Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature

Abstract

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities, and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3'-azido-3'-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.

Association of Simian Virus 40 with a Central Nervous System Lesion Distinct from Progressive Multifocal Leukoencephalopathy in Macaques with AIDS

“…34 AIDS patients with PML frequently have HIV-infected cells among the inflammatory cells in the demyelinating lesion. 26,61,63,66 In situ hybridization failed to identify SIV in the SV40-associated lesions in any animal, although one case with SIV encephalitis (SIVE) had abundant SIV nucleic acid in macrophages and multinucleated cells in the SIVE lesions, and other cases had SIV localized to lymphoid tissue. This confirms previous findings in our laboratory that SIV does not co-localize to sites of inflammation due to opportunistic infections in simian AIDS [67][68][69][70][71] and may represent a difference in pathogenesis of the two lentiviruses, particularly in the terminal stages of disease.…”

Detection of JC Virus Type 1 in Peripheral Lymphocytes, Brain and Cerebrospinal Fluid from Two Korean AIDS Patients with Progressive Multifocal Leukoencephalopathy

“…Copyright © 2002 S. Karger AG, Basel Progressive multifocal leukoencephalopathy (PML) is a chronic demyelinating disease that is seen as a secondary infection in association with HIV infection, lymphoma, leukemia, sarcoidosis, tuberculosis and carcinomatosis. It also occurs in organ transplant recipients receiving immunosuppressive therapy [1,2]. JC virus (JCV), which is a polyomavirus, is the cause of PML [3].…”

Development of Primary Central Nervous System Lymphoma Associated with Human Immunodeficiency Virus and JC Virus Infection

“…First, HIV-related PML usually occurs when CD4-positive T cells are severely suppressed. 4 However, PML may also develop in patients with blood CD4-positive T-cell counts of no less than 200 cells/mL after the initiating ART, or in those without previous immunomodulatory drugs or immunosuppression, while the latter would be the case much more rarely. [5][6][7] Hence, the relatively high number of CD4-positive T cells in the present case does not rule out the diagnosis of PML.…”

“…His previous medical history included hemophilia A and HIV-1 infection through blood product transfusions in infancy. Anti-retroviral therapy (ART) was started in 1993, 1) Hematology, 3) Neurology, 4) Neurosurgery, and 5) Laboratory Medicine, NHO Matsumoto Medical Center, Matsumoto, Japan 2) Division of Hematology, Department of Internal Medicine, 6) but his HIV-1 viral load (VL) had been high because of poor adherence to the prescription and leukocytopenia had been remarkable, with the number of CD4-positive lymphocytes ranging between 200 and 400 × 10 6 /L. The results of repeated tests for drug resistance to HIV-1 were negative.…”