Repeated severe trauma to the body or mild injuries to the head — especially at midlife — raise a person’s risk of ALS, a European case-control study from the EURALS consortium shows.
The new research, “Trauma and amyotrophic lateral sclerosis: a european population-based case-control study from the EURALS consortium,” appeared in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
The study’s senior author is Ettore Beghi, MD, from the Laboratorio di Malattie Neurologiche, IRCCS-Istituto Mario Negri, in Milan, Italy.
Traumatic brain injury (TBI) is the most prevalent cause of nervous tissue damage in developed countries. Besides functional disability, TBI carries a significant economic burden, with the associated loss of work productivity.
TBI is recognized as a risk factor of various neurological diseases, including amyotrophic lateral sclerosis, or ALS. But existing studies exploring the relationship between head trauma and ALS provide mixed results, and indicate that age at first trauma may be a relevant factor in developing TBI.
A previous study by the same research team, conducted in Italy, excluded traumatic events within five years before ALS onset, and found that repeated and severe trauma is a risk factor for ALS. For this reason, the researchers conducted an extension study in a larger cohort, including patients from other European countries, to further evaluate the relationship between ALS and previous traumatic events.
The researchers also aimed to explore the potential association between site of injury and site of ALS onset.
The population-based study was conducted in five European countries: Italy, Ireland, France, U.K., and Serbia. Data on demographic factors, clinical features, and exposures were collected through interview from 575 newly diagnosed ALS patients and 1,150 matched controls.
Trauma was defined as any accidental event causing an injury, and limited to those reported more than five years before symptom onset. Information on injuries comprised date, cause, severity, type, site, and complications.
The results showed a predominance of disabling traumatic events.
But, importantly, a history of two or more head injuries, even mild, was associated with a near three-fold increase in the risk of ALS. “Repeated mild TBI could fire a more chronic process similar to the degeneration of nervous component,” the researchers suggested in the study.
This risk was almost two-fold when trauma occurred between the ages of 35 and 54. This result matched previous findings. As increased levels of testosterone were found in female ALS patients compared to healthy controls, suggesting it could be a marker of susceptibility to ALS, the authors hypothesized that the greater risk in younger male patients may be due to higher testosterone levels.
No relationship was found regarding between site of injury and ALS risk.
Among the study’s limitations, the authors include the small sample size and limited number of events in some of the participating countries. Few study participants in some disease categories, such as spinal-onset ALS, is another limitation. The interview technique used may also lack consistency across countries, the researchers noted.
Overall, the study shows that “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.”
Future studies may benefit from genetic testing of patients. Investigation of biomarkers of neurotrauma would be supported by stratification of individual genetic features in a representative sample, the team observed. This could be accomplished with the EURALS consortium, which represents 30 million Europeans.