Neurology Practice Changers 2014

Bret S. Stetka, MD; Andrew N. Wilner, MD


December 08, 2014

In This Article

Understanding MS

The etiology of multiple sclerosis (MS) is far from fully understood—but it's becoming increasingly clear.

It's been thought for years that MS might have an autoimmune component, and growing evidence suggests that this is the case. At this year's MSBoston 2014 conference, Dr David Hafler from Yale University School of Medicine in New Haven, Connecticut, proclaimed that there is no longer any doubt that MS is an immune-mediated disease with genetic and environmental components. And there's plenty of evidence backing up this claim: Over 180 genetic variants have now been linked with MS, most of which are immune genes; there is an increase in autoreactive white blood cells in MS; and—most important—if you treat MS patients with anti-immune therapies, they improve considerably.[9]

What some experts don't agree on is whether or not the autoimmune activity is the primary pathology in MS. Stephen Krieger, MD, assistant professor at Icahn School of Medicine at Mount Sinai in New York, New York, commented to Medscape:

I believe the autoimmune nature of MS is a crucial element in the disease pathogenesis as we understand it.... The piece that remains incompletely explained is whether there are additional factors driving a neurodegenerative process. This is suggested by the failure of our immune-modulating agents in primary progressive MS and secondary progressive MS without evidence of inflammatory activity. However, no underlying non–immune-mediated mechanisms have been worked out, whereas a great many of the autoimmune mechanisms have.

And it gets still more complicated. As a number of studies [10,11,12] presented at MSBoston found, the microbiota—the trillions of bacteria, fungi, and other single-celled organisms that reside in our gastrointestinal tracts—also appears to influence MS. This has also been shown in other autoimmune disorders, including rheumatoid arthritis and inflammatory bowel disease. Patients with MS appear to have unique proinflammatory gut flora, whereas work in mice has shown that yeast ingestion can prevent the development of MS. Dietary, probiotic, and antibiotic therapy in MS might be a ways away, but these approaches appear worth pursuing.

Environmental factors, including increased salt consumption, vitamin D deficiency, Epstein-Barr virus exposure, and smoking, also appear to increase MS risk. The mechanisms behind these relationships are currently unknown; however, direct interaction with the immune system, or perhaps their influence on the gastrointestinal microbiome, are etiologic possibilities.

Dr Hafler explained that the immune process of MS begins outside the brain, which is affected after peripheral T cells enter the central nervous system via the choroid plexus and cerebrospinal fluid. These are followed by Th17 T cells and Th1 cells that enter the brain parenchyma, which results in chronic inflammation. However, many more details need to be understood to fully explain the pathogenesis of MS inflammation and neurodegeneration.


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