Amyotrophic lateral sclerosis regional progression intervals change according to time of involvement of different body regions.

BACKGROUND AND PURPOSE: The prediction of disease course is one of the main targets of amyotrophic lateral sclerosis (ALS) research, particularly considering its wide phenotypic heterogeneity. Despite many attempts to classify patients into 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. The aim of our study was to evaluate the functional decline in different body regions according to their time of involvement during disease course. METHODS: In a population-based dataset of ALS patients, we analysed the functional decline in different body regions according to time and order of regional involvement. We calculated the regional progression intervals (RPIs) between initial involvement and severe functional impairment using the ALS Functional Rating Scale revised (ALSFRS-r) subscores for the bulbar, upper limb, lower limb and respiratory/thoracic regions. Time-to-event analyses, adjusted for age, sex, ALSFRS-r pre-slope (ΔALSFRS-R), cognitive status, and mutational status were performed. RESULTS: The duration of RPI differed significantly among ALS phenotypes, with the RPI of the first region involved being significantly longer than the RPIs of regions involved later. Cox proportional hazard models showed that in fact a longer time between disease onset and initial regional involvement was related to a reduced duration of the RPI duration in each different body region (bulbar region: hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.06-1.16, p < 0.001; upper limb region: HR 1.16, 95% CI 1.06-1.28, p = 0.002; lower limb 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). CONCLUSIONS: We found that the progression of functional decline accelerates in regions involved later during disease course. Our findings can be useful in patient management and prognosis prediction.

Brain metabolic changes across King's stages in amyotrophic lateral sclerosis: a 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography study.

PURPOSE: To assess the brain metabolic correlates of the different regional extent of ALS, evaluated with the King's staging system, using brain 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). METHODS: Three hundred ninety ALS cases with King's stages 1, 2, and 3 (n = 390), i.e., involvement of 1, 2, and 3 body regions respectively, underwent brain 18F-FDG-PET at diagnosis. King's stage at PET was derived from ALSFRS-R and was regressed out against whole-brain metabolism in the whole sample. The full factorial design confirmed the hypothesis that differences among groups (King's 1, King's 2, King's 3, and 40 healthy controls (HC)) existed overall. Comparisons among stages and between each group and HC were performed. We included age at PET and sex as covariates. RESULTS: Brain metabolism was inversely correlated with stage in medial frontal gyrus bilaterally, and right precentral and postcentral gyri. The full factorial design resulted in a significant main effect of groups. There was no significant difference between stages 1 and 2. Comparing stage 3 to stage 1+2, a significant relative hypometabolism was highlighted in the former in the left precentral and medial frontal gyri, and in the right medial frontal, postcentral, precentral, and middle frontal gyri. The comparisons between each group and HC showed the extension of frontal metabolic changes from stage 1 to stage 3, with the larger metabolic gap between stages 2 and 3. CONCLUSIONS: Our findings support the hypothesis that in ALS, the propagation of neurodegeneration follows a corticofugal, regional ordered pattern, extending from the motor cortex to posterior and anterior regions.

Neck flexor weakness at diagnosis predicts respiratory impairment in amyotrophic lateral sclerosis.

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 <4, forced vital capacity <70%, start of non-invasive ventilation or tracheostomy. Time from diagnosis to dysarthria, dysphagia and walking impairment were considered as secondary outcomes. Cox proportional hazard regression models adjusted for sex, age at diagnosis, diagnostic delay, onset site, genetics status and the MRC scores of other muscle groups were used to assess the prognostic role of neck muscles. RESULTS: A total of 370 patients were included in the study. Fifty-nine (15.9%) patients showed neck flexor weakness at diagnosis; MRC values were mostly in agreement for neck extensors. Neck flexors were the only muscles able to predict survival (hazard ratio 0.49, 95% confidence interval 0.28-0.86; p = 0.01). Furthermore, neck flexor normal strength decreased the risk of respiratory impairment (hazard ratio 0.46, 95% confidence interval 0.22-0.96; p = 0.04) but did not influence any secondary outcomes. DISCUSSION: Neck flexor weakness at diagnosis predicts survival and respiratory impairment in ALS. This result could be valuable for both planning of patients' interventions and clinical trials' design.

Brain metabolic correlates of apathy in amyotrophic lateral sclerosis: An 18F-FDG-positron emission tomography stud.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate brain metabolic correlates of apathy in amyotrophic lateral sclerosis (ALS). METHODS: A total of 165 ALS patients underwent 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG-PET) and Frontal Systems Behaviour Scale (FrSBe) evaluation. FrSBe provides "before" and "after" apathy subscores, referring to premorbid and morbid conditions. "After" apathy subscore and "before-after" gap, i.e. the difference between "before" and "after" subscores, were regressed against whole-brain metabolism. Among patients with a pathological "after" apathy subscore (i.e., ≥65), we compared patients with "before" apathy subscores ≥65 and <65, and patients with "before-after" gaps of <22 and ≥22. RESULTS: In the whole sample, the "after" apathy subscore negatively correlated with metabolism in the dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), ventrolateral prefrontal cortex (VLPFC), premotor cortex (PMC) and anterior cingulate cortex (ACC), and insula bilaterally. A positive correlation was found in the cerebellum and pons. The "before-after" gap negatively correlated with metabolism in bilateral DLPFC, DMPFC and PMC, and left VLPFC and ACC, and positively correlated with cerebellar and pontine clusters. Among patients with an "after" apathy subscore ≥65, we found no difference between those with "before" apathy subscores ≥65 and <65. Patients with a "before-after" gap ≥22, compared to patients with a gap <22, showed relative hypometabolism in bilateral DLPFC and DMPFC, and left ACC and PMC, and relative cerebellar and pontine hypermetabolism. CONCLUSION: No studies on brain 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography correlates of apathy have been performed in ALS. We found that FrSBe "after" apathy subscore correlated with metabolic changes in brain regions known as neuroanatomical correlates of apathy. Furthermore, our findings support the relevance of the gap between premorbid and morbid conditions to detect behavioural changes due to the neurodegenerative process underlying ALS.

The links between diabetes mellitus and amyotrophic lateral sclerosis.

ALS etiology and prognostic factors are mostly unknown. Metabolic diseases and especially diabetes mellitus (DM) have been variously related to ALS. However, pieces of evidence have been variegated and often conflicting so far. This review aims to give an overview of recent contributions focusing on the relationship between DM and ALS. DM seems to reduce the risk of developing ALS if diagnosed at a younger age; conversely, when diagnosed at an older age, DM seems protective against ALS. Such a relationship was not confirmed in Asian countries where DM increases the risk of ALS independently of the age of onset. Interestingly, DM does not affect ALS prognosis, possibly weakening the potential causal relationship between the two diseases. However, since most studies are observational, it is difficult to state the exact nature of such a relationship and several hypotheses have been made. A recent study using Mendelian randomization suggested that DM is indeed protective against ALS in the European population. However, these analyses are not without limits and further evidence is needed. DM is usually the core of a larger metabolic syndrome. Thus, other metabolic changes such as dyslipidemia, body mass index, and cardiovascular diseases should be collectively considered. Finally, hypermetabolism usually found in ALS patients should be considered too since all these metabolic changes could be compensation (or the cause) of the higher energy expenditure.

Metabolic brain changes across different levels of cognitive impairment in ALS: a 18F-FDG-PET study.

OBJECTIVE: To identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) imaging. METHODS: 274 ALS patients underwent neuropsychological assessment and brain 18F-FDG-PET at diagnosis. According to the criteria published in 2017, cognitive status was classified as ALS with normal cognition (ALS-Cn, n=132), ALS with behavioural impairment (ALS-Bi, n=66), ALS with cognitive impairment (ALS-Ci, n=30), ALS with cognitive and behavioural impairment (ALS-Cbi, n=26), ALS with frontotemporal dementia (ALS-FTD, n=20). We compared each group displaying some degree of cognitive and/or behavioural impairment to ALS-Cn patients, including age at PET, sex and ALS Functional Rating Scale-Revised as covariates. RESULTS: We identified frontal lobe relative hypometabolism in cognitively impaired patients that resulted more extensive and significant across the continuum from ALS-Ci, through ALS-Cbi, to ALS-FTD. ALS-FTD patients also showed cerebellar relative hypermetabolism. ALS-Bi patients did not show any difference compared with ALS-Cn. CONCLUSIONS: These data support the concept that patients with cognitive impairment have a more widespread neurodegenerative process compared with patients with a pure motor disease: the more severe the cognitive impairment, the more diffuse the metabolic changes. Otherwise, metabolic changes related to pure behavioural impairment need further characterisation.

Effect modification of the association between total cigarette smoking and ALS risk by intensity, duration and time-since-quitting: Euro-MOTOR.

BACKGROUND: We investigated the association between cigarette smoking and risk of amyotrophic lateral sclerosis (ALS) in a pooled analysis of population-based case-control studies and explored the independent effects of intensity, duration and time-since-quitting. METHODS: ALS cases and controls, matched by age, sex and region, were recruited in the Netherlands, Italy and Ireland (*Euro-MOTOR project). Demographics and detailed lifetime smoking histories were collected through questionnaires. Effects of smoking status, intensity (cigarettes/day), duration (years), pack-years and time-since-quitting (years) on ALS risk were estimated using logistic regression models, adjusting for age, sex, alcohol, education and centre. We further investigated effect modification of the linear effects of pack-years by intensity, duration and time-since-quitting using excess OR (eOR) models. RESULTS: Analyses were performed on 1410 cases and 2616 controls. Pack-years were positively associated with ALS risk; OR=1.26 (95% CI: 1.03 to 1.54) for the highest quartile compared with never smokers. This association appeared to be predominantly driven by smoking duration (ptrend=0.001) rather than intensity (ptrend=0.86), although the trend for duration disappeared after adjustment for time-since-quitting. Time-since-quitting was inversely related to ALS (ptrend<0.0001). The eOR decreased with time-since-quitting smoking, until about 10 years prior to disease onset. High intensity smoking with shorter duration appeared more deleterious than lower intensity for a longer duration. CONCLUSIONS: Our findings provide further support for the association between smoking and ALS. Pack-years alone may be insufficient to capture effects of different smoking patterns. Time-since-quitting appeared to be an important factor, suggesting that smoking may be an early disease trigger.

Regional spreading of symptoms at diagnosis as a prognostic marker in amyotrophic lateral sclerosis: a population-based study.

OBJECTIVE: The lack of prognostic biomarkers in patients with amyotrophic lateral sclerosis (ALS) induced researchers to develop clinical evaluation tools for stratification and survival prediction. We assessed the correlation between patterns of functional involvement, considered as a cumulative number of body regions involved, and overall survival in a population-based series of patients with ALS (PARALS). METHODS: We derived the functional involvement of four body regions at diagnosis using ALSFRS-R subscores for bulbar, upper limbs, lower limbs and respiratory/thoracic regions. We analysed the effect of number of body regions involved (NBRI) at diagnosis on overall survival, adjusting for age at onset, sex, site of onset, diagnostic delay, forced vital capacity, body mass index, mutational status, cognition and comparing it with King's staging system. RESULTS: The NBRI was strongly related to survival, with a progressive increase of death/tracheostomy risk among groups (two body regions HR=1.24, 95% CI 1.06 to 1.45, p=0007; three body regions HR=1.65, 95% CI 1.38 to 1.98, p<0.001; four body regions HR=2.68, 95% CI 2.11 to 3.39, p<0.001). Using ALSFRS-R score, the consistency between the number of regions involved and King's clinical stage at diagnosis was very high (81%). The evaluation of respiratory/thoracic region and cognition allowed to subdivide patients into different prognostic categories. Regional spreading of the disease is associated with survival, independently from the initial region involved. CONCLUSIONS: The evaluation of NBRI, with the inclusion of initial respiratory/thoracic involvement and cognition, can be useful in many research fields, improving the stratification of patients. Our findings highlight the importance of the spatial spreading of functional impairment in the prediction of ALS outcome.

Associations of Electric Shock and Extremely Low-Frequency Magnetic Field Exposure With the Risk of Amyotrophic Lateral Sclerosis.

We explored the associations of occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and electric shocks with the risk of amyotrophic lateral sclerosis (ALS) in a pooled case-control study (European Multidisciplinary ALS Network Identification to Cure Motor Neurone Degeneration (Euro-MOTOR)) of data from 3 European countries. ALS patients and population-based controls were recruited in Ireland, Italy, and the Netherlands between 2010 and 2015. Lifetime occupational and lifestyle histories were obtained using structured questionnaires. We applied previously developed job exposure matrices assigning exposure levels to ELF-MF and potential for electric shocks. Odds ratios and 95% confidence intervals were estimated by means of logistic regression for exposure to either ELF-MF or electric shocks, adjusted for age, sex, study center, education, smoking, and alcohol consumption and for the respective other exposure. Complete occupational histories and information on confounding variables were available for 1,323 clinically confirmed ALS cases and 2,704 controls. Both ever having had exposure to ELF-MF above the background level (odds ratio = 1.16, 95% confidence interval: 1.01, 1.33) and ever having had potential exposure above background for electric shocks (odds ratio = 1.23, 95% confidence interval: 1.05, 1.43) were associated with ALS. Adjustment for the respective other exposure resulted in similar risk estimates. Heterogeneity in risks across study centers was significant for both exposures. Our findings support possible independent associations of occupational exposure to ELF-MF and electric shocks with the risk of ALS.

Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort.

OBJECTIVES: To assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates of weight loss in the early phases of the disease. METHODS: The study cohort included all ALS patients in Piemonte/Valle d'Aosta in the 2007-2011 period. Overall survival and the probability of death/tracheostomy at 18 months (logistic regression model) were calculated. RESULTS: Of the 712 patients, 620 (87.1%) were included in the study. Patients ' survival was related to the mean monthly percentage of weight loss at diagnosis (p<0.0001), but not to pre-morbid BMI or BMI at diagnosis. Spinal onset patients with dysphagia at diagnosis had a median survival similar to bulbar onset patients. About 20% of spinal onset patients without dysphagia at diagnosis had severe weight loss and initial respiratory impairment, and had a median survival time similar to bulbar onset patients. CONCLUSIONS: The rate of weight loss from onset to diagnosis was found to be a strong and independent prognostic factor in ALS. Weight loss was mainly due to the reduction of nutritional intake related to dysphagia, but a subgroup of spinal onset patients without dysphagia at diagnosis had a severe weight loss and an outcome similar to bulbar patients. According to our findings, we recommend that in clinical trials patients should be stratified according to the presence of dysphagia at the time of enrolment and not by site of onset of symptoms.

Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk.

OBJECTIVE: To investigate whether exposure to particulates and combustion products may explain the association between certain occupations and amyotrophic lateral sclerosis (ALS) risk in a large, multicentre, population-based, case-control study, based on full job histories, using job-exposure matrices, with detailed information on possible confounders. METHODS: Population-based patients with ALS and controls were recruited from five registries in the Netherlands, Ireland and Italy. Demographics and data regarding educational level, smoking, alcohol habits and lifetime occupational history were obtained using a validated questionnaire. Using job-exposure matrices, we assessed occupational exposure to silica, asbestos, organic dust, contact with animals or fresh animal products, endotoxins, polycyclic aromatic hydrocarbons and diesel motor exhaust. Multivariate logistic regression models adjusting for confounding factors were used to determine the association between these exposures and ALS risk. RESULTS: We included 1557 patients and 2922 controls. Associations were positive for all seven occupational exposures (ORs ranging from 1.13 to 1.73 for high vs never exposed), and significant on the continuous scale for silica, organic dust and diesel motor exhaust (p values for trend ≤0.03). Additional analyses, adding an exposure (one at a time) to the model in the single exposure analysis, revealed a stable OR for silica. We found similar results when patients with a C9orf72 mutation were excluded. CONCLUSION: In a large, multicentre study, using harmonised methodology to objectively quantify occupational exposure to particulates and combustion products, we found an association between ALS risk and exposure to silica, independent of the other occupational exposures studied.

Association between alcohol exposure and the risk of amyotrophic lateral sclerosis in the Euro-MOTOR study.

OBJECTIVES: Several studies focused on the association between alcohol consumption and amyotrophic lateral sclerosis (ALS), although with inconsistent findings. Antioxidants may play a role since lyophilised red wine was found to prolong SOD1 mice lifespan. The aim of this international population-based case-control study performed in Ireland, The Netherlands and Italy was to assess the role of alcohol, and red wine in particular, in developing ALS. METHODS: Euro-MOTOR is a case-control study where patients with incident ALS and controls matched for gender, age and area of residency were recruited in a population-based design. Logistic regression models adjusted for sex, age, cohort, education, leisure time physical activity, smoking, heart problems, hypertension, stroke, cholesterol and diabetes were performed. RESULTS: 1557 patients with ALS and 2922 controls were enrolled in the study. Exposure to alcohol drinking was not significantly associated with ALS risk. A stratified analysis of exposure to alcohol by cohort revealed significant ORs in The Netherlands and in Apulia, with opposite directions (respectively 0.68 and 2.38). With regard to red wine consumption, only in Apulia the double-fold increased risk (OR 2.53) remained significant. A decreased risk was found for current alcohol drinkers (OR 0.83), while a significantly increased risk was detected among former drinkers (OR 1.63). Analysis of cumulative exposure to alcohol revealed no significant associations with ALS risk. CONCLUSION: With few exceptions, no significant association was found between alcohol consumption and ALS. The study of the association between alcohol and ALS requires a thorough exploration, especially considering the role of different type of alcoholic beverages.

Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis.

OBJECTIVE: To investigate the association between physical activity (PA) and amyotrophic lateral sclerosis (ALS) in population-based case-control studies in three European countries using a validated and harmonised questionnaire. METHODS: Patients with incident ALS and controls were recruited from five population-based registers in The Netherlands, Ireland and Italy. Demographic and data regarding educational level, smoking, alcohol habits and lifetime PA levels in both leisure and work time were gathered by questionnaire, and quantified using metabolic equivalent of task scores. Logistic regression models adjusting for PA-related factors were used to determine the association between PA and ALS risk, and forest plots were used to visualise heterogeneity between regions. RESULTS: 1557 patients and 2922 controls were included. We found a linear association between ALS and PA in leisure time (OR 1.07, P=0.01) and occupational activities (OR 1.06, P<0.001), and all activities combined (OR 1.06, P<0.001), with some heterogeneity between regions: the most evident association was seen in the Irish and Italian cohorts. After adjustment for other occupational exposures or exclusion of patients with a C9orf72 mutation, the ORs remained similar. CONCLUSION: We provide new class I evidence for a positive association between PA and risk of ALS in a large multicentre study using harmonised methodology to objectively quantify PA levels, with some suggestions for population differences.

Amyotrophic Lateral Sclerosis Incidence and Previous Prescriptions of Drugs for the Nervous System.

BACKGROUND: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. METHODS: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014. Exposure to nervous system drugs was measured until 2012, or until 1 year before ALS onset. The association was estimated for ever and cumulative exposure, through Cox proportional Hazards models adjusted for sex, age, education, marital status and drug co-exposure. RESULTS: In the analysis for ever exposure, opioids were significantly inversely associated with ALS risk (hazard ratio (HR) 0.59; 95% CI 0.35-0.97), while antiepileptics (HR 1.35; 95% CI 0.92-2.00) showed a marginally significantly positive association. Examining cumulative exposure, the protective role of opioids associated with more than 4 prescriptions and the risk effect of antiepileptics for over 6 prescriptions was confirmed. CONCLUSIONS: The present study revealed associations of ALS onset with previous exposure to opioids, maybe through the activation of δ receptor and σ receptors and antiepileptics, which are novel findings to our knowledge.

Causal associations of genetic factors with clinical progression in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Recent advances in the genetic causes of ALS reveals that about 10% of ALS patients have a genetic origin and that more than 30 genes are likely to contribute to this disease. However, four genes are more frequently associated with ALS: C9ORF72, TARDBP, SOD1, and FUS. The relationship between genetic factors and ALS progression rate is not clear. In this study, we carried out a causal analysis of ALS disease with a genetics perspective in order to assess the contribution of the four mentioned genes to the progression rate of ALS. METHODS: In this work, we applied a novel causal learning model to the CRESLA dataset which is a longitudinal clinical dataset of ALS patients including genetic information of such patients. This study aims to discover the relationship between four mentioned genes and ALS progression rate from a causation perspective using machine learning and probabilistic methods. RESULTS: The results indicate a meaningful association between genetic factors and ALS progression rate with causality viewpoint. Our findings revealed that causal relationships between ALSFRS-R items associated with bulbar regions have the strongest association with genetic factors, especially C9ORF72; and other three genes have the greatest contribution to the respiratory ALSFRS-R items with a causation point of view. CONCLUSIONS: The findings revealed that genetic factors have a significant causal effect on the rate of ALS progression. Since C9ORF72 patients have higher proportion compared to those carrying other three gene mutations in the CRESLA cohort, we need a large multi-centric study to better analyze SOD1, TARDBP and FUS contribution to the ALS clinical progression. We conclude that causal associations between ALSFRS-R clinical factors is a suitable predictor for designing a prognostic model of ALS.

Self-Rated Health and Psychological Distress among Emerging Adults in Italy: A Comparison between Data on University Students, Young Workers and Working Students Collected through the 2005 and 2013 National Health Surveys.

BACKGROUND: The present study aimed at comparing self-reported physical health and mental health among university students, workers, and working students aged between 19 years and 29 years. METHOD: Using data from National Health Surveys held in 2005 and 2013, a cross-sectional study was conducted on 18,612 Italian emerging adults grouped into three groups: university students, workers, and working students. The odds ratios of self-reported anxiety or depression, poor general health, and poor mental health and physical health (as assessed through SF-12) were estimated through logistic regression models adjusted for potential confounders. RESULTS: Compared with workers, students showed an increased risk of anxiety or depression and a lower risk of poor general health. Students and working students showed an increased risk of reporting weak mental health compared with that in workers, while students displayed a lower risk of poor physical health. Significant differences were not found between the 2005 and 2013 surveys. CONCLUSIONS: These results are of considerable importance for psychologists as well as educational and occupation-based institutions for planning prevention programs and clinical interventions.

Telemedicine for patients with amyotrophic lateral sclerosis during COVID-19 pandemic: an Italian ALS referral center experience.

We describe the telemedicine experience of an Italian ALS tertiary Center during COVID-19 pandemic. A total of 144 visits were scheduled between 6th March and 6th April 2020. These mostly consisted of neurological or psychological visits (139, 96.5%). One hundred thirty-nine (96.5%) visits were performed as telemedicine and mostly via phone call (112, 80.6%). Three (2.1%) visits were considered as urgent and maintained as outpatient care. Additionally, patients were still able to telephone, being put through directly to their neurologists. Many requests of contact were addressed at getting information about the scheduled visits or examinations (45, 43.3%). Globally, patients and caregivers were satisfied with the telemedicine service. However, the majority (85, 65.9%) would prefer a face-to-face visit. In conclusion, telemedicine could be considered a good complement to face-to-face care, even after social restrictions have been eased.

Lifetime sport practice and brain metabolism in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To evaluate the metabolic correlates of lifetime sport practice in ALS through brain 18F-FDG-PET. METHODS: 131 patients completed a questionnaire about lifetime exposures, including physical activity related to sports, hobbies and occupations, and underwent brain 18F-FDG-PET. Exposure to sports was expressed as MET (Metabolic Equivalent of Task). We considered only regular practice (at least 2 h/week, for at least three months). We compared brain metabolism between two groups: subjects who did not report regular sport practice during life (N-group) and patients who did (Y-group). The resulting significant clusters were used in each group as seed regions in an interregional correlation analysis (IRCA) to evaluate the impact of lifetime sport practice on brain networks typically involved by the neurodegenerative process of ALS. Each group was compared to healthy controls (HC, n = 40). RESULTS: We found a significant, relative cerebellar hypermetabolism in the N-group compared to the Y-group. The metabolism of such cerebellar cluster resulted correlated to more significant and widespread metabolic changes in areas known to be affected by ALS (i.e. frontotemporal regions and corticospinal tracts) in the N-group as compared to the Y-group, despite the same level of disability as expressed by the ALS FRS-R. Such findings resulted independent of age, sex, site of onset (bulbar/spinal), presence/absence of C9ORF72 expansion, cognitive status and physical activity related to hobbies and occupations. When compared to HC, the N-group showed more widespread metabolic changes than the Y-group in cortical regions known to be relatively hypometabolic in ALS patients as compared to HC. CONCLUSIONS: We hypothesize that patients of the N-group might cope better with the neurodegenerative process, since they show more widespread metabolic changes as compared to the Y-group, despite the same level of disability. Nevertheless, further studies are necessary to corroborate this hypothesis.

Prognostic role of slow vital capacity in amyotrophic lateral sclerosis.

OBJECTIVES: To compare the prognostic role of FVC and SVC at diagnosis in amyotrophic lateral sclerosis (ALS) patients. METHODS: We included all patients from the Piemonte and Valle D'Aosta ALS register (PARALS) who had been diagnosed with ALS between 1995 and 2015 and underwent spirometry at diagnosis. Survival was considered as time to death/tracheostomy; to assess the prognostic value in typical trial timeframes, survival at 12 and 18 months was calculated too. Cox proportional hazard regression models adjusted by sex, age at diagnosis, diagnostic delay, onset site, and ALSFRS-R total score at the moment of diagnosis were used to assess the prognostic role of FVC and SVC. RESULTS: A total of 795 ALS patients underwent spirometry at diagnosis during the study period. Four hundred and sixteen (52.3%) performed both FVC and SVC, whereas the others performed FVC only. FVC and SVC values were highly correlated (r = 0.92, p < 0.001) in the overall population and slightly less correlated in patients with bulbar onset (r = 0.86, p < 0.001). Both FVC and SVC proved to have a prognostic role with comparable hazard ratios (HRs) (HR 1.83, 95% CI 1.48-2.27 and 1.88, 95% CI 1.51-2.33, respectively). When considering typical trial timeframes, HRs remained similar and were inversely proportional to FVC and SVC values. DISCUSSION: FVC and SVC at diagnosis can be used interchangeably as independent predictors of survival in both clinical and research settings.