Multiple Sclerosis: Damaged Goods Theories on The Causes of Relapses

Abstract

According to the National Multiple Sclerosis Society (NMSS) the vast majority of people in the United States is estimated to be around one million people, mainly women, who are living with multiple sclerosis (MS). The lives of these people have changed forever and there is no cure, only treatments. Treatments are supposed to help control the occurrence of relapses and help control the effects during a relapse. Due to each relapse causing more damage to the person living with MS that there is a higher chance that there will be disabilities such as memory loss, blindness, balance problems, bladder issues, and drop foot, the dropping of the forefoot due to weakness, nerve damage, or paralysis affiliated with the onset of a relapse. Researchers have been studying MS in the hopes of understanding what causes MS and the damage of MS flare ups, or relapses as it is commonly known. There are many theories on what induces a relapse. There are also many unknown factors that can cause a relapse which is being researched as well.

Multiple Sclerosis (MS) is a chronic autoimmune disease with no cure seen in the near future. MS comes in four forms we know of at this time, Clinically Isolated Syndrome (CIS), Relapsing Remitting Multiple Sclerosis (RRMS), Secondary Progressive Multiple Sclerosis (SPMS), and Primary Progressive Multiple Sclerosis (PPMS). The most prominent form of MS is RRMS while PPMS, the worst form of MS, is being diagnosed almost as much as RRMS. Women are affected more than men with most cases found north of the equator. Out of the nearly one million people living with MS, three out of four are women. MS destroys the myelin in the brain and spinal cord. These lesions can cause many different disabilities depending on where in the brain or spine they are located. This disease causes brain atrophy to occur sooner than in a person without MS and can also cause progressive multifocal leukoencephalopathy (PML) for people taking certain treatments if they have tested positive for the John Cunningham Virus (JC Virus).

Researchers are still trying to find out what the cause of MS is and if what causes relapses are a part of what causes MS. However, relapses occur at least once a year, depending on what disease modifying treatments (DMTs) have been used, although the severity of a relapse varies from person to person. In fact, some scholars are researching what they believe to be the causes of relapses in which they are putting their focus and efforts on. In fact, there are many different theories on the causes of MS relapses which will be the focus of this proposal.

Literature Review

Some signs of to determine if a person might have Multiple Sclerosis (MS) is inflammation, numbness, tingling, loss of vision, known as optic neuritis, which could be short term or permanent. These are just a few of the many signs in diagnoses of MS. There has been much research on MS, however, there has not been as much research on the causes of relapses. There are some theories about how relapses occur from seasonal changes, predisposed genes and different types of infections, and diet. Our hypothesis is there is a connection between different theories and the resulting MS relapses or lack thereof. This research is necessary as it helps us understand how relapses may occur and might possibly help find the causes of MS.

According to the National Multiple Sclerosis Society (NMSS) (2019), a relapse happens when the nerves/myelin become inflamed in the white matter of the brain or in the spinal cord. “[It] is the clinical manifestation of acute inflammation and focal demyelination in a clinically eloquent region of the central nervous system (CNS), leading to a discrete episode of neurological dysfunction which may recover fully or partially” (Harding., Tilling., MacIver., et al., 2017). A relapse can cause the inflammation of body parts, optic neuritis, tingling, numbness, temporary or permanent paralysis, temporary or permanent speech impairment, loss of balance, and loss of memory but, not like amnesia, however, a loss of memory like what date it is. A relapse occurs when a lesion in the brain or spinal cord is active, or there is a new lesion in either place. The only medical way to see if there is an active relapse is through an MRI scan of the brain and/or the spinal cord. One might be able to tell by the above mentioned symptoms, but can confirm with the MRI, however, neurologists may be able to tell if a relapse is happening by testing activities of daily living (ADL). While speech can be known by a persons’ family, friends, co-workers (if able to work), etc., a neurologist may want to hear the impairment for themselves. Balance and drop foot is one impairment that can be caused by nerve damage and can be tested by a visual assessment of how a person is walking. There is nerve testing to see if any of the major nerves have been affected by a relapse which would cause impairment of walking. In fact, most tests to see if a person is having a relapse is a visual test by the neurologist.

Seasonal Theory

According to Harding et al. (2017), seasonal variations may be a cause of an MS relapse. Studies previously done have been on a smaller scale in other countries. These studies are longitudinal as a researcher cannot test a theory based on a short time period. Most relapses occur in the summer time when it is hot outside and there is more exposure to UV rays. In fact, some people have died due to the heat and not being able to get to shade while dehydrated. The majority of persons living above the equator are more susceptible to a relapse because of the varying, harsher weather conditions. A part of the seasonal theory is the use of vitamin D supplements improving the odds of not having a relapse. Studies have shown the before and after effects of vitamin D in MS patients in Germany. The study concluded that vitamin D given in the months of January-March, there were more relapses than in the months of October-December where there is less Ultra violet-B (UVB) radiation (Behav, 2017). There are more studies to come in regard to seasonal variation and the effects of an MS relapse.

Predisposed Genes and Oxidation

According to a research analysis approved at the University of California, San Francisco (UCSF) there are seventeen MS susceptibility genes genotyped at their laboratory (Mowry., Carey., Blasco., et al., 2013). Also, in their findings “MPHOSPH9, which has unknown function was associated with greater attack severity. One hypothesis regarding its function is that this SNP is associated with reduced expression of the nearby CDK2AP1 gene, a cell cycle regulator” (2013). Genes play an important role of relapses which occur in white people, as this race was the only one in the study.

Another gene theory of MS and relapses is oxidation. This is a recent theory in regards the genetic causes of MS and relapses. Autopsies were used to test this theory and the finding were, “[w]ithin the global multiple sclerosis population, patients dying in the course of acute multiple sclerosis showed more accumulation of oxidized lipids and DNA in the lesions as compared with those dying in the progressive stage of the disease” (Haden., Fischer., Frischer., et al., 2017). The analysis of oxidized DNA shows a link to the damage caused by a relapse.

Infections and Diet

Systemic infections can be another cause a relapse. When a person with MS gets an upper respiratory infection, a relapse may be on the way. There are many different viruses that can cause and upper respiratory infection and thus only one virus cannot be pin pointed as a cause of a relapse. However, the influenza virus is a main culprit in a persons’ relapse as their immune system has been lowered from what it normally is. This also includes receiving a vaccination to “prevent” catching a flu. According to Steelman (2015), “[there are] many pathogens [that] are associated with upper-respiratory infections, it might be anticipated that the biological mechanism underlying their effect on MS relapse is similar, although alterations in viral pathogenesis could account for some discrepancy.” In fact, having an upper respiratory infection can hospitalize those with MS more quickly than a person without the disease. Bronchitis is another infectious virus that can cause a relapse, especially if it is not treated in a timely manner because it can turn into pneumonia which also effects ones’ immune system when an immune system is already fighting its own body as it is in a person with MS.

“Research regarding the role of diet in [MS] is advancing but currently remains limited. Few studies have been prospective with rigorously collected outcomes, and the few clinical trials that have been conducted have not been of sufficient size or length to adequately assess efficacy” (Sand, 2018). Eating fatty foods is not good for anyone’s health, but more so for those with MS. Saturated fats have been known to increase inflammation and it is also known that saturated fats can lead to heart disease and high blood pressure. Another factor in diet is the use of salt. Too much salt can also lead to a relapse. However, there is no definitive answer from studies if salt intake can cause an MS relapse. There are some diets which may help prevent a relapse such as the Mediterranean diet, the Keto diet, the Paleo diet, the McDougall diet. Researchers have not investigated the Atkins diet and therefore, it is currently excluded until a time where a study can suggest if it will be considered to help to reduce relapses.

Methods

Using the MSBase registry, we will collect past and present data to compare theories about the causes of relapses in people with MS. We will look at previous longitudinal studies and studies currently in progress (two-three years) to see if there have been any changes to the theories already at hand or if new theories have emerged with new clinical trials.

Limitations

With new studies that are going on, not all data will be in the database. There is not a lot of information on some of the theories presented.