title: Time to generalization and prediction of survival in patients with amyotrophic lateral sclerosis: a retrospective observational study.
abstract: A strong association between time to generalization (TTG), considered as the time of spreading of the clinical signs from spinal or bulbar localization to both, and survival was recently identified in patients with amyotrophic lateral sclerosis (ALS). Thus, TTG may be used as an early to intermediate end-point in survival studies. The aim of the present study was to test TTG as a predictor of survival in ALS.
  
  
  
  This was an observational retrospective study of ALS patients from a tertiary referral centre over a 5-year follow-up period.
  
  
  
  In 212 ALS patients, TTG was associated with time to death/tracheostomy [R 0.62, 95% confidence interval (CI) 0.53-0.70; P < 0.001]. In a time-to-event analysis, longer TTG resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (HR) 0.98, 95% CI 0.97-0.99] and multivariate Cox analyses (HR 0.98, 95% CI 0.96-0.99). TTG predicted death/tracheostomy at 4 years (C-statistic 0.58; 95% CI 0.53-0.63) and at 5 years (C-statistic 0.58; 95% CI 0.53-0.62).
  
  
  
  Based on the present results from a large clinical cohort, TTG may be used as a new early to intermediate end-point to describe the ALS natural history. TTG may be potentially useful as a new primary outcome measure for clinical trials.
authors.affiliation: Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tortelli
authors.affiliation: Unit of Biostatistics, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy.|Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.|Geriatric Unit and Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Panza
authors.affiliation: Unit of Biostatistics, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cortese
authors.affiliation: Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Capozzo
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Introna
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: D'Errico
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Zoccolella
authors.affiliation: Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Arcuti
authors.affiliation: Geriatric Unit and Laboratory of Gerontology and Geriatrics, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Seripa
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: I L
authors.initials: IL
authors.lastname: Simone
authors.affiliation: Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro', Tricase, Lecce, Italy.|Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Logroscino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000401:mortality* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D013997:Time Factors; D014139:Tracheostomy
keywords: additional spreading; amyotrophic lateral sclerosis; generalization; prognosis; survival