• amyotrophic lateral sclerosis;
  • epidemiology;
  • risk factors;
  • trauma

Background and purpose

Published reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case–control study done in a large population.


A case–control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population-based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non-degenerative) disease and one with a non-neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee.


The study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non-neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25–2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86–5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36–4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant.


Antecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.