As a chronic disease of the central nervous system (CNS), multiple sclerosis (MS) is characterized by a complex interplay between inflammation, demyelination, remyelination, gliosis, and neuronal injury.¹ it continues to be a major cause of acquired neurologic disability in young adults worldwide, particularly in people of northern european origin.² it affects women with twice the frequency of men and the average age of diagnosis is 37 years.³ The worldwide total estimated prevalence for the past three decades is 83 cases/100,000 population.⁴The clinical course of MS is heterogeneous, with variability both between and within patients, and has been categorized as clinically isolated syndrome (CIS), relapsing–remitting MS (RRMS, which accounts for 85 % of MS patients in the initial disease course), primary progressive MS (PPMs), and secondary progressive MS (SPMS).^5,6 RRMS is characterized by relapses, symptoms of which include numbness, blurred vision, difficulty walking, fatigue, and pain. symptoms are usually temporary and are followed by periods of remission.⁶The immunopathogenesis of MS is thought to be heterogeneous; however, the inflammatory demyelinating plaque is characteristic of all forms of MS.⁷ immune-mediated injury to myelin and oligodendrocytes may occur when peptides in myelin attach to the cleft of major histocompatibility complex (MHC) class ii molecules on antigen-presenting cells (APCS) including macrophages, monocytes, and dendritic cells.⁸ Activation of APcs can trigger an immune response against the bound antigen and leads to secretion of pro-inflammatory cytokines and the differentiation of naive cD4+ T cells into T-helper 1 (Th1) and T-helper 17 (Th17) cells, resulting in inflammation and autoimmunity. Th1 and Th17 cells are capable of migration into the cns and have been identified in active lesions.^9,10 Th1 cells undergo continued proliferation and secretion of pro-inflammatory cytokines, leading to myelin damage and neuronal loss. further activation of resident microglia can lead to cross-reactivity, which maintains inflammation and further damage to the myelin sheath.¹¹ impaired function of regulatory T cells (Tregs), which act against autoimmunity, allows further pathologic activation of autoreactive T cells and exacerbates the feedback loop that causes continual damage to the cns.¹² Additionally, activated B cells appear to be participants in the creation of myelin lesions by producing antibodies that mediate and promote demyelination.<sup>13


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