Cases reported "Encephalitis, Viral"

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1/9. in situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis.

    A 23-month-old girl died after 2 days' illness with rash, fever, and convulsions. Neuropathologic findings were consistent with viral hemorrhagic encephalitis in pontine tegmentum and medial thalamic areas. Human herpesvirus 6 (HHV-6) dna was detected in pontine nuclei by in situ hybridization. In addition, polymerase chain reaction for HHV-6 of serum and paraffin-embedded pontine tissue was positive, and serology indicated an acute primary infection. This is the first case showing HHV-6 dna in the brain cells of an immunocompetent patient with acute encephalitis.
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2/9. Fatal Epstein-Barr virus meningitis: an autopsy report.

    A 3-year-old Asian female presented with fever for 1 week and neck swelling for 1 day. serology revealed a recent Epstein-Barr virus (EBV) infection. Late on the evening of admission, she developed confusion and would not follow commands. A CT scan showed diffuse cerebral edema and a cerebral flow scan demonstrated no blood flow to the brain. She was declared brain dead and expired on the following day. At autopsy, the brain weighted 1175 grams and grossly showed significant edema. Microscopically, the entire neuraxis revealed extensive leptomeningeal infiltrate of mainly CD8 T lymphocytes, the majority of which expressed activated markers, HLA-DR and/or CD45RO, and monocytes/macrophages with intermixed numerous apoptotic/karyorrhectic nuclear fragments. These nuclear fragments were considered to be due to apoptosis of the expanded population of CD8 T lymphocytes. Focal venulitis was noted. EBV-encoded small nuclear rna in situ hybridization revealed positivity in the occasional lymphocytes. Interestingly, most intraparenchymal as well as leptomeningeal vascular endothelium showed HLA-DR immunoreactivity. This finding has been reported primarily in the acute inflammatory/demyelinating conditions, not in the viral meningitis/meningoencephalitis, and was thought to be related to cytokines due to widespread inflammation in our case. Massive edema secondary to severe EBV-meningitis can be fatal.
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3/9. herpes simplex virus brainstem encephalitis in an AIDS patient.

    We report a case of a virulent, atypical herpes simplex infection in the brainstem of a patient with Acquired Immune Deficiency Syndrome (AIDS) which was characterized by demyelination and oligodendroglial tropism. At autopsy the brainstem showed demyelination. Immunocytochemistry, in situ hybridization, and electron microscopy confirmed the presence of herpes simplex virus (HSV). Viral cultures demonstrated HSV type 1. Neuroinvasiveness and neurovirulence were studied by intraperitoneal inoculation of susceptible mouse strains (A/J and Balb/cByJ) with different viral titers. The LD50 of the clinical isolate was 5 orders of magnitude greater than the LD50 of a laboratory HSV strain (HSV type 1 KOS). The brains of the mice inoculated with the clinical isolate showed brainstem and cerebellar demyelination.
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4/9. In situ amplification and detection of hiv-1 dna in fixed pediatric AIDS brain tissue.

    To examine whether latent infection by hiv-1 occurs in the central nervous system, we optimized a procedure for amplification and detection of hiv-1 dna in situ, in formalin-fixed brain tissue from a child with severe hiv-1-associated progressive encephalopathy and severe hiv-1 encephalitis. By the use of a two-step technique, which involved polymerase chain reaction with incorporation of digoxigenin-labeled nucleotides followed by in situ hybridization with biotinylated probes, we found infection of numerous mononuclear cells and astrocytes in the cerebral white matter as well as of perineuronal satellite cells in basal ganglia, but not of neurons. Following PCR amplification, nuclear signal was found in 10 to 20 times as many cells as in parallel, control experiments using conventional, unamplified in situ hybridization.
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5/9. herpes simplex virus type 1 encephalitis in acquired immunodeficiency syndrome.

    herpes simplex (HSV) infection of the central nervous system is uncommon in AIDS and usually has an atypical topography. This review is centred around the case of a 49-year-old homosexual patient with AIDS who died from diffuse encephalopathy. Neuropathological examination revealed necrotic and haemorrhagic changes involving both temporal lobes, insulae and cingulate gyri. Cowdry type A intranuclear inclusion bodies were abundant but inflammation was minimal. Electron microscopy confirmed characteristic herpes virus particles. Immunocyto-chemistry was positive for HSV type 1 and 2. in situ hybridization and PCR, however, were positive for HSV type 1 but excluded HSV type 2. There was associated cytomegalovirus ventriculitis but clearly separated from HSV encephalitis. There were no histological features of HIV encephalitis and HIV could not be demonstrated by immunocytochemistry or by PCR to demonstrate proviral dna. Apoptotic neurons were numerous in areas with a severe macrophage reaction. Only two pathological cases with characteristic limbic distribution and necrotic haemorrhagic histologic have been reported previously. The rarity of these reports suggests that in advanced AIDS, the immune reaction causing a typical necrotizing encephalitis cannot be mounted. Distinction between HSV type 1 and 2 infection may be difficult by immunocytochemistry and usually requires in situ hybridization, tissue culture or PCR. In AIDS patients, HSV-1 has been identified as responsible for encephalitis whereas HSV-2 has been more responsible for myelitis. Associated productive HIV infection of the CNS was found in none of the cases. In contrast, cytomegalovirus encephalitis was found in nine of 11 cases of AIDS-associated HSV encephalitis.
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6/9. Naturally occurring herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus).

    An approximately 1-year-old domestic rabbit showed severe neurologic signs with circling and turning somersaults. Histologically, a nonsuppurative meningoencephalitis with neuronal cell necrosis and numerous intranuclear inclusion bodies in neurons and glial cells was found. Electron microscopic examination revealed herpesvirus particles in affected cells. A human herpes simplex virus was identified by means of immunocytochemistry and in situ hybridization as the causal agent and was further classified as herpes simplex virus 1 by polymerase chain reaction analysis. Because encephalitis is easily induced in rabbits by experimental infection with herpes simplex virus, the source of infection is suspected to be a human with herpes labialis who had close contact with the rabbit.
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7/9. Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8 encephalitis in HIV-positive and -negative individuals.

    OBJECTIVE: Kaposi's sarcoma-associated herpesvirus (KSHV) human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma and a variety of benign lymphoid proliferations including angioimmunoblastic lymphadenitis with dysproteinemia and Castleman's disease. KSHV/HHV-8 has also been associated with inflammatory conditions including interstitial pneumonitis. Although herpesviruses are commonly associated with encephalitis in immunosuppressed individuals, KSHV/HHV-8 has not previously been associated with central nervous system disease other than lymphoma. The first cases of KSHV/HHV-8 associated encephalitis have been described. methods AND DESIGN: KSVH/HHV-8 sequences were evaluated in brain biopsies from three cases of otherwise unexplained encephalitis from three patients, two of whom were positive for HIV. Amplification of the polymerase chain reaction product was confirmed with Southern blot hybridization on three separate occasions, and with appropriate positive and negative controls. RESULTS: All three cases of encephalitis were associated with KSHV/HHV-8 sequences. Characteristic lesions included endothelial cell swelling and perivascular cuffing by lymphocytes. CONCLUSIONS: KSHV/HHV-8 was associated with encephalitis in immunosuppressed individuals, and should have been considered in the differential diagnosis of unexplained viral encephalitis. KSHV/HHV-8 may have tropism for the central nervous system.
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8/9. VZV fulminant necrotizing encephalitis with concomitant EBV-related lymphoma and CMV ventriculitis: report of an AIDS case.

    A case of AIDS with varicella zoster virus fulminant necrotizing encephalitis associated with cytomegalovirus ependymitis-subependymitis and a periventricular Epstein-Barr virus-related lymphoma is described. The patient had no herpes zoster cutaneous eruptions and died three days after the onset of symptoms. Varicella zoster virus and cytomegalovirus antigens were found by immunohistochemistry in the same area around a necrotic periventricular lesion; a periventricular lymphoma, large B cell type, was also observed. in situ hybridization with Epstein-Barr virus-encoded- RNAs probe was positive in about 40% of the neoplastic cells. The association of herpes-related lesions in the same cerebral region should be consistent in AIDS cases with acute neurological symptoms.
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9/9. Profound cerebrospinal fluid pleocytosis and Froin's Syndrome secondary to widespread necrotizing vasculitis in an HIV-positive patient with varicella zoster virus encephalomyelitis.

    Demonstration of the direct involvement of cranial blood vessels by varicella zoster virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalomyelitis (VZVE) is still, however, debated. Most VZVE patients are immunocompromised and show little inflammation, either pre-mortem in cerebrospinal fluid (CSF) or at autopsy. We describe an HIV-positive patient with a moderately depressed CD4 count (304) who presented with massively elevated CSF protein (1800 mg/dl), bloody CSF and pleocytosis (1300 white blood cells (WBC)/mm3). His CSF was positive for VZV dna by PCR. He was treated with acyclovir and foscarnet, but died. At autopsy, an unusually widespread, inflammatory, transmural vasculitis caused by VZV affected meningeal vessels at virtually all brain stem and spinal cord levels, causing multiple subpial hemorrhages and necrosis. Virus dna in multiple areas of brain, brainstem and spinal cord was readily revealed by PCR, but not by the presence of viral inclusions, IHC or ISH. This case, with a clinically confusing presentation for VZVE, illustrates the extensive, albeit infrequent, degree of necrotizing vasculitis and CSF abnormalities that VZV is capable of producing. Antiviral therapy may have inhibited VZV genome replication and subsequent antigen production, resulting in negative ISH and IHC studies, but generated increased VZV genomic fragments that were detectable by the more sensitive PCR technique.
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