Transcranial Magnetic Stimulation as a Potential Biomarker in Multiple Sclerosis: A Systematic Review with Recommendations for Future Research

Nicholas J Snow, Katie P Wadden, Arthur R Chaves, Michelle Ploughman, Nicholas J Snow, Katie P Wadden, Arthur R Chaves, Michelle Ploughman

Abstract

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Disease progression is variable and unpredictable, warranting the development of biomarkers of disease status. Transcranial magnetic stimulation (TMS) is a noninvasive method used to study the human motor system, which has shown potential in MS research. However, few reviews have summarized the use of TMS combined with clinical measures of MS and no work has comprehensively assessed study quality. This review explored the viability of TMS as a biomarker in studies of MS examining disease severity, cognitive impairment, motor impairment, or fatigue. Methodological quality and risk of bias were evaluated in studies meeting selection criteria. After screening 1603 records, 30 were included for review. All studies showed high risk of bias, attributed largely to issues surrounding sample size justification, experimenter blinding, and failure to account for key potential confounding variables. Central motor conduction time and motor-evoked potentials were the most commonly used TMS techniques and showed relationships with disease severity, motor impairment, and fatigue. Short-latency afferent inhibition was the only outcome related to cognitive impairment. Although there is insufficient evidence for TMS in clinical assessments of MS, this review serves as a template to inform future research.

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Copyright © 2019 Nicholas J. Snow et al.

Figures

Figure 1
Figure 1
Flow chart detailing study screening.
Figure 2
Figure 2
Results of study quality and risk of bias assessment. Risk of bias assessment was conducted using a modified version of the National Institutes of Health (NIH) “Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies” [53]. To guide decisions on overall study quality from the NIH tool [53], the Cochrane Risk of Bias Tool was used [62]. An article was deemed to have a high risk of bias (i.e., low quality) if one or more criteria from the NIH tool was unmet and marked “N,” unclear risk (i.e., moderate quality/risk) if one or more criteria were ambiguous and marked “U” and no criterion was marked “N”, and high quality (i.e., low risk) if all 14 criteria were clearly met and marked “Y.” Key confounding variables can be found in .
Figure 3
Figure 3
Summary of (a) transcranial magnetic stimulation (TMS) and (b) clinical outcome measures from studies reviewed. The horizontal axis indicates the outcome measure of interest, and the vertical axis represents number of studies utilizing each outcome measure. The black vertical bars (a and b) represent studies comparing both participants with multiple sclerosis (MS) and healthy control participants (HC). The white vertical bars (a and b) represent studies with statistically significant differences between MS and HC groups. The grey vertical bars (a and b) represent studies that found statistically significant correlations between TMS and clinical outcome measures in participants with MS. The hatched bar (b only) represents studies examining clinical outcome measures in MS participants alone. AMT: active motor threshold; CSP: cortical silent period; iSP: ipsilateral silent period; MEP: motor-evoked potential; RMT: resting motor threshold; CMCT: central motor conduction time; ICF: intracortical facilitation; IHI: interhemispheric inhibition; LICI: long-interval intracortical inhibition; PMd-M1: dorsal premotor cortex-primary motor cortex interactions; SAI: short-latency afferent inhibition; SICF: short-interval intracortical facilitation; SICI: short-interval intracortical inhibition; TST: triple stimulation technique.

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