MULTIPLE SCLEROSIS. Megan Snyder INTRODUCTION TO EPIDEMOLOGY

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1 MULTIPLE SCLEROSIS Megan Snyder INTRODUCTION TO EPIDEMOLOGY

2 Snyder 1 Personal Connection to Multiple Sclerosis Multiple sclerosis (MS) is an extremely painful disease of which not enough is understood. Two of my aunts have had this chronic disease and have dealt with many complications. While not directly related to either of them, having watched them suffer the symptoms during and after their attacks has encouraged me to learn more about this disease and the many new treatments which are currently being developed. Description of the disease. Multiple Sclerosis is a chronic disease which affects the central nervous system. The disease starts to present symptoms anywhere between the ages of twenty and forty. The primary cause of the disease is unknown but it is thought to be an autoimmune disease triggered by a combination of genetic and environmental factors or a possible virus interaction. The disease affects the brain and spinal column when T cells attack the myelin sheath which surrounds and protects the ends of nerve fibers 1. Although the marker antigens have not been identified for multiple sclerosis, it is believed that T-cells are responsible for the destruction of the myelin sheath and is possibly caused by genetic or environmental factors. The disease is also known for prolonged progression of symptoms. These attacks can be unexpected but it is thought that stress is a major risk factor. Some symptoms of this disease include numbness, stiffness of limbs, fatigue, difficulty walking, pain, and sexual dysfunction. These symptoms disrupt patients lives and standard of living. Many patients are unable to walk normally or comfortably and can also loose function in hands and other voluntary muscles. Working while suffering from an attack is usually impossible and can actually cause symptoms to worsen. There are a few different types of MS including Primary Progressive Multiple Sclerosis (PPMS). This disease is characterized by a progressive degeneration of neurological function 2.

3 Snyder 2 Jean Cruveilhier first identified the brain lesions common in patients with severe multiple sclerosis in The disease is thought to be much older but due to lack of medical understanding, the disease was commonly mistaken for different neurological disorders. Recently the diagnosis of Multiple Sclerosis has changed slightly to reflect new research. There are now three diagnosis statuses; MS, possible MS, or not MS. Before this change, people with monosymptomatic forms of the disease were labeled probable MS which made it hard for patients to seek full treatment. The possible MS diagnosis is reserved for people with genetic risk for the disease 4. MS is usually treated with immunosuppressive drugs such as Tysabri and Aubagio 5. There are a number of new treatments in clinical trials which are seeing positive responses. One of those treatments is Fingolimod therapy which is licensed for treating relapsing MS and is in the final stages of clinical trials for treating primary progressive MS. So far, the therapy has been seen to reduce inflammatory lesion activity and brain volume loss over the space of 2 years. As these are significant problems associated with the disease, researchers are hopeful that this therapy will be extremely beneficial to primary progressive MS patients 6. Many other drugs which are in clinical trials or approval stages target immune cells in order to prevent progression of the disease 7. Because so little is known about the disease, there are no preventative treatments to avoid development of MS in healthy people. There is ongoing research into finding genetic markers for those at risk for the disease, however the markers which have been found are so newly discovered that they must undergo more research 1. Recent data has suggested that the causal genes may be MHC type II genes which are much more difficult to screen for than MHC type I genes 8.

4 Snyder 3 Importance of Multiple Sclerosis There is no easy diagnostic assay which can be used to determine whether a person has MS or not. The current and most effective diagnostic tool includes an MRI brain scan. In countries where this technology is not easily accessible or often used, the incidence of MS can be underreported 9. The main issue with this disease is not mortality but progressive physical impairment. Life expectancy is slightly decreased by this disease but those with serious cases can develop severe disability 10. Symptoms can prevent patients from leading a normal life as they may not be able to work for many months at a time. The disease is found in all geographic regions. The total global direct cost of MS per person is about 24,000 United States International Dollars per year. This figure does not include money lost due to work loss or early mortality and can be much higher for people living in the United States. The Multiple Sclerosis International Federation s report on the global economic impact of the disease concluded that MS imposes substantial economic burdens on MS patients, on their families, and on society as a whole 11. Descriptive Epidemiology of Multiple Sclerosis Globally, the average age of onset of MS is This is significant because this is the age when most people try to start their families. Although research does not show decreased fertility rates for women with MS, dealing with the disease can often postpone childbearing until symptoms are reduced 12. Incidence of the disease peaks at 30 years and prevalence peaks at 50 years 8. Women are twice as likely as men to have MS. This statistic is true for all income levels except in Africa, South-East Asia, and the West Pacific, where the ratio is higher for women 9. The disease is usually more severe in men than women. Although there is a genetic component to the disease, it is thought to be much more complicated than other genetic diseases. Being an identical twin of someone with MS does

5 Snyder 4 not increase the risk of having MS any more than it would if the person had a non-sibling relative with the disease 8. An accurate measurement of the incidence or prevalence of MS by race is not currently available due to the difficulties in attaining global data. In the WHO s comprehensive report, published in 2010, most cases reported where in patients of European ancestry. This can be misleading, however, as the disease was found throughout the world and it could be that issues like poor access to health care and inaccurate diagnosis could cause under-reporting in patients with different ethnic backgrounds. The Eastern Mediterranean region has the highest prevalence of MS with 80 patients per 100,000. South-east Asia has the lowest prevalence with 0.3 patients per 100,000. Upper middle class income groups of countries has the highest prevalence and low income countries have the least prevalence. The highest incidence rate is found in Europe at 3.8 per 100, Again, these numbers are the most comprehensive data available and may not be wholly accurate due to underreporting in developing countries. Time changes in incidence and prevalence of Multiple Sclerosis An increase in incidence has been seen in the past 30 years worldwide. The reason for this change could be due to environmental factors which have not been identified, or the ability for physicians to accurately diagnose the disease. Increased prevalence rates have also been identified. This is mainly due to longer life expectancy because of new treatments. It is also seen that the female to male incidence ratio has increased. There has been no definite reason for this but some theories include; more women seeking medical treatment than in the past where men were more likely to receive medical attention, environmental factors interfering at the population level, or possible changes in lifestyle risks for women 8.

6 Snyder 5 Reasons for time, age, sex, race and/or geographical differences in incidence and prevalence There are a number of theories as to why there are twice as many women with MS as men. These theories are the same ones used while attempting to explain many autoimmune diseases which affect more women than men. One long standing, but inconclusive theory is that hormonal differences in women cause increased immune response. Another more recent and more likely theory is that the disease is somehow connected to genes expressed on both X chromosomes, whether through a susceptible effect or an interactive effect. These theories are just hypotheses because the true cause of the disease has not been identified 13. For a long period of time there was thought to be a latitudinal gradient effect and a possible racial effect in terms of incidence of MS. More comprehensive research has found that the gradient was either never existent or that the lower latitudes are increasing in incidence faster than higher latitudes making the gradient of no more use in researching differences in geographical incidence rates 8. Current Issues. One major issue with MS is that a lot is still unknown about the disease. The WHO s Atlas of MS which is known to be the most comprehensive global analysis of MS, is lacking in crucial specific information such as; possible stress triggers, environmental factors, and estimations on misreporting. Extensive research is being done to establish casual factors and possible relationships between environment, viral, and genetic factors. Other significant questions that are still unanswered include the reason for the 2:1 women to men incidence ratio, why incidence is rising globally, and what causes primary progressive MS rather than relapsing-remitting MS. Although diagnostics have improved drastically, doctors in low income countries still do not have the full capability of accurately diagnosing MS and cases in these countries are underreported. It may be a significant period of time before the disease is understood enough in order to create MS specific treatments rather than using solely autoimmune approach treatments.

7 Snyder 6 Another issue with MS is the stigma that surrounds most chronic illnesses. Because it is an invisible disease, those who suffer from it may face many sources of stigma from community members. If there is no education programs in place, community members may not believe that the patient is actually sick because the only symptom (besides paralysis in severe cases) obvious to a spectator is fatigue. In other cases, community members may think the patient or the patient s family did something to deserve the illness and so treat them as such. Because MS is a debilitating disease, many issues which affect paraplegics and other severely handicapped persons also affect patients in the later stages of primary-progressive MS. Depression, anxiety, and suicide are common as well as the belief that a diagnosis means imminent paralysis. Those who have lost the ability to walk or take care of themselves may feel they are burdening their families with undue hardship. Education of communities as well as support and counseling for patients can decrease the severity of these issues 14. Summary & Conclusions Multiple sclerosis is a debilitating disease which, if not diagnosed early, can lead to paralysis and a decreased standard of living. It is important to point out that every case is slightly different and it is nearly impossible to determine how the disease, whether progressive or relapsing, will affect the patient. New treatments in clinical trials are offering relief for patients and so the disease is less difficult to deal with than it may have been 30 years ago. Although women are twice as likely to have MS as men, the disease is generally more severe for men. There are no proven casual factors for the increased incidence rate of the disease. Significantly more research is needed in order to be able to prevent this disease.

8 Snyder 7 Bibliography 1) Gourraud, Pierre-Antoine, Hanne F. Harbo, Stephen L. Hauser, and Sergio E. Baranzini. "The Genetics of Multiple Sclerosis: An Up-to-Date Review." Immunological Reviews (2012): June Web. 29 Oct <http://onlinelibrary.wiley.com.ezaccess.libraries.psu.edu/doi/ /j x x/full>. This article was published online and provided a comprehensive explanation of the thoroughly complex genetic factors which may be involved in the development of the disease. This was helpful to me because I had attempted to read many genetic papers and had very little success in understanding what was being talked about. 2) "What We Know About Primary-Progressive MS (PPMS)." National Multiple Sclerosis Society. National Multiple Sclerosis Society, n.d. Web. 21 Oct <http://www.nationalmssociety.org/aboutmultiple-sclerosis/index.aspx>. This website provided an in-depth analysis of what it is like to live with Multiple Sclerosis including symptoms and support resources for those with the disease. The National Multiple Sclerosis Society is an organization which funds research on MS and drives legislative action with the goal of supporting and aiding anyone with the disease. 3) Compston, A. "The 150th Anniversary of the First Depiction of the Lesions of Multiple Sclerosis." Journal of Neurology, Neurosurgery & Psychiatry (1988): Print. 4) McDonald, W. Ian, Alistair Compston, et al. "Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis." Annals of Neurology 50.1 (2001): Print.

9 Snyder 8 5) Staff, Mayo Clinic. "Multiple Sclerosis." Mayo Clinic. Mayo Foundation for Medical Education and Research, 15 Dec Web. 19 Oct <http://www.mayoclinic.com/health/multiplesclerosis/ds00188>. The Mayoclinic provided another resource for learning about symptoms and treatments for the disease. This resource was particularly helpful in that it broke down how different drugs used to treat MS worked. 6) Radue, Enst-Wilhelm, Paul O'Connor, ET. al. "Impact of Fingolimod Therapy on Magnetic Resonance Imaging Outcomes in Patients with Multiple Sclerosis." JAMA Neurology69.10 (2012): Print. 7) "Treatments in Development." MS Trust. Multiple Sclerosis Trust, 1 July Web. 30 Oct <http://www.mstrust.org.uk/research/drugsindevelopment/>. The Multiple Sclerosis Trust is a charity based in the United Kingdom which gives detailed information on current research being done with Multiple Sclerosis treatments. The website listed drugs in various stages of development and organized by which form of Multiple Sclerosis the drug was targeting. 8) Koch-Henriksen, Nils, and Per Soelberg Sorensen. "The Changing Demographic Pattern of Multiple Sclerosis Epidemiology." The Lancet Neurology 9.5 (2010): Print. 9) Atlas: Multiple Sclerosis Resources in the World N.p.: WHO, Print. 10) Luzzio, Christopher. "Multiple Sclerosis." Multiple Sclerosis. N.p., n.d. Web. 20 Oct <http://emedicine.medscape.com/article/ overview>. This website gave an analysis of the many symptoms associated with MS. This was helpful in learning about the prognosis of the disease, something not explicitly discussed in other sources.

10 Snyder 9 11) Trisolini, Michael, Amanda Honeycutt, Joshua Wiener, and Sarah Lesesne. Global Economic Impact of Multiple Sclerosis. Literature Review. N.p.: Multiple Sclerosis International Federation, Print. 12) Houtchens, Maria. "Multiple Sclerosis and Pregnancy." Clinical Obstetrics and Gynecology 56.2 (2013): Print. 13) Duquette, P. "The Increased Susceptibility of Women to Multiple Sclerosis." Multiple Sclerosis 4.6 (1998): Print. 14) Halper, June. "The Psychosocial Effect of Multiple Sclerosis: The Impact of Relapses." Journal of the Neurological Sciences 256 (2007): S Print.

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