Is there A Multiple Sclerosis Epidemic And Is It The Result Of A Plethora Of Etiological Factors Or Of An As Yet Unknown Or Emergent Latent Risk Factor?

Bernd Krone, Institute of Virology, University Göttingen, Göttingen, Germany, and Laboratory Medicine Institute Kassel, Druseltalstrasse 61, 34131 Kassel, Germany, Email

A recent epidemiologic study by Ajdacic-Gross et al. might give an important impulse for research in the etiology of multiple sclerosis (MS) (1,2). The study has a very broad basis, using WHO world mortality statistics since 1950. It led the authors to claim that there is ‘unequivocal evidence for a veritable MS epidemic’ peaking in most countries in the 1920s. This study is important not only because of its very broad basis but also for its relatively new perspective on MS, enabling it to be used as a touchstone for current and future hypotheses on the etiology of MS. At the present time, however, there are several hypotheses that attempt to explain the data, but the question still remains whether MS is the result of a plethora of etiological factors or whether there is some as yet unknown or only emergent risk factor that is essential for the clinical manifestations of MS.

Our previous and current studies empasise a complex infectious background of MS (3) beside genetic encoded factors, in particular the human leucocyte antigens, and other environmental factors such as vitamin D deficiency, and smoking in the etiology of MS. We performed also studies on melanoma (4). Some observations encouraged us to follow the idea of parallels in the etiology of the two diseases. They led us to suggest a hypothetical melanoma-like neuromelanin (MLN) as the emergent latent risk factor in MS (5). In principle the melanin-based concept is promising and unifying, and can explain the spatial and temporal characteristics of the disease. Unfortunately, there is little or no neuromelanin (precursor of MLN) in the animals used for experimental models in MS. Future studies must verify the relations of diverse MS risk factors to MLN and verify the concept. Hopefully, an understanding of the complex etiology of MS might open the opportunity for prevention and rational therapies. In particular prevention by vaccinating against Epstein-Barr virus in early childhood is a perspective resulting from this concept.

1 Ajdacic-Gross V. Tschopp A, Schmid M, Bopp M, Gutzwiller F. Missed epidemics and missing links: international birth cohort trends in multiple sclerosis (2012) Eur J Neurol; doi: 10.1111/j.1468-1331.2012.03802.x.
2 Krone B, Ramagopalan SV (2012). Evidence for a multiple sclerosis epidemic? (Editorial to ref. 1). Eur J Neurol; doi: 10.1111/j.1468-1331.2012.03823.x.
3 Krone B, Oeffner F, Grange JM. (2009). Is the risk of muliple sclerosis releated to the ‚biography’ of the immune system? J Neurol 256: 1052-1060.
4 Krone B, Grange JM (2010). Melanoma, Darwinian medicine and the inner world. J Cancer Res Clin Oncol 136: 1787-1794.
5 Krone B, Grange JM (2011) Paradigms in multiple sclerosis: time for a change, time for a unifying concept. Inflammopharmacology 19: 187-195.


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