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Progressive multifocal leukoencephalopathy

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https://www.readbyqxmd.com/read/28095350/progressive-multifocal-leukoencephalopathy-in-a-patient-with-systemic-mastocytosis-treated-with-cladribine
#1
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...
December 14, 2016: 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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-pml-in-multiple-sclerosis-european-regulators-perspective
#8
REVIEW
Ruxandra Anton, Manuel Haas, Peter Arlett, Martina Weise, Pavel Balabanov, Giampiero Mazzaglia, Luis Prieto, Brigitte Keller-Stanislawski, June 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 EU 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 MS patients at risk of PML. This article is protected by copyright. All rights reserved...
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27997580/natalizumab-related-progressive-multifocal-leukoencephalopathy-in-multiple-sclerosis-findings-from-an-italian-independent-registry
#9
Luca Prosperini, Nicola de Rossi, Cristina Scarpazza, Lucia Moiola, Mirco Cosottini, Simonetta Gerevini, Ruggero Capra
BACKGROUND: The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV). OBJECTIVE: To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions...
2016: PloS One
https://www.readbyqxmd.com/read/27994897/progressive-multifocal-leukoencephalopathy-in-a-multiple-sclerosis-patient-diagnosed-after-switching-from-natalizumab-to-fingolimod
#10
Tim Sinnecker, Jalal Othman, Marc Kühl, Imke Metz, Thoralf Niendorf, Annett Kunkel, Friedemann Paul, Jens Wuerfel, Juergen Faiss
Background. Natalizumab- (NTZ-) associated progressive multifocal leukoencephalopathy (PML) is a severe and often disabling infectious central nervous system disease that can become evident in multiple sclerosis (MS) patients after NTZ discontinuation. Recently, novel diagnostic biomarkers for the assessment of PML risk in NTZ treated MS patients such as the anti-JC virus antibody index have been reported, and the clinical relevance of milky-way lesions detectable by MRI has been discussed. Case Presentation and Conclusion...
2016: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/27965904/rituximab-associated-inflammatory-progressive-multifocal-leukoencephalopathy
#11
Chandra Punch, Christina Schofield, Penelope Harris
Progressive multifocal leukoencephalopathy (PML) is a rare disease of the immunosuppression that results from neurotropic invasion of the JC virus which leads to demyelination of oligodendrocytes. Immune reconstitution inflammatory syndrome (IRIS), on the other hand, is a condition of inflammation that develops as the immune system reconstitutes. This case report describes a case of a 35-year-old HIV-negative male who presented with three weeks of right lower extremity paresthesias as well as right upper extremity apraxia...
2016: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/27959350/progressive-multifocal-leukoencephalopathy-associated-with-infliximab
#12
L Sammut, D Wallis, C Holroyd
A 69-year-old female with seropositive rheumatoid arthritis presented with progressive cognitive decline following treatment with infliximab and methotrexate. Cranial MRI showed non-enhancing white matter signal abnormality consistent with demyelination was seen in the antero-inferior left frontal lobe extending into the frontal opercular white matter and into the left temporal lobe white matter. Similar appearances were seen in the inferomedial right frontal lobe. Brain biopsy showed histological changes consistent with progressive multifocal leukoencephalopathy...
September 2016: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/27938314/sequential-onset-of-varicella-zoster-virus-encephalomeningitis-and-progressive-multifocal-leukoencephalopathy-in-an-allogeneic-hematopoietic-stem-cell-transplant-recipient
#13
Yukiko Yamashita, Shinsuke Kusakabe, Jun Toda, Kenji Ohshima, Hiroaki Masaie, Toshinari Yagi, Hitoshi Yoshida, Jun Ishikawa
Here, we describe a case of sequential varicella-zoster virus encephalomeningitis and progressive multifocal leukoencephalopathy following an allogeneic hematopoietic stem cell transplant procedure. A 37-year-old male patient presented with fever, incomplete paralysis of bilateral legs, and bullous eruptions 8 months after allogeneic transplant. Polymerase chain reaction assays of cerebrospinal fluid samples for varicella-zoster virus were positive. Bullous eruptions and incomplete paralysis of bilateral legs improved after administration of acyclovir...
December 12, 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27924751/neurological-sequelae-of-cancer-immunotherapies-and-targeted-therapies
#14
REVIEW
Wolfgang Wick, Anne Hertenstein, Michael Platten
Neurological complications of cancer and of anticancer treatments can be substantially disabling to patients, especially with classic chemotherapies. As a rare but important complication, targeted therapies might also result in similar unwanted effects, partly because inhibition of VEGF is a common downstream effect. Therapeutic antibodies, such as the CD20-depleting antibody rituximab, and underlying haematological malignancies, can induce long-lasting cellular immunosuppression, predisposing patients to opportunistic CNS infections, such as progressive multifocal leukoencephalopathy, where treatment-induced recovery can result in severe reconstitution of immune inflammatory syndromes of the central nervous system...
December 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27921221/safety-and-efficacy-of-natalizumab-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis-open-label-extension-study-of-a-phase-2-trial
#15
Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Nobuhisa Ohtsuka, Yan Ling, Shinichi Torii, Nisha Lucas, Geoffrey Kuesters, Deb Steiner, J T Tibung
INTRODUCTION: The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients. METHODS: A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks...
December 5, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27904430/natalizumab-related-progressive-multifocal-leukoencephalopathy-immune-reconstitution-inflammatory-syndrome-a-case-report-highlighting-clinical-and-mri-features
#16
Bela Purohit, Eranga Ganewatte, Spyros S Kollias
Multiple sclerosis (MS) patients treated with natalizumab often face the uncommon but severe complication of developing progressive multifocal leukoencephalopathy (PML). PML may be further complicated by immune reconstitution inflammatory syndrome (IRIS) after the removal of the drug. Since both PML and IRIS are associated with high morbidity and mortality rates, early clinical and radiological diagnosis of these complications is of paramount importance. Here, we report a case of an adult male patient who was diagnosed with PML after receiving natalizumab therapy for 6 years for the treatment of MS...
September 2016: Malaysian Journal of Medical Sciences: MJMS
https://www.readbyqxmd.com/read/27890707/novel-mutation-in-dock8-hies-with-severe-phenotype-and-successful-transplantation
#17
Latifa Al Shekaili, Farrukh Sheikh, Sulaiman Al Gazlan, Hasan Al Dhekri, Hamoud Al Mousa, Abdulaziz Al Ghonaium, Bander Al Saud, Saleh Al Mohsen, Agha M Rehan Khaliq, Safiah Al Sumayli, Mufarreh Al Zahrani, Anas Dababo, Ammar AlKawi, Abbas Hawwari, Rand Arnaout
BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution...
November 23, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27890176/the-risk-of-progressive-multifocal-leukoencephalopathy-in-the-biologic-era-prevention-and-management
#18
REVIEW
Eamonn S Molloy, Cassandra M Calabrese, Leonard H Calabrese
Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, demyelinating central nervous system infection caused by reactivation of the John Cunningham virus that generally occurs in immunosuppressed patients. With an evolving understanding of a greater clinical heterogeneity of PML and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic presentations of rheumatic diseases. Increased awareness of PML among rheumatologists is required, as earlier diagnosis and restoration of immune function may improve the otherwise grim prognosis associated with PML...
February 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/27862809/assessing-understanding-patients-prescribed-natalizumab-for-multiple-sclerosis-individual-risk-and-symptoms-of-progressive-multifocal-leukoencephalopathy
#19
Louise Rath, Nirosen Vijiaratnam, Olga Skibina
BACKGROUND: Natalizumab, a monoclonal antibody directed against α4 integrin, is a highly efficacious treatment commonly used in Relapsing Remitting Multiple Sclerosis (MS). Natalizumab is associated with the potentially fatal rare demyelinating opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). Prognosis and disability from PML is determined by early diagnosis. Written tools are mandated in Australia and other prescribing countries with the aim to help patients understand the risks associated with treatment and ensure familiarity with the early symptoms of PML...
November 9, 2016: Internal Medicine Journal
https://www.readbyqxmd.com/read/27833967/diagnosing-hiv-associated-cerebral-diseases-the-importance-of-neuropathology-in-understanding-hiv
#20
Ioan Alexandru Diaconu, LaurenŢiu MihăiŢă Stratan, Luciana Nichita, Victoria Aramă, Valentina Ruxandra Moroti Constantinescu, Alexandra Ioana Diaconu, Daniela Adriana Ion
The study aims to compare two aspects concerning the diagnosis of acquired immune deficiency syndrome (AIDS)-associated central nervous system (CNS) pathology (neuroAIDS): clinical diagnoses issued ante mortem with pathology results issued post mortem. The group of 39 human immunodeficiency virus (HIV)-positive patients was created over 23 years and is limited by marked heterogeneity. The enrolled cases were treated at the "Prof. Dr. Matei Bals" National Institute for Infectious Diseases, Bucharest, Romania, deceased due to AIDS-related complications and underwent brain necropsies performed in the Pathology Laboratory at the "Colentina" Clinical Hospital, Bucharest...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
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