Multiple Sclerosis

Definition of Disease
A chronic inflammatory disease involving degeneration of central nervous system (CNS) myelin, scarring or formation of plaque, and loss of axons. 0.1% of the population affected, 2.1 million worldwide, higher in whites, and the etiology is unknown. MS is the most prevalent CNS demyelinating disorder.

Pathphysiology
MS is described as occurring when a previous infectious insult to the nervous system has occurred in a genetically susceptible individual with an abnormal CNS immune (Mccance et al., 2014). Auto-reactive T and B cells recognize myelin autoantigens and trigger inflammation in the CNS, leading to irreversible tissue damage: ogliodendrocyte injury, demyelination, and axonal degeneration (Mccance et al., 2014). MS degeneration process begins early and continues to progress throughout life.

Immunopathology (Gold et al., 2011)
Derived from the experimental autoimmune encephalomyelitis animal model (EAE) (Constantinescu et al., 2011). Following environmental triggers and genetic susceptibility, activation of myelin specific auto-reactive CD 4+ and CD8+ T cells cross blood-brain barrier and enter the CNS and attack myelin (Mccance, 2014). Process is driven by the expression of cell surface integrins (VLA-4) on inflammatory cells that mediate their binding to the vascular cell adhesion molecule (VCAM-1) expressed on endothelial cells. VCAM-1 expression is induced by TNF-α and in IFN-γ during inflammation. Matrix metalloproteases (MMPS) are released by the Tcells to facilitate passage through the extracellular matrix.

After entry into the CNS, T cells are reactivated on encountering CNS-related auto-antigentic peptides within class 2 molecules of the MHC expressed by antigen/dendritic cells. Production of IL-17 by Th17 cells play an important role within this process. Myelin disruption occurs, leading to additional inflammation and activation of complement and specific B lymphocytes to site of tissue injury.

Genetics
Not inherited in a Mendelian fashion, first degree relatives have a 1-5 times increased risk of MS, while the concordance rate in monozygotic twins is 35% (Gold & Wolinsky, 2011).

HLA
A genetic link exist exist in the human leukocyte antigen (HLA) complex: a large cluster of genes responsible for many immune functions (Mccance et al., 2014). Patients carrying the class 2 major histocompatability complex (MHC) HLA-DR2 genes are susceptible to MS (Gold et al., 2011). Several risk loci beyond the MHC have been identified, including the interleukin-7 (IL-7) receptor, interleukin-2 receptor alpha chain (IL2RA) and CD58 (Gold et al., 2011).

Epidemiology
Along with several genetic polymrophisms involved, Vitamin D deficiency, cigarette smoking, and Epstein-Barr virus infection are environmental risk factors.

Sign and Symptoms
MS occurs between 20 and 40 years of age (peak at 30 years). Male to female 1:2.