title: What does the ALSFRS-R really measure? A longitudinal and survival analysis of functional dimension subscores in amyotrophic lateral sclerosis.
abstract: ALS functional rating scale (revised) (ALSFRS-R) is the most widely used functional rating system in patients with amyotrophic lateral sclerosis (ALS). However, heterogeneity in ALSFRS-R progression renders analysis challenging. We have explored the characteristics of total ALSFRS-R, and ALSFRS-R subscores in longitudinal and survival models, to determine whether subscore analysis enhances the precision of the instrument.
  
  
  
  All cases with ALSFRS-R scores on the Irish ALS register were included. ALSFRS-R subscores were defined for bulbar, motor and respiratory domains. Longitudinal models were used to visualise fitted total ALSFRS-R and ALSFRS-R subscore progression. In addition, the prognostic value of convenience and computed ALSFRS-R slope and subscore slopes were compared.
  
  
  
  407 incident cases were identified with a complete ALSFRS-R measure. 233 (57%) patients were male, and 125 (31%) had bulbar-onset disease. ALSFRS-R bulbar and motor subscore slopes provided a better fit in prognostic models when combined over the total ALSFRS-R slope. Longitudinal analysis revealed that the ALSFRS-R motor subscore deteriorated earlier in spinal-onset disease over bulbar-onset disease, while in bulbar-onset disease the ALSFRS-R bulbar subscore deteriorated earlier and faster than in spinal-onset disease.
  
  
  
  Our analysis builds on previous knowledge of ALSFRS-R subscores. Decline in ALSFRS-R motor subscores in patients with spinal-onset disease, and decline in ALSFRS-R bulbar subscores in patients with bulbar-onset disease, may predate reported disease onset dates. Respiratory subscores were not prognostically informative after adjustment for bulbar and motor subscores. These results provide robust evidence that the ALSFRS-R should not be reported as a single combined score, but rather as domain specific subscores.
authors.affiliation: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: Rooney
authors.affiliation: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.|Beaumont Hospital, Dublin, Ireland.
authors.forename: Tom
authors.initials: T
authors.lastname: Burke
authors.affiliation: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Alice
authors.initials: A
authors.lastname: Vajda
authors.affiliation: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Heverin
authors.affiliation: Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.|Beaumont Hospital, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007494:Ireland; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D011594:Psychometrics; D012042:Registries; D012720:Severity of Illness Index; D016019:Survival Analysis