title: Detecting clinically-relevant changes in progressive multiple sclerosis.
abstract: OBJECTIVE
  To investigate which changes in different clinical outcome measures contribute most to increased disease impact, as reported by the patient, in progressive multiple sclerosis (MS).
  
  
  METHODS
  From a cohort of prospectively-followed MS patients, we selected progressive patients with two visits, 4-6 years apart. We assessed long-term changes on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and Guy's Neurological Disability Scale (GNDS). We defined the presence or absence of clinically meaningful change by using the Multiple Sclerosis Impact Scale (MSIS-29) as an anchor measure. We also studied change on recently identified sub-scales of GNDS.
  
  
  RESULTS
  Change on GNDS (especially the spinal-plus subscale) contributed most to increased disease impact. Also change on the T25FW contributed largely. Specific profiles of change in T25FW and MSIS seemed to exist (generally, a lower increase in disease impact in patients with longer disease duration and higher baseline impact/disability). In some patients a dissociation existed between increased impact, according to the MSIS-29, and objective physical worsening of the T25FW.
  
  
  CONCLUSIONS
  These results support using GNDS (particularly the spinal-plus domain) and T25FW in outcome measurement in progressive MS. We suggest there is a relation between baseline clinical characteristics and an increased impact at follow-up. This may have implications for patient selection in trials for progressive MS.
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: L V A E
authors.initials: LV
authors.lastname: Bosma
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Sonder
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands/Reinier de Graaf Groep, Delft, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kragt
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands bmj.uitdehaag@vumc.nl.
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis*; D012720:Severity of Illness Index
keywords: Clinical outcome; disability tests; disease progression; multiple sclerosis; outcome measurement; patient reported outcome; study design