Trajectories of impairment in amyotrophic lateral sclerosis: Insights from the Pooled Resource Open-Access ALS Clinical Trials cohort

Muscle Nerve. 2018 Jun;57(6):937-945. doi: 10.1002/mus.26042. Epub 2018 Jan 11.


Introduction: Rate of decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score is a common outcome measure and a powerful predictor of mortality in ALS.

Methods: Observed rate of decline (postslope) of ALSFRS-R, its linearity, and its relationship to decline at first visit (preslope) were examined in the Pooled Resource Open-Access ALS Clinical Trials cohort by using longitudinal mixed effects models.

Results: Mean ALSFRS-R postslope in 3,367 patients was -0.99 points/month. Preslope and postslope were correlated and had powerful effects on survival. ALSFRS-R trajectories were slightly accelerated overall, but slope and direction/degree of curvature varied. Subscore decline was sequential by site of onset. Respiratory subscore decline was the least steep.

Discussion: Variable curvilinearity of ALSFRS-R trajectories confounds interpretation in clinical studies that assume linear decline. Subscore trajectories recapitulate phenotypic diversity and topographical progression of ALS. ALSFRS-R is better used as a multidimensional measure. Muscle Nerve 57: 937-945, 2018.

Keywords: ALSFRS-R; amyotrophic lateral sclerosis; longitudinal mixed effects models; phenotypic variability; prognosis; slope; trajectory.

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged