Several environmental risk factors, such as agricultural workers, have been related to ALS risk, but with inconsistent results. Regarding phenotypic heterogeneity, a recent study failed to identify possible environmental factors underlying ALS clinical presentation.

All ALS patients (diagnosis 2007-2014) belong to the Piemonte and Valle d’Aosta Register (PARALS). Using Regional Environmental Protection Agency (ARPA) data, we established the geographical distribution of agricultural areas in the same period. We calculated the area covered by each culture and patients smoothed incidence and we compared them using linear regression. A proximity score for each environmental factor was calculated using the area of the environmental component enclosed by a circle centered on the residence address, (variable radii 100-2000 meters). 

The regression model for arable crops confirmed a linear increase in ALS incidence in the municipalities with a larger area covered by arable crops. Median incidence increased from 0.75 (IQR 0.00-1.26) cases/100.000/year in municipalities with no area covered by arable crops to 1.81 (IQR 0.75-4.11) cases/100.000/year where arable crops covered more than 60% of total municipality area.  The proximity score analysis confirmed that arable crops proximity (considering a 500, 1000, 1500 meters radii) significantly reduced the age at onset by about 2 years. Linear regression for proximity score and age at onset, significantly confirm this trend (R= -0.51675, p=0.0245). We confirmed the same trend by subgrouping patients according to sex and site of onset.