Demyelinating diseases

MA M12 M12.210 ADAM 10 peptidase Potential drug target for demyelinating disease... 

Certain diseases are characterized by abnormal quantities of these lipids in the tissues, often in the nervous system. They may be classified into two groups (1) true demyelinating diseases and (2) sphingolipidoses. 

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels. 

MS, a chronic demyelinating disease of the CNS, is the most common cause of non-traumatic disability among young adults (Frohman et al. 2006). At the cellular level, MS is mediated by myelin-specific CD4h- T cells that destroy oligodendrocytes... 

Aluminium overload Allergic encephalomyelitis (demyelinating diseases) Ageing... 

Myelin sheaths contain other proteins, some of which have only recently been established as myelin-related. The proteins described above represent most of the well-established myelin proteins that are myelin-specific or have been studied primarily in the context of myelin and demyelinating diseases. However, myelin sheaths contain numerous other proteins in smaller amounts that are also in many other cells and/or have only been identified relatively recently. Some of these are in compact myelin but others are enriched in specialized... 

Nervous system damage in acquired demyelinating diseases is directed rather selectively against myelin or myelin-forming cells, but axons also are often affected 640... 

Multiple sclerosis is the most common demyelinating disease of the central nervous system in humans 641... 

A number of animal diseases caused by viruses involve primary demyelination and often are associated with inflammation. These diseases are studied as animal models, which may provide clues about how a viral infection could lead to immune-mediated demyelination in humans [1, 5, 6]. Canine distemper virus causes a demyelinating disease, and the lesions in dog brain show a strong inflammatory response with some similarities to acute disseminated encephalomyelitis in man [ 1 ]. Visna is a slowly progressive demyelinating disease of sheep caused by a retrovirus [ 1 ]. 

Progressive multifocal leukoencephalopathy (PML) is historically a rare demyelinating disease that is usually associated with disorders of the reticuloendothelial system, neoplasias and immunosuppressive therapy [1, 2]. However, it has become more important in clinical medicine because it is frequently seen as an opportunistic secondary infection in immunocompromised persons with AIDS. PML is characterized by focal lesions that are noninflammatory and caused by infection of oligodendrocytes with the JC papovavirus. 

Canavan s disease Absence of N-acetylaspartate acylase Rapidly progressive demyelinating disease of infancy Gene therapy (experimental)... 

IX.b.3.4. Genetically engineered antibodies. Anti-TNF antibody treatment with infliximab or adalimumab is now accepted as of value in treating severe and fistulating exacerbations of Crohn s disease when standard treatments are not tolerated or have failed. Adverse effects which limit usefulness include the occurrence of tuberculosis and septicaemia, leucopenia and pancytopenia, and risk of exacerbation of demyelinating disease. Considerations of benefits versus risks of such treatment are complex, but probably positive. 

Nervous system (dementia, stroke, epilepsy, extrapyramidal diseases [Parkinson s], demyelinating diseases [multiple sclerosis], neuropathy, myasthenia gravis, psychosis, schizophrenia)... 

Other neurologic disturbances associated with alcoholism include dementia and, rarely, demyelinating disease. 

Most cells of the immune system are ordinarily kept apart from those of the nervous system by means of the blood-brain barrier. However, allergic encephalomyelitis, in which T cells attack the myelin sheath of brain neurons, can easily be induced in mice.506 A similar autoimmune process is thought to be involved in human multiple sclerosis (see Chapter 30, pp. 1769, 1808, and Fig. 30-9).507,508 High levels of circulating IgM are found in some demyelinating diseases of peripheral neurons.508 In Rasmussen s encephalitis, which causes brain inflammation and epilepsy, serum antibodies attack a glutamate receptor subunit GluR3.509... 

Slow viruses are becoming increasingly suspect in the instances of much more common diseases, particularly the autoimmune diseases. An autoimmune disease may be defined as a disease wheiein the immune system of the body does not direct its attack on an invading foreign substance, but instead at the body s own tissue. Many authorities consider rheumatoid arthritis and multiple sclerosis as autoimmune diseases. The precise causes of these diseases have remained obscure. Multiple sclerosis is a demyelinating disease and has variously been described as an autoimmune disease, a viral disease, or an autoimmune disease provoked by a virus. Epidemiological studies indicate that from 3 to 23 years may elapse between the time of exposure to the virus and the onset of symptoms. Further evidence points to involvement of a myxovirus. Measles virus is of this kind. 

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