Demyelination

Neurological symptoms result from demyelination of the spinal cord and are potentially irreversible. The symptoms and signs characteristic of a vitamin B 2 deficiency include paresthesis of the hands and feet, decreased deep-tendon reflexes, unsteadiness, and potential psychiatric problems such as moodiness, hallucinations, delusions, and psychosis. Neuropsychiatric disorders sometimes develop independently of the anemia, particularly in elderly patients. Visual loss may develop as a result of optic atrophy. 

Multiple scelerosis is an autoimmune disease mediated by T and B lymphocytes and macrophages. This is characterized by extensive inflammation and demyelination of the myelin sheath that surrounds the nerve fiber. The death of the nerve fiber results in a variety of symptoms that can lead to impairment of movement, paralysis, and death. 

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

Peripheral neuropathy is degeneration of peripheral nerves. Because motor and sensory axons tun in the same nerves, usually both motor and sensory functions are affected in this disease. Neuropathies may be either acute (e.g., Charcot-Marie-Tooth disease) or chronic (e.g., Guillain-Barre syndrome) and are categorized as demyelinating or axonal. 

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. 

Metachromatic ieukodystrophy Aryisuifatase A Cgp—Gsl—j-OS03 3-Sulfogalactosylceramide Mental retardation and psychologic disturbances in adults demyelination. 

Seroconversion neuropathy Inflammatory demyelinating neuropathy Early pre-AIDS Acute Generalized systemic dlness, mononeuropathies Immune dysfunction... 

Acute inflammatory demyelinating polyradiculopathy Early pre-AIDS Acute Motor to sensory signs NCS show demyelinating features Immune dysfunction complement/macrophage-mediated demyelinating neuropathy... 

Opportunistic infection, eg. CMV Progressive polyradiculopathy AIDS Acute, subacute Multiple, asymmetric mononeuropathies, usually painful CMV infection, Schwann cell infection demyelinating neuropathy... 

DIES-associated neuropathy has a variety of chnical presentations, including painful symmetric or asymmetric sensorimotor neuropathy, distal sensory neuropathy, mononeuritis multiplex, and demyelinating polyneuropathy (Gherardi et al. 1998). Cranial neuropathy without evidence of a more generahzed neuropathy may occur, typically as a facial nerve palsy in association with parotidomegaly (Itescu et al. 1990 Brew 2003). The neuropathy develops subacutely over days to weeks. In some cases, muscle weakness may be a result of an inflammatory myositis (Kazi et al. 1996). 

Electrophysiologic studies usually show axonal neuropathy, but in 15%, it is demyelinating (Moulignier et al. 1997). CSF is remarkable for a mild nonspecific lymphocytic pleocytosis, but with markedly raised protein up to 2 g/L (Brew 2003). Nerve biopsy shows marked angiocentric CD8 infiltrates without mural necrosis... 

Decreased macrophage infiltration and demyelination Decreased CD4+ T cell trafficking into the CNS, impaired viral clearance No effect on CD8+ T cell trafficking into the CNS Enhanced fatality with delayed CD 8+ T cell infiltration No effect CCR5A32 not protective... 

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... 

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