{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:40:45Z","timestamp":1780054845697,"version":"3.54.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":126,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000890","name":"the National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG5063A4\/1\/RFA-2103-37392"],"award-info":[{"award-number":["RG5063A4\/1\/RFA-2103-37392"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"the National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["EGID:P002\/903124\/3743"],"award-info":[{"award-number":["EGID:P002\/903124\/3743"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Evidence of increased healthcare use occurring before paediatric-onset multiple sclerosis presentation suggests a prodromal phase. However, little is known of its duration or features, and few studies have accessed a clinical cohort to examine the period before symptom onset. We compared annual rates of healthcare use before paediatric multiple sclerosis onset in clinical and administrative cohorts versus matched non-multiple sclerosis cohorts. We identified persons with paediatric-onset multiple sclerosis from the Swedish Multiple Sclerosis registry and population-based administrative data using a validated algorithm requiring \u22653 hospital or outpatient multiple sclerosis diagnostic codes recorded on separate dates. The index date was multiple sclerosis symptom onset, as recorded in the multiple sclerosis registry by a neurologist (clinical cohort) or the earliest demyelinating disease-related International Classification of Diseases code (administrative cohort). Individuals with age at index &amp;lt;18 years were matched with up to five individuals from the general population on sex, birth year, county of residence at the index date and residency time. Healthcare use was measured as hospital\/outpatient diagnoses (International Classification of Diseases chapters) and prescription drug classes (Anatomical Therapeutic Chemical classification system, 2nd level). Yearly rates of hospital and outpatient visits (up to 17 years pre-index) and prescription fills (up to 14 years pre-index) were compared using Quasi-Poisson regression. The clinical\/administrative cohorts included 233\/206 paediatric-onset multiple sclerosis and 1151\/1011 matched individuals, with a mean age at the index of 16 years (standard deviation: 2) in all four groups. In both cohorts, individuals with paediatric-onset multiple sclerosis exhibited elevated healthcare use predominantly 1\u201310 years pre-index, including, for example, higher prescriptions filled for corticosteroids for dermatological use (rate ratio range: 2.61\u20133.91) and outpatient visits for ill-defined signs\/symptoms (rate ratio range: 2.17\u20138.64) and unassigned ICD codes (rate ratio range: 2.20\u20134.17). In the year pre-index, individuals with paediatric-onset multiple sclerosis in both cohorts exhibited higher rates of outpatient visits for neoplasms, nervous system disorders, sense organ conditions, ill-defined signs\/symptoms and \u2018other health system contact\u2019 (rate ratio range: 2.05\u201318.00). In the same year, the clinical cohort also had higher rates of prescription fills for \u2018other gynecologicals\u2019 (4.08, 95% confidence interval: 1.04\u201316.09), and the administrative cohort had higher rates for prescriptions filled across eight drug classes (rate ratio range: 1.56\u20136.49). Healthcare use was higher primarily in the 1\u201310 years before paediatric-onset multiple sclerosis versus a matched cohort, suggestive of a prodromal phase. During this period, the paediatric-onset multiple sclerosis cohort was more often identified as having ill-defined signs\/symptoms, neoplasms and skin-related issues.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf180","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T16:54:15Z","timestamp":1746636855000},"source":"Crossref","is-referenced-by-count":6,"title":["Higher healthcare use before paediatric multiple sclerosis onset: a nationwide cohort study"],"prefix":"10.1093","volume":"7","author":[{"given":"Kyla Anne","family":"McKay","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , Stockholm 171 77 ,","place":["Sweden"]},{"name":"Centre for Molecular Medicine, Karolinska Hospital , Stockholm 171 76 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-5762","authenticated-orcid":false,"given":"Ali","family":"Manouchehrinia","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , Stockholm 171 77 ,","place":["Sweden"]},{"name":"Alberta Health Services , Calgary , T5J 3E4","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), University of British Columbia , Vancouver , V6T 2B5","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinshan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), University of British Columbia , Vancouver , V6T 2B5","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Ann","family":"Marrie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dalhousie University , Halifax , B3H 4R2","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-2899","authenticated-orcid":false,"given":"Colleen Jean","family":"Maxwell","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Science, University of Waterloo , Waterloo , N2G 1C5","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Hillert","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet , Stockholm 171 77 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-2535","authenticated-orcid":false,"given":"Helen","family":"Tremlett","sequence":"additional","affiliation":[{"name":"Faculty of Medicine (Neurology), University of British Columbia , Vancouver , V6T 2B5","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"issue":"2","key":"2025062620181656600_fcaf180-B1","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":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"issue":"7","key":"2025062620181656600_fcaf180-B2","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1177\/13524585231171047","article-title":"Pediatric multiple sclerosis: The 2022 ECTRIMS lecture","volume":"29","author":"Banwell","year":"2023","journal-title":"Mult Scler J"},{"key":"2025062620181656600_fcaf180-B3","doi-asserted-by":"crossref","first-page":"761408","DOI":"10.3389\/fneur.2021.761408","article-title":"The multiple sclerosis prodrome: Evidence to 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