Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis

Abstract

In individuals with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) may be employed to assess the integrity of corticospinal system and provides a potential surrogate biomarker of disability. The purpose of this study was to provide a comprehensive examination of the relationship between multiple measures corticospinal excitability and clinical disability in MS (expanded disability status scale (EDSS)). Bilateral corticospinal excitability was assessed using motor evoked potential (MEP) input-output (IO) curves, cortical silent period (CSP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and transcallosal inhibition (TCI) in 26 individuals with MS and 11 healthy controls. Measures of corticospinal excitability were compared between individuals with MS and controls. We evaluated the relationship(s) between age and clinical demographics such as age at MS onset (AO), disease duration (DD) and clinical disability (EDSS) with measures of corticospinal excitability. Corticospinal excitability thresholds were higher, MEP latency and CSP onset delayed and MEP durations prolonged in individuals with MS compared to controls. Age, DD and EDSS correlated with corticospinal excitability thresholds. Also, TCI duration and the linear slope of the MEP amplitude IO curve correlated with EDSS. Hierarchical regression modeling demonstrated that combining multiple TMS-based measures of corticospinal excitability accounted for unique variance in clinical disability (EDSS) beyond that of clinical demographics (AO, DD). Our results indicate that multiple TMS-based measures of corticospinal and interhemispheric excitability provide insights into the potential neural mechanisms associated with clinical disability in MS. These findings may aid in the clinical evaluation, disease monitoring and prediction of disability in MS.

Keywords: Brain; Corticospinal excitability; Expanded disability status scale (EDSS); Human; Multiple sclerosis; Transcranial magnetic stimulation.

Conflict of interest statement

Conflict of interest statement

None of the authors have potential conflicts of interest to be disclosed.

Copyright © 2015 Elsevier B.V. All rights reserved.

Figures

Fig. 1

Mean values of all individuals in MS (black bars) and healthy control (white bars) groups. (A) Resting motor threshold (RMT) expressed as a percentage of maximum stimulator output (%MSO). (B) Active motor threshold (AMT) expressed as %MSO. (C) MEP latency shown in milliseconds. (D) Cortical silent period (CSP) onset shown in milliseconds. (E) Motor evoked potential (MEP) input-output curve data displaying MEP duration in milliseconds across TMS intensity. Bars represent standard error of the mean. *p < 0.05.

Fig. 2

Scatterplots demonstrating the relationship with disease duration (DD), EDSS and TMS-based neurophysiological measures. (A–B) Relationships between DD (years) and (A) RMT (%MSO) and (B) age in MS. (C–D) Relationship between EDSS and (C) iSP duration (ms) and (D) MEP IO curve slope. DD was correlated with RMT and age and EDSS was correlated with iSP duration and MEP IO curve slope. *p < 0.05.

Fig. 3

Partial plots generated by hierarchical regression analyses demonstrating the relationship with age of onset (AO), disease duration (DD), TMS-based neurophysiological measures and EDSS. Panels A–B depicts the relationship between EDSS with AO (years) and DD (years). Panels C–D depicts the relationship between iSP duration and linear slope of the MEP IO curve and EDSS. Asterisks indicate statistically significant (p < 0.05) ΔR2 value in the hierarchical regression models.