Presymptomatic geographical distribution of ALS patients suggests the involvement of environmental factors in the disease pathogenesis.

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.

Plateaus in amyotrophic lateral sclerosis progression: results from a population-based cohort.

BACKGROUND AND PURPOSE: The aim was to assess the frequency of plateaus in amyotrophic lateral sclerosis (ALS) progression using a large population-based cohort. METHODS: Data from the Piemonte and Valle d'Aosta ALS register were used. Patients who were diagnosed between 2007 and 2014 were considered. The follow-up period was extended until 31 December 2018. Visits after tracheostomy were excluded. A plateau was defined as a stable Amyotrophic Lateral Sclerosis Functional Rating Scale revised (ALSFRSr) score lasting at least 6, 12 or 18 months. RESULTS: Out of 1214 patients, 200 (16.5%), 93 (7.7%) and 52 (4.3%) showed at least one plateau lasting a minimum of 6, 12 and 18 months, respectively. Plateaus occurred mostly at high ALSFRSr scores and were more frequent during the initial phases of the disease course. Spinal onset [odds ratio (OR) 1.83, 95% confidence interval (CI) 1.16-2.95, P value 0.01) and predominant upper motor neuron phenotype (OR 2.18, 95% CI 1.36-3.48, P value 0.001) conferred a higher risk for the subsequent appearance of plateaus; conversely, older age at diagnosis (OR 0.25, 95% CI 0.11-0.54, P value 0.002 for >75 year age class) reduced this risk. CONCLUSIONS: Plateaus in ALS progression lasting at least 6 months appear in about one out of six patients and could last even 12, 18 months or more in a smaller subgroup of patients. Plateau occurrence should not lead the neurologist to automatically reconsider ALS diagnosis and should be considered for future clinical trial design.

[Epidemiology of malignant hyperthermia in Piedmont and Valle d'Acosta. A study conducted with 2 different methods]. / Epidemiologia dell'ipertermia maligna in Piemonte e Valle d'Aosta. Studio condotto con due differenti metodiche.

The Authors report on the results of two researchers about malignant hyperthermia (MH) carried out in Piemont and Valle D'Aosta using two different methods. The former, based on a form sent to 492 anaesthesists got 22.7 per cent answers. They indicated 4 cases of MH during the years between 1982 and 1986, out of 213,444 narcoses with an average rate of 1:71,000. The latter was canned and by questioning directly the head physicians of anaesthesia and reanimation wards about the occurrence of MH in Piemont and Valle D'Aosta in the years between 1984 and 1988. According to this research, there were 5 cases out of 891,729 narcoses (that is 1:178,346).