title: Environmental Risk Factors and Amyotrophic Lateral Sclerosis: An Umbrella Review and Critical Assessment of Current Evidence from Systematic Reviews and Meta-Analyses of Observational Studies.
abstract: BACKGROUND
  The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both environmental and genetic factors. Our study aimed at summarising the environmental risk factors for ALS, assessing the evidence for diverse biases, and pinpointing risk factors with high epidemiological credibility.
  
  
  METHODS
  We searched PubMed from inception to August 20, 2015, to identify systematic reviews and meta-analyses of observational studies examining associations between environmental factors and ALS. For each meta-analysis, we estimated the summary effect size by the use of random-effects and fixed-effects models, the 95% CI, the 95% prediction interval (PI), and the between-study heterogeneity. We assessed the evidence of small-study effects and excess significance bias.
  
  
  RESULTS
  Sixteen unique meta-analyses of different risk factors and ALS were considered. Of them, 5 were statistically significant at p < 0.001 under the random-effects model. Only one factor presented robust evidence for a convincing association. This association pertained to chronic occupational exposure to lead (random-effects OR 1.81, 95% CI 1.39-2.35).
  
  
  CONCLUSIONS
  A small number of published meta-analyses on environmental factors and risk of ALS was identified, a phenomenon that could be attributed to the challenges in studying a rare neurological disease. More observational studies with adequate sample size and study design are needed to clarify the environmental component of ALS pathogenesis.
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
authors.forename: Lazaros
authors.initials: L
authors.lastname: Belbasis
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bellou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Evangelou
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D064887:Observational Studies as Topic; D012307:Risk Factors; D000078202:Systematic Reviews as Topic