Comorbidities and lifestyle changes as predictors of the multiple sclerosis prodrome: A prospective cohort study

BACKGROUND: Multiple sclerosis (MS) is increasingly recognized as having a prodromal phase, characterized by non-specific symptoms preceding demyelinating events, yet prospective, longitudinal assessments of relevant signs before the first MS symptom are lacking. OBJECTIVES: To investigate whether a wide range of signs and symptoms occurred more frequently in individuals who later developed MS than in the underlying cohort. METHODS: We followed 113,876 women from the Nurses' Health Study II with prospectively collected data on lifestyle, health indicators, and diet. We examined the trajectory of these factors relative to the date of first symptom in 336 incident MS cases compared with the underlying cohort. RESULTS: Several medical conditions, including migraine, depression, urinary leakage, and restless legs syndrome, were more prevalent in individuals who subsequently developed clinical MS. For example, the prevalence of migraine surpassed the underlying cohort 9-10 years before onset and reached 22.8% versus 19.3% at the time of first symptom. Furthermore, a decline in physical activity, physical function, and vitality occurred years before the first MS symptoms. Dietary changes were less pronounced. CONCLUSION: Several health indicators deteriorated years before typical MS symptoms emerged, suggesting that MS is preceded by a prodromal phase characterized by both specific and non-specific symptoms.