1/20. Rapidly progressive multifocal leukoencephalopathy with substantial cell-mediated inflammatory response and with cognitive decline of non-Alzheimer type in a 75-year-old female patient.autopsy findings of rapidly progressive and widespread multifocal leukoencephalopathy (PML) in a 75-year-old woman with no known predisposing disease are demonstrated. Originally she was given a clinical working diagnosis of syndrome of progressive supranuclear palsy (PSP). The neuropathological investigation revealed widespread white and gray matter changes consistent with PML, and the jc virus was verified by EM, in situ hybridization and immunohistochemistry. In contrast to the few chronic inflammatory cells generally seen in PML in this case there was a substantial cell-mediated inflammatory response reflected in numerous T-helper and T-killer cells. The uncommon, widespread distribution of lesions and substantial cell-mediated response reported might indicate that the rearrangement of viral genome, previously suggested of importance for viral growth in the central nervous system (CNS), is also important for viral spread within the CNS, infectivity of glial cells and for the activation of cell-mediated immunity.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/20. Progressive multifocal leukoencephalopathy in a patient with systemic lupus erythematosus.We describe a patient with longstanding systemic lupus erythematosus (SLE) in remission who presented with recent onset neurological symptoms. magnetic resonance imaging, followed by a brain biopsy and in situ hybridization, confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). The clinical findings in this patient emphasize the importance of considering PML in an individual with SLE and neurological abnormalities.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/20. Progressive multifocal leukoencephalopathy following oral fludarabine treatment of chronic lymphocytic leukemia.Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating disorder of the central nervous system usually affecting immunocompromised individuals and is due to infection of the oligodendrocytes by the jc virus. A case of PML in a chronic lymphocytic leukemia (CLL) patient treated with fludarabine is reported, representing the second such instance in which the diagnosis of the neurological disorder was established by brain biopsy. A 61-year-old man with a 14-year history of B-cell type CLL, for which he had received chlorambucil therapy 10 years earlier, developed progressive paresis of both left extremities at 7 months of receiving low doses of oral fludarabine, when his CD4 count has decreased to 0.08 x 10(9)/l. Cranial magnetic resonance imaging revealed a subcortical focal lesion at the right precentral gyrus and a focal lesion at the right thalamus, and a stereotactic brain biopsy showed pathological findings consistent with PML, namely severe myelin breakdown, reactive astrocytosis, and abnormal, huge glial cells with large bizarre nuclei showing granular basophilic inclusions, whereas the presence of the jc virus was demonstrated by in situ hybridization. The present case, in addition to a few previously reported, calls attention to the possibility that severe neurological side effects can be associated with the immunosuppression provoked by the use of fludarabine in CLL patients.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/20. infection with jc virus and possible dysplastic ganglion-like transformation of the cerebral cortical neurons in a case of progressive multifocal leukoencephalopathy.infection of the cerebral cortical neurons with jc virus (JCV) with possible dysplastic ganglion-like alteration of the infected neurons found in a case of progressive multifocal leukoencephalopathy (PML) is described. The patient was a 21-year-old man with common variable immunodeficiency who died of PML after a 9-month clinical course. At autopsy, the white matter of the cerebrum, brainstem, cerebellum, and spinal cord exhibited extensive demyelination and necrosis. Numerous inclusion-bearing oligodendrocytes and bizarre astrocytes were found. In the occipital and temporal cortex, thick band-like aggregates of dysplastic ganglion-like cells (DGLCs) were found. These DGLCs showed immunohistochemical properties of neurons, and nuclei of some DGLCs were immunoreactive for large T antigen of SV40/JCV and p53, but not for capsid protein JCV VP1. in situ hybridization for mRNA of JCV large T antigen revealed positive signals in the nuclei of some DGLCs. These results indicate that JCV infected neurons and it is suggested that binding of the large T antigen with cellular proteins could have resulted in the dysplastic, ganglion cell-like change of the infected neurons, although the possibility that the aggregates of DGLCs represent a pre-existent malformative lesion of the cortex cannot be excluded completely.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/20. Detection of human herpesvirus 6 and jc virus in progressive multifocal leukoencephalopathy complicating follicular lymphoma.Progressive multifocal leukoencephalopathy (PML), a demyelinating infectious disease caused by jc virus (JCV), occurs almost exclusively in immunocompromised patients usually with malignant diseases. We report here a Japanese female with follicular lymphoma who subsequently developed PML. In addition to JCV, human herpesvirus 6 (HHV-6) was detected in the affected brain lesions of the patient by polymerase chain reaction and by in situ hybridization. HHV-6, recognized as a neurotropic virus, is known to be reactivated during immunosuppression and can cause fatal complications such as encephalitis/encephalopathy. It is likely that impaired immunity associated with lymphoma and the additional immunosuppression following cytopenia-inducing chemotherapies predisposed the patient to reactivated HHV-6 infection. Although it remains to be clarified whether HHV-6 plays an important role as a co-agent with JCV in causing demyelination of the brain, our observation alerts physicians to the possible association of HHV-6 with the pathogenesis of PML.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/20. Vacuolar myelopathy and vacuolar cerebellar leukoencephalopathy: a late complication of AIDS after highly active antiretroviral therapy-induced immune reconstitution.Controversy exists as to whether vacuolar myelopathy (VM) responds to highly active antiretroviral therapy (HAART) in a salutary fashion similar to other primary human immunodeficiency virus (HIV)-related neurologic complications such as acquired immune deficiency syndrome (AIDS) dementia complex and progressive multifocal leukoencephalopathy. Herein, we describe the case of a patient with AIDS, non-Hodgkin's lymphoma, and cytomegalovirus colitis, who began HAART and cytotoxic chemotherapy. After 6 months of therapy, restaging studies showed no residual lymphoma or active opportunistic infection. For 2 years he was maintained on HAART, during which time his HIV viral load remained nondetectable and his CD4 count improved from 20 to 300 cells per microliter. Shortly after developing the acute onset of cerebellar ataxia, he aspirated, developed adult respiratory distress syndrome, and died. At autopsy the spinal cord demonstrated a characteristic vacuolated appearance that extended into the cerebellum. No relation between HIV and the development of VM was discerned by in situ hybridization studies. Experience with this one patient suggests that HAART may not alter the natural history of VM. Whether this case represents yet another variant of the recently described inflammatory immune response syndrome whereby progression of previously quiescent disorders evolve to symptomatic disease after initiation of HAART is uncertain.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/20. Progressive multifocal leukoencephalopathy and gliomas in a HIV-negative patient.A case of progressive multifocal leukoencephalopathy (PML) is reported, detected at autopsy of a 30-year-old patient. The clinical picture was characterized by a progressive course of mental deterioration and ingravescent neurological symptoms. The patient was HIV-negative. He died of bronchopneumonia, after a clinical course of 13 months. autopsy disclosed pulmonary tuberculosis with involvement of regional lymph nodes. In the brain, besides numerous PML-foci of varying age and structure, a pleomorphic astrocytoma was found in the white matter of the right parietal lobe. In the brain stem glial proliferation resembling diffuse gliomatosis was also present. in situ hybridization revealed Papova-virus (JCV) in oligoglial nuclei, but not in neoplastic astrocytes. This is the third report on the concomitant occurrence of PML and glioma in man.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/20. Productive infection of cerebellar granule cell neurons by jc virus in an HIV individual.BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An hiv-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV dna was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/20. Genetic analysis of jc virus and bk virus from a patient with progressive multifocal leukoencephalopathy with hyper IgM syndrome.A case of acute progressive multifocal leukoencephalopathy (PML) with hyper IgM syndrome 1 is reported. Viral dna and VP1 protein of jc virus (JCV) and bk virus (BKV) were detected by immunohistochemistry, in situ hybridization, semi-nested polymerase chain (PCR) and PCR-restriction enzyme analysis. JCV dna and VP1 protein were found in the nuclei of oligodendrocytes. The non-coding control region (NCCR) and VP1 region of the JCV genome were sequenced; this revealed a novel rearrangement pattern of the NCCR in the brain tissue. The VP1 regions of brain and urine JCV were identical and of genotype type 2A. The BKV in the urine sample was genotype I. No BKV genome was found in the brain. The novel genomic rearrangement of the JCV NCCR in the brain tissue may have altered JCV pathogenesis to induce PML; the impaired immunity from hyper IgM syndrome 1 may have enabled the rearrangement. The JCV NCCR rearrangement in the brain may have originated from the archetypal form in the urine through deletion and duplication.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/20. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis.A 46-year-old woman with relapsing-remitting multiple sclerosis died from progressive multifocal leukoencephalopathy (PML) after having received 37 doses of natalizumab (300 mg every four weeks) as part of a clinical trial of natalizumab and interferon beta-1a. PML was diagnosed on the basis of the finding of JC viral dna in cerebrospinal fluid on polymerase-chain-reaction assay and was confirmed at autopsy. Nearly every tissue section from bilateral cerebral hemispheres contained either macroscopic or microscopic PML lesions. There was extensive tissue destruction and cavitation in the left frontoparietal area, large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes, which were positive for jc virus dna on in situ hybridization.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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