Head injuries as a risk factor for amyotrophic lateral sclerosis: A systematic review and meta-analysis

BACKGROUND: Previous studies have suggested that traumatic head injury (THI) is associated with amyotrophic lateral sclerosis (ALS). However, the evidence remains limited and inconsistent, partly due to small sample sizes. OBJECTIVES: In this meta-analysis, we aimed to investigate the association between THI and the risk of ALS. METHODS: 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. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used as effect measures. RESULTS: Eighteen studies comprising 578,815 participants were included. THI was associated with an increased risk of ALS (OR = 1.47; 95% CI: 1.23-1.76). The association was consistent across studies conducted in Europe (OR = 1.60; 95% CI: 1.19-2.15) and the Americas (OR = 1.27; 95% CI: 1.12-1.43). Subgroup analysis by sex showed a significant association among males (OR = 2.27; 95% CI: 1.41-3.66) but it was less significant among females (OR = 1.30; 95% CI: 0.78-2.17). Both single (OR = 1.48; 95% CI: 1.18-1.85) and multiple THIs (OR = 1.34; 95% CI: 1.15-1.56) were associated with ALS. Funnel and doi plots demonstrated asymmetry indicating significant publication bias. CONCLUSIONS: Our analysis demonstrated an association between THI and ALS, however the lack of dose-response relationship suggests it is less likely to be causative.