Trauma and amyotrophic lateral sclerosis: a european population-based case-control study from the EURALS consortium

Abstract

Objectives: To assess the association between amyotrophic lateral sclerosis (ALS) and previous traumatic events, age of trauma, and site of injury. Methods: A population-based case-control study was performed in five European countries (Italy, Ireland, France, United Kingdom, Serbia). Newly diagnosed ALS patients and matched controls were interviewed to collect relevant demographic factors and exposures. Key clinical features at diagnosis were collected in ALS patients. Trauma was any accidental event causing an injury. Injuries were dated and classified according to cause, severity, type, site, and complications. All exposures were censored five years before symptoms onset. Risks were computed as odds ratios (OR) with 95% confidence intervals (CI) using univariate and multivariate conditional logistic regression models. Results: Five hundred and seventy-five ALS patients and 1150 controls were interviewed. Disabling traumatic events predominated in the cases (OR 1.54 (95% CI 1.24–1.92)) and maintained significance after adjustment, with a significant gradient. A history of 2 + head injuries was associated with an almost three-fold increased risk of ALS. The risk was almost two-fold when trauma occurred at age 35–54 years. Site of injury was uneventful. Conclusions: Traumatic events leading to functional disability or confined to the head are risk factors for ALS. Traumatic events experienced at age 35–54 years carry the highest risk.

Keywords:

• Amyotrophic lateral sclerosis
• trauma
• case-control
• Europe
• epidemiology

Acknowledgements

This work was supported by the American ALS Association (ALSA)(#1524) and, in part, by the European Community’s Health Seventh Framework Programme (FP7) 2007-2013 (grant agreement 259867).

Disclosure statement

Dr Pupillo has received funding from the American ALS Association and Italian Ministry of Health for data management and data monitoring of an observational study protocol. She received funding from the Italian Drug Agency (AIFA) for data monitoring and study management of a randomized clinical trial. Dr Logroscino received grants from the European Union, grants from the Italian Ministry of Health, Ministry of School, University and Research, Apulia Region. Dr Chiò reports grants from the European Union, grants from the Italian Ministry of Health, outside the submitted work; and has served on scientific advisory boards for Biogen Idec, Cytokinetics, Inc, and Mitsubishi Tanabe. Dr Hardiman reports grants from the EuropeanÐ Community's Seventh FrameworkÐ Programme (FP7/2007-2013)Ð during the conduct of the study; grants from the Health Research Board, personal fees from Biogen Idec, personal fees from Novartis, grants from Merck Serono, outside the submitted work. Dr Rooney received a grant from the Health Research Board (HPF-2014-527). Dr Beghi reports grants from the Italian Ministry of Health, during the conduct of the study; personal fees from Viropharma, grants from UCB-Pharma, grants from the Italian Drug Agency (AIFA), personal fees from Viropharma, grants from the Italian Ministry of Health, grants from EISAI, grants from the American ALS Association, grants from the Borgonovo Foundation, outside the submitted work.

Dr Calvo acknowledges Fondazione Vialli e Mauro.

Dr Lunetta served on a scientific advisory board for Neuraltus and Italfarmaco and has received grants from Agenzia Italiana per la Ricerca sulla SLA (ARISLA).

Drs Poloni, Bianchi, Giussani, Corbo, Marin, Stevic, Bandettini di Poggio, Filosto, Cotelli, Perini, Riva, Tremolizzo, Vitelli, Zoccolella report no conflicts of interest.

Supplementary material available online.