title: Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy.
abstract: Very few studies examined trend over time of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous studies, then, included only patients attending tertiary ALS Centres. We studied ALSFRS-R decline, factors influencing this trend and survival in a population-based setting. From 2009 onwards, a prospective registry records all incident ALS cases among residents in Emilia Romagna (population: 4.4 million). For each patient, demographic and clinical details (including ALSFRS-R) are collected by caring physicians at each follow-up. Analysis was performed on 402 incident cases (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60 points/month during the first year after diagnosis and 0.34 points/month in the second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated measures mixed model showed that ALSFRS-R score decline was influenced by age at onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01), progression rate at diagnosis (ΔFS) (p < 0.01), El Escorial Criteria-Revised (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at multivariate analysis, only age, site of onset and ΔFS independently influenced survival. In this first population-based study on ALSFRS-R trend, we confirm that ALSFRS-R decline is not homogeneous among ALS patients and during the disease. Factors influencing ALSFRS-R decline may not match with those affecting survival. These disease modifiers should be taken into consideration for trials design and in clinical practice during discussions with patients on prognosis.
authors.affiliation: Department of Neuroscience, St. Agostino-Estense Hospital, Via Pietro Giardini n. 1355, 41100, Modena, Italy. j.mandrioli@ausl.mo.it.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.affiliation: Department of Neurology, Bufalini Hospital, Cesena, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Biguzzi
authors.affiliation: Department of Neurology, Forlì Hospital, Forlì, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Guidi
authors.affiliation: Department of Neurology, St. Anna Hospital, Ferrara, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Sette
authors.affiliation: Department of Neurology, G. Da Saliceto Hospital, Piacenza, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Terlizzi
authors.affiliation: Department of Neurology, Infermi Hospital, Rimini, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ravasio
authors.affiliation: Department of Neurology, Faenza and Ravenna Hospital, Ravenna, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Casmiro
authors.affiliation: Neurology Unit, Bellaria Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Liguori
authors.affiliation: Department of Neurology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Romana
authors.initials: R
authors.lastname: Rizzi
authors.affiliation: Department of Neuroscience, Neurology Unit, University of Parma, Parma, Italy.
authors.forename: Vladimiro
authors.initials: V
authors.lastname: Pietrini
authors.affiliation: Neurology Unit, Maggiore Hospital, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Borghi
authors.affiliation: Department of Neuroscience, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rinaldi
authors.affiliation: Department of Neuroscience, St. Agostino-Estense Hospital, Via Pietro Giardini n. 1355, 41100, Modena, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fini
authors.affiliation: Department of Neurology, Fidenza Hospital, Parma, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Chierici
authors.affiliation: Department of Neurology, Carpi Hospital, Modena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Santangelo
authors.affiliation: Department of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Granieri
authors.affiliation: Department of Neurology, Imola Hospital, Bologna, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Mussuto
authors.affiliation: Department of Biomedical and Neuromotor Sciences, University of Bologna and IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Pasqua
authors.affiliation: Department of Neuroscience, St. Agostino-Estense Hospital, Via Pietro Giardini n. 1355, 41100, Modena, Italy.
authors.forename: Eleni
authors.initials: E
authors.lastname: Georgoulopoulou
authors.affiliation: Department of Neuroscience, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fasano
authors.affiliation: Department of Hospital Services, Emilia Romagna Regional Health Authority, Bologna, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ferro
authors.affiliation: Neuroepidemiology Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Alessandro
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries
keywords: ALSFRS-R; Amyotrophic lateral sclerosis; Disease progression; Heterogeneity; Population-based study