Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis

<b><i>Background:</i></b> Prior studies have suggested that head injury might be a potential risk factor of amyotrophic lateral sclerosis (ALS). However, the association has not been well established. We aimed to provide a synopsis of the current understanding of head injury’s role in ALS. <b><i>Methods:</i></b> We performed a systematic search in PubMed for observational studies that quantitatively investigated the association between head injury and ALS risk published before April 10, 2020. We used a random-effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs). <b><i>Results:</i></b> Fourteen eligible articles including 10,703 cases and 2,159,324 controls were selected in current meta-analysis. We found that head injury was associated with an increased risk of ALS (OR = 1.38, 95% CI: 1.20–1.60) and the association was slightly stronger concerning severe head injury and ALS risk (OR = 1.69, 95% CI: 1.27–2.23). Considering the number of head injuries (<i>N</i>) and ALS risk, the association was weak (OR = 1.23, 95% CI: 1.10–1.37, <i>N</i> = 1; OR = 1.29, 95% CI: 0.89–1.86, <i>N</i> ≥ 2). In addition, a strong association with ALS risk was found in individuals who suffered head injury &#x3c;1 year (OR = 4.05, 95% CI: 2.79–5.89), and when the time lag was set at 1–5, 5–10, and &#x3e;10 years, the pooled OR was 1.13, 1.35, and 1.10, respectively. <b><i>Conclusion:</i></b> This meta-analysis indicates that head injury, especially severe head injury, could increase ALS risk. Although a strong association is found between head injury &#x3c;1 year and ALS risk in the current study, this result suggests a possibility of reverse causation.