# An Overview of Transcranial Magnetic Stimulation and Its Application in Multiple Sclerosis
## 5 TMS Measures in the Diagnosis and Evaluation of MS  
In individuals with MS, measures of CMCT are commonly abnormal due to dysfunction involving the corticospinal tract. Numerous studies [31; 38; 39; 40; 41; 46; 48; 49; 50; 51; 53; 58] have consistently demonstrated markedly prolonged CMCT values in groups of MS patients when compared to control groups. The correlation between CMCT and disability level in MS patients has also been extensively reported, potentially lending credence to CMCT as a marker that could reflect the integrity of the corticospinal pathway. The Expanded Disability Status Scale (EDSS) is the most commonly reported clinical measure, and many studies report a positive association between CMCT and EDSS [31; 38; 39; 41; 44; 45; 50; 51]. One criticism of CMCT and EDSS correlations is that while CMCT can be derived from both upper and lower limb TMS measures, EDSS scores, especially within EDSS 4-6, are more greatly affected by lower limb function [60; 61]. CMCT has also been reported to have an association with other measures of disability or impairment such as the Scripps Neurologic Rating Scale (SNRS), Ambulation Index (AI), and Multiple Sclerosis Functional Composite Measure (MSFC), as well as those involving strength [38; 39; 50; 53]. However, one study that utilized the Multiple Sclerosis Impact Scale (MSIS, a patient reported score of the physical impacts of MS) did not find any association with CMCT in MS patients [48]. CMCT represents a useful means of objectively quantifying motor dysfunction in MS, and may have utility in both diagnosis and prognostication, secondary to current clinical standards. As shown in Table 2, abnormal measures of CMCT in patients with MS are frequently reported. However, a number of studies have also found decreased MEP amplitudes, prolonged MEP latencies, and increased MT in patients with MS [16; 31; 40; 42; 43; 44; 46; 48; 49; 51; 54; 55; 56]. The utility of the MT lies in its ability to serve as potential reflection of cortical excitability, which is often decreased in MS patients. In addition, a few studies have specifically examined MEP amplitude and latency in the context of fatigue and MS patients. A study by [PERSON] et al. [42] involving 16 MS patients with weakness and 16 with normal motor function examined differences in cortical excitability resulting from facilitation via muscle activation of the non-exercised extremity. The study reported that following activation of the homologous non-exercised extremity after fatiguing exercise, MEP amplitude is increased in control and MS patients with normal motor function, but not MS patients with weakness [42]. It is hypothesized that the corpus callosum may play a role in the facilitation of motor responses by inhibiting interneurons that are GABAergic to cortical motor neurons. Thus, the absence of a significant MEP increase following facilitation in MS patients with weakness may suggest a loss in callosal integrity [42]. Another study involving fatigue in MS patients by [PERSON] et al. [56] involved 13 MS patients who reported high fatigability and 13 with low perceived fatigability. Following an exhaustion task, they reported that the highly fatigued group had decreased MEP amplitudes and prolonged MEP latencies, as well as a greater decline in maximal voluntary contraction force. The same paper reported that fatigue severity on the FSS was related to prolonged MEP latencies. However, this was \begin{table}
\begin{tabular}{c c c c c} \hline
**Author et al.** & **Year** & **TMS and MRI** & **Clinical Assessment** & **Relationship between Measures** \\ \hline  & & & & Prolonged CMCT across all four groups (MS controls, MS tremor, MS with pure dysmetria, MS with mixed tremor and dysmetria). \\ \hline [PERSON] et al. [59] & 2022 & CMCT and MEP & 9 HPT & Changes in 9 HPT performance were found to be correlated with changes in CMCT and MEP latency, but only on the left side. \\ \hline  & & & & \\  & & & & \\  & & & & \\ \end{tabular}
\end{table}