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1/4. adult-onset subacute sclerosing panencephalitis: immunocytochemical and electron microscopic demonstration of the viral antigen.

    We report a case of subacute sclerosing panencephalitis (SSPE) in a 52 year-old man, who developed rapidly progressive mental deterioration, myoclonic seizures, quadriplegia, and remained incapacitated until his death 4 years after the onset of symptoms. Immunocytochemical and electron microscopic studies are reported. Titers of measles virus antibodies were consistently high in both serum and cerebrospinal fluid, and periodic synchronous discharges were recorded on EEG. Suppressed cellular immunity was noted in skin test with phytohemagglutinin. The brain was extensively destroyed by inflammatory processes. There were either laminar or widespread areas of cortical necrosis associated with neuronophagia, neuronal loss, glial proliferation, and perivascular lymphocytic cuffing. Numerous intranuclear inclusions, in the neurons and glial cells, stained with immunoperoxidase using antiserum to sspe virus; ultrastructurally, these inclusions were made of tubular nucleocapsids of paramyxovirus. Neurofibrillary changes were occasionally encountered in the pigmented neurons. The white matter showed extensive loss of myelinated fibers and increased numbers of astrocytes with bizarre nuclei. This well-documented case of SSPE in an adult might be related to a condition of impaired cellular immunity.
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2/4. Rapidly progressive subacute sclerosing panencephalitis: an ultrastructural and immunoperoxidase study.

    A case of subacute sclerosing panencephalitis (SSPE) in a 20-year-old male who died within 2 months, is described. light microscopy revealed massive neuronal loss, reactive gliosis, perivascular cuffing and intranuclear (Cowdry type A) and intracytoplasmic inclusions. Immunocytochemical stain with the complement-fixing measles antibody was positive for intranuclear and intracytoplasmic inclusions. The reactive glia cells were positive for glial fibrillary acidic protein. Electron microscopy revealed a paramyxovirus-like structure of the nucleocapsids, occasionally showing a 'fuzzy' appearance in the cytoplasm. Crystal-like intracytoplasmic inclusions were also seen. The inclusions occurred in oligodendroglia cells, astrocytes and neurons. This case illustrates a rapidly progressive form of SSPE which, in some aspects, differs from the chronic form and resembles acute measles encephalitis.
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3/4. subacute sclerosing panencephalitis. An autopsy case with impaired cellular immunity.

    An autopsy case of subacute sclerosing panencephalitis (SSPE) in a 5-year-old boy, with rapid progression to a comatose state in 2 weeks after the onset of right hemiplegia, is described. The levels of antibody to measles virus in the serum and the cerebrospinal fluid were increased, and high levels of IgG in the latter were found. A characteristic pattern of electroencephalogram (EEG) showing periodic suppression of high voltage complexes was also found during the course of the disease. Microscopical examination revealed perivascular cuffing, numerous hypertrophied astrocytes with a diffuse gliosis and sporadic intranuclear inclusions in the brain. In addition to these typical findings of SSPE, impaired cellular immunity was recognized by delayed skin test in vivo, and pathologically severe atrophy of thymus, and follicular atrophy of spleen with amyloid deposition in the wall of the sheathed arteries were found.
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4/4. measles virus antigen in macrophage/microglial cells and astrocytes of subacute sclerosing panencephalitis.

    In two patients with subacute sclerosing panencephalitis (SSPE) of 10 and 25 months duration we demonstrated by immunohistochemistry the presence of measles-virus nucleocapsid antigen (MVNA) in CD68 cells and astrocytes of brain tissues. In both cases, CD68 hematogenous monocyte/ macrophages and perivascular microglial cells (Mphi) were found infiltrating the brain parenchyma, and often partially or completely invested by perivascular reactive astrocytes expressing glial fibrillary acidic protein (GFAP). Mphi with cytoplasmic MVNA were often seen in the Virchow-Robin spaces and in close association with perivascular astrocytes, which often also contained MVNA intracytoplasmic inclusions. Reactive astrocytosis was more severe in the patient with long-standing illness, and a correspondingly elevated number of strongly GFAP MVNA or MVNA- perivascular binucleated astrocytes was observed. An uptake of MVNA cell debris by reactive astrocytes was evident in areas of white matter displaying extensive demyelination and necrosis. Taken together, these observations seem to indicate that the brain infiltration by Mphi carrying measles virus could represent one pathway of virus entry and dissemination in the central nervous system. Virus transfer to perivascular astrocytes via cell-to-cell contacts with infected macrophages is also suggested.
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