multiple sclerosis

Pathol.

a chronic degenerative, often episodic disease of the central nervous system marked by patchy destruction of the myelin that surrounds and insulates nerve fibers, usually appearing in young adulthood and manifested by one or more mild to severe neural and muscular impairments, as spastic weakness in one or more limbs, local sensory losses, bladder dysfunction, or visual disturbances.

[1880-85]

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Disease of the brain and spinal cord in which gradual, patchy destruction of the myelin sheath of nerve fibres causes interruption or disordered transmission of nerve impulses.

Its early symptoms may include limb weakness or trembling, visual problems, sensory disturbances, unsteady walking, and defective bladder control, which come and go irregularly. Attacks grow more severe, and some symptoms become permanent, sometimes with eventual complete paralysis. Average survival from onset is about 25 years, but a rare acute form progresses over months. The cause remains uncertain and treatment unsatisfactory. Corticosteroids may ease symptoms. MS may be due to a delayed immune response that attacks the myelin sheaths; suggested causes include various common viruses. Dietary causes have also been suggested.

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▪ pathology

also called  disseminated sclerosis 

      a progressive disease of the central nervous system (nervous system, human) characterized by the destruction of the myelin sheath (myelin) surrounding the nerve fibres of the brain, spinal cord, and optic nerves (optic nerve). As a result the transmission of nerve impulses becomes impaired, particularly in pathways involved with vision, sensation, and movement.

      MS has a worldwide distribution but is five times more common in temperate regions than in tropical regions. The disease primarily occurs in individuals between the ages of 20 and 40, and women are affected by the disease more often than men. The onset of MS is usually gradual, with alternating intervals of exacerbation and remission of symptoms. Initial symptoms include numbness or tingling in the extremities or on the side of the face, muscle weakness, dizziness, unsteady gait, and visual disturbances such as blurred or double vision and partial blindness. The intensity of these early symptoms subside in most individuals for months or even years, but, as the disease progresses, remissions usually become shorter. In subsequent recurrences, old symptoms become more severe, and new signs and symptoms appear including abnormal reflexes, difficulty in coordinating and controlling movement, bladder dysfunction, and neuropsychological problems such as depression, memory loss, and emotional instability. Eventually the impairment of motor control can develop into complete paralysis. In about 30 percent of cases, the disease progresses without remission; however, most people with MS have a normal life expectancy.

      The cause of MS remains unclear, but in many cases there is evidence of a heritable component. Several genetic variations (called polymorphisms (polymorphism)) associated with MS occur in a cluster of genes (gene) that make up the major histocompatibility complex (MHC; also called human leukocyte antigen, or HLA, system), which regulates immune function. Some of these variations appear to be associated with environmental factors that precipitate the onset of disease. For example, the risk of MS in northern Europeans who carry a particular MHC variant is exacerbated by vitamin D deficiency, which weakens immune function. Thus, vitamin D supplementation in those people who carry the variation may confer some degree of protection against MS.

      There are also variations in genes outside of the MHC that have been identified and associated with MS, including several occurring in genes that encode proteins for signaling molecules known as interleukin receptors (receptor). These receptors are expressed on the cell membranes of B and T lymphocytes (lymphocyte) and play an important role in regulating lymphocyte development. Some variations in interleukin receptor genes are associated with autoimmune (autoimmunity) diseases, such as type 1 diabetes (diabetes mellitus) and Graves disease. There is much evidence suggesting that MS results from an autoimmune reaction in which a malfunctioning immune system produces T cells that react with and damage the body's own cells, specifically the myelin sheath of nerve fibres. The trigger for this autoimmune reaction is not known, but it is suspected to be related to genetic factors, with the interaction of variations in multiple genes, rather than a single gene, being a likely cause. Some scientists believe these changes in immune function could also be the result of exposure to a virus.

      There is no cure for MS, but a number of medications, such as corticosteroids (corticoid), are used to alleviate symptoms. In addition, there are a handful of disease-modifying agents available for MS. These agents can reduce the frequency of relapses and generally slow the progress of the disease. Immunotherapy with different forms of interferon beta, a protein the body normally produces to modulate immune response, is used to reduce the severity and frequency of the exacerbation periods of the disease. Natalizumab (Tysabri), a monoclonal antibody (an antibody clone derived from a single immune cell), is also effective for controlling the severity and frequency of relapses. Natalizumab attaches to molecules on the cell membrane of lymphocytes, preventing them from entering the central nervous system and attacking nerve cells. Another monoclonal antibody, called Alemtuzumab (Campath), which is used to treat chronic lymphocytic leukemia, also binds to the cell membrane of lymphocytes but works by stimulating antibody-mediated destruction of the cells. In clinical trials in patients with early-stage relapsing-remitting MS, this agent not only stopped progression of the disease but also facilitated the restoration of nerve function in some patients. Other disease-modifying agents used to treat MS include glatiramer acetate (Copraxone) and the immunosuppressant drug mitoxantrone (Novantrone).

      Another treatment for MS that has been explored in clinical trials is a form of stem cell therapy called autologous (self) hematopoietic stem cell transplant. This therapy has been tested only in patients who have not responded to conventional treatment regimens and therefore elect to undergo immunosuppressive therapy to destroy lymphocytes that have acquired autoimmune characteristics. Prior to the administration of immunosuppressive drugs, hematopoietic stem cells are harvested from the patient's blood or bone marrow. These cells are then frozen and stored for later reinfusion into the patient following immunosuppressive therapy. Because hematopoietic stem cells have the potential to develop into normally functioning lymphocytes, transplant provides the patient's immune system with an opportunity to recover normal activity. This treatment has proved successful in stopping or delaying disease progression in some patients, and, in rare cases, it has even led to the repair of neurological damage. However, significant risks are associated with stem cell therapy, including increased susceptibility to infection and possibility of transplant failure or relapse of disease.

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