Risk Factors of Amyotrophic Lateral Sclerosis (ALS): An Updated Systematic Review

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease impacting the voluntary motor nervous system. While the origin of ALS remains unclear, existing literature suggests multifactorial pathogenesis. Most cases appear sporadically, implicating the existence of environmental factors, while others suggest an underlying genetic mechanism. This study aims to summarize risk factors associated with the onset and progression of ALS. Methods: Three reviewers searched Medline database for English-language articles published between January 1, 2017 and November 6, 2021. Keywords included, but were not limited to, ALS, motor neuron disease, biomarkers, expos*, risk factors, and others. Included studies directly examined the effect of risk factors on ALS patients. Results were summarized descriptively following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: Overall, 310 unique articles were identified, of which 66 articles spanning 18 countries met the inclusion criteria. Thirty-five articles discussed environmental factors and reported 3 personal characteristics, 13 lifestyle factors, and 22 clinical factors being associated with ALS. Nineteen different genes were also discovered to be associated with ALS, while 13 genes were found to have no association. Discussion: Among environmental factors, lower socioeconomic status occupations were found to have a higher occurrence of ALS. Traumatic brain injuries are another clinical risk factor commonly associated with ALS. There are inconsistent associations between alcohol intake and ALS, and the link between ALS and viruses needs to be further explored due to a potential causal relationship. Some of the genes identified in this review are definitive ALS genes, but others are novel or have little supporting evidence, necessitating further research. Conclusion: With over 90% of ALS cases appearing sporadically, a great amount of research has gone into identifying the risk factors of the fatal illness. This study provides an updated systematic review that encompasses findings from 66 of the most current articles surrounding environmental and genetic risk factors of ALS. This paper provides researchers with a comprehensive summary of these risk factors to provide a springboard for future studies.

The influence of environmental risk factors in the development of ALS in the Mediterranean Island of Cyprus

“…(30) However, in ALS cases, toxic substances, including nicotine and formaldehyde, or poisoning contamination by heavy metals and insecticides are a possible explanation of how smoking increases the risk of ALS (17). Results from our study indicate that smoking increases the risk of developing ALS, which comes to agreement with other studies (13,(31)(32)(33). A previous ALS epidemiological study in Cyprus by Demetriou et al (34) found a statistically significant association between male and female cases (34), supporting our outcome with regard to smoking.…”

“…It is believed that sALS is equally influenced by the interaction of multiple genes (polygenic traits) and environmental risk factors (11). Numerous studies have focused on the environmental risk factors that are positively associated with ALS (12)(13)(14)(15)(16)(17)(18). However, dietary factors such as vitamin E supplements and polyunsaturated fatty acids consumption, as well as type 2 diabetes, have shown an inverse association with ALS since they were associated with a lower risk of ALS (11,16,19).…”