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Relationship between symptom change, relapse activity and disability progression in multiple sclerosis

Journal of the Neurological Sciences, Volume 362, 15 March 2016, Pages 121–126



Symptom changes may serve as a risk factor for relapse activity (RA) and disability progression (DP), which could facilitate multiple sclerosis (MS) treatment decisions.


To assess the relationship of symptom change with RA and DP.


We evaluated the relationship of symptom change with subsequent RA and DP using NARCOMS registry data reported over a five-year period. Symptom change was evaluated using both symptom worsening (SW) and average of Performance Scales (APS) scores. Disability progression was defined as a one-point or more increase in Patient-Determined Disease Steps (PDDS) score between two consecutive updates. Repeated measures logistic regression was used to investigate the relationship between symptom change and RA and DP.


SW and APS were both significant predictors of subsequent RA and DP. Both SW and APS have a significant interaction with levels of disability (Mildly Impaired versus Highly Impaired) for the prediction of the subsequent RA or DP. For Mildly Impaired MS subjects, both SW and APS were significant predictors of both RA and DP. However, for Highly Impaired MS subjects, SW did not significantly predict future RA and neither SW nor APS predicted disability progression.


Changes in self-reported overall symptomatology may precede and predict clinical relapse and future disability progression. The predictive power of symptom changes may only be present at lower levels of disability.


  • Symptom worsening may be a prodromal event to a subsequent relapse or progression.
  • Symptom worsening's predictive power may be limited to lower levels of disability.
  • Patient reported outcomes may provide cues for earlier interventions by clinicians.

Keywords: Multiple sclerosis, Disease modifying therapy, Relapse activity, Disability progression, Symptom worsening, Patient-reported outcomes, PDDS.


a Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

b Division of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA

c Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

d Mellen Center for MS, Cleveland Clinic, Cleveland, USA

Corresponding author at: University of Alabama at Birmingham, School of Public Health, Department of Biostatistics, 1665 University Blvd. Room 410b, Birmingham, AL 35294-0022, USA.

1 While there are multiple performance scales, we use here only the eight subscales described above. Copyright information for these scales is as follows: Performance Scales, Copyright Registration Number/Date: TXu000743629/1996–04-04; assigned to DeltaQuest Foundation, Inc., effective October 1, 2005. U.S. Copyright law governs terms of use.