{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:07:58Z","timestamp":1786975678498,"version":"build-2736575974"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n A growing body of literature suggests the presence of a prodromal period with nonspecific signs and symptoms before onset of multiple sclerosis (MS).<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To systematically assess diseases and symptoms diagnosed in the 5 years before a first MS- or central nervous system (CNS) demyelinating disease\u2013related diagnostic code in pediatric patients compared with controls without MS and controls with another immune-mediated disorder, juvenile idiopathic arthritis (JIA).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This population-based, matched case-control study included children and adolescents (aged &amp;lt;18 years) in Germany with statutory health insurance from January 2010 to December 2020. The study population consisted of 3 groups: case individuals with MS, control individuals without MS, and control individuals with JIA. Data were analyzed from November 2023 to April 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Diagnoses coded according to the\n International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM)<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n \n The main outcome was incident cases of MS, defined as the first confirmed diagnosis of MS (\n ICD-10-GM<\/jats:italic>\n code G35) in 1 quarter between 2013 and 2020 and at least 1 additional diagnosis in the following quarters. In total, 163\n ICD-10-GM<\/jats:italic>\n codes before a first MS diagnosis were assessed using univariable and multivariable logistic regression analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The study population consisted of 1091 children and adolescents with MS, 10\u202f910 without MS, and 1068 with JIA. Of the children and adolescents with MS, 788 (72.2%) were female. Mean (SD) age at disease diagnosis was 15.7 (1.7) years. Nine\n ICD-10-GM<\/jats:italic>\n codes were present more frequently among children and adolescents with MS in the 5 years before their first MS diagnosis than among controls without MS: obesity (adjusted odds ratio [AOR], 1.70; 95% CI, 1.42-2.02), disorders of eye refraction and accommodation (AOR, 1.26; 95% CI, 1.09-1.47), visual disturbances (AOR, 1.31; 95% CI, 1.10-1.55), gastritis and duodenitis (AOR, 1.35; 95% CI, 1.08-1.70), patella disorders (AOR, 1.47; 95% CI, 1.13-1.90), heartbeat abnormalities (AOR, 1.94; 95% CI, 1.27-2.96), flatulence (AOR, 1.43; 95% CI, 1.01-2.01), skin sensation disturbances (AOR, 12.93; 95% CI, 8.98-18.62), as well as dizziness and giddiness (AOR, 1.52; 95% CI, 1.22-1.89). Four of these\n ICD-10-GM<\/jats:italic>\n codes were significantly more prevalent in children and adolescents with MS than in controls with JIA: obesity (AOR, 3.19; 95% CI, 2.03-5.02), refraction and accommodation disorders (AOR, 3.08; 95% CI, 2.33-4.08), visual disturbances (AOR, 1.62; 95% CI, 1.13-2.33), and skin sensation disturbances (AOR, 27.70; 95% CI, 6.52-117.64).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this population-based, matched case-control study, children and adolescents with MS had diverse metabolic, ocular, musculoskeletal, gastrointestinal, and cardiovascular symptoms, signs, or diagnoses within 5 years before their first MS diagnosis. Better characterization of early symptoms and\/or risk factors, comorbid disorders, and possible prodromal features of MS may have considerable implications for early recognition and subsequent progression of the disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.52652","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T11:31:15Z","timestamp":1735299075000},"page":"e2452652","source":"Crossref","is-referenced-by-count":10,"title":["Symptoms Prior to Diagnosis of Multiple Sclerosis in Individuals Younger Than 18 Years"],"prefix":"10.1001","volume":"7","author":[{"given":"Manas K.","family":"Akmatov","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Care Atlas, Central Research Institute of Ambulatory Health Care, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical 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