Exact causes of MS are still elusive but both genetic and environmental factors have been attributed in the etiology of MS.
Genetics: Genome wide association studies (GWAS) have uncovered over 100 genetic loci associated with MS, accounting for ~30% of the disease risk. Majority of these genes belong to the immunological pathways. Among these, human leukocyte antigen HLA-DRB1*15.01 is the most significant genetic susceptibility locus for MS and may increase in the MS risk by threefold. MS has an overall familial recurrence rate of 20%. The concordance rate among monozygotic twins is 24-30% and in dizygotic twins is 3-5%. In addition to siblings, MS is also prevalent in first and second degree relatives.
Environmental factors: Smoking, low Vitamin D levels, and Epstein–Barr virus (EBV) infection are the best-known environmental factors contributing to MS.
Smoking: Cigarette smoking has shown to increase the risk of autoimmune diseases including MS. Duration as well as intensity of smoking independently increase the risk of MS. Smokers are twice as likely to develop MS in comparison to non-smokers. Moreover, passive smoking also increases the risk of MS.
EBV: A significant number of patients with MS show EBV responsive antibodies in their serum. Moreover, EBV-specific CD8+ T-cell responses are significantly higher in patients with MS than in healthy volunteers. How EBV infection contributes to MS is not clear and is a subject of research. EBV-infected B cells in meningeal follicles and in perivascular spaces of blood vessels in the white or gray matter of MS brains may induce a cytotoxic T lymphocyte response with the consequent damage to surrounding tissue.
Vitamin D: Vitamin D deficiency has been linked to MS. Studies have shown that a reduced risk of MS is associated with sunlight exposure and use of vitamin D supplements. Vitamin D may help with the symptoms of MS by suppresses proinflammatory TNFα, IL-12 and inducible NO synthase, and by inducing Th2 cells and anti-inflammatory IL-10 expression. Thus, correction of vitamin D deficiency may be useful in suppressing MS but further research is needed to validate these findings.
Other factors such as obesity, sedentary lifestyle, alcohol, and high consumption of salt have also been reported as risk factors for MS.
Autoimmune encephalitis: A diverse group of neuro-psychiatric disorders recognized recently, presenting acutely or sub acutely with alteration of consciousness, cognitive decline, seizure, abnormal movements.
Cytotoxic T lymphocyte: Lymphocytes that kill other cells such as cells infected with viruses or bacteria, and cancer cells.
Demyelinating condition: Condition of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves.
Epstein–Barr virus (EBV): Also known as human herpesvirus 4 (HHV-4), EBV belongs to viruses in the herpes family, and is one of the most common viruses in humans.
Genome wide association studies (GWAS): Examination of many common genetic variants in different individuals to see if any variant is associated with a trait.
Human leukocyte antigen (HLA): A gene complex encoding the major histocompatibility complex (MHC) proteins in humans.