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