Pre-Diagnostic Features of Multiple Sclerosis in a Diverse UK Cohort: A Nested Case-Control Study

Many patients with Multiple Sclerosis (MS) experience nonspecific symptoms prior to diagnosis. This period-the 'MS prodrome'-has been described in socio-economically homogeneous cohorts to date. It remains unclear to what extent events prior to an MS diagnosis differ according to social determinants of health.

We conducted a retrospective, longitudinal, population-based nested case-control study using data from Clinical Practice Research Datalink (CPRD) Aurum. Associations between pre-diagnostic symptoms and MS risk were evaluated using multivariable logistic regression models in MS cases and matched controls. To determine whether associations differed by potential health determinants, we tested for statistical interactions and used stratified models.

The study population consisted of 15,029 patients with MS (median index age 44.6, 80.3% female) and 81,027 age-matched controls. In the 5 years preceding diagnosis, MS cases were more likely than controls to have coded autonomic (OR 1.87 [1.80-1.94]), cognitive (OR 2.57 [2.06-3.20]), neurological (OR 7.91 [7.58-8.26]), pain (OR 2.21 [2.12-2.29]) and psychiatric (OR 1.75 [1.69-1.82]) symptoms. The direction of effect was consistent across gender, ethnicity, deprivation and location (urban vs. rural) strata, with over-representation of neurological symptoms in males and those living in urban areas. No statistically significant interaction between factors was found.

We report a consistent relationship between the occurrence of prodromal symptoms and MS risk across a diverse UK cohort. No associations were specific to a particular ethnic, gender or socio-economic group. These findings strengthen the concept of pre-diagnostic symptoms reflecting a potential opportunity to identify those at the earliest stages of MS.