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The demyelinating diseases, such as multiple sclerosis (MS), occupy a unique place in neurology. Factors such as the tendency to strike young adults, the diversity of manifestations, frequency, and basic questions that arise regarding pathogenesis challenge even the most skilled clinician. No specific diagnostic tests for demyelinating diseases exist; thus, diagnosis is based on recognition of the distinctive clinical patterns of CNS injury that is produced.
The basic pathologic derangement in MS is the stripping of the myelin sheath surrounding neurons in the CNS. Demyelination, coupled with an inflammatory response, leads to the formation of characteristic MS lesions, or plaques, that are found primarily in the brain, spinal cord, and optic nerves.(1) Neuronal axons, although stripped bare of their myelin sheath, are usually well preserved.(2)
Although MS was first described over 130 years ago, the exact cause(s) still remain a mystery, and there is no known cure. The term "multiple sclerosis" refers to two characteristics of the disease: the numerous affected areas of the brain and spinal cord producing multiple neurologic symptoms that accrue over time, and the characteristic plaques or sclerosed areas that are the hallmark of the disease. MS is usually diagnosed in patients between the ages of 20 and 45 years (although cases in children have been reported), with peak incidence occurring in the fourth decade.(3)
MS is, in general, a disease of temperate climates. In both hemispheres, its prevalence increases with distance from the equator. The highest known prevalence (250 per 100,000) occurs in the Orkney Islands, located north of the mainland of Scotland. Multiple sclerosis is also common in Scandinavia and throughout northern Europe.(4) Prevalence seems to be higher in Caucasians than other racial groups. MS is extremely rare in Japan and in black Africans; however, Japanese Americans and African Americans are at a significantly higher risk for developing the disease, with respective prevalence rates estimated at one-fourth and one third that of Caucasians.
The familial recurrence rate of MS is approximately 10 percent, with siblings being the most commonly reported relationship.(5) Even though this is true, it is unlikely that a simple genetic model for inheritance of MS is valid. It is probably polygenic in nature, each with a relatively small contribution to overall risk, but may provide susceptibility when presented with an as yet unknown etiologic trigger.
In the autoimmune theory, MS results from an autoimmune attack against self-myelin or self-oligodendrocytes antigens. The actual mediator of myelin destruction has not been established, but this activity has been attributed to the action of macophages, T-killer cells, lymphokines, antibodies, or a combination of these elements.(6) T-helper cells appear to be key initiators of myelin destruction. These cells are activated in the periphery, possibly after viral infection, and recognize myelin-associated proteins (myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein, and myelin-associated glycoprotein) as antigens. This cellular recognition creates an inflammatory cascade where the T-helper (CD4) cells are activated. Activated T cells are able to cross the blood brain barrier and produce the autoimmune response that leads to the destruction of myelin. It is also probable that cytokines regulate many of the cellular interactions that occur in MS. A large number of proinflammatory cytokines have been detected in the brain, cerebrospinal fluid (CSF), and peripheral blood of MS patients. Tumor necrosis factor alpha and interferon gamma may contribute directly to tissue damage by injuring oligodendrocytes or the myelin membrane.(4)
Although the exact mechanism has not been found, there are several ways in w
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