Traumatic Brain Injury and Risk of Amyotrophic Lateral Sclerosis Mortality: A Traumatic Brain Injury Model Systems...

Area of Science:

• Neuroscience
• Epidemiology
• Neurology

Background:

• Emerging evidence links traumatic brain injury (TBI) to increased amyotrophic lateral sclerosis (ALS) mortality.
• The temporal relationship and mechanisms underlying this association remain unclear.

Purpose of the Study:

• To evaluate ALS mortality rates in individuals with TBI.
• To examine the temporal patterns of ALS mortality following TBI.
• To investigate the influence of injury severity on ALS mortality.

Main Methods:

• Retrospective cohort study of 20,250 individuals with complicated mild-to-severe TBI from the TBI Model Systems (TBIMS) database (1987-2024).
• Standardized mortality ratios (SMRs) were calculated and adjusted for demographic factors and calendar year.
• Time-stratified analyses and subgroup analyses based on injury severity were performed.

Main Results:

• A significantly elevated ALS mortality was observed in the TBI cohort (SMR = 2.39) compared to the general population.
• Elevated ALS mortality was concentrated within 2 years post-TBI (SMR = 4.30), with no significant elevation after 2 years.
• Higher ALS mortality was noted in severe TBI cases and when including individuals with pre-existing ALS.

Conclusions:

• The findings indicate a temporal association between TBI and ALS mortality, primarily within the first two years post-injury.
• The observed pattern suggests potential reverse causality, where TBI may be a manifestation of pre-symptomatic or prodromal ALS.
• Further research is warranted to explore TBI as a potential indicator of subclinical ALS.