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Joseph R. Berger - One of the best experts on this subject based on the ideXlab platform.
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Progressive Multifocal Leukoencephalopathy.
Neurologic clinics, 2020Co-Authors: Elena Grebenciucova, Joseph R. BergerAbstract:Progressive Multifocal Leukoencephalopathy (PML) is a rare opportunistic infection that occurs in patients whose immune system is compromised either because of an underlying illness or an immunosuppressive medication. John Cunningham virus, prevalent in 60% or more of the adult population as a latent or persistent infection, is responsible for the syndrome of PML. This article reviews PML in association with the most common immunotherapies and discusses risk mitigation and monitoring strategies.
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sorting out the risks in Progressive Multifocal Leukoencephalopathy
Nature Reviews Rheumatology, 2015Co-Authors: Leonard H Calabrese, Eamonn S Molloy, Joseph R. BergerAbstract:Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic viral infection of the central nervous system that is associated with several immunosuppressive therapies. In this Opinion article, Calabrese and colleagues propose a ranking of immunosuppressive agents based on their risk of PML to support a better-informed decision-making process.
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Update on Progressive Multifocal Leukoencephalopathy
Current Neurology and Neuroscience Reports, 2012Co-Authors: Israel Steiner, Joseph R. BergerAbstract:Progressive Multifocal Leukoencephalopathy (PML) is a severe, often fatal, opportunistic viral infection of the central nervous system that is mainly seen in the context of AIDS and certain monoclonal immune-suppressive therapies. The causative agent, a polyoma virus, named JC virus infects only humans and there is no animal model for PML. This update focuses on information gathered in recent years on the pathogenesis of the disorder, on several clinical aspects associated with diagnosis and therapy, and on the immune reconstitution inflammatory syndrome (IRIS), a complication associated with removal of immunosuppressive therapy in PML.
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The basis for modeling Progressive Multifocal Leukoencephalopathy pathogenesis
Current Opinion in Neurology, 2011Co-Authors: Joseph R. BergerAbstract:Purpose of reviewThe appearance of Progressive Multifocal Leukoencephalopathy (PML) in association with newer, highly effective biological agents has increased the importance of understanding the mechanisms by which they and other underlying predisposing causes give rise to the disorder. This review
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determinants of survival in Progressive Multifocal Leukoencephalopathy
Neurology, 2009Co-Authors: Angela Marzocchetti, Joseph R. Berger, Troy Tompkins, David B Clifford, Rajesh T Gandhi, Santosh Kesari, David M Simpson, Mattia Prosperi, A De Luca, Igor J KoralnikAbstract:Background: We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with Progressive Multifocal Leukoencephalopathy (PML). Methods: We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood. Results: Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV− patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL (hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV+ patients with PML with CD4 count 200/μL (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival. Conclusions: The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes (CTL) was associated with a trend toward longer survival in patients with Progressive Multifocal Leukoencephalopathy (PML), which was more pronounced than the impact of CD4 count in HIV+ patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML. CE = contrast enhancement; CI = confidence interval; CTL = cytotoxic T-lymphocytes; HR = hazard ratio; IQR = interquartile range; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; PBMC = peripheral blood mononuclear cells; PML = Progressive Multifocal Leukoencephalopathy.
Igor J Koralnik - One of the best experts on this subject based on the ideXlab platform.
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Hyperperfusion in Progressive Multifocal Leukoencephalopathy is associated with disease progression and absence of immune reconstitution inflammatory syndrome
Brain, 2013Co-Authors: Michael N. Khoury, Sarah Gheuens, Xiaoen Wang, David C. Alsop, Igor J KoralnikAbstract:We sought to characterize perfusion patterns of Progressive Multifocal Leukoencephalopathy lesions by arterial spin labelling perfusion magnetic resonance imaging and to analyse their association with immune reconstitution inflammatory syndrome, and survival. A total of 22 patients with Progressive Multifocal Leukoencephalopathy underwent a clinical evaluation and magnetic resonance imaging of the brain within 190 days of symptom onset. The presence of immune reconstitution inflammatory syndrome was determined based on clinical and laboratory criteria. Perfusion within Progressive Multifocal Leukoencephalopathy lesions was determined by arterial spin labelling magnetic resonance imaging. We observed intense hyperperfusion within and at the edge of Progressive Multifocal Leukoencephalopathy lesions in a subset of subjects. This hyperperfusion was quantified by measuring the fraction of lesion volume showing perfusion in excess of twice normal appearing grey matter. Hyperperfused lesion fraction was significantly greater in Progressive Multifocal Leukoencephalopathy progressors than in survivors (12.8% versus 3.4% P = 0.02) corresponding to a relative risk of progression for individuals with a hyperperfused lesion fraction ≥ 4.0% of 9.1 (95% confidence interval of 1.4–59.5). The presence of hyperperfusion was inversely related to the occurrence of immune reconstitution inflammatory syndrome at the time of scan (P = 0.03). Indeed, within 3 months after symptom onset, hyperperfusion had a positive predictive value of 88% for absence of immune reconstitution inflammatory syndrome. Arterial spin labelling magnetic resonance imaging recognized regions of elevated perfusion within lesions of Progressive Multifocal Leukoencephalopathy. These regions might represent virologically active areas operating in the absence of an effective adaptive immune response and correspond with a worse prognosis.
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determinants of survival in Progressive Multifocal Leukoencephalopathy
Neurology, 2009Co-Authors: Angela Marzocchetti, Joseph R. Berger, Troy Tompkins, David B Clifford, Rajesh T Gandhi, Santosh Kesari, David M Simpson, Mattia Prosperi, A De Luca, Igor J KoralnikAbstract:Background: We sought to characterize the role of immunologic, virologic, and radiologic determinants of survival in patients with Progressive Multifocal Leukoencephalopathy (PML). Methods: We recorded the clinical outcome of 60 patients with PML (73% HIV+) who were prospectively evaluated between 2000 and 2007 for the presence of JC virus (JCV)-specific CD8+ cytotoxic T-lymphocytes (CTL) in blood. Results: Estimated probability of survival at 1 year was 52% for HIV+/PML and 58% for HIV− patients with PML. Patients with PML with detectable CTL within 3 months of diagnosis had a 1-year estimated survival of 73% compared to 46% for those without CTL (hazard ratio [HR] for death = 0.47, 95% confidence interval [CI] 0.13-1.75, p = 0.26). Patients with CTL response had an increased likelihood of having contrast enhancement of PML lesions and immune reconstitution inflammatory syndrome (odds ratio 3.7 and 7.8). Estimated 1-year survival was 48% in HIV+ patients with PML with CD4 count 200/μL (HR for death 1.41, 95% CI 0.27-7.38, p = 0.68). JCV DNA was detected in the urine of 48% and in the blood of 56% of patients with PML, but viruria and viremia were not associated with survival. Conclusions: The presence of JC virus (JCV)-specific cytotoxic T-lymphocytes (CTL) was associated with a trend toward longer survival in patients with Progressive Multifocal Leukoencephalopathy (PML), which was more pronounced than the impact of CD4 count in HIV+ patients with PML early after diagnosis. Despite the association of contrast enhancement and immune reconstitution inflammatory syndrome with JCV-specific CTL, these cannot be considered as surrogate markers for the prognostic value of the CTL. Strategies aiming at improving the cellular immune response may improve the course of PML. CE = contrast enhancement; CI = confidence interval; CTL = cytotoxic T-lymphocytes; HR = hazard ratio; IQR = interquartile range; IRIS = immune reconstitution inflammatory syndrome; JCV = JC virus; PBMC = peripheral blood mononuclear cells; PML = Progressive Multifocal Leukoencephalopathy.
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Progressive Multifocal Leukoencephalopathy in hiv 1 infection
Lancet Infectious Diseases, 2009Co-Authors: Paola Cinque, Igor J Koralnik, Simonetta Gerevini, Jose M Miro, Richard W PriceAbstract:Summary Progressive Multifocal Leukoencephalopathy is caused by the JC polyomavirus (JCV) and is one of the most feared complications of HIV-1 infection. Unlike other opportunistic infections, this disease can present when CD4 counts are higher than those associated with AIDS and when patients are receiving combined antiretroviral therapy, either shortly after starting or, more rarely, during long term successful treatment. Clinical suspicion of the disease is typically when MRI shows focal neurological deficits and associated demyelinating lesions; however, the identification of JCV in cerebrospinal fluid or brain tissue is needed for a definitive diagnosis. Although no specific treatment exists, the reversal of immunosuppression by combined antiretroviral therapy leads to clinical and MRI stabilisation in 50–60% of patients with the disease, and JCV clearance from cerebrospinal fluid. A substantial proportion of patients treated with combined antiretroviral therapy develop inflammatory lesions, which can be associated with either a favourable outcome or clinical worsening. The reasons for variability in the natural history of Progressive Multifocal Leukoencephalopathy and treatment responses are largely undefined, and more specific and rational approaches to management are needed.
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seizures and their outcome in Progressive Multifocal Leukoencephalopathy
Neurology, 2006Co-Authors: Frank W Drislane, Marco A Lima, Igor J KoralnikAbstract:Seizures are not expected in Progressive Multifocal Leukoencephalopathy (PML), a condition considered to be restricted to the white matter. Review of medical records of 89 patients with possible or proven PML showed an 18% prevalence of seizures. Seizures usually responded well to treatment and did not affect survival. The presence of PML lesions immediately adjacent to the hemispheric cortex was the only risk factor associated with seizures in this population.
Eugene O Major - One of the best experts on this subject based on the ideXlab platform.
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Natalizumab related Progressive Multifocal Leukoencephalopathy
Drug Discovery Today: Disease Models, 2020Co-Authors: Lana Zhovtis Ryerson, Eugene O MajorAbstract:Progressive Multifocal Leukoencephalopathy (PML), is an opportunistic brain infection that is caused by the JC virus. It usually occurs in patients with an underlying disease and therapies used to treat such diseases that inhibit normal immune system function. For example, multiple sclerosis patients treated with natalizumab have been identified at risk for PML. This serious adverse event has been very instructive in improving understanding of PML pathogenesis, biomarkers and patient management with this disease in recent years.
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pembrolizumab treatment for Progressive Multifocal Leukoencephalopathy
The New England Journal of Medicine, 2019Co-Authors: Irene Cortese, Pawel Muranski, Yoshimi Enoseakahata, Seungkwon Ha, Bryan Smith, Mariachiara Monaco, Caroline F Ryschkewitsch, Eugene O Major, Joan Ohayon, Matthew K SchindlerAbstract:Abstract Background Progressive Multifocal Leukoencephalopathy (PML) is an opportunistic brain infection that is caused by the JC virus and is typically fatal unless immune function can be restored...
Leila Parvaneh - One of the best experts on this subject based on the ideXlab platform.
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Case report Progressive Multifocal Leukoencephalopathy in purine nucleoside phosphorylase deficiency
2007Co-Authors: Nima Parvaneh, Mahmoud-reza Ashrafi, Mehdi Yeganeh, Nima Pouladi, Fatemeh Sayarifar, Leila ParvanehAbstract:Progressive Multifocal Leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with Progressive Multifocal Leukoencephalopathy. 2006 Elsevier B.V. All rights reserved.
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Progressive Multifocal Leukoencephalopathy in purine nucleoside phosphorylase deficiency.
Brain & Development, 2006Co-Authors: Nima Parvaneh, Mahmoud-reza Ashrafi, Mehdi Yeganeh, Nima Pouladi, Fatemeh Sayarifar, Leila ParvanehAbstract:Progressive Multifocal Leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with Progressive Multifocal Leukoencephalopathy.
Nima Parvaneh - One of the best experts on this subject based on the ideXlab platform.
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Case report Progressive Multifocal Leukoencephalopathy in purine nucleoside phosphorylase deficiency
2007Co-Authors: Nima Parvaneh, Mahmoud-reza Ashrafi, Mehdi Yeganeh, Nima Pouladi, Fatemeh Sayarifar, Leila ParvanehAbstract:Progressive Multifocal Leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with Progressive Multifocal Leukoencephalopathy. 2006 Elsevier B.V. All rights reserved.
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Progressive Multifocal Leukoencephalopathy in purine nucleoside phosphorylase deficiency.
Brain & Development, 2006Co-Authors: Nima Parvaneh, Mahmoud-reza Ashrafi, Mehdi Yeganeh, Nima Pouladi, Fatemeh Sayarifar, Leila ParvanehAbstract:Progressive Multifocal Leukoencephalopathy is a demyelinating disease caused by JC virus, an opportunistic infection of the central nervous system. Although the majority of cases are infected with the human immunodeficiency virus (HIV), other immunocompromised patients are also at risk. Purine nucleoside phosphorylase is an enzyme in the purine salvage pathway that reversibly converts inosine to hypoxanthine and guanosine to guanine. Purine nucleoside phosphorylase deficiency is a combined immunodeficiency with a profound cellular defect. Neurologic abnormalities are salient features of this syndrome. We describe for the first time a patient with this rare disorder presented with Progressive Multifocal Leukoencephalopathy.
