Identify associations of traumatic brain injury (TBI) history and subsequent diagnosis of multiple sclerosis (MS). 

MS prevalence has increased since 2013 and has been linked to environmental factors (e.g., smoking history, obesity, Epstein-Barr Virus). More limited data suggest a link between MS and multiple concussions and TBI. This study examined the association of TBI and MS in Post-9/11 era veterans. 

Our retrospective cohort study included Veterans who received Department of Defense (DoD) care in at least three years FY2000-2019. 

We identified MS using ICD9 (340) or ICD10 codes (G35). We identified TBI exposure using a hierarchical approach prioritizing data from the DoD Trauma Registry, self-reported loss/alteration of consciousness, or post-traumatic amnesia, and then ICD-9/10 diagnosis. TBI was classified as no TBI, mild TBI, moderate/severe TBI, and penetrating TBI. Index dates were the first date of TBI diagnosis or were simulated by drawing from the distribution of true index dates within age brackets for those without TBI. Other covariates included age, sex, race/ethnicity, health behaviors (e.g., smoking, substance use disorders, overdose, obesity) and comorbid health conditions associated with MS (e.g., depression, anxiety, hypertension, hypercholesterolemia, and chronic lung disease). We conducted competing event (Fine-Gray) analyses examining time from TBI/index day to MS diagnosis. 

Of the 2,291,789 Veterans who met inclusion criteria (mean age=33; SD=11) 16.6% had TBI exposure. Time to MS was fastest for women (HR 2.4; 95%CI 2.2-2.6) and veterans with the following clinical characteristics before index date: stroke (HR 2.1; 95%CI 1.8-2.5), other neurological conditions (HR 2.2; 95%CI 1.8-2.6) and TBI severity (penetrating [HR 1.96; 95%CI 1.5-2.6]; moderate/severe [HR 1.5; 95%CI 1.2-1.8]; mild [HR 1.5; 95%CI 1.3-1.6]).

Our  study found that neurological conditions including TBI were the strongest clinical predictors of MS emergence in this younger Veteran cohort, which should be considered in caring for Post-9/11 Veterans with neurological conditions.