Multiple Sclerosis Risk Factors and Pathogenesis

Bardia Nourbakhsh, MD, MAS; Ellen M. Mowry, MD, MCR, FAAN, FANA Multiple Sclerosis and other CNS Inflammatory Diseases p. 596-610 June 2019, Vol.25, No.3 doi: 10.1212/CON.0000000000000725
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PURPOSE OF REVIEW This article summarizes recent advances in the identification of genetic and environmental factors that affect the risk of developing multiple sclerosis (MS) and the pathogenic processes involved in acute relapses and relapse-independent disability progression.

RECENT FINDINGS The number of single-nucleotide polymorphisms associated with increased risk of MS has increased to more than 200 variants. The evidence for the association of Epstein-Barr virus infection, vitamin D deficiency, obesity, and smoking with increased risk of MS has further accumulated, and, in cases of obesity and vitamin D deficiency, the evidence for causal association has strengthened. Interactions between genetic and environmental factors have been studied more extensively. Dietary factors and changes in the gut microbiota are emerging as possible modulators of the disease risk. Several processes important to MS pathogenesis have been newly investigated or investigated more comprehensively, including the role of B cells, innate immune cells, meningeal inflammation, cortical and gray matter demyelination, and early axonal and neuronal loss.

SUMMARY MS is a complex disease in which the interaction between genetic and environmental factors causes a cascade of events, including activation of the adaptive and innate immune system, blood-brain barrier breakdown, central nervous system demyelination, and axonal and neuronal damage with variable degrees of repair. These events manifest as potentially reversible focal neurologic symptoms or progressive nonremitting physical and cognitive disability, or both. Advances in the understanding of the risk factors and pathogenic mechanisms of MS have resulted in improved therapeutic strategies. The results of ongoing or future studies are needed to successfully and fully translate these advances into clinical practice.

Address correspondence to Bardia Nourbakhsh, 600 N Wolfe St, Pathology 627, Baltimore, MD 21287, [email protected].

RELATIONSHIP DISCLOSURE: Dr Nourbakhsh has served on a scientific advisory board for Jazz Pharmaceuticals Inc and has received research/grant support from the National Multiple Sclerosis Society and the Patient-Centered Outcomes Research Institute. Dr Mowry serves as an editor for Frontiers in Neuroepidemiology, ISRN Neuroscience, and Neuroscience Journal. Dr Mowry receives research/grant support from Biogen, the Department of Defense, the National Multiple Sclerosis Society, Sanofi Genzyme, and Sun Pharmaceuticals Industries Ltd and publishing royalties from UpToDate, Inc.


© 2019 American Academy of Neurology.