Migraines, the multiple sclerosis prodrome, and multiple sclerosis susceptibility.

Background: Multiple studies identified an association between migraines and multiple sclerosis (MS).

Objective: To investigate whether migraines increase MS risk or are part of the MS prodrome.

Methods: Incident MS cases and matched controls completed structured interviews that included a detailed headache and MS history. Participants were classified as having migraines if they fulfilled the third edition of the International Classification of Headache Disorders criteria. The association between migraine onset concurrent with or before the first MS symptom/index date was estimated using multivariable logistic regression.

Results: Among the 591 MS cases (70.6% females, 42.0% White), 21.2% developed migraines concurrent with or before the onset of MS compared to 18.7% of the 651 controls (70.4% females, 42.1% White, adjusted odds ratio (aOR) = 1.15, 95% confidence interval (CI) = 0.87-1.53). Migraine onset was more likely to occur either concurrently or 1 year before MS symptom onset/index date among MS cases (n = 18, 14.4%) than controls (n = 8, 6.6%; aOR = 2.52, 95% CI = 1.08-5.86, p = 0.032). However, not when restricted to only those with migraine onset before MS onset.

Conclusion: Migraine was associated with an increased odds of MS only when co-occurrence was considered. These findings imply that migraines are part of the constellation of MS onset symptoms rather than a risk factor for or prodromal symptom of MS.