The identification of the prodromal phase in several chronic neurologic illnesses offers an opportunity to improve early diagnosis and intervention techniques. Research shows that the years following the traditional onset of multiple sclerosis (MS) are related to increased healthcare utilization. Some studies have observed different healthcare patterns before the clinical confirmation of MS symptoms.
To discover early signs, timely diagnosis, and future preventative treatments for disease, it is important to understand the duration of the early phase of MS. In a clinical cohort from British Columbia (Canada), the healthcare indicators were examined for up to 25 years before the onset of MS symptoms. The study was approved by the Clinical Research Ethics Board of the University of British Columbia, with permission granted for data use. The dataset included socioeconomic status and demographic information derived from the postal code.
The researchers verified residency in British Columbia by using the enrolment dates of each individual in the province’s healthcare system. During mid-2024, the population data with unidentified data related to administrative and clinical databases will be provided to researchers by using personal health numbers. Individuals in the MS and matched cohorts were required to have resided in British Columbia for a minimum of 90% of the days in every five years before the MS onset date until their first clinical visit. Researchers used generalized equations with a convertible working correlation structure to adjust within-person correlation and negative binomial regression models for overdispersion.
In an over-dispersed Poisson regression model, with person-time as the model offset, the crude rate ratios (RRs) of physician visits were calculated. SAS (version 4.0.5) and R (version 3.1.0) were used for the analyses. The study included 2038 MS patients with an average age of 37.9 years, of whom 1508 were female.
In the year before the start of MS, the RRs for symptoms and indicators peaked at 1.37 (95% confidence interval: CI, 1.19-1.56) and remained consistently higher than 1.15 up to 15 years before onset. RRs in the three years before MS onset ranged from 1.30 to 1.38; mental health-related RRs were significant from 14 years before onset, except in years 4, 5, and 7. Over the 15 years before MS onset, general practice visit rates were higher across physician specialties, reaching up to 1.23 in the final year. The RRs for neurology and ophthalmology visits were increased markedly in the year before MS onset at 5.46 (95% CI, 4.30-6.93) and 1.64 (95% CI, 1.30-2.08), respectively.
According to biological data, changes in serum neurofilament light chain (sNfL) levels may indicate underlying neuroaxonal damage and neurodegeneration at least 10 years before first MS symptoms. Radiology and emergency medicine visits increased up to five years before onset, while general practice visits showed elevations up to 15 years prior. The prodromal stage was associated with the nervous system and neurologic disorders, including mental health and psychiatric conditions.
References: Ruiz-Algueró M, Zhu F, Chertcoff A, Zhao Y, Marrie RA, Tremlett H. Health care use before multiple sclerosis symptom onset. JAMA Netw Open. 2025;8(8):e2524635. doi:10.1001/jamanetworkopen.2025.24635
