People with a traumatic brain injury (TBI) were more likely to die from ALS within two years of injury, a recent study found, although researchers say the link may reflect undiagnosed ALS.
Researchers said reverse causation may explain the association, meaning people with early, undiagnosed ALS could be more likely to experience falls and other injuries that cause brain damage.
The findings challenge the longstanding idea that brain injury itself may increase the future risk of developing ALS.
“The relationship between TBI and ALS described in the present and prior studies likely represents reverse causation, whereby undiagnosed … ALS increases the risk of trauma, particularly TBI,” the researchers wrote.
ALS, or amyotrophic lateral sclerosis, is a neurological disease that causes progressive muscle weakness.
The condition is almost always fatal, with most patients dying within a few years of diagnosis.
Because ALS symptoms are generally non-specific and several tests may be required to confirm a diagnosis, it often takes a year or longer for patients to be formally diagnosed.
The causes of ALS are not fully understood, but several risk factors have been identified.
One is traumatic brain injury, which has also been identified as a risk factor for death from ALS.
Some researchers have proposed that the link between TBI and ALS mortality may instead be explained by reverse causation, as people with undiagnosed ALS may be more likely to experience falls and accidents that cause brain injury.
If that explanation is correct, TBI would be expected to be linked with ALS mortality in the short term but not over longer periods.
To test the theory, researchers in the US analysed data from more than 20,000 people with TBI who were tracked in a database from 1987 to 2024.
During that period, more than 4,000 people had documented dates of death, including 11 who died from ALS.
Although the number of ALS deaths was small, ALS is a rare disease and rates of ALS-related deaths were more than twice as high among people with TBI as in the general US population.
Using statistical models, researchers examined the association between TBI and the future risk of ALS mortality.
They found TBI was linked with a significantly higher risk of ALS mortality during the two years after the brain injury, but not over longer periods.
The association was particularly strong among people with more severe brain injuries.
“ALS mortality was higher in the [TBI dataset] cohort than in the general population, and this association was confined to within 2 years of injury,” the researchers wrote.
“This pattern suggests potential reverse causality, whereby some TBIs in the [group] may have occurred in the setting of [early, undiagnosed] ALS.”
The researchers stressed that the analysis was based on a small number of people who died from ALS, meaning further research is needed to verify the findings.
“Time-dependent patterns suggest reverse causation, whereby TBI may result from undiagnosed ALS,” they concluded.
“Given the fatal nature of ALS and its public health impact, further research evaluating the role of diagnostic timing and changes in longitudinal functional assessments are needed to clarify the relationship between TBI and ALS.”
