Multicentre assessment of motor and sensory evoked potentials in multiple sclerosis: reliability and implications for clinical trials.

Abstract

BackgroundMotor and sensory evoked potentials (EP) are potential candidate biomarkers for clinical trials in multiple sclerosis.ObjectiveTo determine test -retest reliability of motor EP (MEP) and sensory EP (SEP) and associated EP-scores in patients with multiple sclerosis.MethodsIn three centres, 16 relapsing and five progressive multiple sclerosis patients had MEPs and SEPs 1–29 days apart. Five neurophysiologists independently marked latencies by central reading. By variance component analysis, we estimated the critical difference (absolute reliability) for cross-sectional group comparison, comparison of longitudinal group changes, within-subject minimal detectable change and defined within-subject improvement.ResultsCortical SEP responses and cortico-muscular MEP latencies were more reliable than central conduction times. For comparison of 20 subjects per arm, cross-sectional group difference ranged from 0.7 to 3.9 ms and 1.1 to 1.7, group difference in longitudinal changes from 0.4 to 1.8 ms and 0.36 to 0.62, within-subject minimal detectable change from 1.2 to 5.8 ms and 1.2 to 2.0, within-subject improvement from 0.8 to 3.8ms and 0.8 to 1.3, for single EP modalities and EP scores, respectively.ConclusionsMulticentre EP assessment with central EP reading is feasible and reliable. The critical difference is reasonably low to detect significant group changes and to define responders. The results support the concept of using EP and EP-scores as candidate response biomarkers for quantification of disease progression and for studying remyelination in multiple sclerosis.