Multiple Sclerosis

Description

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 most popular 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 (i.e., a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in MS 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 is suggesting 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). And both diseases have been associated with cow's milk protein. 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. Still, the risk for someone inheriting all the genetic factors contributing to MS is still less than 5%. Advanced techniques called microarray technologies are now making it feasible to scan hundreds of genes and identify those most likely to be contributors to MS.

Infectious Agents

Infectious agents, 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 agent. In fact, one interesting theory suggests that these findings and others offer some 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 Agents Under Suspicion. Although many infectious microorganisms have been investigated, no one agent has emerged as a proven trigger. It is possible different MS 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 MS 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.
• Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation in small vessels. A few studies have reported significantly higher rates of previous Chlamydia infection in MS patients 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.
• Epstein-Barr virus (EBV). Nearly all people with MS have some evidence of EBV infection, the cause of mononucleosis. EBV, however, is also very common in people who never develop mono. (For example, in one study 99% of MS patients had evidence of EBV but so did 93% of people without MS.)

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, however, has found no evidence of any causal association. Research also ruled out a link between any other vaccinations, such as or influenza, and relapses of MS.