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PubMed1985

Progressive multifocal leukoencephalopathy: clinical and radiographic features.

Between April 1982 and March 1984 7 pathologically confirmed cases of progressive multifocal leukoencephalopathy (PML) were diagnosed at our institution. Only 1 case had been seen in the preceding twenty years. Four patients had acquired immunodeficiency syndrome (AIDS). The others had chronic lymphocytic leukemia, Hodgkin's lymphoma, and systemic lupus erythematosus. All patients presented with progressive neurological deficits. In most, the initial computed tomographic (CT) scan was disproportionately less abnormal than the clinical findings. In 5 patients the first CT scan revealed hypodensities of the cerebral white matter which lacked mass effect and did not enhance with contrast agent. The lesions were observed to enlarge progressively on CT scans but often lagged behind the rate of clinical evolution. Although 3 patients were treated with cytosine arabinoside, none improved. PML had similar clinical, radiographic, and pathological features in the AIDS and non-AIDs patients. Of 79 AIDS patients cared for at our institution between December 1979 and December 1983, 3.8% had PML. PML should be suspected in AIDS patients in the presence of the characteristic CT features, especially when CT-clinical dissociation occurs.

Acquired Immunodeficiency Syndrome↗
PubMed2005

New features of progressive multifocal leukoencephalopathy in the era of highly active antiretroviral therapy and natalizumab.

Over the past three decades, progressive multifocal leukoencephalopathy (PML) evolved from being a clinical rarity to become an important cause of neurological complications in acquired immunodeficiency syndrome (AIDS) patients. Recently this disease unexpectedly occurred in patients receiving the novel immunomodulatory medication natalizumab. These changes in the epidemiology of PML also brought new questions with regard to the pathogenesis of this disease. The authors review the current challenges in the diagnosis and management of patients with PML, based on the recent advances in the understanding of the JC virus biology and discuss potential methods to monitor disease evolution and predict outcome.

AIDS-Related Opportunistic Infections↗
PubMed1999

Clinical and virological monitoring during treatment with intrathecal cytarabine in patients with AIDS-associated progressive multifocal leukoencephalopathy.

We describe the clinical and virological outcome of human immunodeficiency virus-infected patients with progressive multifocal leukoencephalopathy (PML) treated with cytarabine. Twenty-seven patients received intrathecal cytarabine, 5 received concomitant intravenous cytarabine, and 20 received concomitant antiretroviral therapy. The median baseline CD4+ cell count was 28/mm3. After 4 weeks, 4 (19%) of 21 evaluable patients had stable disease, whereas the others progressed. The median survival from diagnosis and from onset was 66 and 128 days, respectively. Patients with Karnofsky scores of >50 and those previously taking antiretroviral medications had a higher probability of survival 3 months after diagnosis (P = .003 and P = .05, respectively). Overall, after 4 weeks, median JC virus load in CSF increased by 0.7 log10 copies/mL from baseline (P = NS). The mean JC virus load at 4 weeks was lower in patients with stable disease than in progressors (3.47 vs. 4.47 log10 copies/mL; P = .027). JC virus became undetectable in the only patient who had a long-term stable condition. The concentration of JC virus in CSF showed a correlation with clinical outcome.

AIDS-Related Opportunistic Infections↗
PubMed1988

Progressive multifocal leukoencephalopathy and retroviral encephalitis in acquired immunodeficiency syndrome.

Antigens of human polyomaviruses, the etiologic agents of progressive multifocal leukoencephalopathy (PML), and of human immunodeficiency virus were localized in paraffin sections from brains of six patients who died with the acquired immunodeficiency syndrome. Immunostaining revealed polyomaviral antigens in oligodendrocytes and in some astrocytes. Human immunodeficiency (retro) virus antigens were immunostained in mononuclear macrophages, glial cells, and vascular endothelial cells. Both viral types were found ultrastructurally. The lesions of PML were more destructive than is usually seen in cases without the acquired immunodeficiency syndrome. The retroviral encephalitis could have occurred before the onset of PML. However, a secondary retroviral encephalitis could have resulted if the monocytes responding to an initial polyomaviral lesion were already infected with human immunodeficiency virus before they differentiated into macrophages.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy.

The use of highly active anti-retroviral therapy in patients with HIV-related progressive multifocal leukoencephalopathy is associated with increased survival and disease stabilization. However, approximately half of the patients receive no benefit from these treatments. In a group of HIV-infected patients with histologically or virologically confirmed PML, we recognized two distinct patterns of response, i.e., long survivors versus nonresponders, but could not identify any factors at baseline predictive of PML outcome. In addition, the use of cidofovir did not substantially affect survival. However, the survival rate was higher during the first years of HAART, i.e., 1996-1997, with better outcomes observed in patients receiving a protease inhibitor-containing regimen either irregularly or after a switch from a 2-nucleoside reverse transcriptase inhibitor combination. In contrast, PML outcome was frequently poor in both HAART-naive and -experienced patients who responded promptly to anti-HIV therapy in terms of CD4 increase and viral load decrease. In addition, in a number of patients, PML onset was temporally associated with immune reconstitution. It may be that, in some patients, rapid immune reconstitution due to HAART paradoxically worsens the course of PML. Gradual reversal of immune deficiency might be associated with better outcome.

AIDS-Related Opportunistic Infections↗
PubMed2006

[Neuroradiological study of a possible progressive multifocal leukoencephalopathy using diffusion tensor imaging and proton magnetic resonance spectroscopy].

We report a possible case of progressive multifocal leukoencephalopathy (PML) that was attempted to evaluate the pathogenesis by a novel brain MRI techniques. A 72-year-old woman had developed subacute visual disturbance, right hemiparesis and sensory disturbance. Laboratory examinations revealed liver dysfunction and pancytopenia due to liver cirrhosis (type C) and preclinical status of multiple myeloma. Thus, this patient had these two underlying diseases, while anti-HIV antibody was negative. She was suspected with PML by detection of JCV-DNA in cerebrospinal fluid using with PCR. MRI showed multifocal T2-high signals in the bilateral parieto-occipital deep white matter, basal ganglia and right cerebellar hemisphere. No gadolinium enhancement was found. On FLAIR and diffusion weighted images (DWI), the lesion showed hyperintensity. The hyperintense areas on DWI showed various pattern on apparent diffusion coefficient (ADC) and fractional anisotropy (FA). In particular white matter changes, the course of FA reflected the clinical course more than ADC. Proton magnetic resonance spectroscopy (1H-MRS) in deep brain white matter showed ratios of reduced N-acetyl aspartate (NAA) and increased choline (Cho) to creatine. 1H-MRS by chemical shift imaging were undergone three times between 4 and 6 months after the onset. The change of these chemical markers correlated with her clinical course. We conclude that the approach of diffusion tensor imaging (DTI) and 1H-MRS are useful for evaluating neuropathologic observations and clinical course.

Aged↗
PubMed2000

Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus.

We describe the first reported human immunodeficiency virus (HIV)-seronegative patient treated with cidofovir for progressive multifocal leukoencephalopathy (PML). Marked clinical and radiological progression of PML occurred during cidofovir therapy. The improvement observed during cidofovir therapy of HIV-infected patients may be due to the effect of concomitant antiretroviral therapy rather than cidofovir.

Anti-HIV Agents↗