Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland

Lang, W.; Miklóssy, Judith; Déruaz, J. P.; Pizzolato, Gianpaolo; Probst, A.; Schaffner, Th.; Gessaga, E.; Kleihues, Paul

doi:10.1007/bf00687372

Cited by 194 publications

(76 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the pre-HAART era, PML affected 3% -7% of patients with HIV-1 infection and was the cause of up to 18% of fatal CNS disease. 15 The incidence of PML has decreased from 0.7 per 100 person-years of follow-up in 1994 to 0.07 in 2 001 -2 002. 16 Additionally, one-year survival rates in HIV patients with PML has increased from less than 30% in the pre-HAART era to 38% -62% with HAART.…”

Section: Discussionmentioning

confidence: 99%

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

Augusto¹,

Neves

Reis³

et al. 2015

Acta Med Port

View full text Add to dashboard Cite

Acta Med Port 2015 May-Jun;28(3):286-296 RESUMOIntrodução: A leucoencefalopatia multifocal progressiva é uma patologia desmielinizante causada pelo vírus John Cunningham, geralmente associada a estados de imunodepressão, em particular a infeção pelo vírus da imunodeficiência humana. Pode apresentar múltiplas manifestações clínicas e tem habitualmente um padrão imagiológico típico. A evolução clínica é geralmente progressiva, podendo ocorrer uma melhoria do prognóstico associada à recuperação imunológica. Results: 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). Discussion: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 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. Conclusion: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 associated with better outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Augusto¹,

Neves

Reis³

et al. 2015

Acta Med Port

View full text Add to dashboard Cite

show abstract

“…9 In the pre-HAART era, PML affected 3%-7% of patients with HIV-1 infection and was the cause of up to 18% of fatal CNS disease. 10,11 The incidence of PML has decreased from 0.7 per 100 person-years of follow-up in 1994 to 0.07 in 2001-2002. 11 Unlike many other CNS opportunistic infections, JCV infection occurs early in the course of AIDS with CD4 cell counts Ͼ200/L and can also occur in patients receiving HAART.…”

Section: Epidemiology: Population At Riskmentioning

confidence: 99%

JC Virus Infection of the Brain

Bag¹,

Curé²,

Chapman³

et al. 2010

AJNR Am J Neuroradiol

118

View full text Add to dashboard Cite

SUMMARY:Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE, JCVGCN, and JCM. Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency. IRIS may develop secondary to restoration of immunity in HIV-positive patients with PML receiving antiretroviral therapy. This is of profound clinical significance and needs to be diagnosed promptly. Imaging plays a crucial role in the diagnosis of the disease, monitoring of treatment response, identifying disease progression, and predicting prognosis. In this article, current understanding of the epidemiology, pathogenesis, clinical presentations, and all aspects of imaging of JCV infection of the brain have been comprehensively reviewed.ABBREVIATIONS: ADC ϭ apparent diffusion coefficient; CNS ϭ central nervous system; cPML ϭ classic PML; Cr ϭ creatine; CTL ϭ cytotoxic T-lymphocytes; DWI ϭ diffusion-weighted imaging; FLAIR ϭ fluid-attenuated inversion recovery; HAART ϭ highly active antiretroviral therapy; HIV ϭ human immunodeficiency virus; ICL ϭ idiopathic CD4 lymphocytopenia; iPML ϭ inflammatory PML; IRIS ϭ immune reconstitution inflammatory syndrome; JCE ϭ JCV encephalopathy; JCM ϭ JCV meningitis; JCV ϭ JC virus; JCVGCN ϭ JCV granular cell neuronopathy; mAb ϭ monoclonal antibody; mIns ϭ myo-inositol; MS ϭ multiple sclerosis; MTR ϭ magnetization transfer ratio; NAA ϭ N-acetylaspartate; NIRIS ϭ neuro-IRIS; PCR ϭ polymerase chain reaction; PML ϭ progressive multifocal leukoencephalopathy; PML-IRIS ϭ PML associated with IRIS; RR ϭregulatory region; SLE ϭ systemic lupus erythematosus

show abstract

“…Once a rare disease seen primarily in patients with impaired immune systems due to myeloproliferative and lymphoproliferative disorders, the incidence of PML has been significantly increased due to the AIDS epidemic (27). Clinical studies show that Ͼ4% of AIDS patients with neurologic problems are diagnosed with PML (1,2,6,7,10,18,19,20,26,31,32). JCV infects Ͼ65% of the human population by early childhood with no major clinical symptoms (16,23,28,30).…”

mentioning

confidence: 99%

JC Virus-Induced Changes in Cellular Gene Expression in Primary Human Astrocytes

Radhakrishnan

Otte

Enam

et al. 2003

J Virol

View full text Add to dashboard Cite

Cell-type-specific transcription of the JC virus (JCV) promoter in glial cells initiates a series of events leading to viral replication in the brain and the development of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in patients with neurologic complications due to infection with human immunodeficiency virus type 1. Here we employed an in vitro infection of primary cultures of human astrocytes to compare the transcriptional profile of cellular genes after JCV infection by using an oligonucleotide-based microarray of 12,600 genes. Transcription of nearly 355 genes was enhanced and expression of 130 genes was decreased to various degrees. Many transcripts that were increased upon JCV infection were found to encode proteins with properties that suggest their involvement in cell proliferation, including cyclin A and cyclin B1; signaling pathways, such as transforming growth factor ␤ receptor 1, platelet-derived growth factor receptor and fibroblast growth factor family receptor; and other regulatory events, such as inflammatory responses, including cyclo-oxygenase-2 (Cox-2). Microarray-based data for several cell cycle-regulatory genes were further examined by using Western blot analysis of in vitro infected astrocytes harvested early and late during the infection. Results demonstrate that protein levels of all upregulated genes were found to increase at some point during the infection time course. In parallel, immunohistochemical assessment of cell cycle proteins, including cyclins A, B1, E, and Cdk2, showed positive staining of astrocytes within PML lesions of brain tissue from patients with neuro-AIDS. Microarray analysis was found to be a useful predictor of gene expression in infected cells; however, it may not directly correlate with protein levels during infection with JCV.The human polyomavirus, JC (JCV), is the etiologic agent for the fatal demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy (PML) (for review see references 5 and 11). Once a rare disease seen primarily in patients with impaired immune systems due to myeloproliferative and lymphoproliferative disorders, the incidence of PML has been significantly increased due to the AIDS epidemic (27). Clinical studies show that Ͼ4% of AIDS patients with neurologic problems are diagnosed with PML (1,2,6,7,10,18,19,20,26,31,32). JCV infects Ͼ65% of the human population by early childhood with no major clinical symptoms (16,23,28,30). Reactivation of the viral genome that preferentially occurs in oligodendrocytes and astrocytes leads to cytolytic destruction of the myelin-producing oligodendrocytes and degeneration of the myelin sheath in white matter. The chief pathological features of PML are the presence of altered oligodendrocytes whose nuclei are two to three times the size of normal cells and are filled with virions and viral antigens (34-36); giant, bizarre astrocytes with pleomorphic, hyperchromatic nuclei; and occasional mitotic figures. Early studies revealed that expre...

show abstract

Neuropathology of the acquired immune deficiency syndrome (AIDS): a report of 135 consecutive autopsy cases from Switzerland

Cited by 194 publications

References 46 publications

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

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

JC Virus Infection of the Brain

JC Virus-Induced Changes in Cellular Gene Expression in Primary Human Astrocytes

Contact Info

Product

Resources

About