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Progressive multifocal leukoencephalopathy

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https://www.readbyqxmd.com/read/28214184/-systemic-lupus-erythematosus-and-lymphopenia-clinical-and-pathophysiological-features
#1
M Martin, A Guffroy, X Argemi, T Martin
Lymphopenia is frequent in systemic lupus erythematosus (SLE) and profound (<500/mm(3)) in 10% of cases. T lymphocytes, especially CD4+, are more affected than B cells. The pathophysiological mechanisms are complex, involving lymphocytotoxic antibodies, excess of apoptosis, increased susceptibility of T cells to complement mediated cytolysis, as well as lymphopoiesis impairment and lymphocyte sequestration. Lymphopenia in SLE is independent from other cytopenia and immunosuppressive drug regiments, and associated with disease activity, risk of flare and damage scores...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28202068/the-dna-damage-response-promotes-polyomavirus-jc-infection-by-nucleus-to-cytoplasm-nf-kappab-activation
#2
Martyn K White, Anna Bellizzi, Gabriele Ibba, Valeria Pietropaolo, Anna T Palamara, Hassen S Wollebo
BACKGROUND: Infection of glial cells by human neurotropic polyomavirus JC (JCV), the causative agent of the CNS demyelinating disease progressive multifocal leukoencephalopathy (PML), rapidly inflicts damage to cellular DNA. This activates DNA damage response (DDR) signaling including induction of expression of DNA repair factor Rad51. We previously reported that Rad51 co-operates with the transcription factor NF-κB p65 to activate JCV early transcription. Thus Rad51 induction by JCV infection may provide positive feedback for viral activation early in JCV infection...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28176617/progressive-multifocal-leukoencephalopathy-in-a-kidney-transplant-recipient
#3
Federico Cicora, Javier Roberti
Progressive multifocal leukoencephalopathy (PML) is a debilitating and often fatal viral disease of the central nervous system. A 39-year-old male kidney transplant recipient presented to our hospital with weakness of the left arm and leg, his immunosuppressive regimen consisted of tacrolimus, mycophenolate sodium, and meprednisone. Magnetic resonance imaging of the brain revealed hypercellularity in neural tissue and a lesion affecting the right ventral and lateral areas of the thalamus and the posterior limb of the internal capsule...
February 7, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28174598/review-on-the-role-of-the-human-polyomavirus-jc-in-the-development-of-tumors
#4
REVIEW
Serena Delbue, Manola Comar, Pasquale Ferrante
Almost one fifth of human cancers worldwide are associated with infectious agents, either bacteria or viruses, and this makes the possible association between infections and tumors a relevant research issue. We focused our attention on the human Polyomavirus JC (JCPyV), that is a small, naked DNA virus, belonging to the Polyomaviridae family. It is the recognized etiological agent of the Progressive Multifocal Leukoencephalopathy (PML), a fatal demyelinating disease, occurring in immunosuppressed individuals...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28168372/high-b-value-diffusion-weighted-imaging-in-progressive-multifocal-leukoencephalopathy-in-hiv-patients
#5
Claudia Godi, Enrico De Vita, Enrico Tombetti, Indran Davagnanam, Lewis Haddow, Hans Rolf Jäger
OBJECTIVES: An ill-defined hyperintense edge and hypointense core on diffusion-weighted imaging (DWI) is typical of progressive multifocal leukoencephalopathy (PML). We aimed to investigate whether a b-value of 3,000 s/mm(2) (b3000) can improve visualisation of PML, or provide different structural information compared to 1,000 s/mm(2) (b1000). METHODS: We retrospectively identified HIV-positive patients with confirmed PML studied under a clinical protocol including both b1000 and b3000 DWI...
February 6, 2017: European Radiology
https://www.readbyqxmd.com/read/28167648/natalizumab-for-multiple-sclerosis-a-case-in-point-for-the-impact-of-translational-neuroimmunology
#6
Afsaneh Shirani, Olaf Stüve
Advances in translational neuroimmunology over the last two decades have revolutionized the treatment of relapsing forms of multiple sclerosis. A pathological hallmark of multiple sclerosis is the presence of leukocytes in the areas of disease activity in the CNS. Natalizumab inhibits the trafficking of lymphocytes from the blood into the brain and spinal cord by blocking the adhesion molecule α4-integrin. Representing the enormous success of a molecular targeted approach, natalizumab was the first mAb approved for the treatment of relapsing-remitting multiple sclerosis...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28165319/progressive-multifocal-leukoencephalopathy-in-two-natalizumab-treated-stepsisters-an-intriguing-coincidence
#7
Frédéric Bacchetta, Amandine Mathias, Myriam Schluep, Renaud Du Pasquier
BACKGROUND: Natalizumab, a treatment used in multiple sclerosis (MS), is associated with cases of progressive multifocal leukoencephalopathy (PML). OBJECTIVE: We describe two cases of PML in related but not genetically apparented natalizumab-treated MS patients who are stepsisters. Reported cases/outcomes: While Patient 1 developed PML, Patient 2 was on natalizumab and had contacts with Patient 1. Patient 2 was diagnosed with PML 5 months after Patient 1. CONCLUSION: The clinical and temporal data highly suggest that there was JC virus (JCV) transmission from one patient to the other with development of PML as primo-infection in Patient 2...
February 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28163944/immune-reconstitution-inflammatory-syndrome-opening-pandora-s-box
#8
Mariana Meireles, Conceição Souto Moura, Margarida França
One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm(3) (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with severe sepsis...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28147349/leukocyte-anti-trafficking-strategies-current-status-and-future-directions
#9
REVIEW
Bruce E Sands
BACKGROUND: In inflammatory bowel diseases (IBD), a pivotal step in the initiation and perpetuation of mucosal inflammation entails the recruitment of inflammatory leukocytes to the gut. Understanding the carefully coordinated series of molecular events that culminate in the recruitment of leukocytes to the gut has resulted in novel interventions with new capabilities in treating both Crohn's disease and ulcerative colitis. Key Messages: Natalizumab, an anti-α4 integrin antibody, was the first agent to demonstrate the efficacy of this approach for the induction and maintenance of response and remission in Crohn's disease...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28130412/update-on-disease-modifying-therapies-for-multiple-sclerosis
#10
Diana L Vargas, William R Tyor
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). It predominantly affects young women and is one of the most common causes of disability in young adults. MS is characterized by formation of white matter lesions in the CNS as a result of inflammation, demyelination, and axonal loss. Treatment has been a focus of neurological research for over 60 years. A number of disease-modifying therapies (DMTs) have become available making MS a treatable disease. These compounds target the inflammatory response in MS...
January 27, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28112019/natalizumab-associated-progressive-multifocal-leukoencephalopathy-is-not-preceded-by-elevated-drug-concentrations
#11
Zoé LE van Kempen, Cyra E Leurs, Anke Vennegoor, Mike P Wattjes, Theo Rispens, Bernard Mj Uitdehaag, Joep Killestein
BACKGROUND: In recent years, a small but increasing number of neurologists choose to extend dose intervals of natalizumab with the aim of reducing the risk of progressive multifocal leukoencephalopathy (PML). This idea is based on the hypothesis that high drug concentrations increase the risk of PML. OBJECTIVE: We investigated the relation between longitudinal natalizumab concentrations in patients who developed PML and patients who did not develop PML. METHODS: In a prospective observational cohort study of 219 patients with relapsing-remitting multiple sclerosis treated with natalizumab, serum samples were taken every 12 weeks prior to natalizumab infusion...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28104935/neurotuberculosis-immune-reconstitution-inflammatory-syndrome-in-the-setting-of-hiv-infection-a-case-report-and-review-of-literature
#12
Deepasree Jaganmohan, Sunitha V Chakkalakkoombil, Anjana A Beena, Nagarajan Krishnan
Immune reconstitution inflammatory syndrome (IRIS) is an exaggerated immune response which can occur with various coinfections in human immunodeficiency virus (HIV) infected patients, of which the most commonly implicated in central nervous system (CNS)-IRIS are progressive multifocal leukoencephalopathy (PML), cryptococcosis, and tuberculosis (TB). TB-IRIS is a known complication of pulmonary TB or TB lymphadenitis coinfection in HIV infected patients who are on antituberculosis treatment (ATT) after the initiation of antiretroviral therapy (ART)...
October 2016: Indian Journal of Radiology & Imaging
https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#13
Karl B Alstadhaug, Randi Fykse Halstensen, Francis Odeh
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the human polyomavirus JC (JCPyV). A particular problem with the drug cladribine seems to be prolonged suppression of the CD4+ T-cells, a well-known risk factor for PML. CASE DESCRIPTION: A 67-year-old male presented with a 3-weeks history of unsteady gait, dysarthria and a dysfunctional right arm. Seven years earlier, he had been diagnosed with urticaria pigmentosa, and 2 years later aggressive systemic mastocytosis...
March 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28087821/selection-of-first-line-therapy-in-multiple-sclerosis-using-risk-benefit-decision-analysis
#14
David Bargiela, Matthew T Bianchi, M Brandon Westover, Lori B Chibnik, Brian C Healy, Philip L De Jager, Zongqi Xia
OBJECTIVE: To integrate long-term measures of disease-modifying drug efficacy and risk to guide selection of first-line treatment of multiple sclerosis. METHODS: We created a Markov decision model to evaluate disability worsening and progressive multifocal leukoencephalopathy (PML) risk in patients receiving natalizumab (NTZ), fingolimod (FGL), or glatiramer acetate (GA) over 30 years. Leveraging publicly available data, we integrated treatment utility, disability worsening, and risk of PML into quality-adjusted life-years (QALYs)...
January 13, 2017: Neurology
https://www.readbyqxmd.com/read/28052269/observational-study-of-switching-from-natalizumab-to-immunomodulatory-drugs
#15
Ramón Villaverde-González, Julia Gracia Gil, Angel Pérez Sempere, Jorge Millán Pascual, José Marín Marín, María Carcelén Gadea, Laura Gabaldón Torres, Antonio Moreno Escribano, Antonio Candeliere Merlicco
OBJECTIVE: To determine the effect of disease-modifying drugs (DMDs) on disease activity rebound in patients discontinuing natalizumab (NTZ). METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis (RRMS) treated with NTZ for ≥1 year and who switched to DMDs (glatiramer acetate [GA] or interferon) were followed up for 12 months in clinical practice. Clinical outcomes after NTZ cessation were assessed every 3 months for 1 year and MRI was performed at 12 months...
January 5, 2017: European Neurology
https://www.readbyqxmd.com/read/28036121/study-of-the-anti-jcv-antibody-levels-in-a-spanish-multiple-sclerosis-cohort
#16
María I Dominguez-Mozo, Macarena Rus, Jose L Santiago, Guillermo Izquierdo, Ignacio Casanova, Victoria Galan, M Angel Garcia-Martinez, Ana M Arias-Leal, Marta García-Montojo, Silvia Pérez-Pérez, Rafael Arroyo, Roberto Alvarez-Lafuente
One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of multiple sclerosis (MS) patients during natalizumab treatment MATERIALS AND METHODS: All MS patients from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them two PML cases...
December 30, 2016: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28007993/myelin-phagocytosis-by-astrocytes-after-myelin-damage-promotes-lesion-pathology
#17
Gerald Ponath, Sriram Ramanan, Mayyan Mubarak, William Housley, Seunghoon Lee, F Rezan Sahinkaya, Alexander Vortmeyer, Cedric S Raine, David Pitt
Astrocytes are key players in the pathology of multiple sclerosis and can assume beneficial and detrimental roles during lesion development. The triggers and timing of the different astroglial responses in acute lesions remain unclear. Astrocytes in acute multiple sclerosis lesions have been shown previously to contain myelin debris, although its significance has not been examined. We hypothesized that myelin phagocytosis by astrocytes is an early event during lesion formation and leads to astroglial immune responses...
December 21, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28005037/-a-case-of-progressive-multifocal-leukoencephalopathy-in-a-hiv-infected-female-patient
#18
E A Samotolkina, A V Pokrovskaya, E S Samotolkina, S L Voznesensky, E V Petrova
Progressive multifocal leukoencephalopathy (PML) caused by JC virus is a severe central nervous lesion developing in the presence of obvious immunodeficiency. In most cases, the disease results in a fatal outcome within a few months. Antiretroviral therapy is currently considered to be the only method for the prevention and treatment of PML in HIV-infected patients. The paper describes a positive experience in treating the HIV-infected female patient with the established diagnosis of PML.
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28004598/natalizumab-treatment-of-multiple-sclerosis-new-insights
#19
Serena Delbue, Manola Comar, Pasquale Ferrante
Natalizumab is a monoclonal antibody directed against the α4 chain of the very late activating antigen 4 and α4β7 integrins, present on the leukocytes surface, used as monotherapy for the treatment of relapsing-remitting multiple sclerosis. It substantially reduces relapse rate and the accumulation of disability, but its use is associated with a very adverse event, that is the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disease of the CNS, due to the lytic replication of the human polyomavirus JC...
December 22, 2016: Immunotherapy
https://www.readbyqxmd.com/read/28001298/drug-induced-progressive-multifocal-leukoencephalopathy-in-multiple-sclerosis-european-regulators-perspective
#20
R Anton, M Haas, P Arlett, M Weise, P Balabanov, G Mazzaglia, L Prieto, B Keller-Stanislawski, J Raine
Progressive multifocal leukoencephalopathy (PML) has been associated with the use of a number of multiple sclerosis (MS) immunomodulatory therapies and has assumed a critical place in the evaluation of their benefit/risk. In this review, we discuss the European Union regulatory approach to drug-induced PML in MS, highlight a number of key issues related to the current knowledge on PML, and outline possible paths to help progress the risk management of patients with MS at risk of PML.
December 21, 2016: Clinical Pharmacology and Therapeutics
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