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Progressive multifocal leukoencephalopathy

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/27817117/differences-in-t-cell-cytotoxicity-and-cell-death-mechanisms-between-progressive-multifocal-leukoencephalopathy-herpes-simplex-virus-encephalitis-and-cytomegalovirus-encephalitis
#7
Susanne Laukoter, Helmut Rauschka, Anna R Tröscher, Ulrike Köck, Etsuji Saji, Kurt Jellinger, Hans Lassmann, Jan Bauer
During the appearance of human immunodeficiency virus infection in the 1980 and the 1990s, progressive multifocal leukoencephalopathy (PML), a viral encephalitis induced by the JC virus, was the leading opportunistic brain infection. As a result of the use of modern immunomodulatory compounds such as Natalizumab and Rituximab, the number of patients with PML is once again increasing. Despite the presence of PML over decades, little is known regarding the mechanisms leading to death of infected cells and the role the immune system plays in this process...
November 5, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27815407/cd62l-test-at-2-years-of-natalizumab-predicts-progressive-multifocal-leukoencephalopathy
#8
Béatrice Pignolet, Nicholas Schwab, Tilman Schneider-Hohendorf, Florence Bucciarelli, Damien Biotti, Delphine Averseng-Peaureaux, Olivier Outteryck, Jean-Claude Ongagna, Jérôme de Sèze, Bruno Brochet, Jean-Christophe Ouallet, Marc Debouverie, Sophie Pittion, Gilles Defer, Nathalie Derache, Patrick Hautecoeur, Ayman Tourbah, Pierre Labauge, Giovanni Castelnovo, Pierre Clavelou, Eric Berger, Jean Pelletier, Audrey Rico, Hélène Zéphir, David Laplaud, Sandrine Wiertlewski, William Camu, Eric Thouvenot, Olivier Casez, Thibault Moreau, Agnès Fromont, Sandra Vukusic, Caroline Papeix, Patrick Vermersch, Manuel Comabella, Christine Lebrun-Frenay, Heinz Wiendl, David Brassat
No abstract text is available yet for this article.
December 6, 2016: Neurology
https://www.readbyqxmd.com/read/27812788/jc-polyomavirus-expression-and-bell-shaped-regulation-of-its-sf2-asf-suppressor-during-the-follow-up-of-multiple-sclerosis-patients-treated-with-natalizumab
#9
Elena Uleri, Gabriele Ibba, Claudia Piu, Maurizio Caocci, Stefania Leoni, Giannina Arru, Caterina Serra, GianPietro Sechi, Antonina Dolei
Natalizumab is effective against multiple sclerosis (MS), but is associated with progressive multifocal leukoencephalopathy (PML), fatal disease caused by the JCV polyomavirus. The SF2/ASF (splicing factor2/alternative splicing factor) inhibits JCV in glial cells. We wondered about SF2/ASF modulation in the blood of natalizumab-treated patients and if this could influence JCV reactivation. Therefore, we performed a longitudinal study of MS patients under natalizumab, in comparison to patients under fingolimod and to healthy blood donors...
November 3, 2016: Journal of Neurovirology
https://www.readbyqxmd.com/read/27803638/disability-progression-after-switching-from-natalizumab-to-fingolimod-or-interferon-beta-glatiramer-acetate-therapies-a-narcoms-analysis
#10
Stacey S Cofield, Robert J Fox, Tuula Tyry, Amber R Salter, Denise Campagnolo
Background: Physicians must weigh the benefits against the risk of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab, especially beyond 2 years. However, disability progression associated with switching therapies versus continuing natalizumab therapy after 2 years has not been fully evaluated. Methods: In this retrospective analysis using the NARCOMS Registry, disability progression (Patient-Determined Disease Steps [PDDS] scale) and physical health-related quality of life (HRQOL) worsening (12-item Short Form Health Status Survey Physical Component Score [SF-12 PCS]) were compared between participants switching to fingolimod (n = 50) or interferon beta (IFNβ)/glatiramer acetate (GA) (n = 71) therapy and those continuing natalizumab (n = 406) after 2 years or more of treatment (median follow-up: natalizumab, 4 years; fingolimod, 4...
September 2016: International Journal of MS Care
https://www.readbyqxmd.com/read/27795410/deep-sequence-identification-and-role-in-virus-replication-of-a-jc-virus-quasispecies-in-patients-with-progressive-multifocal-leukoencephalopathy
#11
Kenta Takahashi, Tsuyoshi Sekizuka, Hitomi Fukumoto, Kazuo Nakamichi, Tadaki Suzuki, Yuko Sato, Hideki Hasegawa, Makoto Kuroda, Harutaka Katano
: JC virus (JCV) is a DNA virus causing progressive multifocal leukoencephalopathy (PML) in immunodeficient patients. In the present study, 22 genetic quasispecies with more than 1.5% variant frequency were detected in JCV genomes from six clinical samples of PML by next-generation sequencing. A mutation from A to C at nt 3495 in JCV Mad1 resulting in a V to G amino acid substitution at aa position 392 of the large T antigen (TAg) was identified in all six cases of PML at 3%-19% variant frequencies...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27786246/hiv-associated-opportunistic-cns-infections-pathophysiology-diagnosis-and-treatment
#12
REVIEW
Lauren N Bowen, Bryan Smith, Daniel Reich, Martha Quezado, Avindra Nath
Nearly 30 years after the advent of antiretroviral therapy (ART), CNS opportunistic infections remain a major cause of morbidity and mortality in HIV-positive individuals. Unknown HIV-positive disease status, antiretroviral drug resistance, poor drug compliance, and recreational drug abuse are factors that continue to influence the morbidity and mortality of infections. The clinical and radiographic pattern of CNS opportunistic infections is unique in the setting of HIV infection: opportunistic infections in HIV-positive patients often have characteristic clinical and radiological presentations that can differ from the presentation of opportunistic infections in immunocompetent patients and are often sufficient to establish the diagnosis...
October 27, 2016: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/27782080/in-vitro-and-in-vivo-models-for-the-study-of-human-polyomavirus-infection
#13
REVIEW
Heidi Barth, Morgane Solis, Wallys Kack-Kack, Eric Soulier, Aurélie Velay, Samira Fafi-Kremer
Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated...
October 22, 2016: Viruses
https://www.readbyqxmd.com/read/27772622/bk-and-other-polyomaviruses-in-kidney-transplantation
#14
Jennifer Trofe-Clark, Deirdre Sawinski
For more than 40 years, polyomaviruses (BK virus and JC virus) have been known to cause disease in human beings. Recently, 11 new polyomaviruses were discovered. However, the majority of these viruses are rare in renal transplant recipients and BK and JC viruses remain the most important polyomaviruses to impact this population. BK virus presents as BK virus nephropathy and has, in rare instances, been associated with hemorrhagic cystitis or ureteral strictures. JC virus can cause progressive multifocal leukoencephalopathy or nephropathy in this population as well, but is uncommon...
September 2016: Seminars in Nephrology
https://www.readbyqxmd.com/read/27766611/jcv-serology-in-time-3%C3%A2-years-of-follow-up
#15
M Cambron, N Hadhoum, E Duhin, A Lacour, A Chouraki, P Vermersch
OBJECTIVES: Although many neurologists are reluctant to use natalizumab in MS (multiple sclerosis) given the increased risk for PML (progressive multifocal leukoencephalopathy), trust was regained with the introduction of JCV antibody titres as a potent disease-modifying therapy. Literature shows that in patients with a negative JCV serology, the risk of PML is virtually non-existent. Unfortunately, seroconversion causes concern amongst many neurologists. Furthermore, when patients seroconvert, it is still unclear what the risk is of passing the important threshold of 1...
October 20, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27766364/applicability-of-predictive-toxicology-methods-for-monoclonal-antibody-therapeutics-status-quo-and-scope
#16
Arathi Kizhedath, Simon Wilkinson, Jarka Glassey
Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few...
October 20, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27760868/rituximab-in-multiple-sclerosis-a-retrospective-observational-study-on-safety-and-efficacy
#17
Jonatan Salzer, Rasmus Svenningsson, Peter Alping, Lenka Novakova, Anna Björck, Katharina Fink, Protik Islam-Jakobsson, Clas Malmeström, Markus Axelsson, Mattias Vågberg, Peter Sundström, Jan Lycke, Fredrik Piehl, Anders Svenningsson
OBJECTIVE: To investigate the safety and efficacy of rituximab in multiple sclerosis (MS). METHODS: In this retrospective uncontrolled observational multicenter study, off-label rituximab-treated patients with MS were identified through the Swedish MS register. Outcome data were collected from the MS register and medical charts. Adverse events (AEs) grades 2-5 according to the Common Terminology Criteria for Adverse Events were recorded. RESULTS: A total of 822 rituximab-treated patients with MS were identified: 557 relapsing-remitting MS (RRMS), 198 secondary progressive MS (SPMS), and 67 primary progressive MS (PPMS)...
November 15, 2016: Neurology
https://www.readbyqxmd.com/read/27756172/safety-of-monoclonal-antibodies-for-the-treatment-of-multiple-sclerosis
#18
Marisa P McGinley, Brandon P Moss, Jeffrey A Cohen
Monoclonal antibodies are a potent therapeutic approach for relapsing-remitting multiple sclerosis. This group of medications comprises diverse mechanisms of action resulting in both shared and unique adverse effects. Areas covered: The major trials and safety profiles of natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab are discussed. While each drug has a unique safety profile, one of the potential safety concerns for all of these drugs is infection, including for some progressive multifocal leukoencephalopathy...
October 19, 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27747531/rituximab-for-rheumatoid-arthritis
#19
Marc D Cohen, Edward Keystone
Rituximab is a chimeric monoclonal antibody directed at the CD20 molecule on the surfaces of some but not all B cells. It depletes almost all peripheral B cells, but other niches of B cells are variably depleted, including synovium. Its mechanism of action in rheumatoid arthritis (RA) is only partially understood. Rituximab was efficacious in clinical trials of patients with RA, including those who are methotrexate naïve, those with an incomplete response to methotrexate, and those with an incomplete response to tumor necrosis factor inhibitors...
December 2015: Rheumatol Ther
https://www.readbyqxmd.com/read/27736027/drug-induced-progressive-multifocal-leukoencephalopathy-a-case-noncase-study-in-the-french-pharmacovigilance-database
#20
Olivier Colin, Sylvie Favrelière, Alexandre Quillet, Jean-Philippe Neau, Jean-Luc Houeto, Claire Lafay-Chebassier, Marie-Christine Pérault-Pochat
Progressive multifocal leukoencephalopathy (PML) is an often fatal demyelinating disease of the central nervous system. As effective treatment is unavailable, identification of all drugs that could be associated with PML is essential. The objective of this study was to investigate the putative association of reports of PML and drugs. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of PML in the FPVD between January 2008 and December 2015. Noncases were all other reports during the same period...
October 13, 2016: Fundamental & Clinical Pharmacology
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