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Progressive multifocal leukoencephalopathy

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https://www.readbyqxmd.com/read/29044559/discovery-and-characterization-of-novel-trans-spliced-products-of-human-polyoma-jc-virus-late-transcripts-from-pml-patients
#1
A Sami Saribas, Julia DeVoto, Akhil Golla, Hassen S Wollebo, Martyn K White, Mahmut Safak
Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost a half century ago, understanding the molecular mechanisms governing its biology remains highly elusive. JCV infects oligodendrocytes and astrocytes in the central nervous system (CNS) and causes a fatal brain disease known as progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals including AIDS. It has a small circular DNA genome (∼ 5 kb) and generates two primary transcripts from its early and late coding regions, producing several predicted alternatively spliced products mainly by cis-splicing...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29034436/natalizumab-therapy-is-associated-with-changes-in-serum-jc-virus-antibody-indices-over-time
#2
John Peters, Eric Williamson
To examine changes in anti-JC Virus (JCV) index measurements over time in multiple sclerosis (MS) patients to better understand this test, which is used in assessing risk of progressive multifocal leukoencephalopathy (PML) with natalizumab. We aim to describe and compare seroconversion rates, variability of JCV antibody index values, and changes in index values over time between patients on natalizumab therapy and patients naïve to natalizumab. Anti-JCV index values are used to help decide whether to start, continue, or stop treatment...
October 16, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/29025774/posterior-fossa-progressive-multifocal-leukoencephalopathy-first-presentation-of-an-unknown-autoimmune-disease
#3
Paulette Scholten, Peter Kralt, Bram Jacobs
We present a case of a 57-year-old man who presented with progressive cerebellar dysarthria and cerebellar ataxia. Additional investigations confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML) in the posterior fossa. This is a demyelinating disease of the central nervous system, caused by an opportunistic infection with John Cunningham virus. PML has previously been considered a lethal condition, but because of careful monitoring of patients with HIV and of patients using immunosuppressive drugs it is discovered in earlier stages and prognosis can be improved...
October 11, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29023856/to-do-or-not-to-do-plasma-exchange-and-timing-of-steroid-administration-in-pml
#4
Cristina Scarpazza, Luca Prosperini, Nicola De Rossi, Lucia Moiola, Maria Pia Sormani, Simonetta Gerevini, Ruggero Capra
OBJECTIVE: To retrospectively analyze the effect of plasma exchange (PLEX, yes=PLEX+, no=PLEX-) and steroids administration timing (prophylactically -proST- or therapeutically -therST-) on the longitudinal clinical course of patients with natalizumab related progressive multifocal leukoencephalopathy (PML) and full blown immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: Clinical and radiological data of 42 Italian patients with PML were analyzed. Patient's data are available until 12 months after PML diagnosis...
October 10, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28991888/commonly-prescribed-antiretroviral-therapy-regimens-and-incidence-of-aids-defining-neurological-conditions
#5
Ellen C Caniglia, Andrew Phillips, Kholoud Porter, Caroline A Sabin, Alan Winston, Roger Logan, John Gill, Marie-Anne Vandenhende, Diana Barger, Sara Lodi, Santiago Moreno, José Ramón Arribas, Antonio Pacheco, Sandra W Cardoso, George Chrysos, Charalabos Gogos, Sophie Abgrall, Dominique Costagliola, Laurence Meyer, Remonie Seng, Ard van Sighem, Peter Reiss, Roberto Muga, Santiago Pérez Hoyos, Dominique Braun, Christoph Hauser, Pilar Barrufet, Maria Leyes, Janet Tate, Amy Justice, Miguel A Hernán
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest...
October 4, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28991708/post-cart-progressive-multifocal-leukoencephalopathy-era-in-a-brazilian-center
#6
Marco A Lima, Marcus Tulius T Silva, Livia A Afonso, Beatriz J P Vaz
Progressive multifocal leukoencephalopathy (PML) is lytic infection of oligodendrocytes caused by JC virus (JCV). While PML incidence in developing countries has decreased after the introduction of combination antiretroviral therapy (cART), data in developing countries is scarce and limited to few cohorts. We described the epidemiological and clinical profile of a group of Brazilian HIV infected patients with PML in the cART era. A total of 27 patients were included in the study. The median age at PML onset was 42years (range: 27-67years) and 18 (66...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28989935/pathologic-findings-of-chronic-pml-iris-in-a-patient-with-prolonged-pml-survival-following-natalizumab-treatment
#7
Mai Himedan, Sandra Camelo-Piragua, Elizabeth A Mills, Avneesh Gupta, Rany Aburashed, Yang Mao-Draayer
Immune reconstitution inflammatory syndrome (IRIS) is a common complication during treatment for natalizumab-associated progressive multifocal leukoencephalopathy (PML). Although severe IRIS can result in acute worsening of disability and is associated with poor prognosis, effective immune reconstitution may account for the high survival rate of this cohort of PML patients. We present pathological evidence of chronic IRIS 3.5 years after diagnosis with natalizumab-associated PML. Our case showed that the IRIS initially developed after plasma exchange therapy and resolved clinically and radiologically following a combination treatment with corticosteroids, maraviroc, and cidofovir...
July 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28989857/jc-polyomavirus-attachment-and-entry-potential-sites-for-pml-therapeutics
#8
Colleen L Mayberry, Christian D S Nelson, Melissa S Maginnis
PURPOSE OF REVIEW: JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML...
September 2017: Current Clinical Microbiology Reports
https://www.readbyqxmd.com/read/28975841/progressive-multifocal-leukoencephalopathy-and-monoclonal-antibodies-a-review
#9
Chandrashekar Bohra, Lubomir Sokol, Samir Dalia
Progressive multifocal leukoencephalopathy (PML) is a viral infection predominantly seen in patients with HIV infection. However, with the increased use of monoclonal antibodies (MAB) for various lymphoproliferative disorders, we are now seeing this infection in non-HIV patients on drugs such as natalizumab, rituximab, and so on. The aim of this article is to review the relationship between the occurrence of PML and MAB used in the treatment of hematological malignancies and autoimmune diseases. Review of articles from PubMed-indexed journals which study PML in relation to the use of MAB...
October 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28974941/multidisciplinary-rehabilitation-is-efficacious-and-induces-neural-plasticity-in-multiple-sclerosis-even-when-complicated-by-progressive-multifocal-leukoencephalopathy
#10
Elisabetta Groppo, Francesca Baglio, Davide Cattaneo, Eleonora Tavazzi, Niels Bergsland, Sonia Di Tella, Riccardo Parelli, Ilaria Carpinella, Cristina Grosso, Ruggero Capra, Marco Rovaris
A 48-year-old woman with multiple sclerosis (MS), treated with natalizumab for more than one year without clinical and magnetic resonance imaging (MRI) signs of disease activity, was diagnosed with definite progressive multifocal leukoencephalopathy (PML). She presented with subacute motor deficit of the right upper limb (UL), followed by involvement of the homolateral leg and urinary urgency. The patient was treated with steroids and plasma exchange. On follow-up MRI scans, the PML lesion remained stable and no MS rebounds were observed, but the patient complained of a progressive worsening of the right UL motor impairment, becoming dependent in most activities of daily living...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28969984/risk-of-natalizumab-associated-progressive-multifocal-leukoencephalopathy-in-patients-with-multiple-sclerosis-a-retrospective-analysis-of-data-from-four-clinical-studies
#11
Pei-Ran Ho, Harold Koendgen, Nolan Campbell, Bill Haddock, Sandra Richman, Ih Chang
BACKGROUND: Previous estimates of risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis receiving natalizumab were stratified by three risk factors: anti-John Cunningham virus (JCV) antibodies in serum, previous immunosuppressant use, and treatment duration, which were estimated using population-based assumptions. We aimed to calculate PML risk estimates from patient-level risk-factor data and to stratify risk by concentrations of anti-JCV antibody in serum (anti-JCV antibody index)...
November 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28968776/archetype-jc-polyomavirus-prevails-in-a-rare-case-of-jc-polyomavirus-nephropathy-and-in-stable-renal-transplant-recipients-with-jc-polyomavirus-viruria
#12
Hanna M Seppälä, Ilkka T Helanterä, Pia Ks Laine, Irmeli T Lautenschlager, Lars G Paulín, Timo J Jahnukainen, Petri Ov Auvinen, Eeva Auvinen
Background: JC polyomavirus (JCPyV) is reactivated in approximately 20% of renal transplant recipients and it may rarely cause JCPyV-associated nephropathy (JCPyVAN). Whereas progressive multifocal leukoencephalopathy of the brain is caused by rearranged neurotropic JCPyV, little is known about viral sequence variation in JCPyVAN due to the rarity of this condition. Methods: Using single-molecule real-time sequencing, characterization of full-length JCPyV genomes from urine and plasma of one JCPyVAN patient and twenty stable renal transplant recipients with JCPyV viruria was attempted...
August 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28962961/natalizumab-associated-primary-central-nervous-system-lymphoma
#13
REVIEW
Menarvia Nixon, Richard P Menger, Piyush Kalakoti, Jai Deep Thakur, Rimal H Dossani, Kanika Sharma, Anil Nanda, Bharat Guthikonda
Natalizumab, a selective adhesion molecule inhibitor binding to α-4 subunit of integrin, has emerged to be an effective immuno-modulator especially in the treatment of relapsing-remitting Multiple Sclerosis and Crohn's disease. Literature documenting the development of progressive multifocal leukoencephalopathy from its use is widely available. However, only handful of reports cites the development of a more concerning pathology, primary CNS lymphoma (PCNSL) from its administration, thereby triggering a debate on a possible causal association...
September 26, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28961770/effect-of-pf-00547659-on-central-nervous-system-immune-surveillance-and-circulating-%C3%AE-7-t-cells-in-crohn-s-disease-report-of-the-tosca-study-madcam-1antibody-and-cns-immune-surveillance
#14
Geert D'Haens, Severine Vermeire, Harald Vogelsang, Matthieu Allez, Pierre Desreumaux, Andre Van Gossum, William J Sandborn, Daniel C Baumgart, Richard M Ransohoff, Gail M Comer, Alaa Ahmad, Fabio Cataldi, John Cheng, Robert Clare, Kenneth J Gorelick, Annamarie Kaminski, Vivek Pradhan, Sunday Rivers, Matthew O Sikpi, Yanhua Zhang, Mina Hassan-Zahraee, Walter Reinisch, Olaf Stuve
Background & Aims: Progressive multifocal leukoencephalopathy, a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central-nervous-system immune surveillance leading to this infection has been reported in patients with multiple sclerosis or Crohn's disease treated with anti-integrin antibody natalizumab. PF-00547659 is an investigational human monoclonal antibody for inflammatory bowel disease targeted against α4β7-mucosal addressin cell-adhesion molecule-1 (the integrin ligand selectively expressed in the gut)...
September 16, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28932291/neurological-safety-of-fingolimod-an-updated-review
#15
REVIEW
Fumihito Yoshii, Yusuke Moriya, Tomohide Ohnuki, Masafuchi Ryo, Wakoh Takahashi
Fingolimod (FTY) is the first oral medication approved for treatment of relapsing-remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long-term post-marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side-effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28928709/insight-into-metabolic-1-h-mrs-changes-in-natalizumab-induced-progressive-multifocal-leukoencephalopathy-brain-lesions
#16
Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Gisa Ellrichmann, Ralf Gold, Carsten Lukas
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, especially of natalizumab in relapsing-remitting multiple sclerosis (MS). Metabolic changes within PML lesions have not yet been described in natalizumab-associated PML in MS patients. OBJECTIVE: To study metabolic profiles in natalizumab-associated PML lesions of MS patients by (1)H magnetic resonance spectroscopy ((1)H-MRS) at different stages during the PML course...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28927823/t-cell-therapies-for-human-polyomavirus-diseases
#17
REVIEW
Sarah I Davies, Pawel Muranski
Rapid restoration of virus-specific T immunity via adoptive transfer of ex vivo generated T cells has been proven as a powerful therapy for patients with advanced cancers and refractory viral infections such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV). BK virus (BKV), John Cunningham virus (JCV), and Merkel cell carcinoma virus (MCV) are the members of the rapidly growing human polyomavirus (hPyV) family that commonly infects most healthy humans. These viruses have a clearly established potential for causing severe end-organ damage or malignant transformation, especially in individuals with weakened immunity who are unable to mount or regain endogenous T-cell responses as a result of underlying leukemia or iatrogenic immunosuppression in autoimmunity, bone marrow and solid organ transplant settings...
September 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28916311/lenalidomide-maintenance-after-first-line-therapy-for-high-risk-chronic-lymphocytic-leukaemia-cllm1-final-results-from-a-randomised-double-blind-phase-3-study
#18
Anna Maria Fink, Jasmin Bahlo, Sandra Robrecht, Othman Al-Sawaf, Ali Aldaoud, Holger Hebart, Kathleen Jentsch-Ullrich, Steffen Dörfel, Kirsten Fischer, Clemens-Martin Wendtner, Thomas Nösslinger, Paolo Ghia, Francesc Bosch, Arnon P Kater, Hartmut Döhner, Michael Kneba, Karl-Anton Kreuzer, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Sebastian Böttcher, Barbara Eichhorst, Michael Hallek
BACKGROUND: The combined use of genetic markers and detectable minimal residual disease identifies patients with chronic lymphocytic leukaemia with poor outcome after first-line chemoimmunotherapy. We aimed to assess lenalidomide maintenance therapy in these high-risk patients. METHODS: In this randomised, double-blind, phase 3 study (CLLM1; CLL Maintenance 1 of the German CLL Study Group), patients older than 18 years and diagnosed with immunophenotypically confirmed chronic lymphocytic leukaemia with active disease, who responded to chemoimmunotherapy 2-5 months after completion of first-line therapy and who were assessed as having a high risk for an early progression with at least a partial response after four or more cycles of first-line chemoimmunotherapy, were eligible if they had high minimal residual disease levels or intermediate levels combined with an unmutated IGHV gene status or TP53 alterations...
October 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28913726/diagnosis-and-treatment-of-progressive-multifocal-leukoencephalopathy-associated-with-multiple-sclerosis-therapies
#19
REVIEW
Eric M L Williamson, Joseph R Berger
Progressive multifocal leukoencephalopathy (PML) is a rare, but serious, complication encountered in patients treated with a select number of disease-modifying therapies (DMTs) utilized in treating multiple sclerosis (MS). PML results from a viral infection in the brain for which the only demonstrated effective therapy is restoring the perturbed immune system-typically achieved in the patient with MS by removing the offending therapeutic agent or, in the case of HIV-associated PML, treatment with highly active antiretroviral therapies...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28912987/cerebellar-involvement-in-an-immunocompetent-patient-presenting-with-progressive-multifocal-leukoencephalopathy
#20
Rafael Garcia-Carretero, Blanca San Jose Montano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC virus, a polyomavirus that can be reactivated under certain immunosuppressive conditions, such as AIDS, immunomodulatory therapy, and haematological malignancies. However, a few cases of immunocompetent patients have been reported in which no immunodeficiency was present. We describe the case of an 83-year-old immunocompetent man who presented with severe cerebellar symptoms with an MRI scan suggestive of severe demyelinating disease...
2017: Case Reports in Neurological Medicine
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