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DEBATE: Are infections key environmental factors in MS? CON View SEE also PRO POSITION and COMMENTARY

Etiology and Pathogenesis of MS

October 30, 2010


Congress:The 4th World Congress on Controversies in Neurology (CONy)
Presenter:A. Chaudhuri

Multiple Sclerosis (MS) is a chronic neurological disorder, which ranks second to trauma, as a cause of disability among young people in the western world. The cause of MS is unknown. A hypothetical autoimmune model of pathogenesis has been assumed based on superficial resemblance of the disease with acute disseminated encephalomyelitis (ADEM) and its animal model, experimental allergic encephalomyelitis (EAE). There is little evidence that treatment paradigms based on an autoimmune pathogenesis of MS has delivered long-term tangible benefit to patients over the years, although it has been associated with treatment- related fatalities and serious complications.
Infection and immunisation are two major environmental risks for ADEM. However, infection does not appear to be a key risk factor in MS which is postulated to be a metabolically dependent neurodegenerative disorder1. It is essential to look beyond autoimmunity to grasp the key risk factors in MS and develop effective strategies to prevent the disease2.
It is acknowledged from twin studies that genetic role in MS is at best low and the major risk is environmental. The best proof of low genetic susceptibility is the substantially higher incidence of the disease seen among second generation African and Asian population born to parents migrating to the northern European countries. A legitimate environmental risk factor for MS must, therefore, explain the following key epidemiological features of the disease:
• geographic prevalence with a striking latitudinal gradient in both northern and southern hemispheres
• significantly higher prevalence in women (F: M currently approaching 3:1) • risk of the disease (and the reversal of risk) associated with population migration
before the late teenage years • relatively slower disease progression in cases acquired in paediatric life • season of birth effect suggesting a prenatally acquired risk of the disease in utero • non-transmissibility of the disease
There is no single infectious agent which can meet these requirements. Epstein Barr Virus (EBV) is probably the only infectious agent which comes somewhere close to meet these requirements, but fails as the primary environmental factor because of two reasons: EBV infection alone does not explain the reduction in the risk of the disease among migrants from high to low prevalence areas; second, it cannot explain the observation that the risk of MS during the ages of 6-15 years is inversely related to solar exposure (ultraviolet radiation)3. EBV infection is also unlikely to be the cause of paediatric onset MS between the age of 5-12 years 4. Non-EBV infections are even less likely to account for the observed epidemiological features of MS.
What emerges from the epidemiological data is the singular fact that vitamin D/solar exposure is the single most important and modifiable environmental risk factor for MS. Vitamin D hypothesis explains the key epidemiological features of the disease, the antenatal risk and the protective effect of vitamin D-rich diet in northern population. Clearly, there can be little doubt that vitamin D supplementation should be routinely offered during pregnancy and
childhood to prevent MS 5. References
1. Chaudhuri A, Behan PO. Multiple sclerosis is not an autoimmune disease. Arch Neurol 2004 ; 61: 1610- 1612.
2. Chaudhuri A, Behan PO. Multiple sclerosis: looking beyond autoimmunity. J R Soc Med 2005; 98: 303-306.
3. van der Mei IAF, Posonby A-L, Dwyer T, et al. Past exposure to sun, skin phenotype and risk of multiple sclerosis: case control study. BMJ 2003; 327: 316-321.
4. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol 2007; 61; 288-299.
5. Chaudhuri A. Why we should use routine supplementation of vitamin D in pregnancy and childhood to prevent multiple sclerosis. Med Hypotheses 2005; 64: 608-18.

Category: Neurology; Multiple Sclerosis; pathogenesis;