Immune Reconstitution Associated With Progressive Multifocal Leukoencephalopathy in Human Immunodeficiency Virus

2008 ◽  
Vol 14 (5) ◽  
pp. 321-326 ◽  
Author(s):  
Jennifer Travis ◽  
Anoop Varma ◽  
Daniel duPlessis ◽  
Ian Turnbull ◽  
F Javier Vilar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution ◽  
Immunodeficiency Virus

scholarly journals Clinical and Radiological Characterization of Progressive Multifocal Leukoencephalopathy in HIV-Infected Patients: A Retrospective Analysis and Review of the Literature

2015 ◽  
Vol 28 (3) ◽  
pp. 286 ◽  
Author(s):  
Luís Augusto ◽  
Nélia Neves ◽  
Carina Reis ◽  
Cândida Abreu ◽  
António Sarmento
Keyword(s):  
Magnetic Resonance Imaging ◽  
Human Immunodeficiency Virus ◽  
Magnetic Resonance ◽  
Virus Infection ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Resonance Imaging ◽  
Immunodeficiency Virus ◽  
Inflammatory Syndrome

<p><strong>Introduction:</strong> Progressive multifocal leukoencephalopathy is a demyelinating disease of the central nervous system caused by John Cunningham virus, mostly associated with immunodeficiency conditions, such as the human immunodeficiency virus infection. Progressive multifocal leukoencephalopathy can have multiple clinical features and usually presents a typical lesion pattern on brain magnetic resonance imaging. Its course may be rapidly progressive, although immunological responsiveness can be associated with<br />an improved prognosis.<br /><strong>Material and Methods:</strong> We performed a retrospective analysis of the clinical and radiological data from patients admitted in our institution between January 2005 and April 2014 with the diagnosis of definitive progressive multifocal leukoencephalopathy (ICD10:A81.2) in the setting of human immunodeficiency virus infection.<br /><strong>Results:</strong> Twenty-one patients were included in our study, mostly men (n = 20, 95.2%). Mean age at diagnosis was 39 years. Motor deficits were the most common clinical finding. John Cunningham virus-DNA was detected in the cerebral spinal fluid in 20 patients (95.2%). Brain imaging studies most commonly disclosed bilateral supratentorial, asymmetric lesions. Four (19%) patients developed immune reconstitution inflammatory syndrome in the follow-up. Therapeutic approach included initiation and continuation/optimization of antiretroviral therapy, with adjunctive therapy with corticosteroids in four patients. Seventeen (81%) patients died during the study period; median survival time following progressive multifocal leukoencephalopathy diagnosis was 3 months (range 1 - 13).<br /><strong>Discussion:</strong> The results of our study are in accordance with the data previously published on progressive multifocal leukoencephalopathy in human immunodeficiency virus patients. Progressive multifocal leukoencephalopathy is predominantly associated with severe immunosuppression, particularly in patients who are not under anti-retroviral therapy, and usually presents with motor and cognitive<br />symptoms and signs. A typical bilateral asymmetric pattern in conventional magnetic resonance imaging is present in the majority of the patients. There is no specific therapy for progressive multifocal leukoencephalopathy and it is usually fatal, although outcomes can improve with highly active anti-retroviral therapy. Immune reconstitution inflammatory syndrome is also an important complication related with progressive multifocal leukoencephalopathy, usually associated with anti-retroviral therapy. Progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome presents with different imaging characteristics from progressive multifocal leukoencephalopathy and treatment with steroids can improve survival.<br /><strong>Conclusion: </strong>The mortality rate and long-term neurological morbidity associated with progressive multifocal leukoencephalopathy are quite high. These data should increase clinician awareness to the occurrence of progressive multifocal leukoencephalopathy among human immunodeficiency virus patients and highlight the important role of magnetic resonance imaging, as early diagnosis may be<br />associated with better outcome.</p>

Evidence for Involvement of Transforming Growth Factor β1 Signaling Pathway in Activation of JC Virus in Human Immunodeficiency Virus 1–Associated Progressive Multifocal Leukoencephalopathy

2004 ◽  
Vol 128 (3) ◽  
pp. 282-291
Author(s):  
Sahnila Enam ◽  
Thersa M. Sweet ◽  
Shohreh Amini ◽  
Kamel Khalili ◽  
Luis Del Valle
Keyword(s):  
Human Immunodeficiency Virus ◽  
Growth Factor ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Transforming Growth Factor ◽  
Jc Virus ◽  
Transforming Growth Factor Β1 ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Human Immunodeficiency Virus 1

Abstract Context.—Progressive multifocal leukoencephalopathy is a fatal demyelinating disease of the central nervous system frequently seen in patients with impaired immune systems, particularly acquired immunodeficiency syndrome. JC virus (JCV), a human neurotropic polyomavirus, is the etiologic infectious agent of this disease. Objective.—The significantly higher incidence of progressive multifocal leukoencephalopathy in patients with acquired immunodeficiency syndrome than in patients with other immunosuppressive conditions suggests that molecular interactions between human immunodeficiency virus 1 and JCV, via the Tat protein, are responsible for the activation of the JCV enhancer/promoter and the development of progressive multifocal leukoencephalopathy. An indirect mechanism through activation of cytokines, such as transforming growth factor β1 and Smads 3 and 4, may also be responsible for the enhancement of JCV gene expression. Design.—Immunohistochemical analysis in progressive multifocal leukoencephalopathy samples and chloramphenicol acetyl transferase assays on cell cultures were performed to corroborate this hypothesis. Results.—The JCV capsid protein VP-1 was found in the nuclei of oligodendrocytes and in the nuclei and cytoplasm of bizarre astrocytes. Human immunodeficiency virus proteins, including p24 and Tat, were detected in the cytoplasm of astrocytes. Tat, but not p24, was detected in oligodendrocytes, suggesting that extracellular Tat accumulates in the nuclei of oligodendrocytes, where JCV gene transcription takes place. High levels of transforming growth factor β1 and Smads 3 and 4 were detected in JCV-infected oligodendrocytes. Results from in vitro studies confirm activation of the JCV early and late promoters by Smads 3 and 4. Conclusions.—These observations support our model, suggesting that the induction of transforming growth factor β1 by human immunodeficiency virus 1 Tat can stimulate its downstream factors, including Smads 3 and 4, which in turn augment transcription of the JCV promoter in glial cells.

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