20","author":"Herdman","year":"2011","journal-title":"Qual Life Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1159\/000376585","article-title":"The WHO-5 Well-Being Index: a systematic review of the literature","volume":"84","author":"Topp","year":"2015","journal-title":"Psychother Psychosom."},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.4135\/9781412984713","volume-title":"Latent Class Analysis","author":"McCutcheon","year":"1987"},{"key":"B28","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1097\/NNR.0b013e3182539f4c","article-title":"Latent variable mixture modeling: a flexible statistical approach for identifying and classifying heterogeneity","volume":"61","author":"Schmiege","year":"2012","journal-title":"Nursing Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1080\/10705510701575396","article-title":"Deciding on the number of classes in latent class analysis and growth mixture modeling: a monte carlo simulation study","volume":"14","author":"Nylund","year":"2007","journal-title":"Struct Equat Model."},{"key":"B30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12916-019-1311-z","article-title":"A step beyond the hygiene hypothesis-immune-mediated classes determined in a population-based study","volume":"17","author":"Ajdacic-Gross","year":"2019","journal-title":"BMC Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S0895-4356(00)00314-0","article-title":"Adjusting for multiple testing\u2013when and how?","volume":"54","author":"Bender","year":"2001","journal-title":"J Clin Epidemiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1007\/s00415-009-0039-7","article-title":"Natural history comparisons of primary and secondary progressive multiple sclerosis reveals differences and similarities","volume":"256","author":"Tremlett","year":"2009","journal-title":"J Neurol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"418","DOI":"10.3389\/fneur.2018.00418","article-title":"Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset","volume":"9","author":"Tao","year":"2018","journal-title":"Front Neurol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1177\/0284185115578689","article-title":"Limbic pathway lesions in patients with multiple sclerosis","volume":"57","author":"Sahin","year":"2016","journal-title":"Acta Radiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1136\/jnnp-2013-307275","article-title":"Isolated cognitive relapses in multiple sclerosis","volume":"85","author":"Pardini","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B36","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ncl.2017.08.008","article-title":"The dynamics of the gut microbiome in multiple sclerosis in relation to disease","volume":"36","author":"Mowry","year":"2018","journal-title":"Neurol Clin."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1007\/s00415-015-7674-y","article-title":"The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset","volume":"262","author":"Tedeholm","year":"2015","journal-title":"J Neurol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.ncl.2011.01.001","article-title":"Natural history of multiple sclerosis: early prognostic factors","volume":"29","author":"Mowry","year":"2011","journal-title":"Neurol Clin."},{"key":"B39","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1212\/CON.0000000000000737","article-title":"Phases and phenotypes of multiple sclerosis","volume":"25","author":"Kantarci","year":"2019","journal-title":"Continuum."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1177\/1352458513506505","article-title":"Epstein-Barr virus is a necessary causative agent in the pathogenesis of multiple sclerosis: yes","volume":"19","author":"Pakpoor","year":"2013","journal-title":"Mult Scler."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e12496","DOI":"10.1371\/journal.pone.0012496","article-title":"An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis","volume":"5","author":"Handel","year":"2010","journal-title":"PLoS ONE."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e318","DOI":"10.1212\/NXI.0000000000000318","article-title":"Epstein-Barr-negative MS: a true phenomenon?","volume":"4","author":"Dobson","year":"2017","journal-title":"Neurol Neuroimmunol Neuroinflamm."},{"key":"B43","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1097\/00001648-200105000-00009","article-title":"Multiple sclerosis and age at infection with common viruses","volume":"12","author":"Hernan","year":"2001","journal-title":"Epidemiology."},{"key":"B44","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s11481-010-9201-3","article-title":"Epstein-barr virus infection and multiple sclerosis: a review","volume":"5","author":"Ascherio","year":"2010","journal-title":"J Neuroimmune Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1093\/emph\/eot004","article-title":"Microbial 'Old Friends', immunoregulation and stress resilience","volume":"2013","author":"Rook","year":"2013","journal-title":"Evol Med Public Health."},{"key":"B46","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1111\/j.1600-0404.1996.tb00050.x","article-title":"Environmental risk factors in MS: a case-control study in Moscow","volume":"94","author":"Gusev","year":"1996","journal-title":"Acta Neurol Scand."},{"key":"B47","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1471-2377-13-41","article-title":"Surgery and risk for multiple sclerosis: a systematic review and meta-analysis of case-control studies","volume":"13","author":"Lunny","year":"2013","journal-title":"BMC Neurol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"102131","DOI":"10.1016\/j.msard.2020.102131","article-title":"Tonsillectomy in multiple sclerosis patients: retrospective, case-controlled, exploratory study","volume":"42","author":"Jakimovski","year":"2020","journal-title":"Mult Scler Relat Disord."},{"key":"B49","doi-asserted-by":"publisher","first-page":"102062","DOI":"10.1016\/j.msard.2020.102062","article-title":"Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study","volume":"42","author":"Hughes","year":"2020","journal-title":"Mult Scler Relat Disord."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jaut.2016.06.007","article-title":"Tonsillectomy associated with an increased risk of autoimmune diseases: a national cohort study","volume":"72","author":"Ji","year":"2016","journal-title":"J Autoimmun."},{"key":"B51","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1159\/000437371","article-title":"Upper respiratory infections and MRI activity in relapsing-remitting multiple sclerosis","volume":"45","author":"Kneider","year":"2015","journal-title":"Neuroepidemiology."},{"key":"B52","first-page":"647","article-title":"Environmental risk factors for inflammatory bowel diseases: an umbrella review of meta-analyses","volume-title":"Gastroenterology.","author":"Piovani","year":"2019"},{"key":"B53","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1097\/EDE.0000000000000946","article-title":"Increased risk of inflammatory bowel disease in families with tonsillectomy: a danish national cohort study","volume":"30","author":"Bager","year":"2019","journal-title":"Epidemiology."},{"key":"B54","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s10654-013-9853-4","article-title":"Smoking and multiple sclerosis susceptibility","volume":"28","author":"Hedstrom","year":"2013","journal-title":"Eur J Epidemiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1001\/archneurol.2009.122","article-title":"Smoking and disease progression in multiple sclerosis","volume":"66","author":"Healy","year":"2009","journal-title":"Arch Neurol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1950","DOI":"10.1212\/WNL.0000000000009371","article-title":"Vitamin D, smoking, EBV, and long-term cognitive performance in MS: 11-year follow-up of BENEFIT","volume":"94","author":"Cortese","year":"2020","journal-title":"Neurology."},{"key":"B57","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1177\/1352458511399610","article-title":"Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis","volume":"17","author":"Hedstrom","year":"2011","journal-title":"Mult Scler."},{"key":"B58","doi-asserted-by":"publisher","first-page":"101872","DOI":"10.1016\/j.msard.2019.101872","article-title":"Environmental risk factors for multiple sclerosis in Japanese people","volume":"38","author":"Sakoda","year":"2020","journal-title":"Mult Scler Relat Disord."},{"key":"B59","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1177\/1352458520912500","article-title":"Exposure to passive smoking during adolescence is associated with an increased risk of developing multiple sclerosis","volume":"27","author":"Oturai","year":"2020","journal-title":"Mult Scler."},{"key":"B60","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1212\/WNL.0b013e3181b59c40","article-title":"Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis","volume":"73","author":"Hedstrom","year":"2009","journal-title":"Neurology."},{"key":"B61","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1177\/1352458511416487","article-title":"Increased risk of multiple sclerosis among women with migraine in the Nurses' Health Study II","volume":"18","author":"Kister","year":"2012","journal-title":"Mult Scler."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1177\/1352458512438240","article-title":"Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis","volume":"18","author":"Roshanisefat","year":"2012","journal-title":"Mult Scler."},{"key":"B63","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/JID.2015.350","article-title":"Risk of multiple sclerosis in patients with psoriasis: a danish nationwide cohort study","volume":"136","author":"Egeberg","year":"2016","journal-title":"J Invest Dermatol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nrneurol.2017.33","article-title":"Comorbidity in multiple sclerosis: implications for patient care","volume":"13","author":"Marrie","year":"2017","journal-title":"Nat Rev Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1007\/s00415-012-6790-1","article-title":"Autoimmune disease in people with multiple sclerosis and their relatives: a systematic review and meta-analysis","volume":"260","author":"Dobson","year":"2013","journal-title":"J Neurol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1177\/1352458510369146","article-title":"Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study","volume":"16","author":"Langer-Gould","year":"2010","journal-title":"Mult Scler."},{"key":"B67","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1177\/1352458514564490","article-title":"A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis","volume":"21","author":"Marrie","year":"2015","journal-title":"Mult Scler."},{"key":"B68","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1007\/s00415-016-8340-8","article-title":"Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis","volume":"264","author":"Kosmidou","year":"2017","journal-title":"J Neurol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1093\/aje\/kwn408","article-title":"Are individuals with an autoimmune disease at higher risk of a second autoimmune disorder?","volume":"169","author":"Somers","year":"2009","journal-title":"Am J Epidemiol."},{"key":"B70","unstructured":"Clinical aspects of multiple sclerosis in north-east Scotland with particular reference to its course and prognosis1597628\n            PhadkeJG\n          10.1093\/brain\/113.6.15972276037Brain.1131990"},{"key":"B71","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1002\/ana.21117","article-title":"Environmental risk factors for multiple sclerosis. Part I: the role of infection","volume":"61","author":"Ascherio","year":"2007","journal-title":"Ann Neurol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1177\/1352458516646863","article-title":"Level of education and multiple sclerosis risk over a 50-year period: Registry-based sibling study","volume":"23","author":"Bjornevik","year":"2017","journal-title":"Mult Scler."},{"key":"B73","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/s10995-012-1010-2","article-title":"Low income\/socio-economic status in early childhood and physical health in later childhood\/adolescence: a systematic review","volume":"17","author":"Spencer","year":"2013","journal-title":"Matern Child Health J."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1093\/ntr\/ntw266","article-title":"Association between cigarette smoking prevalence and income level: a systematic review and meta-analysis","volume":"19","author":"Casetta","year":"2017","journal-title":"Nicotine Tob Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1159\/000323948","article-title":"Smokers with multiple sclerosis are more likely to report comorbid autoimmune diseases","volume":"36","author":"Marrie","year":"2011","journal-title":"Neuroepidemiology."},{"key":"B76","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1097\/WCO.0b013e3283533a7e","article-title":"Vitamin D and multiple sclerosis: epidemiology, immunology, and genetics","volume":"25","author":"Simon","year":"2012","journal-title":"Curr Opin Neurol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"e113","DOI":"10.1016\/j.lpm.2015.01.001","article-title":"Environmental factors in multiple sclerosis","volume":"44","author":"Pantazou","year":"2015","journal-title":"Presse Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"2055102915612271","DOI":"10.1177\/2055102915612271","article-title":"Stress and multiple sclerosis: a systematic review considering potential moderating and mediating factors and methods of assessing stress","volume":"2","author":"Briones-Buixassa","year":"2015","journal-title":"Health Psychol Open."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.693440\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T02:53:06Z","timestamp":1625539986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.693440\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":78,"alternative-id":["10.3389\/fneur.2021.693440"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.693440","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"article-number":"693440"}}