Transcranial magnetic stimulation outcomes as biomarkers of multiple sclerosis disease progression: A structured literature review

Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) disease and a leading cause of disability in young adults. Chronic disability progression is an unmet challenge for persons with MS and an area of interest for the development of biomarkers. Transcranial magnetic stimulation (TMS) is a putative technique for the development of MS biomarkers. However, TMS outcomes have not been extensively reviewed as biomarkers of disability progression in MS to date. This structured literature review assessed longitudinal and cross-sectional studies of TMS and disability progression in MS. Of the TMS techniques reviewed, central motor conduction time (CMCT), motor evoked potential (MEP) onset latency, and MEP amplitude demonstrated the best clinical performance as markers of CNS demyelination and neuro-axonal damage. While studies showed notable cross-sectional differences in TMS outcomes between persons with progressive and relapsing MS, these findings were less well-supported by longitudinal studies. Across studies, effect sizes were variable, sensitivity and specificity were underreported, and correlations with disability outcomes were heterogeneous. Studies were limited by small sample sizes, short follow-up periods, lack of standardized disability progression definition and TMS methods, and low reporting of diagnostic accuracy. We found insufficient evidence to presently justify the use of TMS techniques as biomarkers of MS disease progression. Future studies should address current limitations.