28 results on '"Chiò, Adriano"'
Search Results
2. Brain 18fluorodeoxyglucose-positron emission tomography changes in amyotrophic lateral sclerosis with mutations.
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Canosa, Antonio, Calvo, Andrea, Moglia, Cristina, Vasta, Rosario, Palumbo, Francesca, Fuda, Giuseppe, Di Pede, Francesca, Cabras, Sara, Arena, Vincenzo, Novara, Andrea, Salamone, Paolina, Matteoni, Enrico, Sbaiz, Luca, Gallone, Salvatore, Grassano, Maurizio, Manera, Umberto, Chiò, Adriano, and Pagani, Marco
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BRAIN ,GENETIC mutation ,AMYOTROPHIC lateral sclerosis ,EMISSION-computed tomography - Published
- 2022
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3. Metabolic brain changes across different levels of cognitive impairment in ALS: a 18F-FDG-PET study.
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Canosa, Antonio, Moglia, Cristina, Manera, Umberto, Vasta, Rosario, Torrieri, Maria Claudia, Arena, Vincenzo, D'Ovidio, Fabrizio, Palumbo, Francesca, Zucchetti, Jean Pierre, Iazzolino, Barbara, Peotta, Laura, Calvo, Andrea, Pagani, Marco, and Chiò, Adriano
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COGNITION disorders ,FRONTOTEMPORAL lobar degeneration ,MOTOR neuron diseases ,POSITRON emission tomography ,AMYOTROPHIC lateral sclerosis ,MUSCULAR atrophy - Published
- 2021
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4. Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.
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Al-Chalabi, Ammar, Chiò, Adriano, Merrill, Charlotte, Oster, Gerry, Bornheimer, Rebecca, Agnese, Wendy, and Apple, Stephen
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AMYOTROPHIC lateral sclerosis ,FRONTOTEMPORAL lobar degeneration ,DISEASE progression ,RESEARCH ,TIME ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,BLIND experiment ,NEUROPROTECTIVE agents ,KAPLAN-Meier estimator ,RESEARCH funding - Abstract
Objective: This was a post hoc analysis of the Edaravone Phase III Study MCI186-19 ('Study 19') to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS).Methods: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised item scores from Study 19 were retrospectively mapped to King's stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King's and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King's stage.Results: During double-blind treatment, the percentage of patients who experienced a progression in King's stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo-edaravone arm than among those in the edaravone-edaravone arm (log-rank test, p<0.001).Conclusions: The King's and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Regional spreading of symptoms at diagnosis as a prognostic marker in amyotrophic lateral sclerosis: a population-based study.
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Manera, Umberto, Calvo, Andrea, Daviddi, Margherita, Canosa, Antonio, Vasta, Rosario, Torrieri, Maria Claudia, Grassano, Maurizio, Brunetti, Maura, D'Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Moglia, Cristina, D'Ovidio, Fabrizio, Mora, Gabriele, Mazzini, Letizia, and Chiò, Adriano
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AMYOTROPHIC lateral sclerosis ,BODY mass index ,LEG ,ARM ,OVERALL survival ,DELAYED diagnosis ,DISEASE progression ,RESEARCH ,RESEARCH methodology ,PROGNOSIS ,RESPIRATORY measurements ,EVALUATION research ,MEDICAL cooperation ,COMPARATIVE studies ,SYMPTOMS ,DISEASE complications - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2020
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6. Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk.
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Visser, Anne E., D'Ovidio, Fabrizio, Peters, Susan, Vermeulen, Roel C. H., Beghi, Ettore, Chiò, Adriano, Veldink, Jan H., Logroscino, Giancarlo, Hardiman, Orla, Van Den Berg, Leonard H., Vermeulen, Roel Ch, and Euro-MOTOR consortium
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AMYOTROPHIC lateral sclerosis ,COMBUSTION products ,MEDICAL sciences ,FRONTOTEMPORAL lobar degeneration - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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7. Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort.
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Moglia, Cristina, Calvo, Andrea, Grassano, Maurizio, Canosa, Antonio, Manera, Umberto, D'Ovidio, Fabrizio, Bombaci, Alessandro, Bersano, Enrica, Mazzini, Letizia, Mora, Gabriele, Chiò, Adriano, and Piemonte and Valle d’Aosta Register for ALS (PARALS)
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AMYOTROPHIC lateral sclerosis ,WEIGHT loss - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Association between alcohol exposure and the risk of amyotrophic lateral sclerosis in the Euro-MOTOR study.
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D'Ovidio, Fabrizio, Rooney, James P. K., Visser, Anne E., Manera, Umberto, Beghi, Ettore, Logroscino, Giancarlo, Vermeulen, Roel C. H., Veldink, Jan Herman, van den Berg, Leonard H., Hardiman, Orla, Chiò, Adriano, and Euro-MOTOR consortium
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ALCOHOL drinking ,RISK exposure ,AMYOTROPHIC lateral sclerosis ,LEISURE ,STROKE - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis.
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Visser, Anne E., Rooney, James P. K., D'Ovidio, Fabrizio, Westeneng, Henk-Jan, Vermeulen, Roel C. H., Beghi, Ettore, Chiò, Adriano, Logroscino, Giancarlo, Hardiman, Orla, Veldink, Jan H., van den Berg, Leonard H., and Euro-MOTOR consortium
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AMYOTROPHIC lateral sclerosis ,PHYSICAL activity ,HETEROGENEITY ,NEURODEGENERATION ,NEUROTROPHINS ,DISEASE risk factors - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2018
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10. Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).
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Dalla Bella, Eleonora, Tramacere, Irene, Antonini, Giovanni, Borghero, Giuseppe, Capasso, Margherita, Caponnetto, Claudia, Chiò, Adriano, Corbo, Massimo, Eleopra, Roberto, Filosto, Massimiliano, Giannini, Fabio, Granieri, Enrico, La Bella, Vincenzo, Lunetta, Christian, Mandrioli, Jessica, Mazzini, Letizia, Messina, Sonia, Monsurrò, Maria Rosaria, Mora, Gabriele, and Riva, Nilo
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Introduction Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumulation and endoplasmic reticulum overload. Guanabenz proved to rescue motoneurons from misfolding protein stress both in in vitro and in vivo ALS models, making it a potential disease-modifying drug in patients. It is conceivable investigating whether its neuroprotective effects based on the inhibition of eIF2α dephosphorylation can change the progression of ALS. Methods and analyses Protocolised Management In Sepsis is a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial with futility design. We will investigate clinical outcomes, safety, tolerability and biomarkers of neurodegeneration in patients with ALS treated with guanabenz or riluzole alone for 6 months. The primary aim is to test if guanabenz can reduce the proportion of patients progressed to a higher stage of disease at 6 months compared with their baseline stage as measured by the ALS Milano-Torino Staging (ALS-MITOS) system and to the placebo group. Secondary aims are safety, tolerability and change in at least one biomarker of neurodegeneration in the guanabenz arm compared with the placebo group. Findings will provide reliable data on the likelihood that guanabenz can slow the course of ALS in a phase III trial. Ethics and dissemination The study protocol was approved by the Ethics Committee of IRCCS 'Carlo Besta Foundation' of Milan (Eudract no. 2014-005367-32 Pre-results) based on the Helsinki declaration. [ABSTRACT FROM AUTHOR]
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- 2017
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11. C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis.
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Rooney, James, Fogh, Isabella, Westeneng, Henk-Jan, Vajda, Alice, McLaughlin, Russell, Heverin, Mark, Jones, Ashley, van Eijk, Ruben, Calvo, Andrea, Mazzini, Letizia, Shaw, Christopher, Morrison, Karen, Shaw, Pamela J., Robberecht, Wim, Van Damme, Phillip, Al-Chalabi, Ammar, van den Berg, Leonard, Chiò, Adriano, Veldink, Jan, and Hardiman, Orla
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AMYOTROPHIC lateral sclerosis ,SPINAL cord diseases - Abstract
Introduction: The C9orf72 repeat expansion has been reported as a negative prognostic factor in amyotrophic lateral sclerosis (ALS). We have examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset.Methods: C9orf72 status and demographic/clinical data from 4925 patients with ALS drawn from 3 prospective ALS registers (Ireland, Italy and the Netherlands), and clinical data sets in the UK and Belgium. Flexible parametric survival models were built including known prognostic factors (age, diagnostic delay and site of onset), gender and the presence of an expanded repeat in C9orf72. These were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data (IPD) meta-analysis was used to estimate HRs for results of particular importance.Results: 457 (8.95%) of 4925 ALS cases carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival HR of 1.36 (1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion was being driven by spinal onset males (HR 1.56 (95% CI 1.25 to 1.96).Conclusions: This study represents the largest combined analysis of the prognostic characteristics of the C9orf72 expansion. We have shown for the first time that the negative prognostic implication of this variant is driven by males with spinal onset disease, indicating a hitherto unrecognised gender-mediated effect of the variant that requires further exploration. [ABSTRACT FROM AUTHOR]- Published
- 2017
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12. Influence of cigarette smoking on ALS outcome: a population-based study.
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Calvo, Andrea, Canosa, Antonio, Bertuzzo, Davide, Cugnasco, Paolo, Solero, Luca, Clerico, Marinella, De Mercanti, Stefania, Bersano, Enrica, Cammarosano, Stefania, Ilardi, Antonio, Manera, Umberto, Moglia, Cristina, Marinou, Kalliopi, Bottacchi, Edo, Pisano, Fabrizio, Mora, Gabriele, Mazzini, Letizia, and Chiò, Adriano
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AMYOTROPHIC lateral sclerosis ,SMOKING & psychology ,PHENOTYPES ,POPULATION-based case control ,PHYSICAL activity ,DISEASE risk factors ,AGE factors in disease ,LONGITUDINAL method ,OBSTRUCTIVE lung diseases ,PROGNOSIS ,SMOKING ,SURVIVAL analysis (Biometry) ,ACTIVITIES of daily living ,PROPORTIONAL hazards models ,KAPLAN-Meier estimator ,DISEASE complications ,DIAGNOSIS - Abstract
Objective: To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients.Methods: A total of 650 patients with ALS from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis.Results: Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2-3.4) compared with former (2.3 years, IQR 1.5-4.2) and never smokers (2.7 years, IQR 1.8-4.6) (p=0.001). Also COPD adversely influenced patients' prognosis. Both smoking habits and CODP were retained in Cox multivariable model.Conclusions: This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose-response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS. [ABSTRACT FROM AUTHOR]- Published
- 2016
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13. The MITOS system predicts long-term survival in amyotrophic lateral sclerosis.
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Tramacere, Irene, Bella, Eleonora Dalla, Chiò, Adriano, Mora, Gabriele, Filippini, Graziella, Lauria, Giuseppe, Dalla Bella, Eleonora, and EPOS Trial Study Group
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AMYOTROPHIC lateral sclerosis ,SURVIVAL analysis (Biometry) ,RANDOMIZED controlled trials ,DISEASE progression ,RECOMBINANT erythropoietin ,SENSITIVITY & specificity (Statistics) ,LOGISTIC regression analysis ,RECEIVER operating characteristic curves ,ARTIFICIAL respiration ,COMMUNICATION ,DEGLUTITION ,NEUROLOGIC examination ,RESPIRATION ,HEALTH self-care ,WALKING ,PREDICTIVE tests ,BLIND experiment ,DIAGNOSIS - Abstract
Objective: The choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.Methods: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or >23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models.Results: Disease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or >23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37/45) and 63% specificity (95% CI 55% to 71%, n=92/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50/70) and 68% specificity (95% CI 60% to 77%, n=76/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to predict survival at 12 and 18 months was 1 for the ALS-MITOS (ie, loss of at least one function) and a decline ranging from 6 to 9 points for the ALSFRS-R.Conclusions: The ALS-MITOS system can reliably predict the course of ALS up to 18 months and can be considered a novel and valid outcome measure in RCTs. [ABSTRACT FROM AUTHOR]- Published
- 2015
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14. Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.
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Lauria, Giuseppe, Bella, Eleonora Dalla, Antonini, Giovanni, Borghero, Giuseppe, Capasso, Margherita, Caponnetto, Claudia, Chiò, Adriano, Corbo, Massimo, Eleopra, Roberto, Fazio, Raffaella, Filosto, Massimiliano, Giannini, Fabio, Granieri, Enrico, La Bella, Vincenzo, Logroscino, Giancarlo, Mandrioli, Jessica, Mazzini, Letizia, Monsurrò, Maria Rosaria, Mora, Gabriele, and Pietrini, Vladimiro
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AMYOTROPHIC lateral sclerosis treatment ,ERYTHROPOIETIN ,PLACEBOS ,CLINICAL drug trials ,ADVERSE health care events ,RILUZOLE ,TRACHEOTOMY ,THERAPEUTICS - Abstract
Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-generated by blocks, stratified by centre, disease severity (ALSFRS-R cut-off score of 33) and onset (spinal or bulbar). The main outcome analysis was performed in all randomised patients and by intentionto- treat for the entire population and patients stratified by severity and onset. The study is registered, EudraCT 2009-016066-91. Results We randomly assigned 208 patients, of whom 5 (1 rhEPO and 4 placebo) withdrew consent and 3 (placebo) became ineligible (retinal thrombosis, respiratory insufficiency, SOD1 mutation) before receiving treatment; 103 receiving rhEPO and 97 placebo were eligible for analysis. At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline. Withdrawal due to AE was 16.5% in rhEPO and 8.3% in placebo. No differences were found for secondary outcomes. Conclusions RhEPO 40 000 IU fortnightly did not change the course of ALS. [ABSTRACT FROM AUTHOR]
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- 2015
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15. Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy.
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Montuschi, Anna, lazzolino, Barbara, Calvo, Andrea, Moglia, Cristina, Lopiano, Leonardo, Restagno, Gabriella, Brunetti, Maura, Ossola, Irene, Presti, Anna Lo, Cammarosano, Stefania, Canosa, Antonio, and Chiò, Adriano
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AMYOTROPHIC lateral sclerosis ,COGNITION disorders ,FRONTOTEMPORAL dementia ,MOTOR neurons ,GENETIC code ,SUPEROXIDE dismutase ,PUBLIC health - Abstract
Background There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. Methodology Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), nonclassifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients' general practitioners. Results Out of the 281 incident patients, 207 (71.9%) underwent the neuropsychological testing; of these, 19 were excluded from the analysis due previous conditions affecting cognition. Ninety-one (49.7%) patients were cognitively normal, 23 (12.6%) had ALS-FTD, 36 (19.7%) ALS-ECI, 10 (5.5%) ALS-NECI, 11 (6.0%) ALS-Bi and 11 (6.0%) non-classifiable cognitive impairment, 1 had comorbid Alzheimer's disease. Patients with ALS-FTD were older, had a lower education level, and had a shorter survival than any other cognitive group. Of the nine cases with C9ORF72 mutation, six had ALS-FTD, two ALS-ECI and one was cognitively normal; one of the five patients with SOD1 mutations and one of the five patients with TARBDP mutations had ALS-Bi. Conclusions About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD. [ABSTRACT FROM AUTHOR]
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- 2015
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16. Development and evaluation of a clinical staging system for amyotrophic lateral sclerosis.
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Chiò, Adriano, Hammond, Edward R., Mora, Gabriele, Bonito, Virginio, and Filippini, Graziella
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AMYOTROPHIC lateral sclerosis , *MEDICAL quality control , *DISEASE progression , *SEVERITY of illness index , *MEDICAL care costs , *DIAGNOSIS - Abstract
Background Staging of disease severity is useful for prognosis, decision-making and resource planning. However, no commonly used, validated staging system exists for amyotrophic lateral sclerosis (ALS). Our purpose was to develop an ALS staging system (ALS Milano-Torino Staging) that captures the observed progressive loss of independence and function. Methods Clinical milestones in ALS progression were defined by loss of independence in four key domains on the ALS Functional Rating Scale (ALSFRS): swallowing, walking/self-care, communicating and breathing. Stages were defined as follows: stage 0, functional involvement but no loss of independence on any domain; stages 1 - 4, number of domains in which independence was lost; and stage 5, death. Staging criteria were applied to patients enrolled in a Quality of Care in ALS (QOC) study; endpoints included function (ALSFRS), quality of life (QOL; Short Form-36) and health service costs. Between-stage transition probabilities were assessed in the QOC study and in a second clinical study of lithium carbonate in ALS. Results 70/118 (59.3%) participants in the QOC study progressed to higher stages of disease at 12 months compared with their baseline stage. Functional (ALSFRS) and QOL measures were inversely related to disease stage. Health service costs were directly related to increasing disease stages from 0 to 4 (p<0.001). Probabilities for transitioning from a given stage at baseline in both studies were usually greatest for the next highest stage. Conclusions The proposed ALS Milano-Torino Staging system correlates well with assessments of function, QOL and health service costs. Further studies are warranted to validate this system. [ABSTRACT FROM AUTHOR]
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- 2015
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17. Genetic counselling in ALS: facts, uncertainties and clinical suggestions.
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Chiò, Adriano, Battistini, Stefania, Calvo, Andrea, Caponnetto, Claudia, Conforti, Francesca L., Corbo, Massimo, Giannini, Fabio, Mandrioli, Jessica, Mora, Gabriele, Sabatelli, Mario, Ajmone, Clara, Mastro, Enza, Pain, Debora, Mandich, Paola, Penco, Silvana, Restagno, Gabriella, Zollino, Marcella, and Surbone, Antonella
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GENETIC counseling , *FRONTOTEMPORAL dementia , *PRESENILE dementia , *PHENOTYPES , *MEDICAL care , *GENE therapy , *PATIENTS - Abstract
The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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18. Evidence of multidimensionality in the ALSFRS-R Scale: a critical appraisal on its measurement properties using Rasch analysis.
- Author
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Franchignoni, Franco, Mora, Gabriele, Giordano, Andrea, Volanti, Paolo, and Chiò, Adriano
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AMYOTROPHIC lateral sclerosis ,PSYCHOMETRICS ,DIMENSION reduction (Statistics) ,RESPIRATORY insufficiency ,PUBLIC health - Abstract
Objective: To examine dimensionality, reliability and validity of the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) using traditional classical test theory methods and Rasch analysis in order to provide a rationale for possible improvement of its metric quality. Methods: Methodological research on ALSFRS-R collected in a consecutive sample of 485 patients with amyotrophic lateral sclerosis (ALS) attending three tertiary ALS centres. Results: The ALSFRS-R items showed good internal consistency but dimensionality analysis argues against the use of ALSFRS-R as a single score because the scale lacks unidimensionality. Parallel analysis and exploratory factor analysis revealed three factors representing the following domains: (1) bulbar function; (2) fine and gross motor function; and (3) respiratory function. Rasch analysis showed that all items in each domain fitted the respective constructs to measure, except for item No 9 'climbing stairs' and item No 12 'respiratory insufficiency'. Rating categories did not comply with the criteria for category functioning. Collapsing the scale's 5 level ratings into 3 levels improved its metric quality. Conclusions: The ALSFRS-R fails to satisfy rigorous measurement standards and should be, at least in part, revised. At present, ALSFRS-R should be considered as a profile of mean scores from three different domains (bulbar, motor and respiratory functions) more than a global total score. Further studies on ALSFRS-R using modern psychometric methods are warranted to confirm our findings and refine the metric quality of this scale, through a step by step process. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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19. ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations.
- Author
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Chiò, Adriano, Restagno, Gabriella, Brunetti, Maura, Ossola, Irene, Calvo, Andrea, Canosa, Antonio, Moglia, Cristina, Floris, Gianluca, Tacconi, Paolo, Marrosu, Francesco, Marrosu, Maria Giovanna, Murru, Maria Rita, Majounie, Elisa, Renton, Alan E., Abramzon, Yvegeniya, Pugliatti, Maura, Sotgiu, Maria Alessandra, Traynor, Bryan J., and Borghero, Giuseppe
- Subjects
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GENETIC mutation , *INTRONS , *MISSENSE mutation , *RESPIRATORY insufficiency , *HAPLOTYPES , *NEURODEGENERATION - Abstract
Background In the isolated population of Sardinia, a Mediterranean island, ∼25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of the C9ORF72 gene. Objective To describe the co-presence of two genetic mutations in two Sardinian ALS patients. Methods We identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene. Results The index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus. Conclusions Our data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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20. Non-invasive ventilation in amyotrophic lateral sclerosis: a 10 year population based study.
- Author
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Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Gamna, Federica, Mattei, Alessio, Mazzini, Letizia, and Mora, Gabriele
- Subjects
- *
ARTIFICIAL respiration , *NONINVASIVE diagnostic tests , *AMYOTROPHIC lateral sclerosis , *HEALTH outcome assessment , *EPIDEMIOLOGY , *MARITAL status , *RESPIRATORY insufficiency - Abstract
Objective To evaluate the clinical characteristics and outcome of non-invasive ventilation (NIV) in an epidemiological based series of amyotrophic lateral sclerosis (ALS) patients. Methods The study was performed using data from the Piemonte and Valle d'Aosta Register for ALS, a prospective epidemiological register enrolling all ALS incident cases in two Italian regions. Results Among the 1260 patients incident in the period 1995e2004, 259 (20.6%) underwent NIV. Young male patients and subjects attending the tertiary ALS centres were more likely to undergo NIV. There was a progressive significant increase in the use of NIV during the study but was limited to patients attending the ALS tertiary centres. Median survival after NIV was 289 days (95% CI 255 to 333). Conclusions In an epidemiological setting, NIV represents an increasingly utilised option for the treatment of respiratory disturbances in ALS and has favourable effects on survival, in particular among patients followed by tertiary ALS centres. Sociocultural factors, such as age, gender and marital status, strongly influence the probability of undergoing NIV. Efforts should be made to remove these obstacles in order to spread the use of NIV in all ALS patients with respiratory failure. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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21. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study.
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Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Mazzini, Letizia, and Mora, Gabriele
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AMYOTROPHIC lateral sclerosis , *MOTOR neuron diseases , *DISEASE incidence , *EPIDEMIOLOGY , *ETIOLOGY of diseases , *PROGNOSIS - Abstract
Background Different amyotrophic lateral sclerosis (ALS) phenotypes have been recognised, marked by a varying involvement of spinal and bulbar upper and lower motor neurons. However, the differential characteristics of these phenotypes are still largely unknown. Objective To define the epidemiology and outcome of ALS phenotypes in a population based setting. Methods All ALS cases incident in two Italian regions were prospectively collected from 1995 to 2004 in an epidemiological register. Cases were classified according to established ALS phenotypes: classic, bulbar, flail arm, flail leg, pyramidal, respiratory, pure lower motor neuron (PLMN) and pure upper motor neuron (PUMN). Results ALS phenotype were determined in 1332 out of 1351 incident patients (98.6%). Classic and bulbar phenotypes had similar mean annual incidence rates. Gender specific incidence rates showed a male preponderance in respiratory, flail arm, classic and PLMN phenotypes; in all other phenotypes, men and women had similar incidence rates. Age at onset was significantly lower in pyramidal, PLMN and PUMN phenotypes and higher in the bulbar phenotype. The best outcomes were observed in PUMN, pyramidal, PLMN and flail arm phenotypes and the worst in respiratory and bulbar phenotypes. Conclusions Our epidemiological findings suggest that ALS phenotypes carry distinctive and easily distinguishable clinical and prognostic characteristics, strongly related to a complex interplay between gender and age. The categorisation of ALS patients according to more homogenous clinical groups is relevant in identifying biological markers for ALS and should be considered for the design of clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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22. Incidence of amyotrophic lateral sclerosis in Europe.
- Author
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Logroscino G, Traynor BJ, Hardiman O, Chiò A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E, EURALS, Logroscino, Giancarlo, Traynor, Bryan J, Hardiman, Orla, Chiò, Adriano, Mitchell, Douglas, Swingler, Robert J, Millul, Andrea, Benn, Emma, and Beghi, Ettore
- Abstract
Background: Geographical differences in the incidence of amyotrophic lateral sclerosis (ALS) have been reported in the literature but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied populations. To address these issues, the authors undertook a pooled analysis of European population based ALS registries.Methods: All new incident ALS cases in subjects aged 18 years old and older were identified prospectively in six population based registries in three European countries (Ireland, UK and Italy) in the 2 year period 1998-1999, with a reference population of almost 24 million.Results: Based on 1028 identified incident cases, the crude annual incidence rate of ALS in the general European population was 2.16 per 100 000 person years; 95% CI 2.0 to 2.3), with similar incidence rates across all registries. The incidence was higher among men (3.0 per 100 000 person years; 95% CI 2.8 to 3.3) than among women (2.4 per 100 000 person years; 95% CI 2.2 to 2.6). Spinal onset ALS was more common among men compared with women, particularly in the 70-80 year age group. Disease occurrence decreased rapidly after 80 years of age.Conclusions: ALS incidence is homogeneous across Europe. Sex differences in incidence may be explained by the higher incidence of spinal onset ALS among men, and the age related disease pattern suggests that ALS occurs within a susceptible group within the population rather than being a disease of ageing. [ABSTRACT FROM AUTHOR]- Published
- 2010
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23. A familial ALS case carrying a novel p.G147C SOD1 heterozygous missense mutation with non-executive cognitive impairment.
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Canosa, Antonio, Calvo, Andrea, Moglia, Cristina, Iazzolino, Barbara, Brunetti, Maura, Restagno, Gabriella, Cistaro, Angelina, Fania, Piercarlo, Carrara, Giovanna, Valentini, Maria Consuelo, Tanel, Raffaella, and Chiò, Adriano
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AMYOTROPHIC lateral sclerosis ,MISSENSE mutation ,AMINO acids ,CYSTEINE ,GLYCINE ,RESPIRATORY insufficiency ,PATIENTS - Abstract
The article presents the case study of familial amyotrophic lateral sclerosis (ALS) patient with p. G147C SOD1, a heterozygous missense mutation, which leads to amino acid substitution and substitution of cysteine for glycine. It mentions case studies of two brothers who died because of respiratory failure as a result of ALS. It states other missense mutations that have been reported in ALS including p.G147R, p.G147D and p.G147C.
- Published
- 2014
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24. Physical fitness and amyotrophic lateral sclerosis: dangerous liaisons or common genetic pathways?
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Chiò, Adriano and Mora, Gabriele
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PHYSICAL fitness research , *AMYOTROPHIC lateral sclerosis , *SMOKING , *NEUROLOGICAL disorders , *PHYSICAL activity - Abstract
The article focuses on a study related to the association between physical fitness and amyotrophic lateral sclerosis (ALS) in human beings. According to the study, the relevant cause of the ALS remains unclear but the possible factor associated with the occurrence of this neurological disease is cigarette smoking. It also reflects on a new perspective concerning the relationship between physical activity and the ALS.
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- 2012
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25. Brain 18 fluorodeoxyglucose-positron emission tomography changes in amyotrophic lateral sclerosis with TARDBP mutations.
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Canosa A, Calvo A, Moglia C, Vasta R, Palumbo F, Fuda G, Di Pede F, Cabras S, Arena V, Novara A, Salamone P, Matteoni E, Sbaiz L, Gallone S, Grassano M, Manera U, Chiò A, and Pagani M
- Subjects
- Brain diagnostic imaging, Humans, Mutation genetics, Positron-Emission Tomography methods, Amyotrophic Lateral Sclerosis diagnostic imaging, Amyotrophic Lateral Sclerosis genetics
- Abstract
Competing Interests: Competing interests: ACal has received a research grant from Cytokinetics. ACh serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, Cytokinetics, Denali Therapeutics, Amylyx and AveXis.
- Published
- 2022
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26. Metabolic brain changes across different levels of cognitive impairment in ALS: a 18 F-FDG-PET study.
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Canosa A, Moglia C, Manera U, Vasta R, Torrieri MC, Arena V, D'Ovidio F, Palumbo F, Zucchetti JP, Iazzolino B, Peotta L, Calvo A, Pagani M, and Chiò A
- Abstract
Objective: To identify the metabolic changes related to the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using
18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18 F-FDG-PET) imaging., Methods: 274 ALS patients underwent neuropsychological assessment and brain18 F-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., Competing Interests: Competing interests: ACan, CM, UM, RV, MCT, VA, FD’O, FP, JPZ, BI, LP and MP: no disclosures. ACal has received a research grant from Cytokinetics. ACh serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen and Cytokinetics, and has received a research grant from Italfarmaco. The sponsor organisations had no role in data collection and analysis and did not participate to writing and approving the manuscript. The information reported in the manuscript has never been reported elsewhere., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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27. Clinical features and outcomes of the flail arm and flail leg and pure lower motor neuron MND variants: a multicentre Italian study.
- Author
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Schito P, Ceccardi G, Calvo A, Falzone YM, Moglia C, Lunetta C, Marinou K, Ticozzi N, Scialo C, Sorarù G, Trojsi F, Conte A, Tortelli R, Russo M, Zucchi E, Pozzi L, Domi T, Carrera P, Agosta F, Quattrini A, Fazio R, Chiò A, Sansone VA, Mora G, Silani V, Volanti P, Caponnetto C, Querin G, Tedeschi G, Sabatelli M, Logroscino G, Messina S, Mandrioli J, Riva N, and Filippi M
- Subjects
- Age of Onset, Aged, Female, Humans, Italy, Male, Middle Aged, Motor Neuron Disease pathology, Phenotype, Retrospective Studies, Sex Factors, Arm physiopathology, Leg physiopathology, Motor Neuron Disease diagnosis, Motor Neuron Disease physiopathology, Motor Neurons pathology
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2020
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28. Prospective epidemiological registers: a valuable tool for uncovering ALS pathogenesis.
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Chiò A, Canosa A, and Calvo A
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- Female, Humans, Male, Amyotrophic Lateral Sclerosis epidemiology, Population Surveillance
- Published
- 2011
- Full Text
- View/download PDF
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