ALS Risk More Than Doubled After Traumatic Brain Injury, Reverse Causality Possible
Traumatic brain injury (TBI) was linked with a 2.6-fold higher risk of a subsequent amyotrophic lateral sclerosis (ALS) diagnosis than in the general population, according to a study published in JAMA Network Open.
“However, this higher risk was restricted to the first 2 years immediately following TBI and diminished thereafter,” wrote corresponding author William Stewart, MBChB, PhD, of the Queen Elizabeth University Hospital Department of Neuropathology, Glasgow, Scotland, and study coauthors.
The retrospective cohort study included 85,690 patients 18 years and older with documented TBI in the United Kingdom who were matched for age, sex, and area deprivation with 257,070 comparators from the general UK population.
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Over a median 5.72 years of follow-up, 150 incident ALS diagnoses were recorded among all 342,760 participants, reflecting an ALS incidence of 7.05 diagnoses per 100,000 person-years. By TBI status, ALS was diagnosed in 69 patients with TBI and 81 patients without TBI, for ALS incidences of 13.12 and 5.05, respectively, per 100,000 person-years.
The risk of ALS with a history of TBI was associated with a hazard ratio of 2.61 compared with no TBI history, according to the study.
A time-dependent analysis showed the highest ALS risk in the 2 years immediately following TBI (researchers reported a hazard ratio of 6.18). Afterward, the risk of ALS in patients with TBI did not differ from the risk in matched population comparators.
With previous studies showing ALS symptoms occurring up to 2 years before an ALS diagnosis, the increased ALS risk observed in the early years after TBI in this study could actually reflect reverse causality, researchers noted.
“In other words, rather than TBI precipitating a neurodegenerative process culminating in ALS, TBI might represent an early complication of disease in individuals with preclinical ALS at risk of falls or other events culminating in TBI,” the authors wrote. “Thereafter, in the months or years following TBI, the diagnosis of ALS emerges, consistent with the typical timeline to secure a diagnosis from first symptom presentation.”
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