TOPLINE:

A history of traumatic brain injury (TBI) is associated with a more than 2.6 fold higher risk for amyotrophic lateral sclerosis (ALS) compared to no history of TBI, but only in the first 2 years after injury, a new retrospective study showed.

METHODOLOGY:

• Researchers conducted a retrospective, population-based cohort study using UK-wide electronic health record (EHR) data from the Clinical Practice Research Datalink, linked to hospital and mortality records, from 2005 to 2020.
• Among nearly 343,000 adult participants (mean age, 51 years; 50% men) followed for a median duration of 5.7 years, more than 85,000 had TBI.
• They were matched by age, sex, and socioeconomic status to more than 257,000 control participants without TBI.
• Investigators assessed the incidence of ALS, as well as the association between a history of TBI and the risk for subsequent ALS.

TAKEAWAY:

• The overall incidence rate of ALS was 7.05 (95% CI, 6.0-8.3) per 100,000 person-years. The ALS incidence rate was higher in patients with TBI (13.1 [95% CI, 10.4-16.6] per 100,000 person-years) compared to control participants (5.05 [95% CI, 4.1-6.3] per 100,000 person-years).
• ALS was diagnosed in 69 members of the TBI group vs 81 in the control group (0.08% vs 0.03%; hazard ratio [HR], 2.6; P < .001).
• Time-dependent analyses showed that the risk for ALS was highest within 2 years post-TBI (HR, 6.2; P < .001) and returned to baseline thereafter (HR, 1.04).
• There were no significant differences in the mean age at ALS diagnosis or age at death between individuals with and without TBI.

IN PRACTICE:

“We identified an approximately 2.6 fold increased risk of ALS following TBI. However, this higher risk was restricted to the first 2 years immediately following TBI and diminished thereafter. Further investigation should explore the potential for reverse causality,” the investigators wrote.

SOURCE:

This study was led by Xingxing Zhu, PhD, University of Glasgow, Glasgow, Scotland. It was published online on October 2 in JAMA Network Open.

LIMITATIONS:

The study relied on EHR diagnostic coding, which may have led to the exclusion of mild or unreported TBIs. Coded TBIs poorly overlapped with self-reported head injuries, suggesting the population was biased toward moderate-to-severe injuries. The 16-year follow-up period may have failed to capture any delayed increases in risk beyond that period. Additionally, the study lacked granular data on the risk factors for ALS and sufficient information on ethnicity.

DISCLOSURES:

This study was funded by the Motor Neuron Disease Scotland, the National Institutes of Health, the Department of Defense, the Medical Research Council, a National Health Service Research Scotland Senior Fellowship, the University of Glasgow Reinvigorating Research Fund, and the Chief Scientist Office. The investigators reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.