Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T-cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic Factors

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious Organisms

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

• The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
• Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 and 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is also very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
• Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

• HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
• Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
• Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing-- but not the sole-- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.