title: Electrophysiological markers and predictors of the disease course in primary progressive multiple sclerosis.
abstract: BACKGROUND
  Currently no valid surrogate marker exists for primary progressive multiple sclerosis (PPMS).
  
  
  OBJECTIVE
  Our aim was to prospectively investigate multimodal evoked potentials (EPs) as markers and predictors of the disease course in PPMS.
  
  
  METHODS
  Twenty-two PPMS patients were prospectively examined with visual, somatosensory and motor EPs and Expanded Disability Status Scale (EDSS) assessments at baseline (T0) and at six-month intervals over three years. Spearman rank correlation was used to determine the relationship between EP measures and EDSS. The relationship between disease evolution and a numerical score derived from z-transformed EP-latencies (s-EP-Q) and baseline characteristics was further assessed using multivariable linear regression analysis.
  
  
  RESULTS
  s-EP-Q correlated with EDSS score at all points in time in cross-sectional comparison (0.53≤rs ≤0.68; 0.0007≤p≤0.0232) and also longitudinally by trend (rs=0.46, p=0.0740). The s-EP-QT0 correlated with the EDSS score at year 3 (T6) (r s=0.77, p<0.0001). The s-EP-Q changes became statistically significant six months before corresponding changes were seen in the EDSS score. EDSST6 as predicted by EDSST6 = -1.027+0.037* age+0.217* s-EP-QT0 + 0.695* EDSST0 correlated with the observed values (rs=0.92, p<0.0001).
  
  
  CONCLUSIONS
  Multimodal EPs correlate well with disability in PPMS, and allow some prediction of the disease course over three years. These findings support a role of EPs as surrogate markers in clinical trials in PPMS.
authors.affiliation: Department of Neurology, University Hospital Basel, Switzerland.
authors.forename: Regina
authors.initials: R
authors.lastname: Schlaeger
authors.forename: Marcus
authors.initials: M
authors.lastname: D'Souza
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Leticia
authors.initials: L
authors.lastname: Grize
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Peter
authors.initials: P
authors.lastname: Fuhr
mesh_terms: D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D018450:Disease Progression; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000150:complications* / Q000503:physiopathology*
keywords: Evoked potentials; primary progressive multiple sclerosis; prognosis; surrogate markers