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The prediction of the disease course is one of the main targets of ALS research, particularly considering its wide phenotypic heterogeneity. Despite many attempts to classify patients in prognostic categories according to the different spreading patterns at diagnosis, a precise regional progression rate and the time of involvement of each region has yet to be clarified.In a population-based dataset of ALS patients, we analyse the functional decline in different body regions according to time and order of regional involvement. We calculated the regional progression intervals (RPIs) from the initial involvement (Inv) to the severe functional impairment (SevI), using the ALS Functional Rating Scale revised (ALSFRS-r) subscores of bulbar, upper limbs, lower limbs and respiratory/thoracic regions. Time-to-event analyses, adjusted for age, sex, ALSFRS-r pre-slope (ΔALSFRS-R), cognitive and mutational status were performed.RPI duration differed significantly among ALS phenotypes, being the RPI of first region involved significantly longer than RPIs of regions involved later. Cox proportional hazard models showed that the time between disease onset and initial regional involvement is invariably related to a reduced RPI duration in each different body region (bulbar region, HR 1.11, 95% CI 1.06-1.16, p0.001; upper limbs region, HR 1.16, 95% CI 1.06-1.28, p=0.002; lower limbs region, HR 1.11, 95% CI 1.03-1.19, p=0.009; respiratory/thoracic region, HR 1.10, 95% CI 1.06-1.14, p=0.005).We found that the progression of functional decline accelerates in regions involved later during disease course. Our findings can be useful in patients' management and prognosis prediction.

BACKGROUND AND PURPOSE The purpose was to assess the prognostic role of neck muscle weakness at diagnosis in amyotrophic lateral sclerosis (ALS) patients with respect to survival and respiratory impairment. METHODS A retrospective cohort study was conducted. All ALS patients seen in the Turin ALS Centre from 2007 to 2014 were included. Muscle strength at diagnosis was evaluated using the Medical Research Council (MRC) scale. Survival was considered as the time from diagnosis to death or tracheostomy; time to respiratory impairment was considered as the interval from diagnosis to the first event amongst an ALS Functional Rating Scale revised item 10

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.

Background and purpose The analysis of the spatial distribution of cases could give important cues on putative environmental causes of a disease. Our aim was to perform a spatial analysis of an amyotrophic lateral sclerosis (ALS) cohort from the Piedmont and Aosta Valley ALS register (PARALS) over a 20-year period. Methods The address at the moment of diagnosis was considered for each ALS case. Municipalities' and census divisions' resident populations during the 1995-2014 period were obtained. A cluster analysis was performed adopting both Moran's index and the Kulldorff spatial scan statistic. Results A total of 2702 ALS patients were identified. An address was retrieved for 2671 (99%) patients. Moran's index was -0.01 (P value 0.83), thus revealing no clusters. SaTScan identified no statistically significant clusters. When census divisions were considered, Moran's index was 0.13 (P value 0.45); SaTScan revealed one statistically significant small cluster in the province of Alessandria. Here, 0.0099 cases were expected and three cases were observed (relative risk 304.60; 95% confidence interval 109.83-845.88, P value 0.03). Discussion Our study showed a substantial homogeneous distribution of ALS cases in Piedmont and Aosta Valley. The population-based setting and the adoption of proper statistical analyses strengthen the validity of our results. Such a finding further suggests the involvement of multiple environmental and genetic factors in ALS pathogenesis.

Background and purpose: To assess the prevalence and characteristics of pain in an epidemiological series of patients with amyotrophic lateral sclerosis (ALS) compared to population-based controls. Methods: Of the 183 patients with ALS resident in the province of Torino, Italy, 160 accepted to be interviewed. Controls were randomly selected from the lists of general practitioners. Pain was assessed using the Brief Pain Inventory. Results: Patients with ALS reported pain more frequently than controls [91 (56.9%) vs. 53 (33.1%); P = 0.001]. Pain frequency and intensity were correlated with a worse functional score and a longer disease duration. In patients with ALS, pain was more frequently located at the extremities (P = 0.006). Pain interfered with all areas of daily function, but patients reported a greater interference than controls in the domains of enjoyment of life and relation with other people. Sixty-four patients (70.3% of those with pain) and 24 controls (45.3% of those with pain) (P = 0.003) were treated for pain, most frequently with non-steroidal anti-inflammatory drugs. ALS cases were also more frequently prescribed non-opioid analgesics and opioids than controls. Conclusions: Our study indicates that pain is frequent in all stages of ALS, but that it often goes underrecognized and undertreated. It is significantly more frequent in patients with ALS than in population-based controls. Future studies need to clarify the mechanisms of pain in ALS and determine the most effective treatment strategy.