Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials
Martin Hardmeier, Regina Schlaeger, Agustina M. Lascano, L. Toffolet, Christian Schindler, Claudio Gobbi, Patrice H. Lalive, Jens Kühle, Ludwig Kappos, Peter Fuhr
Abstract
To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0–6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45–0.69; p < 0.01) and follow-up (Rho: 0.59–0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R2adj: 0.24), while EDSS and age did not. Tibial qSEP (R2adj: 0.22) and qMEP (R2adj: 0.26) were the best single modality predictors, outperformed by their combination (R2adj: 0.32). Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS.