Health Care Use Before Multiple Sclerosis Symptom Onset

Importance: Health care use increases before multiple sclerosis (MS) onset. However, most studies have focused on the 5 to 10 years preceding the first demyelinating disease code from administrative data. Few studies have examined patterns before clinically determined MS symptom onset from clinical records. Objective: To examine health care use 25 years before MS symptom onset in a clinical cohort from British Columbia, Canada. Design, Setting, and Participants: This matched cohort study accessed data prospectively collected from January 1991 to September 2018. All data were released mid-2024 for analysis. The study was conducted in British Columbia using publicly funded universal health insurance data. Patients with MS were identified from MS clinic records and matched with up to 5 individuals randomly selected without replacement from the general population by sex, birth year, socioeconomic status, and postal code of residency. Main Outcomes and Measures: Linked clinical and administrative data were used to compare physician visit rates 25 years before MS onset using adjusted negative binomial models and 15 years before MS onset by International Classification of Diseases, Ninth Revision (ICD-9) chapter and physician specialty. Results: A total of 2038 patients with MS (mean [SD] age at symptom onset, 37.9 [10.9] years; 1508 female [74.0%]) and 10 182 matched individuals were included. All-cause physician visit rate ratios (RRs) for patients with MS were consistently elevated from 14 years before onset (adjusted RR [ARR], 1.19; 95% CI, 1.07-1.33), peaking the year before MS onset (ARR, 1.28; 95% CI, 1.21-1.35). The RRs for ill-defined symptoms and signs were consistently elevated 15 years before onset, exceeding 1.15 and peaking at 1.37 (95% CI, 1.19-1.56) the year before MS onset. Mental health-related RRs from 14 years before onset were significant (excluding years 7, 5, and 4), with RRs in the 3 years before MS onset ranging from 1.30 (95% CI, 1.05-1.58) to 1.38 (95% CI, 1.12-1.68). Sensory, musculoskeletal, and nervous system RRs were elevated 8, 5, and 4 years before onset, respectively, with, for example, a peak of 2.42 (95% CI, 1.90-3.07) for nervous system concerns the year before MS onset. By physician specialty, general practice visit RRs were significantly elevated in each of the 15 years before MS onset, reaching 1.23 (95% CI, 1.17-1.30) in the year before onset. Psychiatry visit RRs were elevated 12 years before onset (2.59; 95% CI, 1.23-5.47). Neurology and ophthalmology RRs were significantly higher up to 8 to 9 years before onset, peaking the year before MS onset at 5.46 (95% CI, 4.30-6.93) for neurology and 1.64 (95% CI, 1.30-2.08) for ophthalmology. Conclusions and Relevance: In this matched cohort study of people with and without MS, health care use was higher among patients with MS 14 to 15 years before MS symptom onset, suggesting that MS may have started earlier than previously thought. Mental health and psychiatric issues along with ill-defined signs and symptoms might be among the earliest features of the prodromal period preceding nervous system-related and neurologic visits by 7 to 11 years.

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