What causes multiple sclerosis?
The ultimate cause of multiple sclerosis is unknown. The probable cause is thought to be a combination of hereditary factors, an environmental trigger like a virus and a defect in the immune system. Multiple sclerosis is an autoimmune disease, meaning its cause is an attack by the body's own immune system. For unknown reasons, immune cells attack and destroy the myelin sheath that insulates neurons in the brain and spinal cord. This myelin sheath, created by other brain cells called glia, speeds transmission and prevents electrical activity in one cell from short-circuiting to another cell. Disruption of communication between the brain and other parts of the body prevent normal passage of sensations and
control messages, leading to the symptoms of multiple sclerosis. The demyelinated areas appear as plaques, small round areas of gray neuron without the white myelin covering. The progression of symptoms in multiple sclerosis is correlated with development of new plaques in the portion of the brain or spinal cord controlling the affected areas. Because there appears to be no pattern in the appearance of new plaques, the progression of multiple sclerosis can be unpredictable.
Multiple sclerosis is a progressive, disabling, neurological illness that affects the brain and spinal cord. Nerve cells normally are surrounded by an insulating sheath made of a fatty substance called myelin that helps to transmit nerve impulses. In multiple sclerosis, this myelin sheath is inflamed or damaged, which disrupts or slows nerve impulses and leaves areas of scarring called sclerosis. These areas of myelin damage and scarring are called multiple sclerosis plaques. The disruption of nerve signals causes a variety of symptoms that can affect vision, sensation and body movements. These symptoms usually come and go through a series of episodes when symptoms suddenly get worse (called relapses) alternating with periods of recovery when symptoms improve (called remissions). Many patients have a long history of multiple sclerosis attacks over several decades. In these cases, the disease may worsen in "steps," when the attacks occur. For others, the disease progresses steadily. In a minority of patients, multiple sclerosis causes relatively few problems.
It is widely accepted that a special subset of white blood cells, called T cells, play a key role in the development of multiple sclerosis. Under normal circumstances, these lymphocytes can distinguish between self and non-self. In a person with multiple sclerosis, however, these cells recognize healthy parts of the central nervous system as foreign, and attack them as they would a virus. In multiple sclerosis, the part of the nervous system primarily attacked is myelin. Myelin is a fatty substance that covers the axons of nerve cells, and which is important for proper nerve conduction. Normally, there is a tight barrier between blood and brain, called the blood-brain barrier (BBB), built up of endothelial cells lining the blood vessel walls.
In multiple sclerosis, the BBB breaks down; autoreactive T cells cross the BBB and trigger an inflammatory process, also mediated by other immune cells and soluble factors, such as cytokines and antibodies. Due to this abnormal behavior of the immune system, multiple sclerosis is considered to be an autoimmune disorder. The inflammatory process finally leads to a destruction of myelin called demyelination. Repair processes, called remyelination, also play an important role. This is one of the reasons why, especially in early phases of the disease, symptoms tend to decrease or disappear temporarily after days to months. Nevertheless, axonal damage and irreversible loss of neurons occur early during the course of the disease. However, due to its plasticity the brain can often compensate for some portion of the damage. Multiple sclerosis symptoms develop as a result of multiple lesions in the brain and spinal cord, and can vary greatly between different individuals, depending on where the lesions occur.
The risk of developing multiple sclerosis is higher if another family member is affected, suggesting the influence of genetic factors. Thus, a brother, sister, parent, or child of a person with multiple sclerosis stands a one to three-percent chance of developing multiple sclerosis. Similarly, an identical twin runs a 30% chance of acquiring multiple sclerosis whereas a non- identical twin has only a four-percent chance if the other twin has the disease. In addition, the higher prevalence of multiple sclerosis among people of northern European background suggests some genetic susceptibility. The chance increases in families where a first-degree relative has the disease. These statistics suggest that genetic factors play a major role in multiple sclerosis. However, other data suggest that environmental factors also have an important role.
The role of an environmental factor is suggested by studies of the effect of migration on the risk of developing multiple sclerosis. Age plays an important role in determining this change in risk--young people in low-risk groups who move into countries with higher multiple sclerosis rates display the risk rates of their new surroundings, while older migrants retain the risk of their original home country. One interpretation of these studies is that an environmental factor, either protective or harmful, is acquired in early life; the risk of disease later in life reflects the effects of the early environment.
These same data can be used to support the involvement of a slow-acting virus, one that is acquired early on but begins its destructive effects much later. Slow viruses are known to cause other diseases, including AIDS. In addition, viruses have been implicated in other autoimmune diseases. Many claims have been made for the role of viruses, slow or otherwise, as the trigger for multiple sclerosis, but as of 1997, no strong candidate has emerged.
How a virus could trigger the autoimmune reaction is also unclear. There are two main models of virally-induced autoimmunity. The first suggests the immune system is actually attacking a virus (one too well-hidden for detection in the laboratory), and the myelin damage is an unintentional consequence of fighting the infection. The second model suggests the immune system mistakes myelin for a viral protein, one it encountered during a prior infection. Primed for the attack, it destroys myelin because it resembles the previously-recognized viral invader.