Hospital-Diagnosed Traumatic Head Injury and Associated Risk of Developing ALS: A Nationwide Population-Based Case-Control Study

Abstract

Background and objectives Previous studies have suggested that traumatic head injury (THI) may be a risk factor of amyotrophic lateral sclerosis (ALS) development, yet the association remains unclear. We aimed to determine whether hospital-diagnosed THI is an important ALS risk factor, and we investigated the magnitude and duration of associated ALS risk. Methods In this population-based case-control study, we used individual-level data linkage across nationwide health registers from 1980 to 2021 to identify patients with hospital-diagnosed ALS. Each patient was matched 1:10 with individuals from the general population by age, sex, and diagnostic index date. We used conditional logistic regression to examine the relative risk of ALS associated with having previous hospital-diagnosed THI. To avoid the effect of reverse causation, we investigated ALS risk within several time windows and repeated all analyses after restricting THI exposures to more than 3 years before the date of ALS diagnosis. Results THI was observed in 4.7% of 5,943 ALS cases vs 3.7% of 59,426 controls, with a matched odds ratio (OR) of 1.3 (95% CI 1.1-1.4). However, the risk of ALS declined considerably with increasing time since head injury, with a high OR of 4.5 (95% CI 2.8-7.3) observed within the 6 months before ALS diagnosis. If head injury was suffered 6-12 months before ALS diagnosis, the OR was 2.4 (95% CI 1.4-4.0). Restricting the analysis to THI suffered more than 3 years before ALS diagnosis, we f…