Multiple sclerosis was originally described in 1868 by Dr. Jean Charcot in Paris. So, we’ve had nearly 150 years to study MS. That means we know everything we need to know about this disease, right? If anyone believes that, I’ve got a bridge in Brooklyn to sell you. Obviously, we have learned much about MS, but we still have much more to learn. Research from the past decade has changed the way we think about who gets MS, why they get it, and how we treat it.
Who Gets MS?
MS is considered an autoimmune disorder, in the same family as lupus, rheumatoid arthritis, Crohn’s disease, juvenile diabetes mellitus, and ulcerative colitis. With the exception of diabetes mellitus and ulcerative colitis, autoimmune diseases are much more common in women than men. In the past, women diagnosed with MS outnumbered men by 2.5 to 1. More recent surveys have shown a ratio of 4 to 1.
The reason MS is becoming more frequent in women is unclear, yet we do know that sex hormones (estrogen, progesterone, and testosterone) play a role in MS. The exception to this gender discrepancy in MS is primary progressive MS, which is more common in men. Later, we’ll discuss how sex hormones may be used as potential MS therapies.
MS has traditionally been thought of as a condition that affects Caucasians more than other races. While this still holds true, we are seeing many more African Americans, Hispanics, and other races diagnosed. Researchers in South and Central America are finding increasing rates of MS in those regions.
While MS remains very uncommon in Africa, we see a significant number of African Americans with MS here in the U.S. It is estimated that African Americans develop MS at half the rate of Caucasian Americans – one in 1,500 people, rather than one in 750. Studies have also shown that MS may follow a more aggressive course in African Americans.
Finally, while MS is typically diagnosed in young adults (ages 20 to 40), we are coming to a better understanding of the wide variation in age at the time of diagnosis. Teenagers and children represent a significant minority of the MS community (estimates of those diagnosed with MS before 18 range from 5 to 9 percent). The National MS Society recognized that caring for these young people presents unique challenges and helped establish centers of excellence for pediatric MS care across the country.
Why Do People Get MS?
Most research still points towards MS having both genetic and environmental causes. First-degree relatives (brothers, sisters, children, and parents) of a person with MS have a roughly 2.5 percent risk of MS in their lifetime. If one identical twin has MS, there is a one-third chance that the other will as well. These findings are consistent with a genetic contribution of some nature to the risk of MS.
MS is more common as one moves away from the equator, which may be due to various factors. Researchers propose that exposure to common viruses before age 15 may play a role in fooling the immune system and lead to an auto-immune disease like MS. These viruses may be more commonly encountered as we move away from the equator. Research has also suggested that low levels of vitamin D may be associated with a higher MS risk. Due to less sunlight exposure, vitamin D levels tend to be lower as we get further from the equator.
Several studies have shown that the majority of people with MS have low levels of vitamin D (as measured by 25 hydroxy vitamin D levels in the blood). We know that vitamin D plays an important role in bone health, but its role in the immune system is equally important.
Increased levels of vitamin D are associated with increased numbers of T regulatory cells. These cells may help dampen the immune over-activity seen in disorders like MS. Vitamin D is obtained both through diet and sunlight exposure. Correcting Vitamin D deficiencies in people with MS may make a difference. A small study at the University of Toronto demonstrated fewer relapses in people with MS treated with oral Vitamin D.
Recently our working hypothesis of how MS occurs has been challenged by Paolo Zamboni, M.D., a cardiovascular surgeon in Italy. Dr. Zamboni discovered evidence of inadequate venous outflow from the central nervous system in people with MS and has labeled the condition chronic cerebrospinal venous insufficiency (CCSVI). He believes that CCSVI causes iron deposition around small veins in the brain and spinal cord, leading to inflammation and demyelination.
This condition has been treated using a procedure known as the “Liberation Treatment.” In this procedure, stents are used to open blocked veins that drain blood from the brain and spinal cord. Studies to further assess the relationship between CCSVI and MS are underway in the U.S. Stanford is exploring the possibility of a clinical trial and the University of Buffalo has already announced preliminary data from its first study.
Though the success of this procedure will need to be evaluated over time, people who have had the procedure are posting their results at www.thisisms.com. As with any potential medical breakthrough, caution and careful consideration of the risks and benefits of new therapies are warranted.
How Do We Treat MS?
Management of MS can be divided into treating relapses, improving symptoms, and altering the long-term course of MS. We’ve not seen too much change in the way we treat relapses, but there are advances in the other two areas.
In January of this year, the FDA approved Ampyra® (dalfampridine) for use in people with MS. This twice daily oral prescription drug was shown to improve walking as measured by walking speed in MS. In two trials of the drug, about 40 percent of people demonstrated improved walking. Ampyra is the FDA-approved version of 4- aminopyridine (4-AP), a drug that has been used in MS for years through compounding pharmacists. There is a small risk of seizures with Ampyra.
Many drugs are being researched to alter the course of MS. These include the oral medications cladribine, fingolimod, teriflunomide, laquinamod, and BG000012. Some drugs in research, such as alemtuzumab, appear very effective in relapsing forms of MS. As these new therapies become available, we’ll need to ask ourselves several questions. How does this drug compare to existing therapies? Is it safe? Is it convenient?
Stem cell research in MS continues on many fronts. Several MS centers in the U.S. and Canada are using the patient’s own autologous stem cells to “reboot” the immune system. Stem cells may hold potential for slowing or reversing the course of MS. Many people with MS have been drawn to explore cell therapies being offered abroad, in places like China or Costa Rica. These for-profit centers do not participate in organized research. This is definitely a case of caveat emptor, or “buyer beware.”
We mentioned CCSVI earlier. Time and research will reveal whether this is truly an important discovery in our under-standing of MS. Perhaps it contributes to the pathology of MS in many ways or in only a few. The medical community working with the MS community has the duty to promote legitimate research into new ideas, while at the same time guarding against the risk of unproven therapies.
Finally, the association between sex hormones and MS activity in women is best illustrated by how well some women with MS do during the second and third trimesters of pregnancy. (It should be noted that the risk of relapses is somewhat higher for three to six months after the baby is born.) Research is pointing towards estriol and progesterone as being at least partly responsible for this protective effect. Early studies with estriol confirmed this protective effect in women with MS and a much larger trial is in progress.
In Conclusion
The changing face of MS presents both challenges and opportunities. We’ve long suspected that this thing we call MS may actually be a mixture of different pathologies and causes. The next several years should be exciting as we look at new and improved treatments and even theories that challenge our basic concepts of what MS is.
Ben Thrower, M.D., is the senior medical advisor for the MSF.
(Last reviewed 5/2010)