Do ecological factors influence the clinical presentation of amyotrophic lateral sclerosis

Since its first description by Charcot, amyotrophic lateral sclerosis (ALS) has been classified as a single neurodegenerative disease involving motor neurons. More recently, however, it has become clear that ALS is pleiotropic and its phenotype could vary depending on several factors: age of onset, prevalent damage to the upper (UMN) or the lower motor neuron, body region mostly affected, progression rate and presence of non-motor symptoms, the most frequent being cognitive impairment.1 As a consequence, different phenotypes have been described.2 It remains unclear whether these presentations should be considered as distinct clinical entities or as variants of the same disease.3 More importantly, we do not know if different aetiologies justify this variability.3 Despite these uncertainties, we approach clinical trials by administering the same treatment to all patients with ALS.3 Spatial epidemiology could give some clues on aetiology by identifying clusters and subsequently seeking for causative genetic or environmental factors. Previously, we analysed the spatial distribution of a large ALS cohort in Northwestern Italy. Patients resulted to be homogeneously distributed, suggesting either that a single environmental factor was evenly distributed or that multiple factors acted on distinct subgroups, the latter being the more likely.4 Moving from the hypothesis that aetiology could vary according to phenotypes, here we performed a spatial analysis of ALS cases stratified according to their clinical presentation. Data from the Piemonte and Valle d’Aosta ALS Register were used.4 All patients with ALS diagnosed between 2007 and 2014 and who were resident in Piemonte at the time of diagnosis were included. The cluster analysis was conducted considering municipalities; …