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Background and purpose Trace elements ( TEs) may play a role in the pathogenesis of amyotrophic lateral sclerosis ( ALS) and volcanic degassing is the major natural source of TEs. Mount Etna, in the province of Catania, is the largest active volcano in Europe. Our aim was to assess the incidence of ALS in the province of Catania during 2005-2010 and its spatial distribution with respect to volcanic gas deposition. Methods Cases from all neurological centres of the province of Catania and of the boundary provinces were retrospectively collected. Patients who had onset during 2005-2010 and fulfilled the El Escorial revised diagnostic criteria were included. The incidence of ALS was estimated for the entire province and separately for the population living on the eastern and western flank of Mount Etna, respectively, the most and least exposed areas to volcanogenic TEs, considered as a possible risk factor for ALS. Results One hundred and twenty-six (57 men) ALS patients were enrolled. The mean annual crude incidence rate was 2.0/100 000 person-years (95% confidence interval 1.7-2.4). A higher incidence rate was found in the population living on the eastern flank compared to the western flank (2.4/100 000 and 0.9/100 000 respectively) with a relative risk of 2.75 (95% confidence interval 1.64-4.89; P < 0.001). Conclusions The incidence of ALS in the province of Catania is close to those reported worldwide. The incidence was higher amongst the population living on the eastern flank of Mount Etna, which could be interpreted as a possible role of volcanogenic TEs. Further research on TEs and genetic factors is necessary to support this assumption. [ABSTRACT FROM AUTHOR]