Multiple sclerosis

Multiple sclerosis (MS) is a non-contagious chronic disease of the brain and spinal cord characterized by a variety of neurologic symptoms caused by demyelination of neurons. Multiple sclerosis results from attack by a patient's own immune system on their central nervous system and is thus categorized as an autoimmune disease.

Pathophysiology

The ultimate cause of MS is unknown. It is hypothesised that a viral infection or other environmental factor in childhood might prime the immune system for an abnormal reaction later in life. On a molecular level, there might be a structural similarity between an unidentified infectious agent and components of the central nervous system, causing confusion in the immune system later in life (a process called "molecular mimicry"). However, so far there is no known "MS virus". Certainly MS is not contagious. The importance of genetic factors has been discussed above.

Related Topics:
Viral - Molecular - Immune system

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It is widely accepted that a special subset of white blood cells, called T cells, play a key role in the development of MS. Under normal circumstances, these lymphocytes can distinguish between self and non-self. In a person with MS, however, these cells recognize healthy parts of the central nervous system as foreign, and attack them as they would a virus. In MS, 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.

Related Topics:
White blood cell - T cell - Lymphocyte - Myelin - Axon - Nerve cells - Blood-brain barrier - Endothelial cell - Blood vessel

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In MS, 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, MS is considered to be an autoimmune disorder. The inflammatory process finally leads to opening of the BBB; this can cause a number of factors, such as edema, upregulation of adhesion molecules on endothelial cells. This also causes activation of macrophages, activation of MMPs, other proteases and cytokines. This will lead to a destruction of myelin, called demyelination.

Related Topics:
Cytokine - Antibodies - Macrophages

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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. MS 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.

Related Topics:
Lesion - Spinal cord

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The original oligodendrocytes that form the myelin sheath are incapable of re-creating the sheath once it has been destroyed. However, the brain is capable of recruiting progenitor cells, which migrate from other unknown regions of the brain, differentiate into mature oligodendrocytes, and re-make the myelin sheath. This new myelin sheath is often not as large or effective as the original, though, and repeated attacks will have successively less effective remyelinations, until a plaque is built up around the damaged axons. Progenitor cells are very capable of differentiating and remyelinating axons in vitro; it is therefore suspected that inflammatory conditions and/or axonal damage inhibit progenitor cell differentiation in vivo.

Related Topics:
Oligodendrocyte - Myelin sheath - In vitro - In vivo

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