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.
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Contributors UM: study concept and design, drafting on the manuscript, critical revision of the manuscript for important intellectual content and study supervision. AndC, AdrC, FD: drafting on the manuscript, critical revision of the manuscript for important intellectual content and study supervision. GM and LM: drafting on the manuscript, critical revision of the manuscript for important intellectual content. CM, MARD, AntC, RV, MCT, MG, MB, SD, LC and FDM: drafting on the manuscript, critical revision of the manuscript for important intellectual content, administrative, technical and material support.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer The sponsor organizations had no role in data collections and analysis and did not participate to writing and approving the manuscript. The information reported in the manuscript has never been reported elsewhere.
Competing interests Adriano Chiò serves on scientific advisory boards for Mitsubishi Tanabe, Roche, Biogen, and Cytokinetics, and has received a research grant from Italfarmaco. Andrea Calvo has received research grant from Cytokinetics.Umberto Manera, Margherita Daviddi, Antonio Canosa, Rosario Vasta, Maria Claudia Torrieri, Maurizio Grassano, Maura Brunetti, Sandra D’Alfonso, Lucia Corrado, Fabiola De Marchi, Cristina Moglia, Fabrizio D’Ovidio, Letizia Mazzini, report no conflicts of interest.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.