myelin-basic-protein and Leukoencephalopathy--Progressive-Multifocal

Myelin basic protein (MBP) is a major component of the myelin sheath of both the central and peripheral nervous systems. A number of neurological diseases in humans are associated with demyelination of the central and/or peripheral nervous systems, including multiple sclerosis and its variants such as acute disseminated encephalomyelitis (AD), acute hemorrhagic leukoencephalopathy, and idiopathic polyneuritis (Guilliame-Barre syndrome), as well as tropical spastic paraparesis (TSP), and progressive multifocal leukoencephalopathy (PML). Multiple sclerosis (MS) is perhaps the most common demyelinating disease and is one of great importance to the clinical neurologist. The underlying cause of the demyelination seen in multiple sclerosis patients is unknown. However, patients frequently have unusually high antibody titers to a number of common viruses, leading to speculation that viral infections may participate in the pathogenesis of MS. On the other hand, studies on maternal and paternal twins have suggested the involvement of genetic factors in the predisposition of an individual toward developing MS. PML, once a rare demyelinating disease of elderly patients with lymphoproliferative disorders, is now a much more common disease affecting patients of all ages due to the increasingly widespread use of immunosuppressive chemotherapy and the prevalence of AIDS. PML is the result of productive infection of oligodendrocytes, the myelin producing cells of the CNS, with the human polyomavirus, JCV. In this article, we have focused our attention on PML, and the role of JCV in disrupting myelin sheaths by affecting myelin basic gene expression, ultimately leading to demyelination.

Topics: Genes, Viral; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath

Degradation of purified myelin basic protein (MBP) was studied by SDS gel electrophoresis after addition of CSF samples obtained from HIV-1-infected patients. An increase in MBP degradation was detected in patients with neurological complications, such as AIDS dementia complex (ADC) or progressive multifocal leukoencephalopathy (PML), when compared with patients with no neurological symptoms (NA) or with other neurological opportunistic infections (OI). In the ADC and PML patients, in addition to CSF proteolytic activity, an increase in CSF-MBP levels and presence of white matter lesions were also observed by neuroimaging (MRI). In other opportunistic infections of the brain, MBP levels but not anti-MBP proteolytic activity increased. Results suggest the involvement of proteases in the virus-induced demyelination.

Topics: Adult; AIDS Dementia Complex; AIDS-Related Opportunistic Infections; Cerebrospinal Fluid; Demyelinating Diseases; HIV Infections; HIV-1; Humans; Leukoencephalopathy, Progressive Multifocal; Myelin Basic Protein; Nervous System Diseases; Peptide Hydrolases

A case of leukoencephalopathy induced by tegafur, an antineoplastic derivative of 5-FU, is reported. The patient received 600 mg of tegafur p.o. for 16 days before excision of rectal cancer. After the operation, gait disturbance and mental abnormalities appeared. He became akinetic and mute within a few days following readministration of tegafur. Serial studies of brain CT, somatosensory evoked potentials (SEP) were made, and myelin basic proteins (MBP) in the cerebrospinal fluid were measured. The level of MBP was about twice the normal value and the central conduction time (CCT) of SEP was prolonged at admission. The value of MBP and CCT improved with recovery from akinetic mutism.

Topics: Akinetic Mutism; Evoked Potentials, Somatosensory; Humans; Leukoencephalopathy, Progressive Multifocal; Male; Middle Aged; Myelin Basic Protein; Neural Conduction; Rectal Neoplasms; Tegafur

The loss of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) was compared by quantitative immunocytochemistry in demyelinating lesions of measles encephalomyelitis (ME), multiple sclerosis (MS), and progressive multifocal leukoencephalopathy (PML). Serial sections from paraffin-embedded tissue were reacted with antisera for MAG and MBP, and areas of staining loss were compared morphometrically. Lesions in ME showed MAG loss equal to that of MBP, lesions of PML showed MAG loss greater than that of MBP, and MS lesions showed a mixture of patterns. These data demonstrate distinctive patterns of MAG and MBP loss in these three diseases.

Topics: Central Nervous System; Demyelinating Diseases; Encephalomyelitis; Humans; Immunoenzyme Techniques; Leukoencephalopathy, Progressive Multifocal; Measles; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Nerve Fibers, Myelinated

In MS, there are many mechanisms by which viruses can produce demyelinating diseases in humans and experimental demyelinating infections in animals.

Topics: Brain; Distemper Virus, Canine; Encephalomyelitis; Humans; Leukoencephalopathy, Progressive Multifocal; Maus Elberfeld virus; Multiple Sclerosis; Murine hepatitis virus; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Spinal Cord; Virus Replication; Viruses; Visna-maedi virus

To study how viruses interact with oligodendroglia and produce demyelination, we immunostained paraffin and epon sections of lesions from patients with progressive multifocal leukoencephalopathy (PML) with antisera to papovaviruses, oligodendroglial myelin-associated glycoprotein (MAG), and myelin basic protein (MBP) according to the peroxidase-antiperoxidase method. In paraffin sections from a rapidly progressive case of PML, hyperimmune JC virus antiserum stained single oligodendroglia which were located in white matter that appeared normal histologically and stained normally with MAG and MBP antisera. In zones surrounding areas of demyelination, virus containing oligodendroglia were most numerous and MAG staining of periaxonal regions was decreased, but there was little change in MBP staining. In demyelinated regions, both MAG and MBP staining were severely altered; also there was much less JC virus staining. In tissue from three other chronic cases, viral antiserum stained fewer oligodendrocytes and the differences in MAG and MBP staining were much less striking. In epon sections from two biopsies of central nervous system tissue, we studied the electron microscopic appearance of oligodendroglia that also had been stained by JC virus antiserum. Virions were present in all nuclei and in some cytoplasmic regions. The results suggest that changes in MAG distribution are useful indicators of early oligodendroglial abnormalities which can cause myelin breakdown.

Topics: Aged; Brain; Brain Chemistry; Female; Humans; Leukemia, Lymphoid; Leukoencephalopathy, Progressive Multifocal; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin Proteins; Papillomaviridae; Polyomaviridae