Volume 4, Number 34;  September 07, 2005

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Patient: 41 year old Aftrican-American male with history of discoid lupus, presenting with fever, headache, left facial droop, and headaches.  After several refusals patient agrees to HIV testing.  HIV status returned as positive and JC Virus testing returned positive.

Session Handout:

Clinical Question: 

1) What kinds of conditions can lead to progressive multifocal leukoencephalopathy (PML) in non-AIDS patients?

Readings:

Link Directly to Fulltext article in Ovid

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Unique Identifier [PMID]: 14872029

Authors: Lai R. Abrey LE. Rosenblum MK. DeAngelis LM.

Institution: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Title: Treatment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study.[see comment]. [Review] [33 refs]

Comments Comment in: Neurology. 2004 Feb 24;62(4):532-3; PMID: 14981164

Source: Neurology. 62(3):451-6, 2004 Feb 10.

Abstract: BACKGROUND: Treatment-related leukoencephalopathy is the leading toxicity after successful treatment of primary CNS lymphoma (PCNSL). Its mechanism is poorly understood and there are no autopsy data available on such patients. METHODS: From a database of immunocompetent patients with PCNSL diagnosed between 1985 and 2001, the authors identified five autopsied patients who died of leukoencephalopathy. The authors reviewed their clinical records, MRI, and autopsy findings. RESULTS: The median age was 74 years (range 41 to 79) at PCNSL diagnosis. Symptoms of neurotoxicity developed a median of 1 month after treatment completion, and median survival was 30 months (range 22 to 68 months) after neurotoxicity onset. All had white matter hyperintensity on T2-weighted MRI, and two developed enhancing lesions 5 and 14 months following completion of treatment. At autopsy no PCNSL was identified. Myelin and axonal loss, gliosis, pallor, spongiosis, and rarefaction of the white matter were found in all; two patients had tissue necrosis that correlated with the enhancement on MRI, and one had fibrinoid necrosis of vessels. Four of the five patients had atherosclerosis of large cerebral vessels in the circle of Willis and all had small vessel disease; two had recent strokes at autopsy. CONCLUSIONS: Treatment-induced leukoencephalopathy is not a late delayed consequence of neurotoxic treatment but can be seen very early in some patients. Vascular disease may be a component of this white matter injury. [References: 33]

Publication Type: Case Reports. Journal Article. Review. Review, Multicase.

Link Directly to Fulltext article in Ovid

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Unique Identifier [PMID]: 12470182

Authors: Richardson-Burns SM. Kleinschmidt-DeMasters BK. DeBiasi RL. Tyler KL.

Institution: Neuroscience Program, University of Colorado Health Sciences Center, Denver Veterans Affairs Medical Center, 80262, USA.

Title: Progressive multifocal leukoencephalopathy and apoptosis of infected oligodendrocytes in the central nervous system of patients with and without AIDS.

Source: Archives of Neurology. 59(12):1930-6, 2002 Dec.

Abstract: CONTEXT: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV) that occurs in immunocompromised patients. Demyelination of the CNS is a consequence of virus-induced killing of oligodendrocytes, although the exact mechanism of cell death is unknown. OBJECTIVE: To examine archival autopsy and surgical pathologic specimens from 8 patients with PML, including 6 patients with human immunodeficiency virus (HIV)-associated PML and 2 patients with non-HIV-associated PML, for evidence of apoptosis. DESIGN: Apoptotic cells were identified by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end in situ labeling) or immunohistochemical detection of activated caspase 3. The JCV-infected cells were identified by in situ hybridization for viral transcripts or immunohistochemical analysis for JCV T antigen. RESULTS: Apoptosis of JCV-infected oligodendrocyte apoptosis was a prominent feature in all cases of both HIV- and non-HIV-associated PML. There were no differences between number or distribution of apoptotic cells identified by TUNEL or immunohistochemical analysis for activated caspase 3. Bizarre astrocytes were occasionally positive for JCV but were not apoptotic. Neurons, astrocytes, macrophages, and oligodendrocytes remote from lesions were neither apoptotic nor JCV infected. CONCLUSIONS: Our study demonstrates that apoptosis occurs in oligodendrocytes associated with demyelinated lesions of patients with both HIV-associated and non-HIV-associated PML. There were no differences in degree, location, or type of infected or apoptotic cells between patients with HIV-associated and non-HIV-associated PML. The extent of apoptosis did not correlate with the presence or intensity of host inflammatory response. Accumulation of viral particles in nuclei of infected cells made it difficult to identify morphologic changes in the nucleus typically associated with apoptosis.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 7718940

Authors: Newton HB. Makley M. Slivka AP. Li J.

Institution: Department of Neurology, Ohio State University, Columbus, USA.

Title: Progressive multifocal leukoencephalopathy presenting as multiple enhancing lesions on MRI: case report and literature review. [Review] [15 refs]

Source: Journal of Neuroimaging. 5(2):125-8, 1995 Apr.

Abstract: This report describes an immunocompetent patient with memory loss and motor abnormalities whose magnetic resonance images demonstrated multiple enhancing white matter lesions, including one that was cystic, suggestive of metastatic tumors or abscesses. Neuropathological evaluation at biopsy and subsequent autopsy revealed progressive multifocal leukoencephalopathy. Magnetic resonance evidence of enhancement and cystic changes are rare findings in progressive multifocal leukoencephalopathy, but should be considered in the differential diagnosis, especially in patients without evidence for primary malignancy or infection. [References: 15]

Publication Type: Case Reports. Journal Article. Review. Review, Tutorial.

Resident Report / Department of Medicine & Grady Branch Library

Emory University School of Medicine

2005 Edition

Participating Faculty:  Carlos Del Rio MD  / Joyce Doyle MD / Lorenzo Difrancesco MD / Erich Folch MD / Alicia Hidron  MD  

Contact: Karl Woodworth