Head trauma and environment progression of amyotrophic lateral sclerosis: long-term data from the National ALS Registry

Background Environmental exposures have been linked to increased risk of amyotrophic lateral sclerosis (ALS); however, their impact on disease progression remains unclear. This study examined whether prior environmental and occupational exposures influenced functional decline in patients with an established ALS diagnosis. Methods We conducted a retrospective cohort analysis using the National ALS Registry from 2010 to 2024. Participants with complete exposure histories were included. Disease progression was measured with the ALS Functional Rating Scale-Revised (ALSFRS-R) at baseline and every 3 months. Mixed-effects linear regression models assessed associations between exposures and ALSFRS-R decline, adjusting for age, sex and time since diagnosis. Results The cohort included 8618 participants with ALS. The median time from diagnosis to enrolment was 2 years (IQR= 1.1–2.9), with a median of 1 year of follow-up (IQR=1–4). Exposure to herbicides (β=−0.57. IC 95% =−0.86 to −0.28, p<0.001), metal dust and fumes (β=−0.28, IC 95% =−0.51 to −0.04, p=0.020) and oil paint (β=−0.27, IC 95% =−0.48 to −0.06, p=0.011) prior to diagnosis were each associated with accelerated decline. Head injury was associated with an overall lower ALSFRS-R score (β=−1.74, IC 95% =−2.21 to −1.27, <0.001), based on our non-linear mixed effects model. Conclusion Environmental and occupational exposures, particularly herbicides, metal dust/fumes and oil-based paints, were associated with faster ALS progression, and head injury was associated with overall worse function.