Objective: Considering the characteristics of multiple sclerosis (MS) disease and its impact on motor disability, this study aims to assess the functional integrity of the corticospinal tract by examining motor evoked potentials (MEPs), Expanded Disability Status Scale (EDSS) scores, magnetic resonance imaging (MRI) lesion counts, and psychological and physical status reported by patients with relapsing-remitting MS (RRMS). Methods: In 23 RRMS subjects (17 in the follow-up), the corticospinal tract for upper and lower extremity muscles was longitudinally studied over 2 years using navigated transcranial magnetic stimulation (nTMS) and MEP scoring. MRI parameters included lesion detection by applying McDonald's criteria and additional lesion detection of the corticospinal tract. EDSS scoring included evaluation of the EDSS general score, EDSS functional pyramidal score, and EDSS functional pyramidal score for each extremity. Longitudinal analyses of nTMS (MEP), EDSS, and MRI parameters were conducted using linear mixed models with time, sex, age, and disease duration as fixed effects and individual-specific random intercepts. The correspondence of MRI and nTMS scoring with the EDSS pyramidal scoring was tested using McNemar's or Fisher's exact test. Results: RRMS patients with altered MEP latency had significantly higher general EDSS scores (β = -2.06, p = 0.006) and overall pyramid EDSS scores (β = -1.96, p = 0.002) compared to those with non-altered MEP latency. This difference was also observed in lower extremity pyramid EDSS scores, with higher scores in the right (β = -1.70, p = 0.001) and left leg (β = -1.50, p = 0.032) in the altered MEP latency group. RRMS patients with altered MEP latency had significantly more lesions in the corpus callosum (β = 2.38, p = 0.03) compared to subjects with non-altered MEP latency findings. The correspondence of MRI and nTMS (MEP latency) with EDSS scoring was confirmed. Conclusions: RRMS subjects with altered MEP latency findings (prolonged MEP latency or absent MEP response) compared to subjects with non-altered MEP latency findings, had higher EDSS scores in lower extremity muscles as well as a higher number of lesions in the corpus callosum. This is the first longitudinal nTMS study to perform four-limb cortical mapping of corticospinal tract integrity in RRMS. The study opens perspectives for the nTMS as an objective method for longitudinally assessing MS motor disability.

Background: ClinicalTrials.gov identifier: NCT04604041.