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Research paper
Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort
  1. Cristina Moglia1,2,
  2. Andrea Calvo1,2,
  3. Maurizio Grassano1,
  4. Antonio Canosa1,
  5. Umberto Manera1,
  6. Fabrizio D'Ovidio1,
  7. Alessandro Bombaci1,
  8. Enrica Bersano3,
  9. Letizia Mazzini3,
  10. Gabriele Mora4,
  11. Adriano Chiò1,2,5
  12. Piemonte and Valle d’Aosta Register for ALS (PARALS)
    1. 1 ALS Center, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Turin, Italy
    2. 2 Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino, Italy
    3. 3 ALS Center, Department of Neurology, Azienda Ospedaliera Universitaria Maggiore della Carità, Novara, Italy
    4. 4 ALS Center, Istituti Clinici Scientifici Maugeri IRCCS, Milan, Italy
    5. 5 National Research Council (CNR), Institute of Cognitive Sciences and Technologies, Rome, Italy
    1. Correspondence to Adriano Chiò, ALS Center, ‘Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Turin 10126, Italy; achio{at}usa.net

    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.

    • amyotrophic lateral sclerosis
    • body mass index
    • weight loss
    • dysphagia
    • respiratory function
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    Footnotes

    • Collaborators Stefania Cammarosano, Rosario Vasta, Maria Claudia Torrieri, Luca Solero, (ALS Center, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Torino Italy). Marinella Clerico, Stefania De Mercanti, (Azienda Ospedaliera Universitaria San Luigi, University of Torino, Orbassano, Italy). Alessandro Mauro, Luca Pradotto (Istituto Auxologico Italiano, IRCCS, Piancavallo, Italy). Fabiola De Marchi (University of Eastern Piedmont, Novara, Italy). Luisa Sosso (Ospedale Mauriziano, Torino, Italy). Daniela Leotta (Ospedale Martini, Torino, Italy). Lucia Appendino, Daniele Imperiale (Ospedale Maria Vittoria, Torino, Italy). Roberto Cavallo (Ospedale San Giovanni Bosco, Torino, Italy). Claudio Geda (Ospedale di Ivrea, Ivrea, Italy). Fabio Poglio (Ospedale di Pinerolo, Pinerolo, Italy). Paola Santimaria (Ospedale di Vercelli, Vercelli, Italy). Umberto Massazza (Azienda Sanitaria, Biella, Italy). Antonio Villani, Roberto Conti (Ospedale di Domodossola, Domodossola, Italy). Luigi C Ruiz, Mario Palermo (Azienda Ospedaliera Nazionale Santi Ambrogio e Biagio e Cesare Arrigo, Alesssandria, Italy). Franco Vergnano (spedale di Casale Monferrato, Casale Monferrato, Italy). Eugenia Rota (Ospedale di Novi Ligure, Novi Ligure, Italy). Maria Teresa Penza (Ospedale di Valenza, Valenza, Italy). Marco Aguggia (Ospedale di Asti, Asti, Italy). Piero Meineri (Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy). Paolo Ghiglione (Ospedale di Savigliano, Savigliano, Italy). Nicola Launaro (Ospedale di Saluzzo, Saluzzo, Italy). Giuseppe Astegiano (Ospedale di Alba, Alba, Italy). Giovanni Corso (Azienda Unitaria Sanitaria Locale di Aosta, Aosta, Italy). Role: Site investigator (Stefania Cammarosano, Rosario Vasta, Maria Claudia, Luca Solero, Stefania De Mercanti, Luca Pradotto, Fabiola De Marchi, Luisa Sosso, Daniela Leotta, Lucia Appendino, Daniele Imperiale, Roberto Cavallo, Fabio Poglio, Paola Santimaria, Umberto Massazza, Roberto Conti, Mario Palermo, Franco Vergnano, Eugenia Rota, Maria Teresa Penza, Marco Aguggia, Piero Meineri, Paolo Ghiglione, Nicola Launaro, Giovanni Corso), Advisory committee (Marinella Clerico, Claudio Geda, Antonio Villani, Luigi C Ruiz, Giuseppe Astegiano). Contribution: Case ascertainment and follow-up (Stefania Cammarosano, Rosario Vasta, Maria Claudia, Luca Solero, Stefania De Mercanti, Luca Pradotto, Fabiola De Marchi, Luisa Sosso, Daniela Leotta, Lucia Appendino, Daniele Imperiale, Roberto Cavallo, Fabio Poglio, Paola Santimaria, Umberto Massazza, Roberto Conti, Mario Palermo, Franco Vergnano, Eugenia Rota, Maria Teresa Penza, Marco Aguggia, Piero Meineri, Paolo Ghiglione, Nicola Launaro, Giovanni Corso). Local data revision; Case ascertainment and follow-up: (Claudio Geda, Antonio Villani, Luigi C Ruiz, Giuseppe Astegiano).

    • Contributors Study concept and design: CM, AC, UM, FD’O, LM, GM, AC. Acquisition of data: MG, UM, AB, De Marchi. Analysis and interpretation of data: CM, AC, MG, UM, FD’O, LM, GM, AC. Drafting of the manuscript: AC, GM. Critical revision of the manuscript for important intellectual content: CM, MG, AC, AC, UM, FD’O, AB, De Marchi, LM, GM, AC. Obtained funding: AC. Administrative, technical, and material support: CM, MG, AC, AC, UM, FD’O, ABi, De Marchi, LM, GM, AC. Study supervision: GM, AC. AC has full access to data. The corresponding author confirms that all authors have read and approved the final draft of the manuscript and given written permission to include their names in the manuscript.

    • Funding This study was funded by FP (7259867) and also Joint Programme - Neurodegenerative Disease Research (Brain-Mend), Ministero della Salute, Ricerca Sanitaria Finalizzata, 2010 (RF-2010-2309849), Ministero dell'Istruzione, dell'Università e della Ricerca (Dipartimenti di Eccellenza 2018 – 2022) and Joint Programme - Neurodegenerative Disease Research (Strength).

    • Competing interests AC serves on a scientific advisory board for Mitsubishi Tanabe, Roche, and Cytokinetics.

    • Patient consent for publication Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Anonymised data will be shared upon request from any qualified investigator.

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