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PubMed1978

Atypical progressive multifocal leukoencephalopathy and primary cerebral malignant lymphoma.

Atypical progressive multifocal leukoencephalopathy occurred in an 82-year-old man with long-standing chronic lymphocytic leukemia. The multifocal white matter lesions revealed demyelination and gliosis, relative preservation of axons and a prominent plasma cell infiltrate. Bizarre astrocytes were uncommon. There were no changes in the oligodendroglial nuclei and no inclusion bodies. Electron and immunohistofluorescence microscopy for papova virus were negative. In addition to this leukoencephalopathy a small primary cerebral lymphoma was present in the right occipital lobe. The tumor cells were plasmacytoid in appearance and their cytoplasm stained well with pyronin. They contained IgG by immunohistofluorescence microscopy. The neoplasm was considered an immunoblastic sarcoma (reticulum cell sarcoma) and thought to arise directly within foci of demyelination. Both disease processes, leukoencephalopathy and lymphoma, may have occurred on a background of immunosuppression.

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PubMed2005

[Clinical investigation of the 8 cases with AIDS (acquired immunodeficiency syndrome)-associated progressive multifocal leukoencephalopathy (PML)].

We experienced 8 cases of progressive multifocal leukoencephalopathy (PML) complicated by human immunodeficiency virus (HIV) type-1 infection from 1985 to 1999. These cases showed dementia, bradykinesia, dysarthria, hemiparesis, and so on. All of the cases were severely immunocompromised hosts, because none had more than 150/mm3 CD4 + lymphocytes; indeed, 5 of the cases were below 20/mm3. Other neurological complications except PML were primary CNS lymphoma, HIV encephalitis, and CMV encephalitis. The mean life durations was 7.6 months after the first symptom appeared, for all but one of the patients; the exceptional patient lived for 24 months after. Autopsy studies of the central nervous systems were performed for 7 cases, all of which showed extensive demyelinating lesions of the white matter, and in some cases these extended into the spinal cord. In contrast to Western countries, in Japan there have been few reports of AIDS-associated PML. Thus, this report was thought to be important here.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[CT and MRT in progressive multifocal leukoencephalopathy (PML)].

Radiological findings and course of progressive multifocal leukoencephalopathy in 14 patients (1 woman, 13 men; 13 HIV seropositive, 1 chronic lymphatic leukaemia) were analysed retrospectively and correlated with clinical symptoms. A total of 21 CT and 16 MRI studies were evaluated. CT scans and MR images of 9 patients, which had been obtained in less than two weeks, could be compared to each other. MRI was superior to CT: 6 lesions with a diameter of 1 cm and below were not detected on CT scans, in 5 patients the extent of lesions was underestimated. Cortical involvement, mass effect or signs of atrophy were missing. Only 1 of 67 lesions showed a tiny enhancement after Gd injection. Due to the pattern and spread of lesions, which showed a close correlation to the neurologic symptoms, three different types of PML are suggested: 1. initial precentral demyelinisation with contralateral hemiparesis (n = 8); 2. lesions in temporo-occipital locations with visual disturbances (n = 2); 3. predominantly bilateral lesions of cerebellar white matter with ataxia (n = 4).

Adult↗
PubMed2002

Detection of JC virus infection in progressive multifocal leukoencephalopathy: the first documented case in Thailand.

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating brain disease caused by human polyoma JC virus (JCV). This disease is an important cause of morbidity and mortality in AIDS patients. Definite diagnosis currently requires a brain biopsy. PCR for JCV of CSF, an emerging diagnostic tool, has a high specificity for the diagnosis of PML in patients with characteristics on clinical and neuroradiological findings. The authors report a 36-year-old woman who presented with prolonged fever, progressive weakness, and slow speech for 2 months. Clinical features and MRI findings were compatible with PML. Qualitative PCR for JCV of CSF showed a positive result. This report emphasizes the yield of PCR, the CSF for JCV in a diagnosis of PML, which may reduce the need for a brain biopsy in such cases.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Increased frequency of JC virus type 2 and of dual infection with JC virus type 1 and 2 in Italian progressive multifocal leukoencephalopathy patients.

To verify the possibility of different role of JC virus genotypes in the etiology of progressive multifocal leukoencephalopathy, we analysed several JC virus isolates amplified from AIDS patients with and without progressive multifocal leukoencephalopathy and healthy controls by nucleotide sequencing. Cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs) and urine from 52 AIDS patients suffering from various neurological diseases including 21 cases of progressive multifocal leukoencephalopathy, and PBMCs and urine from healthy subjects were evaluated by nested polymerase chain reaction (PCR) for the presence of DNA belonging to the highly conserved large T antigen (LT) of JC virus. The different JC virus subtypes were identified by nucleotide sequence analysis of the virion protein (VP1) genomic region. JC virus DNA was detected in all the CSF samples from the progressive multifocal leukoencephalopathy patients, but not in the CSF from non-progressive multifocal leukoencephalopathy cases, while the frequency of JC virus DNA detection in the PBMCs and urine did not differ among the three groups studied. JC virus type 2 was detected only in progressive multifocal leukoencephalopathy patients, and in particular in 52.4% of their CSF samples. Moreover, in the CSF of 19.0% of the progressive multifocal leukoencephalopathy cases, dual infection with both JC virus types 1 and 2 was found. The data obtained in this study indicate that the unexpected involvement of JC virus type 2, a strain not common in Italy, and the high frequency of dual infection with both JC virus types 1 and 2 in progressive multifocal leukoencephalopathy CSF, can be indications of risk factors for progressive multifocal leukoencephalopathy development.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Progressive multifocal leukoencephalopathy in a child with acquired immunodeficiency syndrome (AIDS).

Progressive multifocal leukoencephalopathy is a rare viral-induced demyelinating disease associated to immunodeficiency. A 10-year-old boy with AIDS is reported, who developed subacute cerebellar signs and symptoms with multiple cranial nerve involvement and dementia. A computed tomography scan revealed a focal nonenhancing area of low attenuation in the cerebellum. On magnetic resonance imaging high signal lesions in T2 weighted sequences were shown. The biopsy of one of those lesions showed the typical histological findings of progressive multifocal leukoencephalopathy. It seems important to consider this diagnosis in children with AIDS who present with progressive neurological features.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Macrophage association of polyomavirus in progressive multifocal leukoencephalopathy: an immunohistochemical and ultrastructural study. Case report.

Progressive multifocal leukoencephalopathy (PML) in a patient following autologous bone marrow transplantation for a non-Hodgkin's centroblastic lymphoma was studied by immunohistochemistry and transmission electron microscopy. Our observations indicate that a large amount of polyomavirus, most probably JC virus, is taken up and segregated within vacuoles of macrophages by phagocytosis. A relevant role of macrophages in the pathogenesis of PML is emphasized.

Brain↗
PubMed2005

Head tremor and progressive multifocal leukoencephalopathy in AIDS patients: report of two cases.

Progressive multifocal leukoencephalopathy (PML) is caused by replication of JC virus in oligodendrocytes of immunocompromised patients. Common manifestations are focal motor and sensory deficits, gait abnormalities, speech and language disturbances, cognitive disorders, headache, and visual impairment. Although the occurrence of movement disorders is rare in PML, bradykinesia, rigidity, dystonia, myoclonic jerks and myoclonic ataxia have been described. Head tremor associated with PML has not been previously reported. We report two cases of PML in whom head tremor was present.

AIDS-Related Opportunistic Infections↗
PubMed2000

A "cortico-basal degeneration"-like syndrome as first sign of progressive multifocal leukoencephalopathy.

We report an unusual case of probable progressive multifocal leukoencephalopathy (PML), who initially presented with a right-sided movement disorder, including upper limb dystonia, tremor, and dyspraxia, reminiscent of corticobasal degeneration. In the further course, the patient developed disorientation, confusion, and bradyphrenia. The appearance of white matter MRI lesions as well as a positive PCR test result for JC-virus in the cerebrospinal fluid finally led to the correct diagnosis.

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PubMedDate not supplied

Progressive multifocal leukoencephalopathy fifty-seven months after heart transplantation.

Progressive multifocal leukoencephalopathy (PML), a subacute and usually fatal demyelinating disease of the brain, is caused by an opportunistic viral infection in immunocompromised patients. Only one case of PML after heart transplantation has been reported; it was discovered at the autopsy of a patient who died of multiorgan system failure. We describe an otherwise asymptomatic heart transplant recipient who had neurologic complaints that could be specifically attributed to PML, demonstrate the pertinent pathologic findings, and review the PML literature germane to heart transplantation. PML may become more prevalent as the population of heart transplant recipients increases.

Brain↗
PubMed1992

Cerebellar form of progressive multifocal leukoencephalopathy in a patient with chronic renal failure.

Progressive multifocal leukoencephalopathy (PML) developed in a 64-year-old woman who had undergone hemodialysis treatment due to chronic renal failure (CRF) for 6 yr. Her initial symptom was ataxia, and computed tomographic (CT) scan and magnetic resonance imaging (MRI) suggested a demyelinating disease of the cerebellum. Her cell-mediated immunity was impaired. At autopsy, the cerebellar disease was confirmed as PML by ultrastructural and immunohistochemical studies. Moreover, the JC type of papova virus infection was verified by Southern blot analysis.

Cerebellar Diseases↗
PubMed2000

Progressive multifocal leukoencephalopathy presenting with an isolated focal movement disorder.

Progressive multifocal leukoencephalopathy (PML) is a rare but fatal papovavirus infection of the central nervous system predominantly affecting immunocompromised patients. Although the basal ganglia circuitry may be involved in the pathology of PML, movement disorders are exceedingly rare as presenting symptoms and have not been described as isolated features in such patients. We report a previously healthy, immunocompetent 24-year-old woman with histologically proven PML who presented with a focal movement disorder of the left arm as an isolated symptom for many months before diagnosis.

Adult↗
PubMed1990

[Progressive multifocal leukoencephalopathy associated with leukopenia of unknown (iatrogenic?) origin].

Progressive multifocal leukoencephalopathy is a virtually always opportunistic infection of central nervous system caused by papova viruses, which clinically presents with symptoms and signs of involvement of different encephalic levels. We report a case with a double interest: on the one hand, both clinical features and lesions were limited to the brainstem and cerebellum; on the other hand, the disease developed in a previously healthy female in whom laboratory evidence of immunodeficiency of unknown origin was demonstrated. A reason for immunodeficiency was also not found at autopsy, being speculated that it could have been iatrogenically associated with antidepressant drugs.

Brain Stem↗
PubMedDate not supplied

[Progressive multifocal leukoencephalopathy after renal transplantation. Report of two cases].

Progressive multifocal leukoencephalopathy (PML) occurred in two patients after kidney transplantation. Two years after such a transplantation associated with immunosuppressive chemotherapy, a 54-year-old male developed polyneuropathy, diffuse alterations of the central nervous system and he died with the suspicion of hypertensive encephalopathy due to progressive renal failure. A 45-year-old female had kidney transplantation first complicated by Listeria monocytogenes meningoencephalitis. She was cured from this disease and had a satisfactory social rehabilitation for two years. Afterwards, she suffered from various neurological ailments, including epilepsy, that were attributed to combined renal failure and developing hydrocephalus. One year after the onset of these neurological symptoms, the grafted kidney was removed and chemotherapy was discontinued but she died a few weeks later. Both patients had typical PML. By electron microscopy, performed on formalin fixed brain tissue, intranuclear round particles (40-50 nm) could be recognized in the first case only. These two cases are confronted with the six published observations of PML following organ transplantation. The frequency of PML has been estimated at 1 for 5000 kidney transplantation, 1 for 2000 chronic lymphoid leukemia and 1 for 10,000 Hodgkin's disease.

Brain↗
PubMed1988

Prolonged survival and partial recovery in AIDS-associated progressive multifocal leukoencephalopathy.

Two human immunodeficiency virus seropositive patients with progressive multifocal leukoencephalopathy (PML) exhibited a dramatic though incomplete recovery of neurologic function and have survived for more than 30 months since the onset of symptoms. PML was the initial manifestation of the acquired immune deficiency syndrome (AIDS) in both patients, though other opportunistic infections have subsequently supervened in one. Brain tissue from both patients obtained by stereotactic biopsy showed the typical features of PML, but was also characterized by an unusually prominent inflammatory response. Neurologic improvement did not appear to correlate with clinical or laboratory measurements of immunologic improvement. One patient continued to display neurologic recovery despite the development of other opportunistic infections. Though atypical, PML in AIDS may be associated with prolonged survival.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Cytarabine and highly active antiretroviral therapy in HIV-related progressive multifocal leukoencephalopathy.

We assessed survival in AIDS-related progressive multifocal leukoencephalopathy (PML) and the effect of cytarabine and antiretroviral therapy in a retrospective analysis of a series of consecutive 35 patients with AIDS-related PML in an academic AIDS referral center over 15 years. Treatment regimens consisted of highly active antiretroviral treatment (HAART), intravenous cytarabine, or both. Median survival after diagnosis in the overall series was 88 days. Patients with low CD4 cell count tended to have shorter survival. Seven patients (20%) had prolonged survival (> 1 year). Cytarabine did not affect survival. Seven patients were treated with HAART, which did not significantly improve survival. We conclude that the prognosis of AIDS-related PML is still poor, with a median survival of 3 months.

Adult↗
PubMed1986

Isolation of JC virus capsomer-like structures from progressive multifocal leukoencephalopathy brain.

Brain tissue from a patient with progressive multifocal leukoencephalopathy (PML) was analyzed by molecular biological and electron-microscopic techniques. Viral DNA was isolated directly from brain tissue, cloned into a plasmid vector, and subjected to restriction endonuclease analysis. The pattern of restriction fragments identified by gel electrophoresis was almost indistinguishable from that of prototype JC virus. By this procedure the etiologic agent of PML in this patient was identified without the isolation of infectious virus. After centrifugal clarification of brain homogenates, high speed centrifugal pellets were studied by electron microscopy. Large numbers of 9-nm polygonal particles, sometimes in paracrystalline arrays, were observed. It was thought likely that these particles were capsomer subunits of 41-43 nm JC virus virions. That the particles were capsomers was supported by negative stain electron microscopy, including reconstruction studies with simian virus 40.

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