What Causes Multiple Sclerosis
Multiple sclerosis results from complex interactions between genetic susceptibility and environmental triggers—particularly Epstein-Barr virus infection—that lead to immune system dysregulation, causing pro-inflammatory B cells and T cells to attack the central nervous system and destroy myelin. 1, 2
Multifactorial Etiology
The cause of MS involves three interconnected components that must converge to trigger disease:
Genetic Susceptibility
- Over 200 single-nucleotide polymorphisms have been identified that increase MS risk, though genetic factors alone are insufficient to cause the disease 3
- Genetic predisposition creates vulnerability but requires environmental triggers for disease manifestation 4, 5
Environmental Triggers
Epstein-Barr virus (EBV) stands out as the key environmental trigger that initiates immune dysregulation in genetically susceptible individuals 1, 2. This represents the strongest evidence linking a specific pathogen to MS causation.
Additional environmental factors that increase MS risk include:
- Vitamin D deficiency and low sunlight exposure are consistently associated with increased disease risk 1, 2, 3
- Smoking contributes to disease development 3, 6
- Obesity shows causal association with MS risk 3
- Geographic location affects prevalence, with higher incidence in regions with lower sunlight exposure 1
Other infectious agents implicated (though with less definitive evidence than EBV) include human herpesvirus 6, varicella-zoster virus, cytomegalovirus, Helicobacter pylori, Chlamydia pneumoniae, and Mycoplasma pneumoniae 6, 7
Immunological Mechanisms
Once triggered, the pathogenic cascade involves:
- Activation and migration of pro-inflammatory B cells and T cells into the CNS, where they attack myelin 1, 2
- B cells contribute through antibody production and antigen presentation 2
- Myelin-specific CD4+ and CD8+ T cells drive autoimmune-mediated demyelination 2
- Innate immune cells and meningeal inflammation amplify the destructive process 3
Pathological Consequences
The immune attack produces two interconnected pathological processes:
- Inflammatory component: Autoimmune-mediated demyelination with focal degradation of the myelin sheath 1, 2
- Neurodegenerative component: Irreversible demyelination, axonal transection, neuronal loss, and progressive disability that begins early in the disease course 2
Clinical Pitfalls
A common misconception is that MS is purely inflammatory—the neurodegenerative component with axonal and neuronal loss begins early and progresses independently of relapses 2. This explains why current disease-modifying therapies, which primarily target inflammation, cannot fully halt disease progression or promote remyelination 1, 2.
The disease shows a long latent period from initial infection (particularly EBV) to symptom onset, followed by progressive acceleration, making early environmental exposures critical to understanding individual disease development 1.