Abstract
Background:ALS clustering is important to describe as it may be helpful for uncovering/studying potential causes of ALS.Objectives:To describe a clustering of ALS cases in a small hamlet in the French Alps and discuss potential exposures in the patients’ environment.Cases: Between 1991 and 2013, five ALS cases were described in the small hamlet of Montchavin, Savoie, France. Two of them were spouses. They have all lived in the hamlet since early childhood or birth. Patients were all neighbours and the hamlet comprised 200 persons livinghere on a regular basis. Between 2010 and 2015, seven other cases of ALS were identified in individuals that did not originate from thevillage but spent a part of their life in the area. One had lived here since 2009, another spent half of his lifetime in Montchavin, two were present during holidays for more than 20 years, and two others lived in close villages and had an activity, professional or leisure, in the hamlet.Results:The study of the cases did not identify any genetic/familial relationships between the patients and, when possible, a genetic analysis was performed and was negative. For the 5 ALS patients originating from the area, given the interval of observation, 22 years, the population of 200and the incidence of ALS, 2.5/100,000, the standardized incidence ratio¼ 45 (p50.00001). It does not seem possible to estimate an incidence ratio for the whole group of 12 patients in the cluster area, as the population during winter and summertime greatly increases, and forseven of them, exposure was not continuous.Exposures:Common exposures were found between the 12 patients: all but one practiced sport intensively, eight had a vegetable garden, six used to eat local mushrooms, five were ski teachers, and four had a restaurant. The water used for the vegetable gardens was collected immediately downstream from the ski area where snow guns were intensively using snomax for artificial snow, with a mix containing bacteria. Among the five ALS cases originating from the area, four of them were chronically exposed to polycyclic aromatic hydrocarbons, and in two houses an abnormally high level of radon was measured (4400 Beq/m3, with a maximum at 1116).Discussion:We present a highly significant cluster of ALS in a small hamlet in the French Alps. Patients are neighbours and share many exposures, some of them being known for their toxicity regarding neuronal/cellular metabolism. Others factors are more exploratory, such as vegetable gardens where heavy metals may be implicated.The investigation of BMAA is underway in the area, as well as in the patients’ brains that have been collected. four patients are still alive and these brains may be collected in the future.