What Causes Multiple Sclerosis?
The protective myelin covering of the nerve fibers in the central nervous system is damaged in people with multiple sclerosis. Myelin is a fatty material that forms a sheath around a nerve and permits electrical impulses to be conducted along the nerve fiber with speed and accuracy, much like the insulation around an electrical wire does. When myelin is damaged, the nerves do not conduct the nerve impulses properly, which may lead to various bodily dysfunction.
The precise causes of multiple sclerosis (MS) are not yet known, however, scientific research indicates that that a number of factors in combination are probably involved.
It is now generally accepted that MS involves an auto-immune processâ€”an abnormal response by the immune system directed against the central nervous system (CNS). In patients with MS, the body's immune system cannot differentiate between virus proteins and its own myelin and therefore launches an attack against itself. The exact target (antigen) the immune cells are sensitized to attack remains unknown. However, researchers have recently been able to identify which immune cells are mounting the attack; how they are activated to attack; and some of the sites, or receptors, on the attacking cells that appear to be attracted to the myelin to begin the destructive process. The destruction of myelin (the fatty sheath that surrounds and insulates the nerve fibers) causes the nerve impulses to be slowed or halted and produces the symptoms of MS. Researchers are looking for highly specific immune modulating therapies to stop this abnormal immune response without harming normal immune cells.
Studies of MS have taken into account variations in geography, socioeconomics, genetics, and other factors (epidemiology) and migration patterns. These studies have shown that people who are born in an area of the world with a high risk of MS and move to an area with a lower risk, acquire the risk of their new home, if the move occurs before the age of 15 years. Such data suggest that exposure to some environmental agent that occurs before puberty may predispose a person to develop MS in later years.
In the U.S., multiple sclerosis occurs more frequently in states that are above the 37th parallel than in states below it. From east to west, the 37th parallel extends from Newport News, Virginia, to Santa Cruz, California and runs along the northern border of North Carolina to the northern border of Arizona and including most of California. The MS prevalence rate for the region below the 37th parallel is 57 to 78 cases per 100,000 people. The prevalence rate for those above the 37th parallel is almost double that of those below the 37th parallel: 110 to 140 cases per 100,000 people.
Initial exposure to numerous viruses occurs during childhood. Since viruses are well recognized as causes of demyelination and inflammation, it is possible that a virus is the triggering factor in MS. More than a dozen viruses including measles, canine distemper, and herpes (HHV-6) have been investigated to determine if they are involved in the development of MS. Researchers have also discovered epidemics of MS. For example, four epidemics of MS have occurred in the Faroe Islands (between Iceland and Scandinavia) between 1943 and 1989. This region was occupied by British troops during World War II. Since the incidence of MS has increased each year for 20 years after World War II in this region, researchers believe the British troops unknowingly brought a disease-causing agent with them during their occupation. However, it has not yet been definitively proven that any one virus triggers MS.
Multiple sclerosis is not directly hereditary. However, having a first-degree relative such as a parent or sibling with MS increases a person's risk of developing the disease many times above the risk for the general population. Studies show there is a higher prevalence of certain genes in populations with high rates of MS. Common genetic factors have also been found in some families where there is more than one person with MS. Some neurologists theorize that MS develops because a person is born with a genetic predisposition to react to some environmental agent, which, upon exposure, triggers an autoimmune response. Sophisticated new techniques for identifying and mapping genes may help answer questions about the role of genetics in the development of multiple sclerosis.
The role of trauma in causing multiple sclerosis or in triggering subsequent MS exacerbation (also referred to as attacks, relapses or flares) has been a controversial subject for many years. Until recently, opinion on this issue was based upon anecdotal reports or retrospective information that relied on the memories of patients.
A prospective study, conducted by researchers at the University of Arizona, followed 170 MS patients and 134 control subjects, over a period of eight years. Prospective studies follow a group of people with a given disorder over a specific period of time, beginning before the occurrence of the events being studied. The results of this study, published in 1991 (Sibley, WA et al, Journal of Neurology, Neurosurgery, and Psychiatry 54:584-9), concluded that except for electrical injuries, there was no evidence of a direct relationship between traumatic injury and an MS exacerbation.
A second study, performed at the Mayo Clinic, supported the Sibley group's findings that traumatic injury is not related to exacerbation of MS. The Mayo study also indicated there is no relationship between traumatic injury and the onset of MS. Although the Mayo study, published in 1993 (Siva, A et al, Neurology 43:1878-82) was retrospective, it was based upon the detailed clinical records of 164 long term patients with definite MS, actively followed at the Mayo Clinic.
Both studies showed that there are more traumatic events among people with MS than in the healthy control group. Many traumas were caused by symptoms such as lack of coordination, impaired balance, or abnormalities of gait or vision. These events, however, were not precipitating factors in the disease.
For additional information on what causes multiple sclerosis, please visit the National Multiple Sclerosis Society.