Five years before multiple sclerosis onset: Phenotyping the prodrome

Background: The multiple sclerosis (MS) prodrome is poorly characterized. Objective: To phenotype the MS prodrome via health care encounters. Methods: Using data from a population-based cohort study linking administrative and clinical data in four Canadian provinces, we compared physician and hospital encounters and prescriptions filled (via International Classification of Diseases chapters, physician specialty or drug classes) for MS subjects in the 5 years before the first demyelinating claim in an administrative cohort or the clinical symptom onset in an MS clinic-derived cohort, to age-, sex- and geographically matched controls. Rate ratios (RRs), 95% confidence intervals (95% CIs) and proportions were estimated. Results: The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous (RR (range) = 2.31; 95% CI: 1.05-5.10 to 4.75; 95% CI: 3.11-7.25), sensory (RR (range) = 1.40; 95% CI: 1.34-1.46 to 2.28; 95% CI: 1.72-3.02), musculoskeletal (RR (range) = 1.19; 95% CI: 1.07-1.33 to 1.70; 95% CI: 1.57-1.85) and genito-urinary systems (RR (range) = 1.17; 95% CI: 1.05-1.30 to 1.59; 95% CI: 1.48-1.70). Cases had more psychiatrist and urologist encounters (RR (range) = 1.48; 95% CI: 1.36-1.62 to 1.80; 95% CI: 1.61-2.01), and higher proportions of musculoskeletal, genito-urinary or hormonal-related prescriptions (1.1-1.5 times higher, all p < 0.02). However, cases had fewer pregnancy-related encounters than controls (RR = 0.78; 95% CI: 0.71-0.86 to 0.88; 95% CI: 0.84-0.92). Conclusion: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible.