Study finds traumatic brain injury may be sign, not cause, of ALS

People who sustain a traumatic brain injury (TBI) are more likely to die within two years from amyotrophic lateral sclerosis (ALS), according to a new analysis. But the association may reflect an early manifestation of the disease, rather than a cause.

Researchers said a phenomenon called reserve causation may be at play, meaning that people with early, undiagnosed ALS are more likely to experience falls and other injuries that can lead to brain damage.

The findings challenge the longstanding idea that brain injury itself may increase future ALS risk.

“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.

The study, “Traumatic Brain Injury and Risk of Amyotrophic Lateral Sclerosis Mortality: A Traumatic Brain Injury Model Systems Study,” was published in Neurotrauma Reports.

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TBI as risk factor

ALS is a neurological disease that causes progressive muscle weakness. The condition is virtually always fatal, with most patients dying within a few years after ALS diagnosis. However, because ALS symptoms are generally not specific and multiple tests are required to confirm a diagnosis, it often takes a year or longer for patients to be formally diagnosed with the disease.

The causes of ALS aren’t fully understood, but several risk factors have been identified. One such factor is TBI, which has also been identified as a risk factor for mortality due to ALS.

Some researchers have proposed that the link between TBI and ALS mortality risk may be due to reverse causation, as people with undiagnosed ALS are more likely to experience falls and accidents that can cause brain injury. If that’s true, then it would be expected that TBI would be linked with ALS mortality in the short term, but not in the long term.

To test that idea, researchers in the U.S. analyzed data from more than 20,000 people with TBI who were tracked in a database from 1987 to 2024. Over that time, more than 4,000 of the individuals had documented death dates, including 11 people who died from ALS.

Though the number of deaths from ALS was small, ALS is a rare disease, and statistically, rates of ALS-related deaths were more than twice as high among people with TBI as in the general U.S. population.

Using statistical models, the researchers examined the association between TBI and the future risk of ALS mortality. They found that TBI was linked with a significantly higher risk of ALS mortality in the two years following brain injury, but not over longer timeframes. This association was especially strong in 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,” they 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 their analyses were limited to data on a small number of ALS patients, so further work is needed to verify the results.

“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.”