To investigate the association between THI and the risk of developing ALS.

Previous studies have suggested that traumatic head injury (THI) may contribute to the development of amyotrophic lateral sclerosis (ALS). However, the evidence remains limited and inconsistent, partly due to small sample sizes.

We conducted a systematic review and meta-analysis of studies assessing the relationship between THI and ALS. The exposure of interest was THI, and the outcome of interest was ALS development. We further examined the association by sex (male vs female), geographic region (Americas vs. Europe), and number of injuries (single vs multiple). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used as effect measures.

Eighteen studies comprising 578,815 participants were included. THI was associated with an increased risk of ALS (HR = 1.47; 95% CI: 1.23–1.76). Subgroup analysis by sex showed a significant association among males (HR = 2.27; 95% CI: 1.41–3.66) but not females (HR = 1.30; 95% CI: 0.78–2.17). The association was consistent across studies conducted in Europe (HR = 1.60; 95% CI: 1.19–2.15) and the Americas (HR = 1.27; 95% CI: 1.12–1.43). Both single (HR = 1.48; 95% CI: 1.18–1.85) and multiple THIs (HR = 1.34; 95% CI: 1.15–1.56) were associated with ALS.

THI was associated with an increased risk of ALS. The association did not differ by the number of injuries. Our analysis indicates that the relationship between THI and ALS is not causative.