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Multiple Sclerosis Michele Hull Blackhawk Technical Institute

2 Multiple Sclerosis In 1868, Dr. Jean-Martin Charcot, a French neurologist, used the phrase, "Sclrose en plaques" to name the condition we later called Multiple Sclerosis. Although people with symptoms of the disease can be documented as early as the 1400s, Charcot was the first to give it a name and one of the first neurologists to study the disease. Charcot documented symptoms of several patients, including tremors, slurred speech, and difficulty walking and muscle spasms. When one of his patients died he discovered scarring in the nerve pathways of her brain tissue. This scarring, or plaques, are what he named the disease after. Although the understanding of this disease was in its infancy at this time, Charcot was the first to formulate a method for MS diagnosis: a triad of symptoms including nystagmus, intention tremor and scanning speech. Ten years later, in 1878, Dr. Louis-Antoine Ranvier discovered myelin, the protective sheath covering nerves. The nodes of Ranvier, gaps in the myelin sheath in nerve cells, were named after him. In the intervening 150 years we have seen many medical breakthroughs which have allowed us to expand our understanding of this disease. In the 1920s it was thought that MS was a mans disease, as women displaying the symptoms that would lead to a diagnosis were thought to be suffering from hysteria. In the 1940s it was thought that the cause of MS could be blood clots, and treatment consisted of drugs used to improve circulation. In the 1960s the focus changed to allergies, and vitamins and antihistamines were prescribed to treat it. In 1996, it was postulated that the disease could be an autoimmune response linked to a virus, and treatment with steroids became the norm. Today it is generally accepted as an immune-mediated disease. Scientists know that the myelin sheath is under attack from the immune system, and that damage to myelin

3 is what causes most of the physical manifestation of the disease. They are not certain, however, what triggers the immune system to attack the myelin. There are many different manifestations of MS, and they differ from patient to patient. We know that Multiple Sclerosis is not inherited. It also isnt contagious; nevertheless, it has been postulated that there may be a link between MS and viruses, but the medical community is uncertain exactly what the link may be. It affects more women than men (two-thirds of those who suffer from MS are female), and it is more prevalent among people with northern European ancestry. The majority of MS patients are diagnosed between the ages of 20 and 40. MS does not affect all the nerves in the body, but rather the nerves located in the brain and spinal column, and therefore it shows up differently from person to person. MS can go through periods of dormancy followed by periods in which it is active. Some of the symptoms that are commonly experienced by patients include tingling, numbness, pain, slurred speech and blurred or double vision. Since the most common form of MS is the relapsing/remitting type, there may be days, particularly in the early stages of the disease, in which the patient seems fine, followed by periods of relapse where they experience the symptoms listed, as well as extreme fatigue, muscle weakness, balance issues, muscle spasms, and paralysis (either temporary or permanent). Relapses can be triggered by heat or hot water, and extreme cold can be associated with dizziness and disorientation. One aspect of MS that tends to be overlooked is the development of cognitive changes, such as memory loss, trouble concentrating, or depression and mood swings. MS is not a terminal disease, but patients with the progressive form of MS (about 10% of all MS patients) eventually become severely disabled, and either wheelchair- or bed-bound. Patients with advanced, debilitating MS are at risk for depression and suicidal thoughts and behaviors. However, it is important to note that the vast majority of MS patients have the

4 relapsing/remitting form of the disease and are able to live lives that are, for the most part, pretty normal when they are in remission. There is ongoing research in the treatment of MS; doctors are continuing to seek out the underlying cause for the attack of myelin by the immune system, and at the same time they are looking for ways to treat the symptoms and halt progression of the disease. It is currently being postulated that people who develop MS are genetically susceptible to a reaction to environmental agents. What those agents are is unknown at this time, but the theory is that when certain people encounter certain environmental agents, it triggers an autoimmune response. It has also been noticed that MS tends to occur much more frequently in people of Northern European heritage; the farther from the equator, the higher the rates of MS. Scotland, for example, has the highest incidence of MS anywhere in the world. It has been noted that there is also a high incidence of Vitamin D deficiency among the 10,500 MS patients in Scotland. This has led some scientists to think that MS may be in some way correlated to a lack of vitamin D. Another possibility being examined is a link between viruses/bacteria, and the triggering of the autoimmune system. There is research going on currently on several viruses, among them measles, the human herpesvirus 6 (HHV-6), and Epstein - Barr virus. It is possible that future treatment of MS may include antiviral medications or perhaps stem cell treatments. 1 One study, published on April 11, 2013 and conducted by investigators at the Santa Lucia Foundation in Rome, Italy, stated that there is a correlation of the Epstein Barr virus and active periods of the MS disease in patients with relapsing-remitting multiple sclerosis (MMRS): The study, conducted by investigators at the Santa Lucia Foundation in Rome, Italy examined cytotoxic (CD8+) T-cells, which are cells that kill infected or abnormal cells in the body. They found an increased response to the antigens

5 produced by active EBV in the blood of MS patients during relapses, as compared with samples taken during periods of remission. Antigens are substances that the body sees as foreign or harmfulincluding toxins from viruses like EpsteinBarrand deploys an immune response to find and kill. Currently the FDA has approved several therapies for treatment of MS; interferon, immunoglobulins, and corticosteroids are among those in use today. It seems clear that there is still a lot of studying and work to be done in the treatment of MS; the struggle is complicated by the fact that MS does not have a single, easily defined cause. AIDS is an example of a disease which is triggered by a defined virus HIV. Multiple sclerosis, on the other hand, could be triggered by a number of factors environment, viruses, nutrition, or maybe something that has not yet been discovered. Until the trigger or triggers are defined, scientists will continue to try new treatments and attempt to prove new theories that may hold the key to arresting the progression of MS.

6 References Diagnosing MS. (2012). Retrieved 10/08/2013 from Donati D, Jacobson S. Viruses and Multiple Sclerosis. In: Brogden KA, Guthmiller JM, editors. Polymicrobial Diseases. Washington (DC): ASM Press; 2002. Chapter 6. Available from: Healthline: 4 Possible Causes of MS. (2013). Retrieved 11/26/2013 from Jean-Martin Charcot: The Father of Neurology. (2011). Retrieved 11/26/2013 from Mini Med School: Multiple Sclerosis. (2012). Retrieved 10/08/2013 from Northrop, D. E., & Frankel, D. National Multiple Sclerosis Society, Professional Resource Center. (2009). Nursing home care of individuals with multiple sclerosis (BR0053). Retrieved from National MS Society website: The History of multiple Sclerosis. (2011). Retrieved 11/26/2013 from

7 Endnotes

For a detailed discussion of the pathogenesis of the link between MS and viruses, see Donati D, Jacobson S. Viruses and Multiple Sclerosis. In: Brogden KA, Guthmiller JM, editors. Polymicrobial Diseases. Washington (DC): ASM Press; 2002. Chapter 6. Donati and Jacobson give a detailed description of how viruses can trigger autoimmune reactions leading to demyelination.