Multiple Sclerosis Overview

Multiple Sclerosis (MS), historically named for the "multiple scars" or lesions found on post-mortem neural tissue, is a neurodegenerative disease in which prolonged inflammation damages the myelin insulation of CNS neurons. The cause is not directly known, although theories state it could be a combination of a viral infection (such as measles, Epstein Barr), environmental stressors, and a genetic predisposition (especially if primary relatives suffer from autoimmunity) are likely responsible.

Interestingly, MS has a younger onset (ages 15 to 50) than the other neurodegenerative diseases we have discussed, and also has a positive correlation with increasing latitudes from the equator. This is associated with the finding that Caucasians in North American and Europe have a higher prevalence than Africans and other cultures located around the equator. Researchers believe Vitamin D deficiencies may play a role in susceptibility to the disease.

The most common type of MS is Relapsing-Remitting MS (RRMS), comprising around 80% of the MS population. Gender plays a role in this type as females are 3x more likely to suffer from RRMS than males. People with RRMS tend to experience temporary bouts or exacerbations of symptoms lasting up to three months before returning to a recovered or attenuated state. The most common symptoms include:

- Sensory disturbances (numbness, tingling)

- Optic neuritis (inflammation of optic nerve resulting in vision impairment)

- Diplopia (double vision - think Foreigner's 1978 album)

Primary-Progressive MS is second highest in prevalence with 20% of MS population and is characterized by a slow onset and gradual accumulation of neurological damage. Other types differ in severity, as Secondary-Progressive MS results from untreated RRMS and has more severe symptoms during disease exacerbation and Malignant MS describes a sudden onset and rapid destruction of neural tissue. Clinicians also observe a Benign type in which there are few attacks or symptoms over a period of decades.

INFLAMMATION - What is it's role?

Another interesting finding regarding MS is that the inflammatory process that destroys the myelin and thus causes the degeneration and debilitating cognitive symptoms, also serves a regulatory role supporting myelin deposition. Although it is the myelin-specific T and B cells that damage the neurons, these same lymphocytes activate local microglial cells to secrete IL-12 inhibitors and anti-inflammatory prostaglandin E2. TNF-a, usually the bearer of bad news in inflammatory disorders, also contributes in a regenerative manner by inducing the proliferation of oligodendrocytes (the myelin producing cells in the CNS).

Thus, there are components of the Th1 type response that are actually helping to limit and control the inflammation in active lesions. This observation is supported in the result that treating mice induced with experimental autoimmune encephalomyelitis (EAE) with interferon gamma (pro-inflammatory cytokine) antibodies, the morbidity rate increased from 20% to 80%. Furthermore, when researchers attempt to block TNF-a, similar increases in exacerbation is seen as well as when Th2 responses are enhanced in the absence of a Th1 response.

Research has much to discover regarding the inter-workings of the multiple sclerotic inflammatory process. Results indication exactly what is being attacked (specific myelin antigens vs. oligodendrocyte surface markers), and how the blood brain barrier's pathology and degradation plays a role in lymphocyte and monocyte migration and edema would be particularly important in making beneficial steps towards future treatments.

Sources:

www.msassociation.org

Martino G, et al. Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurology 2002; 1: 499-509