Currently no valid surrogate marker exists for primary progressive multiple sclerosis (PPMS).

Our aim was to prospectively investigate multimodal evoked potentials (EPs) as markers and predictors of the disease course in PPMS.

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.

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 (r_s=0.46, p=0.0740). The s-EP-Q_T0 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. EDSS_T6 as predicted by EDSS_T6= –1.027+0.037* age+0.217* s-EP-Q_T0 + 0.695* EDSS_T0 correlated with the observed values (r_s=0.92, p<0.0001).

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.