PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Leukoencephalopathy, Progressive Multifocal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1976

Virus-cell interaction in oligodendroglia, astroglia and phagocyte in progressive multifocal leukoencephalopathy. An electron microscopic study.

A 46-year-old female, with an 11 year history of malignant lymphoreticular disease, developed a neurological illness clinically manifested by a focal mass lesion in the left frontal lobe. In biopsied tissue, immunofluorescence study revealed the presence of JC antigen in the glial cells. Histologically, the lesion was characteristic of PML consisting of PML consisting of focal necrosis in the subcortical white matter, numerous fat laden macrophages and marked hypertrophy of oligodendrocytes and astrocytes. By electron microscopy, hypertrophic astrocytes contained intranuclear viral particles consistent with papova virions and aggregates of intracytoplasmic viral particles consisting of a single to several virions tightly surrounded by a single membrane. The membrane appeared to have been derived from that of the cellular vesicles. Fusion of the virus-associated membrane to the astroglial plasmalemma occurred when the virions appeared to shift towards extracellular space. The virioncontaining astrocytes showed cytoplasmic "fibrillar hypertrophy" similar to the characteristic gigantic astroglias of PML. This fact would provide an additional evidence that these gigantic cells, although lacking identifiable viral structures, were the result of anaplastic transformation by JC virus. Many virus-bearing astroglias were noted to be in the early stage of cellular necrosis, of "edematous degeneration". This further indicates that the JC virus is capable of inducing both lytic and abortive astroglial infections. Many oligodendroglias were hypertrophic due to the presence of intranuclear viral particles and markedly increased numbers of microtubules and free ribosomes in the cytoplasm. Membrane-bound intracytoplasmic viral particles were also noted in the oligodendroglias. Some fat laden macrophages contained large intracytoplasmic viral bodies, presumably originating from phagocytized virus-bearing cells.

Astrocytes↗
PubMed2000

[Clinico-epidemiologic manifestations of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome (AIDS)].

BASIS: Severely immunosuppressed patients, including those with AIDS in advanced stage, can suffer opportunistic infections, between them PML. The purpose of this study is to determine epidemiological, clinical and neuroradiological parameters of HIV infected patients diagnosed of PML. METHOD: Retrospective review of clinical histories and clinical as well as radiological characteristics, of seven patients diagnosed of AIDS and PML in the Infectious Diseases Unit of our center between January 1990 and December 1997. RESULTS: Seven patients out of 1093 HIV infected patients were diagnosed of PML (0.76%). All of them were male, intravenous drug users, with a mean age of 32.1 years. Five patients were diagnosed before 1994. In four cases PML was the first opportunistic infection. The mean survival time was 119 +/- 82.2 days (27-231 days). At the moment of diagnosis four patients (57.1%) showed cerebellar symptoms, three (42.8%) sensory deficits and two (28.5%) cognitive dysfunction. There were multiple neurological symptoms in five cases. The mean CD4 cell count was 63.4 cells/mm3. None of the patients showed other concomitant opportunistic infections neither disturbances of cerebrospinal fluid (CSF). CT and NMR showed typical lesions in frontal lobe and cerebellum in four patients. Other affected areas were occipital and parietal lobe, basal ganglia and brain stem. The diagnosis of PML was established by clinical and neuroradiological criteria in six patients and by autopsy in one patient. CONCLUSIONS: The diagnosis of PML in HIV infected patients can be made by clinical and neuroradiological criteria. In the last years, and probably due to the new antiretroviral agents, it has been observed a decrease of the PML incidence in these patients. Nevertheless its prognosis is still dreadful and at present there is no specific curative treatment.

AIDS-Related Opportunistic Infections↗
PubMed1989

The identification of cells containing JC papovavirus DNA in progressive multifocal leukoencephalopathy by combined in situ hybridization and immunocytochemistry.

A double-labelling technique combining in situ hybridization and immunocytochemistry is described which was used to characterize cells in the central nervous system containing JC virus DNA in formalin-fixed, paraffin-embedded tissues from four cases of progressive multifocal leukoencephalopathy. All four cases showed positive nuclear labelling for JC virus in both oligodendrocytes and astrocytes. The latter gave a strongly positive cytoplasmic staining reaction using antibodies to glial fibrillary acidic protein and vimentin. No nuclear labelling of neurones or endothelial cells was noted. The results confirm previous suggestions that glia are the main cells infected by JC virus in this disorder and show that the distribution of viral DNA in the brain is more extensive than suggested by routine microscopy alone. In situ hybridization for JC virus may be useful in confirming the diagnosis of progressive multifocal leukoencephalopathy in both surgical biopsies and post-mortem brain tissue.

Adult↗
PubMed1998

Progressive multifocal leukoencephalopathy (PML) and cerebral toxoplasmosis in an adult patient, with no symptoms of underlying immunosuppressing illness.

We present a case of the coincidence of progressive multifocal leukoencephalopathy (PML) and central nervous system (CNS) toxoplasmosis in an adult patient, without a detectable cause of cell-mediated immunity impairment. The proper diagnosis was made postmortem on the basis of histological changes typical of both pathological processes. PML was characterized by the presence of subcortical focal demyelination, containing enlarged, densely basophilic oligodendrocyte nuclei, often with intranuclear inclusion, and bizarre astrocytes, mimicking neoplastic cells. PML was confirmed by detecting numerous papova virus particles in oligo- and astroglial nuclei by thin-section electron microscopy. Cerebral toxoplasmosis was characterized by the presence of multiple well-circumscribed necrotizing abscesses. Numerous Toxoplasma gondii (T. gondii) cysts and free, non-encysted protozoan parasites were found among the inflammatory infiltrates. The diagnosis of cerebral toxoplasmosis was further confirmed by immunocytochemistry. In order to detect putative immunosuppressive background underlying both pathological processes, HIV infection was taken into consideration, however, no histopathological changes indicative of AIDS either in the CNS or in the peripheral organs were eventually found. Moreover no HIV provirus genome was identified in the formalin-fixed, paraffin embedded brain tissue by the polymerase chain reaction (PCR). Current view on the selected aspects of the pathogenesis of both disorders were discussed.

Antigen Presentation↗
PubMed1995

AIDS-associated progressive multifocal leukoencephalopathy revealed by new-onset seizures.

PURPOSE: To describe the clinical features of new-onset seizures in HIV-1-infected persons with progressive multifocal leukoencephalopathy (PML), and to discuss potential mechanisms. PATIENTS AND METHODS: Forty-nine consecutive HIV-1-infected patients with PML attended our institutions between January 1988 and September 1993. We retrospectively analyzed cases with seizures as the presenting symptom of PML. RESULTS: Twenty percent of the HIV-1-infected patients with PML presented with new-onset seizures of various types, generalized or partial. None of them met the criteria of the AIDS dementia complex or had a concomitant opportunistic infection. Their mean CD4 cell count was < 60/mm3. Brain magnetic resonance imaging showed areas of increased signal intensity on T2-weighted images in 9 cases, and atrophy in only 1 case. Lesions most often involved subcortical white matter in parieto-occipital or frontal lobes, but 2 patients had posterior fossa lesions. Image-guided stereotactic brain biopsies in 8 cases and postmortem examination in 2 confirmed the diagnosis of PML. Typical histological lesions were observed in all cases, and positive immunolabelling of oligodendroglial nuclei was obtained in all cases with the polyclonal antibody directed against late SV40 antigens. Putative causative factors for the seizures include demyelinated lesions adjacent to the cerebral cortex acting as irritative foci, axonal conduction abnormalities, or disturbances of the neuron-glia balance. CONCLUSION: These cases illustrate that PML should be considered as a possible cause of new-onset seizures in patients with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Progressive multifocal leukoencephalopathy and human immunodeficiency virus-associated white matter lesions in AIDS: magnetization transfer MR imaging.

PURPOSE: To determine the magnetization transfer features of progressive multifocal leukoencephalopathy (PML) and human immunodeficiency virus (HIV)-associated white matter lesions (WML) (hereafter, HIV-WML) on magnetic resonance (MR) images obtained in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Conventional MR imaging and magnetization transfer MR imaging were performed in 21 AIDS patients with 42 areas of white matter hyperintensity on MR images (13 patients had 25 PML lesions, eight patients had 17 WML). The magnetization transfer ratio was calculated for each lesion. RESULTS: Compared with normal-appearing white matter (magnetization transfer ratio = 47.9%), both PML and HIV-WML showed reduced magnetization transfer ratio. The magnetization transfer ratio was significantly lower in PML lesions (magnetization transfer ratio = 26.1%) than in HIV-WML (magnetization transfer ratio = 38.0%, P < .0001), and there was no overlap in the magnetization transfer ratio between PML lesions and HIV-WML. The separation in magnetization transfer ratio between the two lesion types was valid for lesion as small as 0.5 cm2. CONCLUSION: The larger reduction in magnetization transfer ratio for PML lesions is most likely due to demyelination, whereas the reduction in HIV-WML may be associated primarily with gliosis. PML lesions appear to cause strong reductions in magnetization transfer ratio early in the course of disease. Magnetization transfer MR imaging is a noninvasive tool that improves the differentiation between PML and HIV-WML in patients with AIDS.

AIDS Dementia Complex↗
PubMed2000

Progressive multifocal leukoencephalopathy: simultaneous detection of JCV DNA and anti-JCV antibodies in the cerebrospinal fluid.

We report on a case of biopsy-proven progressive multifocal leukoencephalopathy (PML) in a patient without obvious immunodeficiency. Analysis of the cerebrospinal fluid revealed the simultaneous presence of JC virus DNA and of locally produced, anti-JC virus antibodies. The intrathecal humoral immune response increased throughout the course of the disease, whereas the detection of the JC genome became ultimately negative in spite of the continuous extension of the lesions with fatal outcome.

Aged↗
PubMed1998

Treatment of AIDS-associated progressive multifocal leukoencephalopathy with highly active antiretroviral therapy.

OBJECTIVES: To evaluate the efficacy of highly active antiretroviral therapy (HAART) in 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML). PATIENTS AND METHODS: The diagnosis of PML was established by brain biopsy in six patients and by neuroimaging findings and PCR detection of JC virus in cerebrospinal fluid (CSF) in six patients. We also studied 13 consecutive AIDS patients with biopsy-proven PML cared for in the same institution before HAART was available. Eleven patients of the HAART group and eight patients of the control group received intravenous arabinoside cytosine cycles. RESULTS: With HAART, the median decrease in the HIV viral load was 3.58 log10 copies/ml and the median increase in the CD4 cell count was 74x10(6)/l. The median survival time after PML diagnosis was 545 days in the HAART group and 60 days in the control group (P<0.001, log-rank test). In the HAART group, the neurological deficits improved substantially in six patients and stabilized in six patients. Eleven patients underwent follow-up cranial computed tomography or magnetic resonance scan that showed improvement of PML lesions in 10 patients and stabilization in one patient. Follow-up CSF analysis showed clearance of JC virus in six out of seven patients who had an initial positive result. CONCLUSIONS: This study shows that HAART may increase the survival, clinical status and radiological features of AIDS patients with PML. Clearance of JC virus from CSF has been found, suggesting that immune reconstitution can interrupt the JC virus lytic cycle.

AIDS-Related Opportunistic Infections↗
PubMed1993

Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure.

We have compared the promoter/enhancer structure of human polyomavirus JC (JCV) isolates from 11 progressive multifocal leukoencephalopathy brains. The duplications and deletions of the regulatory region were different in each patient, and usually only one sequence was found in each. The sites of strand breakage in the promoter were not random; four or five preferred sites or areas exist. Alignment of the JCV prototype Mad-1 regulatory region with the unduplicated archetypal structure defines six blocks of sequence, A to F. The preferred sites of strand breaks delineate these regions, although Mad-1 is an unusual promoter containing a break site not observed in other isolates, and an additional site is targeted in several promoters. Region A, containing the TATA box, and the first half of region C, containing several enhancer elements, and region E are consistently retained. Region B, the 23 bp insertion in the archetypal structure (relative to Mad-1) was also retained in all 11 isolates. Region D, the 66 bp insertion, was retained in isolates from three patients. Regions A and D were never duplicated, whereas regions C and E usually were duplicated or triplicated. Variation in the exact point of breakage within the preferred sites, alternative use of the sites in individual promoters and occasional short deletions at other sites result in sequences that are unique in each case. At the same time, the limited choice of break sites and the characteristic fates of the regions themselves result in three broad patterns of repeat sequences. The patterns do not correspond to the viral genotypes 1 and 2 defined by coding region base changes, and do not appear to be a stable feature of the virus. Rather, rearrangements appear to be generated in the host from a basic archetypal sequence.

Base Sequence↗
PubMed1988

Human immunodeficiency virus (HIV) and JC virus in acquired immune deficiency syndrome (AIDS) patients with progressive multifocal leukoencephalopathy.

Of the 93 acquired immune deficiency syndrome (AIDS) patients autopsied between 1983 and 1986, 27 had evidence of viral encephalitis of which 3 had progressive multifocal leukoencephalopathy (PML), confirmed by electron microscopy. Using in situ hybridization with biotinylated JC virus probes, paraffin sections from the brains of these 27 patients were examined. JC virus was found only in those patients with histologically proven PML, while no evidence of JC virus was detected in the brains of the other 24 AIDS patients despite the presence of white matter pathology. Brain biopsies of the PML patients demonstrated human immunodeficiency virus (HIV)-infected macrophages infiltrating regions of demyelination. When the patients died (2 to 6 months after diagnosis of PML), many more macrophages contained HIV antigens and some had fused to form multinucleated giant cells. These findings suggest that in AIDS patients, papovaviruses not only cause damage by directly infecting oligodendroglia but causes additional damage by eliciting the ingress of macrophages latently infected with HIV. As was seen with other infections (e.g., cytomegalovirus) of the CNS this might be a general mechanism of HIV entry into the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Improved detection of JC virus DNA in cerebrospinal fluid for diagnosis of AIDS-related progressive multifocal leukoencephalopathy.

Several methods to increase the sensitivity of JC virus (JCV) DNA detection in cerebrospinal fluid (CSF) for a noninvasive diagnosis of AIDS-related progressive multifocal leukoencephalopathy (PML) were investigated. When CSF collected at clinical presentation was tested, JCV DNA was detected in 8 of 19 patients with PML by standard PCR (sensitivity, 42%; 95% confidence interval [CI], 21 to 66%) and in 14 of 19 by nested PCR (sensitivity, 74% [95% CI, 49 to 90%]; P = 0.014 [McNemar's test]. For multiple serial CSF samples, standard PCR yielded JCV DNA for 11 of 19 PML patients (sensitivity, 58% [95% CI, 34 to 79%]) and nested PCR yielded JCV DNA for 17 of 19 patients (sensitivity, 90% [95% CI, 66 to 98%]; P = 0.014). The majority of the false-negative samples were found to contain PCR inhibitors. Standard PCR did not detect JCV DNA in CSF from any of the 83 AIDS patients with other diagnosis (100% specificity [95% CI, 95 to 100%]); JCV DNA was found in CSF from one control patient by nested PCR (99% specificity [95% CI, 93 to 100%]).

AIDS-Related Opportunistic Infections↗
PubMed1992

Two major types of JC virus defined in progressive multifocal leukoencephalopathy brain by early and late coding region DNA sequences.

A 610-bp region of the JC virus (JCV) genome sequenced from brains of 11 progressive multifocal leukoencephalopathy (PML) patients contains 20 sites of point mutations that allow reliable classification of JCV isolates into two types. These type-determining sites were located in the region extending from position 2131 in the VP1 gene, through the intergenic region, to position 2740 in the T antigen gene. At these 20 sites the presence of different nucleotides creates two distinct patterns of substitution, with six isolates having the Type 1 pattern and five having the Type 2 pattern. Only four of the 11 isolates had 'crossovers' to the opposite type consensus DNA sequence at a small number of sites, indicating a very high type specificity. Additionally, three type-determining sites occur in the non-coding region to the left of the origin of replication. Other mutations occurred at random sites, making each strain unique, although one strain, 105, is identical to the Type 1 consensus. The JCV prototype strain Mad-1 was found to be Type 1 and differs from the consensus sequence at five sites. The other previously sequenced JCV strain, GS/B, is Type 2. At three sites out of five in the T antigen C terminus there is a type-specific amino acid substitution; however, none of the type-determining mutations in the VP1 gene cause an amino acid substitution. Comparison of each type's consensus DNA sequence to that of BK virus suggests that Type 2 represents the ancestral JCV sequence from which Type 1 diverged during human evolution.

Antigens, Polyomavirus Transforming↗
PubMed2000

Human herpesvirus 6-meningoencephalitis in an HIV patient with progressive multifocal leukoencephalopathy.

Human herpesvirus 6 (HHV6) has been reported as a rare cause of meningoencephalitis and leukoencephalitis. We present an HIV-infected patient with lesions of progressive multifocal leukoencephalopathy (PML), but also meningoencephalitis apparently due to HHV6. Immunohistochemistry for HHV6 antigens and in situ polymerase chain reaction for HHV6 genome showed many positive lymphocytes and microglia in the meningeal and cortical lesions. More importantly, dead and dying neurons were conspicuous; some were undergoing neuronophagia and some displayed evidence of HHV6 infection. A pathogenic role for this almost universal, and usually commensal, virus in inflammatory brain lesions and PML is briefly discussed.

Adult↗
PubMed1999

Relation of JC virus DNA in the cerebrospinal fluid to survival in acquired immunodeficiency syndrome patients with biopsy-proven progressive multifocal leukoencephalopathy.

The detection and semiquantitation of JC virus (JCV) DNA in cerebrospinal fluid (CSF) is prognostic of survival and is a marker of the course of progressive multifocal leukoencephalopathy (PML). CSF samples from 15 acquired immunodeficiency syndrome (AIDS) patients with biopsy-proven PML were analyzed by semiquantitative polymerase chain reaction (PCR). A low JCV burden was predictive of longer survival compared with a high JCV burden (median survival from entry, 24 [2-63] vs 7.6 [4-17] weeks). Further analyses indicated a possible threshold of 50 to 100 copies/microl separating high- and moderate-risk cases. Patients with a JCV load below this level survived longer than those with a JCV load above it.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Progressive multifocal leukoencephalopathy. A case report with special reference to SV40 etiology.

Clinical, light- and electron microscopic, and immunohistochemical findings of a 44-year-old woman with progressive multifocal leukoencephalopathy were presented. Autopsy revealed a wide distribution of the demyelinating lesion in the cerebrum, cerebellum, brain stem and spinal cord, and intranuclear inclusion bodies and papova-like virions in transmission electron microscopy in the nuclei of oligodendrocytes. SV40 antigen was immunohistochemically detected in these inclusion bodies. The widespread extension of the lesions seemed to correlate with the duration of the patient's illness. The prolongation of the clinical course in this case may be dependent upon the lack of serious underlying diseases except for a small nodule of thyroid carcinoma, SV40 infection rather than JC virus infection and/or improved care of that kind of patient.

Adenocarcinoma↗