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At least 19 recordsLinked to original sources
PubMed2001

Progressive Multifocal Leukoencephalopathy.

Progressive multifocal leukoencephalopathy is a subacute demyelinating disease that occurs in patients with defects in cell-mediated immunity, including those with AIDS and lymphoproliferative disorders. It is caused by reactivation of JC virus (JCV), which infects 70% to 90% of the population by adulthood, but remains latent in normal hosts. Once reactivated, JCV infects oligodendrocytes and astrocytes, with resultant cell lysis, leading to focal areas of demyelination and necrosis in cerebral white matter causing focal neurologic deficits and characteristic findings on MRI. Polymerase chain reaction for the detection of JCV is a sensitive and specific test, replacing brain biopsy as the initial diagnostic test in the appropriate clinical setting. Historically, the prognosis of progressive multifocal leukoencephalopathy is poor, with most patients dying within 6 months of diagnosis. Antiviral medications targeted against JCV have shown little success. However, with the use of highly active antiretroviral therapy, survival of AIDS patients with progressive multifocal leukoencephalopathy has improved.

Journal Article↗
PubMed2005

JC virus granule cell neuronopathy: A novel clinical syndrome distinct from progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) typically affects the CNS white matter of the central nervous system. We present an human immunodeficiency virus-infected patient with polyomavirus JC infection restricted to granule cell neurons of the cerebellum and with corresponding neurological symptomatology. Magnetic resonance imaging demonstrated cerebellar atrophy without white matter lesions and stereotactic biopsy showed selective infection of the cerebellar granular cell layer, with preservation of Purkinje cells and absence of classic progressive multifocal leukoencephalopathy histopathology in underlying white matter. Evolution over 8 years was marked by symptomatic improvement corresponding to highly active antiretroviral therapy (HAART), with modest increase in CD4(+) T-cell counts. We propose to call this novel syndrome JCV granule cell neuronopathy (JCV GCN).

Adult↗
PubMed1998

Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) complicating the acquired immunodeficiency syndrome (AIDS) is typically inexorably progressive with death usually occurring within 6 months of symptom onset. Occasional patients have been observed to survive longer than 1 year, often with remission of clinical features. In this study, we identify predictive factors for prolonged survival in patients with biopsy proven, AIDS-associated PML, by comparing 7 patients with survival exceeding 12 months from symptom onset with 45 patients with shorter survivals. PML was the presenting manifestation of AIDS in 5 (71.4%) of 7 long-term survivors compared with 8 (17.8%) of 45 short-term survivors. CD4 T-lymphocyte counts were substantially higher in the long-term survivors, with 3 (42.9%) of 7 having counts exceeding 300 cells/mm3 in comparison with only 1 (4.3%) of 23 short-term survivors. Contrast enhancement on radiographic imaging was observed in 3 (50%) of 6 long-term survivors in comparison with 4 (8.9%) of 45 short-term survivors. Neurological recovery and radiographic improvement were not observed in any short-term survivors but were seen in 5 (71.4%) long-term survivors. There was no association between treatment modalities and survival. Predictors of long-term survival in AIDS patients with PML include PML as the heralding manifestation of AIDS, high CD4 T-lymphocyte count at disease onset, lesion enhancement on computed tomographic scan or magnetic resonance imaging, and evidence of recovery of neurological function.

AIDS-Associated Nephropathy↗
PubMed1988

Progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy, a demyelinating disease of the central nervous system, is caused by a polyomavirus. This opportunistic virus is demonstrable in affected brain tissue obtained by biopsy or at autopsy. The disease commonly occurs in immunocompromised patients secondary to lymphoproliferative disease, immunosuppressive therapy, autoimmune disorders and acquired immunodeficiency syndrome. The prognosis is poor.

Adult↗
PubMed2003

Challenges for clinical trials to treat progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy is a lethal complication of immunodeficiency for which no direct therapy has been achieved. The issues that have made this disease especially difficult to address are discussed, and an outline for development of future interventions is provided. A controlled trial of therapy utilizing an international group of trial groups is proposed.

Antiviral Agents↗
PubMed1976

Absence of imune deficiencies in a case of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare disease related to a slow virus infection of the central nervous system; it is usually seen in patients who have impaired immunologic function. The present patient with biopsy-proved PML was found to have no demonstrable defects in either cellular or humoral immunity as assessed by multiple parameters. Thus, it appears that PML may occur in the presence of intact immune responses.

Biopsy↗
PubMedDate not supplied

[Progressive multifocal leukoencephalopathy].

Progressive multifocal leukoencephalopathy (PML) is rare and very severe disease, classified into the group of subacute and viral infections of central nervous system (CNS), and can simulate clinical pictures of numerous degenerative diseases of nervous system. PML was firstly described in 1958, and pathologic-morphologic substrate was explained in papers of Astron et al. Many years later, definitive diagnosis of PML was histopathologic, on the autopsy material. The fact that it is very rare and severe disease, very rarely diagnosed in clinical conditions, is the reason of our decision to present this case.

Adult↗
PubMed2000

Lack of disease-specific amino acid changes in the viral proteins of JC virus isolates from the brain with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system caused by a ubiquitous human polyomavirus designated as JC virus (JCV). JCVs in the brain of PML patients (PML-type JCVs) contain various regulatory regions generated from the archetypal regulatory region during persistence in the patients. We determined the complete DNA sequences of 2 PML-type isolates and 5 archetype isolates. Amino acid sequences of individual viral proteins were deduced from complete DNA sequences, and were compared among 16 isolates (6 PML types and 10 archetypes). From the data obtained, we concluded that PML-associated amino acid changes did not occur in the viral proteins of PML-type JCVs.

Amino Acid Sequence↗
PubMed1997

[Progressive multifocal leukoencephalopathy].

Progressive multifocal leukoencephalopathy (PML) is the only polyomavirus infection in human caused by JC virus. Clinically PML is diagnosed by neurological signs, supported by MRI and PET, but its pathologic diagnosis at brain biopsy remains to be a confirmative method, although the PCR method, using csf, gives a predictive value. Virological study of the regulatory region of viral genome has suggested that PML-inducing viral type may be derived from the urine-excreted virus (archetype) by mechanisms involving nucleotide deletion and duplication. Viral neurotropism has been shown to be closely related to transcriptional function of the viral promoter-enhancer which cellular proteins bind to and is activate by. Of these, NF-1 binding proteins, glial factor-1, Tst-1 (SCIP, Oct-6) and others should be tested for their specificity to human glial cell.

Humans↗
PubMed2002

Traffic of JC virus from sites of initial infection to the brain: the path to progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the human brain caused by infection with the human polyomavirus, JC. Up to 80% of humans express serum antibodies to JC virus (JCV), yet considerably fewer people develop PML-predominantly those under immunosuppressive conditions. Recent research showed JCV infection in multiple tissues throughout the body, suggesting sites for viral latency. These observations allow the proposal of pathways that JCV may use from sites of initial infection to the brain. Results from investigations into cell-surface receptors, intracellular DNA-binding proteins, and variant viral regulatory regions also suggest mechanisms that may regulate cellular susceptibility to JCV infection. Together, these data elucidate how JCV may establish infection in various cell types, persist latently or become reactivated, and ultimately reach the brain to cause PML.

Brain↗
PubMed1986

JC papovavirus large tumor (T)-antigen expression in brain tissue of acquired immune deficiency syndrome (AIDS) and non-AIDS patients with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a JC papovavirus infection of the central nervous system in immunocompromised patients. It is well established that demyelination in PML is caused by JC virus infection of oligodendroglia, but whether the nonstructural regulatory protein, large tumor (T) antigen, is detectable in infected human tissue was not known. Using a modification of the peroxidase-antiperoxidase technique, we found T antigen expressed in the nuclei of cells in virus-infected sites in five cases of PML studied, including two with acquired immune deficiency syndrome (AIDS). PML occurs in AIDS at a much higher frequency than in other immunosuppressive disorders, and PML in AIDS may represent a more severe form of JC virus infection of the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy results from an opportunistic infection of myelin-producing oligodendrocytes by the glia-specific human papovavirus JC. In this report, evidence is presented that the glial transcription factor Tst-1, a member of the POU-domain family, stimulates transcription of both early and late viral genes. Stimulation was dependent on site-specific binding of Tst-1 to the JC viral regulatory region and on the presence of an intact amino-terminal transactivation domain within Tst-1. Because of its ability to increase the expression of viral large tumor antigen, Tst-1 stimulated viral DNA replication, without participating directly in the replication event. Our results suggest that Tst-1 is one of the determining factors in the glia specificity of JC virus.

Base Sequence↗
PubMedDate not supplied

A case study: the use of cidofovir for the management of progressive multifocal leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic infection of the brain in advanced stages of AIDS. PML is caused by the JC virus, which leads to a decline in mental acuity and motor functions over a period of weeks or months. Currently, there is no treatment or cure for PML. Cidofovir, an antiviral agent, at the standard dosages for the treatment of cytomegalovirus (CMV) was implemented in the treatment and management of a 35-year-old, newly diagnosed AIDS, White male with PML. The patient presented with impaired motor functions of the left upper and lower extremities, which resulted in hemiparalysis and hemiparesis. The use of cidofovir infusions at standard recommendations for treatment and management of CMV has resulted in improvement and some resolution of the patient's paralysis and paresthesia. The patient has remained on the cidofovir for more than a year, with no signs of advancement of his PML or AIDS. Further investigation and extensive clinical trials are needed in the treatment and management of PML with the use of cidofovir.

AIDS-Related Opportunistic Infections↗
PubMed1997

Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a subacute viral infection of oligodendrocytes by JC virus occurring almost exclusively in immunocompromised patients. By use of partially purified recombinant VP1 as antigen, the IgG response was analyzed by a quantitative ELISA of paired cerebrospinal fluid (CSF) and serum samples. An intrathecal immune response to VP1, defined as an antibody-specificity index of CSF to serum antibody titers > or =1.5, was found in 76% of PML patients (47/62) but in only 3.2% of controls (5/155) (P < .001). Intra-blood-brain barrier synthesis of VP1-specific IgG antibodies is 76% sensitive and 96.8% specific for the diagnosis of PML. Furthermore, the excellent correlation (r = .985) between the plasma cell count in brain tissue and the humoral intrathecal immune response to VP1 in PML patients suggests a role for B cells in this disorder.

Adolescent↗
PubMed1995

[MRI aspects of progressive multifocal leukoencephalopathy].

Progressive Multifocal Leukoencephalopathy is a demyelinating disease. MRI shows high signal intensity areas on T2w sequence and low intensity aeras on T1w sequence, without enhancement after intravenous contrast injection. The involvement of arcuate fiber (U fibers) creates a sharp border with the cortex. There is no mass effect. Involvement of parieto-occipital areas is frequent. The lesions may be uni or bilateral, single or multiple; bilateral lesions are asymmetric. This typical appearance on MR images occurs in 90% of the patients with PML. Some atypical patterns may occur: focal hemorrhage, atrophy, faint peripheral enhancement and involvement of deep gray matter (basal ganglia). In most cases, the clinical and MR features provide the diagnosis. The main differential diagnosis, in MRI, is HIV-leukoencephalitis, but lesions are diffuse, less intense on T2w sequence and not visible on T1, without involvement of the arcuate fibers. Stereotactic biopsy should be performed only for atypical lesions, particularly in case of predominant involvement of deep gray structures.

AIDS Dementia Complex↗
PubMed1992

Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

Base Sequence↗
PubMed2003

Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than nonresponders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Cellular and humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a fatal, demyelinating disease caused by JC virus (JCV) in patients with severe immunosuppression. We studied the JCV-specific cellular and humoral immune response in 7 healthy donors (HD), 6 human immunodeficiency virus-1 (HIV-1)-infected patients without PML (HIV), 4 HIV-1-negative patients with PML (PML), and 8 HIV-1-positive patients with PML (HIV/PML). As antigens, recombinant virus-like particles of the major structural protein VP1 (VP1-VLP) of JCV, tetanus toxoid (TT), or the mitogen phytohemagglutinin (PHA) were used. Proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with the VP1-VLP was significantly suppressed in PML and HIV/PML patients compared to HD. After antigen stimulation the production of interferon-gamma (IFN-gamma) was reduced in PML, in HIV/PML, and in HIV patients. The production of interleukin-10 (IL-10), however, was elevated in HIV/PML patients. Neither proliferation nor cytokine production correlated with the presence of JCV DNA in PBMC. The immunoglobulin G serum antibody titer to the VP1-VLP was slightly elevated in HIV, elevated in PML, and highly elevated in HIV/PML patients compared to HD. The development of PML appears to coincide with a general impairment of the Th1-type T-helper cell function of cell-mediated immunity.

Cytokines↗