Biology 103 Fall 2005 Papers Forum on Serendip

Multiple sclerosis (or MS) is an incredibly frightening disease that belongs to the class of diseases known as autoimmune disorders. MS is a chronic neurological condition that affects the central nervous system and essentially causes it to deteriorate slowly. The areas that can be affected by MS are muscle control and strength, balance, vision, sensation and mental functions (1). One of the reasons that this disease is so frightening is that it occurs in younger adults. With an onset typically between the ages of 21 and 40 (1), this is a disorder that causes numerous people to be dependent upon others for care and financial stability for a large portion of their adult lives. Needless to say, the emotional affects of MS are great on the patient and his or her loved-ones. Initially, I had planned to find out what it is that causes MS, but as I began to sort through MS information, I realized that this question was not one that will be answered any time in the near future. There is, however, a great deal of information on the factors influencing MS and through evidence for these factors, we may be able to gain a better understanding of multiple sclerosis.

Before being able to understand how these outside factors affect various aspects of multiple sclerosis, it is imperative to have a basic understanding of how the disease progresses. MS is the process of demyelination and subsequent disruption of nerve impulse flow, as nerve impulses flow through the myelin sheath of neurons (1). T cells, a subset of white blood cells, recognize parts of the central nervous system as foreign and attack the myelin sheath (2). The cells that create myelin (oligodendrocytes) are also destroyed in the process (1, 2). Progenitor cells migrate from other places in the brain and replace the myelin, but new myelin sheath is not as large or effective. This process of remyelination causes periods of time when symptoms are not present, but as the disease progresses, remyelination will eventually become impossible (2). There are four types of MS: relapse-remitting (symptoms fade and recur at random), secondary progressive (begins at relapse-remitting but progresses over time), primary progressive (progressive from start), and progressive relapsing (progresses from start but symptoms appear randomly) (1). The differences in these paths are important for implicating how patients can best be treated.

The first subject to be addresses in answering the question of what factors influence multiple sclerosis is who is affected by multiple sclerosis. MS affects 2.5 million people worldwide and about 1 in 1,000 people in the United States (1). Genetics seems to be an important factor in the epidemiology of MS. There is a higher risk for people with a family who has MS (1) and twin studies show that there is a 50% concordance between identical twins (who share all of their genetic make-up) while there is only a 5% concordance between fraternal twins (2). This is an extremely significant difference, however, no single gene is responsible for MS but a few genes may be correlated with increased susceptibility (2). A gene called neuregulin was recently found to be the "switch" responsible for producing myelin (5). As previously stated, the onset of MS symptoms is generally between the ages of 21 and 40, peaks at 24 and is very rare, but not impossible, prior to the age of ten and after the age of 60 (1). Women are three times as likely to develop MS, indicated that it may be linked to sex hormones (1). Another extremely interesting piece of evidence is that instances of MS increase as the distance from the equator increases in the northern hemisphere (1). Generally speaking, people of Western European ancestry are more likely to develop MS than other ethnic groups and those who are particularly immune to MS include, but are not limited to, Native Americans, Eskimos and Africans (1).

Naturally, the next question seems to be "why are certain people more likely to develop MS than others?" Although there is little concrete evidence about this matter, multitudes of theories and evidence to support them have been proposed. It was mentioned before that people farther north of the equator may be more susceptible to MS. It has also been found that if a person lived in one of these colder environments before age 15, even if they moved to or from such a climate, they had a greater risk of developing MS than a person who had lived in a warmer, sunnier climate until age 15 (1). One of the reasons that could explain this is the amount of sun exposure that they receive. The body produces vitamin D when exposed to the sun which has been correlated with the reduction of MS risk (6). A preliminary study showed that women who take vitamin D supplements are 40% less likely to develop MS (2). Further evidence for this comes from the finding that fair-skinned people are at greater risk for MS than darker-skinned people (6). This evidence in inconclusive in that it has no reasoning behind why sunlight and vitamin D affect multiple sclerosis, only that there is a negative correlation between instances of MS and the amount of sunlight that a person receives.

Another theory about the etiology of MS regards the immune and nervous systems during childhood. It is suggested that there is a possible structural similarity between unidentified infectious agent and components of the central nervous system causing confusion in immune system later in life, called molecular mimicry (2). These infectious agents could be a viral infection during childhood as there is evidence that viral infections can trigger an autoimmune reaction where the immune system attacks its own myelin sheath (1). Obviously, this type of hypothesis would be hard to study as viral infections during childhood are extremely common and it is difficult to predict which children might develop MS and would thereby be candidates for study.

One of the most compelling factors affecting MS is estrogen levels. We already know that women are about three times as likely to develop MS than men. According to studies, levels of estrogen and testosterone are the only sex hormones that have an impact on MS. Women with MS were found to have significantly low levels of testosterone, while men with MS were found to have levels of the hormone similar to those of men without MS. However, men with MS and have higher levels of estradiol, a form of estrogen, have more damage to the central nervous system (7). Further evidence for this hormonal influence comes from the use of oral contraceptives, which typically contain estrogen. Women taking oral contraceptives are 40% less likely to develop MS (4). Also, the risk of MS onset is lower during pregnancy, when estrogen levels are high, but in the six months following pregnancy, the risk is increased dramatically (3). This six-month period is when estrogen levels drop after delivery. This evidence is also in concordance with previous studies on other animals: high levels of estrogen prevent and ease the symptoms of MS (3). What is incredibly striking about this evidence is something so extremely obvious, yet does not seem to have been addressed in any research or articles: if high levels of estrogen prevent and ease the symptoms of MS, why is it that women are three times as likely to develop MS than men? One would think that the opposite would be true: men, who lack high levels of estrogen, would be more likely to have MS than females who do have high levels of estrogen. There is little information on why estrogen has this affect on MS only in women. Another topic that these findings raise is the specific effect of estrogen on the immune system. In researching the topic, there is only information stating that estrogen modifies the immune system in some way, but it is uncertain as to in what way and how. Clearly, there is much more research to be done on the affects of estrogen on MS.

In addition to these factors, there is a plethora of other theories concerning the etiology of MS. Research in Sweden shows that some forms may be linked to a rare allergic reaction to mercury in dental fillings. One can now be tested for this allergy and if the results are positive, the fillings can be done with ceramic fill (2). Another study showed that the month in which a baby is born may affect his or her development of the disease. Babies born in May have a 13% increased risk compared to babies born in November (8). It has been proposed that iron in the brain can cause symptoms of multiple sclerosis. If this is the case, it is likely that there will be a treatment for this in the near future (9). Another factor that may be a culprit is smoking. Although it is not known whether smoking increases overall risk of developing multiple sclerosis, studies show that MS patients who smoke cigarettes or have smoked cigarettes in the past are more than three times more likely to have a rapid progression of MS than those patients who have not smoked (10). These are some of the more interesting theories about the etiology of MS, but they are certainly not the only ones out there. Some of them seem so arbitrary that it makes one wonder how researchers decided what factors may be important to research and why. None of the articles suggested that there was any underlying evidence for why these factors were chosen over others. It calls into question the whole research process: how were these hypotheses formed? What prior observations were made to indicate that these factors were worth investigating?

The variation in findings of factors linked to multiple sclerosis demonstrates the lack of knowledge there is about the specific causes of the disease. It seems that the strongest arguments are for hormonal influences as well as amount of sunlight a person gets, but clearly there are other factors affecting the development of MS. All of these factors need to be investigated to discover exactly how they influence MS and by examining this information, we will be able to know more concretely the causes of the disease and thereby be closer to finding more effective treatments or possibly even a cure. Because multiple sclerosis affects so many people in America and we do not know the causes of it, it should be one the top research priorities for those in the field of medical research.