# An Overview of Transcranial Magnetic Stimulation and Its Application in Multiple Sclerosis
## 4 Overview of Multiple Sclerosis  
Multiple sclerosis is a chronic autoimmune disease of the central nervous system pathologically characterized by focal and CNS compartmentalized inflammation, demyelination, and axonal loss. It is estimated that 2.8 million people live with MS across the world, with a global increase in prevalence year after year [3]. Clinically, patients with MS often develop prominent motor impairment through their disease including weakness, spasticity, and gait dysfunction, reflective of focal demyelinating lesions involving central motor pathways of the brain and spinal cord [1]. While the pathophysiology of MS involves a heterogeneous spectrum of both focal and diffuse inflammatory and degenerative processes which are present at all disease timepoints, it is classically categorized into discrete clinical phenotypes which have diagnostic, prognostic, and therapeutic implications. These subtypes will be summarized below in Table 1. Only when biomarkers (such as TMS) are established as adequate surrogates of the underlying mechanisms of injury and repair will the field be able to move beyond these crude categorical clinical descriptors. The Use of TMS Measures in MS  
In this paper, several studies that have examined TMS measures in patients with MS have been compiled. Where applicable, any MRI measures were also included. The relationship between the TMS measures, clinical assessment measures, and/or MRI measures reported by each study has been summarized below in Table 2. Assessments of conduction both to the upper limbs and lower limbs using TMS have been reported within these studies. However, it is important to note that sensorimotor impairments of the lower limb are often prominent in patients with MS, and so they are the primary focus of many studies [37]. One potential limitation to the generalizability of studies assessing TMS and MS associations is that patients with various subtypes of MS are often grouped together, or limited to certain subtypes of MS. \begin{table}
\begin{tabular}{c c c} \hline \hline  & RRMS is the most common clinical phenotype of MS that affects approximately 85\% of patients. RRMS is dominated by unpredictable waves of focal inflammatory injury and demyelination, reflected by clinical relapses and the emergence of new lesions via MRI. Subsequent to this injury, varying degrees of repair and remission follow [36]. \\ \hline \multirow{4}{*}{**Primary Progressive MS** (**PPMS**)} & PPMS affects approximately 10\% of patients with MS. Thought to be reflective of more CNS compartmentalized injury, it is clinically characterized by worsening disability from initial onset, without clear clinical relapses, along with occasional plateaus and temporary improvements [36]. MRI scans may show silent or minimally symptomatic accumulation of white matter lesions. \\ \hline \multirow{4}{*}{**Secondary Progressive MS** (**SPMS**)} & With conventional therapies, approximately one half of patients with RRMS convert to SPMS after around a decade with the illness. SPMS is characterized by an initial relapsing disease course, followed by progression with (active) or without (non-active) occasional relapses and plateaus [36]. \\ \hline \hline \end{tabular}
\end{table} 
Table 1: A summary of clinical phenotypes of MS and their characteristics.