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PubMed2000

Progressive multifocal leukoencephalopathy and idiopathic CD4+lymphocytopenia: a case report and review of reported cases.

Progressive multifocal leukoencephalopathy (PML) is a well recognized demyelinating neurological disorder caused by JC virus. Idiopathic CD4(+) lymphocytopenia (ICL) is a syndrome first described by the Centers for Disease Control and Prevention as a CD4(+) count <300 cells/mm(3) or a CD4(+) count that is <20% of the total T cell count on 2 occasions, with no evidence of human immunodeficiency virus (HIV) infection on testing, and absence of any defined immunodeficiency or therapy that depresses the levels of CD4(+) T cells. To the best of our knowledge, this is the third reported case of PML and ICL, and also the first reported case of the use of cidofovir to treat PML in a patient not infected with human immunodeficiency virus.

Antiviral Agents↗
PubMed1993

Presence of papova-like viral particles in cerebrospinal fluid of AIDS patients with progressive multifocal leukoencephalopathy. An additional test for "in vivo" diagnosis.

An "in vivo" diagnosis of progressive multifocal leukoencephalopathy (PML), a neurological opportunistic viral infection in AIDS patients, can be made only by brain biopsy. In order to identify viral particles, we examined the cerebrospinal fluid (CSF) of 15 AIDS patients with focal neurological signs by electron microscopy using negative staining technique. In 2 out of 3 patients with clinical and neuroradiological presumptive diagnosis of PML, the CSF examination revealed papova-like viral particles. Our results support the hypothesis that the severe cell-mediated immunodeficiency reactivates papovavirus from a latent state in the brain, leading to PML. Therefore, the CSF study by negative staining might be a useful test for an "in vivo" diagnosis of PML.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Detection of JC virus by polymerase chain reaction in cerebrospinal fluid from two patients with progressive multifocal leukoencephalopathy.

The polymerase chain reaction (PCR) was used to identify JC virus (JCV) in the cerebrospinal fluid of two patients with progressive multifocal leukoencephalopathy confirmed by brain biopsy. In addition, JCV viremia was demonstrated by PCR in one case. JCV detection in spinal fluid by PCR may be the first non-invasive technique available for the diagnostic confirmation of progressive multifocal leukoencephalopathy.

DNA, Viral↗
PubMed1999

[Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases].

The progressive multifocal leukoencephalopathy (PML), a complication of the acquired immunodeficiency syndrome (AIDS) in 4%-5% of all cases, is an encephalitis caused by the JC papovavirus. The prognosis is very poor with a mean survival time after diagnosis of 3 to 6 months. No effective therapy is known to date. Therapeutic trials in small groups of patients with alpha-interferon, didanosine, and arabinoside were of minor success. A controlled study with cytarabine did not show any efficacy. Single case reports on a therapy with cidofovir (Vistide), an approved nucleotide-analogone in the therapy of cytomegalovirus-retinitis in AIDS-patients without renal dysfunction, showed positive results. We describe 2 more cases of a therapy of cidofovir in AIDS-associated PML. Out of 22 cases described in the literature, including these 2 cases, with a therapy of cidofovir in AIDS-associated PML, 16 patients improved under therapy, 2 remained stable, and only 4 patients still worsened fulminantly. These results indicate an additive antiviral effect of cidofovir against JC-virus. This may be used in the therapy of PML in AIDS-patients because no alternative antiviral therapy of PML is available at present. The efficacy of cidofovir for the therapy of PML is suggested by case reports. The exact mechanisms leading to an improvement under a therapy with cidofovir in the 16 cases described so far should be evaluated in a randomised, controlled study with an adequate size of cohorts.

AIDS-Related Opportunistic Infections↗
PubMed2006

Progressive multifocal leukoencephalopathy: lessons from AIDS and natalizumab.

The dramatic increase in the incidence of progressive multifocal leukoencephalopathy (PML) that occurred as a consequence of the AIDS pandemic and the recent association of PML with the administration of natalizumab, a monoclonal antibody to alpha4 integrin that blocks inflammatory cell entry into the brain, has stimulated a great deal of interest in this previously obscure viral demyelinating disease. The etiology of this disorder is JC virus (JCV), a polyoma virus, observed in 80% of the population worldwide. Seroepidemiological studies indicate that infection with this virus typically occurs before the age of 20 years. No primary illness owing to JCV infection has been recognized and the means of spread from person to person remains obscure. Following infection, the virus becomes latent in bone marrow, spleen, tonsils and other tissues. Periodically the virus reactivates during which time it can be demonstrated in circulating peripheral lymphocytes. The latter is significantly more commonly observed in immunosuppressed populations than that in normal subjects. Despite the large pool of people infected with JCV, PML remains a relatively rare disease. It is seldom observed in the absence of an underlying predisposing illness, typically one that results in impaired cellular immunity. A variety of factors are likely responsible for the unique increase in frequency of PML in HIV infection relative to other underling immunosuppressive disorders. Preliminary data suggests that natalizumab appears to distinctively predispose recipients to PML relative to other infectious complications. Studies in these populations will be invaluable in understanding the mechanisms of disease pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases.

Progressive multifocal leukoencephalopathy, a common complication of infections with human immunodeficiency virus (HIV), occurs in as many as 3.8% of patients with the acquired immunodeficiency syndrome (AIDS). We report 16 cases and review 12 previously reported cases of progressive multifocal leukoencephalopathy associated with HIV infection. This illness was the presenting manifestation of HIV infection in 8 cases. Limb weakness, gait abnormalities, visual loss, aand altered mental status were the commonest initial complaints. Computed tomography of the brain frequently showed hypodense, nonenhancing white matter lesions. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions. Cerebrospinal fluid analysis and electroencephalography were nondiagnostic. Impaired cell-mediated immunity was typically noted, even in the absence of other immunodeficiency-associated illnesses. Death occurred within 10 days to 18 months of the onset of symptoms in 22 patients. However, 4 patients remain alive at 3 to 23 months; of these 4, 2 have had significant improvement without treatment. Various therapies were unsuccessful.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Progressive multifocal leukoencephalopathy and hemochromatosis. Pathological study of a case (author's transl)].

A case of progressive multifocal leukoencephalopathy (P.M.L.) with humoral immunologic deficiency and hemochromatosis has been studied by light and electron microscopy. Widespread demyelination of white substance, gigantic astrocytes, inflammatory perivascular cuffs and numerous nuclear and cytoplasmic viral inclusions, suggesting Papovavirus were observed. The relationship between P.M.L. and hemochromatosis is discussed.

Adult↗
PubMed1983

[Progressive multifocal leukoencephalopathy. Clinical, CT scan and neuropathologic findings. Apropos of 4 cases].

Four cases of progressive multifocal leukoencephalopaty are reported, 3 of them with an ultrastructural study and 2 with a C.T. scan study. In 2 cases, there were no other associated pathological condition. In 1 case chronic alcoholism only was present; in the last case a primitive hemochromatosis with a prevailing hepatic dysfunction was evidenced. In 2 of these cases, the initial clinical picture was made of mental disorders while it was made of a progressive left hemiparesis in one case and of a brain stem syndrome in the other case. The results of neuroradiological and isotopical investigations remained negative throughout the evolution in the 4 cases except for some C.T. scan abnormalities. Indeed, in 2 cases the C.T. scan evidenced brain lesions identified as large demyelinated areas. These were low density areas non altered by contrast and unaccompanied by any mass effect. These areas were not seen when the first clinical signs were present and thus, normality of C.T. scan appears not to allow infirmation of the diagnosis of progressive multifocal leukoencephalopathy. In the 4 cases the pathological study showed characteristic lesions of the white matter. Mononucleated cells inflammatory infiltration was observed at the periphery of the demyelinizated regions. This may be related with the primitive aspect of these cases. An ultrastructural study was performed in 3 cases: viral inclusions were present not only in the nucleus of oligodendrocytes but also in their cytoplasm and in some astrocytes.

Adult↗
PubMed1977

Isolation of simian virus 40 from rhesus monkeys (Macaca mulatta) with spontaneous progressive multifocal leukoencephalopathy.

Isolates of virus from the brain tissue of two naturally occurring cases of progressive multifocal leukoencephalopathy in rhesus monkeys (Macaca mulatta) have been characterized. Both isolates were demonstrated to be simian virus 40 (SV40) by serological tests and analysis of cleavage fragments of viral deoxyribonucleic acid produced by restriction endonuclease from Haemophilus influenzae. SV40 virions and the nonvirion T antigen were demonstrated in the brain lesions of one monkey by the fluorescent antibody staining technique. SV40 was not demonstrated in the brain of normal rhesus monkeys from the same colony with use of the same methods of viral isolation or demonstration of antigen.

Animals↗
PubMed2004

Progressive multifocal leukoencephalopathy successfully treated with highly active antiretroviral therapy and cidofovir in an adolescent infected with perinatal human immunodeficiency virus (HIV).

Progressive multifocal leukoencephalopathy is an infectious demyelinating brain disease caused by the JC virus that is associated with significant morbidity and mortality in the immunocompromised host. We report a case of progressive multifocal leukoencephalopathy successfully treated with highly active antiretroviral therapy and cidofovir in an adolescent patient perinatally infected with human immunodeficiency virus (HIV).

AIDS-Related Opportunistic Infections↗
PubMed2002

Progressive multifocal leukoencephalopathy after stem cell transplantation, unsuccessfully treated with cidofovir.

We report a patient with progressive multifocal leukoencephalopathy (PML) after autologous stem cell transplantation (SCT) for non-Hodgkin's lymphoma (NHL). This is an unusual association, and to date only seven cases have been reported. This is the first case of PML after SCT treated with cidofovir, and the fifth case treated with this drug in a patient without human immunodeficiency virus (HIV) infection. In the previous four patients treated with cidofovir the outcome was discouraging, as was the case in this patient.

Antineoplastic Combined Chemotherapy Protocols↗