Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials

M Hardmeier; R Schlaeger; A M Lascano; L Toffolet; C Schindler; C Gobbi; P Lalive; J Kuhle; L Kappos; P Fuhr

doi:10.1016/j.clinph.2022.02.019

Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials

Clin Neurophysiol. 2022 May:137:152-158. doi: 10.1016/j.clinph.2022.02.019. Epub 2022 Mar 7.

Authors

M Hardmeier¹, R Schlaeger², A M Lascano³, L Toffolet⁴, C Schindler⁵, C Gobbi⁶, P Lalive³, J Kuhle⁷, L Kappos⁷, P Fuhr⁷

Affiliations

¹ Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland. Electronic address: martin.hardmeier@usb.ch.
² Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland; Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland.
³ Neurology, University Hospital of Geneva (HUG), Geneva, Switzerland.
⁴ Multiple Sclerosis Center (MSC), Department of Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁵ University of Basel, Swiss Tropical and Public Health Institute, Basel, Switzerland.
⁶ Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland; Multiple Sclerosis Center (MSC), Department of Neurology, Neurocenter of Southern Switzerland, Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Lugano, Switzerland.
⁷ Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.

PMID: 35316624
DOI: 10.1016/j.clinph.2022.02.019

Abstract

Objective: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities.

Methods: 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.

Results: 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 (R²_adj: 0.24), while EDSS and age did not. Tibial qSEP (R²_adj: 0.22) and qMEP (R²_adj: 0.26) were the best single modality predictors, outperformed by their combination (R²_adj: 0.32).

Conclusions: 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.

Significance: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS.

Keywords: Biomarker; Clinical trial design; Evoked Potentials; Prognosis; Progressive Multiple Sclerosis; Quantitative EP Score.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Disability Evaluation
Disease Progression
Evoked Potentials / physiology
Humans
Multiple Sclerosis*
Multiple Sclerosis, Chronic Progressive* / diagnosis
Prognosis

Substances

Biomarkers