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Progressive multifocal leukoencephalopathy

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)...
October 19, 2016: Neurology
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
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
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
C Warnke, M P Wattjes, O Adams, H-P Hartung, R Martin, T Weber, M Stangel
Progressive multifocal leukoencephalopathy (PML) is a disease of immunosuppressed patients caused by the JC polyomavirus (JCPyV). Due to the elevated risk in patients treated with natalizumab for multiple sclerosis (MS) and also treatment with other biologicals for different indications, the relevance of PML has increased in recent years. This article summarizes the published knowledge on the biology and pathogenesis of PML with a focus on the role of cerebrospinal fluid diagnostics in the work-up for PML and the current PML case definition...
October 11, 2016: Der Nervenarzt
Linda Cook
Over the last 10 years, the number of identified polyomaviruses has grown to more than 35 subtypes, including 13 in humans. The polyomaviruses have similar genetic makeup, including genes that encode viral capsid proteins VP1, 2, and 3 and large and small T region proteins. The T proteins play a role in viral replication and have been implicated in viral chromosomal integration and possible dysregulation of growth factor genes. In humans, the Merkel cell polyomavirus has been shown to be highly associated with integration and the development of Merkel cell cancers...
August 2016: Microbiology Spectrum
Jiju Mani, Lei Wang, Angela G Hückelhoven, Anita Schmitt, Alma Gedvilaite, Nan Jin, Christian Kleist, Anthony D Ho, Michael Schmitt
Human JC and BK polyomaviruses (JCV/BKV) can establish a latent infection without any clinical symptoms in healthy individuals. In immunocompromised hosts infection or reactivation of JCV and BKV can cause lethal progressive multifocal leukoencephalopathy (PML) and hemorrhagic cystitis, respectively. Vaccination with JCV/BKV derived antigen epitope peptides or adoptive transfer of virus-specific T cells would constitute an elegant approach to clear virus-infected cells. Furthermore, donor leukocyte infusion (DLI) is another therapeutic approach which could be helpful for patients with JCV/BKV infections...
October 1, 2016: Oncotarget
Emanuele D'Amico, Aurora Zanghì, Carmela Leone, Hayrettin Tumani, Francesco Patti
Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so of JCV reactivation...
September 30, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Ankita Srivastava
Belimumab is the only approved biological agent for the treatment of systemic lupus erythematosus (SLE). It is a fully humanized IgG1γ monoclonal antibody directed against soluble B lymphocyte stimulator (BLyS). It is indicated as an add-on therapy for the treatment of adult patients with active, autoantibody-positive SLE, who are receiving standard therapy. Belimumab is generally well-tolerated, common adverse effects include infections, infusion reactions, hypersensitivity, headache, nausea, and fatigue...
September 2016: Indian Journal of Dermatology
Deanna Saylor, Arun Venkatesan
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by the human neurotropic polyomavirus JC (JCV). The disease occurs virtually exclusively in immunocompromised individuals, and, prior to the introduction of antiretroviral therapy, was seen most commonly in the setting of HIV/AIDS. More recently, however, the incidence of PML in HIV-uninfected persons has increased with broader use of immunosuppressive and immunomodulatory medications utilized in a variety of systemic and neurologic autoimmune disorders...
November 2016: Current Infectious Disease Reports
David B Clifford, Tarek A Yousry, Eugene O Major
The interplay between each of the stakeholder's responsibilities and desires clearly has resulted in continued widespread use of natalizumab with substantial risks and an ongoing quest for better risk mitigation. In the United States, regulatory actions codified the process of risk acceptance-and risk transfer-by escalating monitoring and information transfer to physicians and patients. Management of medication-related risks is a core function of regulatory agencies such as the Food and Drug Administration (FDA), European Medicines Agency (EMA), and the medical community...
September 27, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Brian T Nguyen, Arthur M Gershkoff, Cora H Brown, Alexander Feng
No abstract text is available yet for this article.
September 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
Eiichi Ohnuki, Shinya Asayama, Tomoko Asayama, Kazuo Nakamichi, Masayuki Saijo, Satoru Kosaka
An 83-year-old man with chronic renal failure was referred to our hospital because of subacute progressive right hemiparesis. A brain MRI showed high-intensity lesions in bilateral middle cerebellar peduncles and white matter of the left frontal lobe on T2-weighted images. The lesions increased gradually, so we suspected a brain tumor because (1)H-MRS images showed elevated Cho and decreased NAA, and also pathologic findings of the brain biopsy suggested glioblastoma. However, JC virus (JCV) in cerebrospinal fluid was revealed highly positive by PCR...
September 16, 2016: Rinshō Shinkeigaku, Clinical Neurology
Jahir Andres Miranda Acuña, Bianca Weinstock-Guttman
BACKGROUND: Natalizumab (NTZ) is an effective therapy for multiple sclerosis (MS). A common concern related to NTZ therapy is the risk of developing progressive multifocal leukoencephalopathy (PML). CLINICAL CASE: A patient that after seven years on NTZ therapy, testing on every 3 months repeated evaluations negative for anti-JCV status became positive (>3 units) 4 weeks after receiving influenza vaccine. Despite continuous therapy on NTZ for additional 2 years her anti-JCV index progressively declined to a level 0...
September 2016: Multiple Sclerosis and related Disorders
Leah T Le, Serena S Spudich
Since the advent of combination antiretroviral therapy (cART), HIV has transformed from a fatal disease to a chronic illness that often presents with milder central nervous system (CNS) symptoms laced with related confounders. The immune recovery associated with access to cART has led to a new spectrum of immune-mediated presentations of infection, phenotypically distinct from the conditions observed in advanced disease.HIV-associated neurocognitive disorder (HAND) entails a categorized continuum of disorders reflecting an array of clinical presentation, outcome, and increasing level of severity: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD)...
August 2016: Seminars in Neurology
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MED WATCH program (800-FDA-1088). If you have reported an interesting, preventable ADR to MED WATCH, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: Your report will be published anonymously unless otherwise requested...
November 2015: Hospital Pharmacy
Nicolae Sarbu, Robert Y Shih, Robert V Jones, Iren Horkayne-Szakaly, Laura Oleaga, James G Smirniotopoulos
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease)...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Robert Hoepner, Eva M Kolb, Stefanie Dahlhaus, Kerstin Hellwig, Ortwin Adams, Ingo Kleiter, Anke Salmen, Ruth Schneider, Carsten Lukas, Andrew Chan, Joseph R Berger, Ralf Gold
OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is an emerging complication of immunosuppressive therapies, especially natalizumab in multiple sclerosis (MS). Factors associated with functional outcome of natalizumab-associated PML (natalizumab-PML) have not been sufficiently described. METHODS: We retrospectively analyzed medical records of all patients with natalizumab-PML (n = 32) treated in our hospital since 2009. Disability measured by Expanded Disability Status Scale (EDSS) at two different time points (highest available EDSS during PML and last available EDSS after PML diagnosis) served as functional outcome parameters...
September 6, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Deirdre Kelly, Bernadette Monaghan, Eileen McMahon, Geoffrey Watson, Eoin Kavanagh, Killian O'Rourke, John McCaffrey, Desmond Carney
We present the case of a 60-year-old man who developed subacute neurologic changes, in the setting of stage III non-Hodgkin's follicular lymphoma, and was treated with induction chemotherapy, followed by a year of maintenance rituximab. Magnetic resonance imaging of the brain with gadolinium was pathognomonic for progressive multifocal leukoencephalopathy (PML). He was treated with sequential plasmapheresis and intravenous immunoglobulin with clinical improvement. A literature review of the diagnostic workup of rituximab-induced PML was undertaken...
September 2016: Radiology case reports
Hanna Seppälä, Elina Virtanen, Mika Saarela, Pia Laine, Lars Paulín, Laura Mannonen, Petri Auvinen, Eeva Auvinen
BACKGROUND:  Progressive multifocal leukoencephalopathy (PML) is a fatal disease caused by reactivation of JC polyomavirus (JCPyV) in immunosuppressed individuals and lytic infection by neurotropic JCPyV in glial cells. The exact content of neurotropic mutations within individual JCPyV strains has not been studied to our knowledge. METHODS:  We exploited the capacity of single-molecule real-time sequencing technology to determine the sequence of complete JCPyV genomes in single reads...
August 28, 2016: Journal of Infectious Diseases
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