Traumatic Brain Injury and Risk of Amyotrophic Lateral Sclerosis

1. Traumatic brain injury (TBI) was associated with a transiently increased amyotrophic lateral sclerosis (ALS) risk confined to the two years following injury.

2. The findings likely indicate reverse causality rather than a causal link between TBI and ALS.

Evidence Rating Level: 2 (Good) 

This large retrospective cohort study investigated whether TBI increases the risk of ALS using UK-wide electronic health records from over 340,000 adults between 2005 and 2020. The study included 85,690 individuals with TBI and 257,070 matched controls (matched by age, sex, and socioeconomic area). ALS incidence was compared using Cox proportional hazards regression. Over a median follow-up of 5.7 years, 150 ALS cases were recorded (7.05 per 100,000 person-years). Individuals with prior TBI had a higher ALS risk (HR 2.61; 95% CI, 1.88–3.63), but this association was limited to the first two years post-injury (HR 6.18; 95% CI, 3.47–11.00) and disappeared thereafter. No significant differences were found in age at ALS diagnosis or death between groups. The authors suggest that this time-limited risk likely reflects reverse causality. Namely, early, subclinical ALS may predispose individuals to falls or injuries leading to TBI, rather than TBI causing ALS. The study’s strengths include its large, population-based design and comprehensive linkage of national datasets, though limitations include potential under-recording of mild TBI and lack of data on confounding factors.

Click here to read this study in JAMA Network Open

Image: PD

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