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Progressive multifocal leukoencephalopathy

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https://www.readbyqxmd.com/read/29903436/the-neuropathology-of-the-adult-cerebellum
#1
Arnulf H Koeppen
This chapter summarizes the neuropathologic features of nonneoplastic disorders of the adult cerebellum. Gait ataxia and extremity dysmetria are clinical manifestations of diseases that interrupt the complex cerebellar circuitry between the neurons of the cerebellar cortex, the cerebellar nuclei (especially the dentate nuclei), and the inferior olivary nuclei. The cerebellum is a prominent target of several sporadic and hereditary neurodegenerative diseases, including multiple system atrophy, spinocerebellar ataxia, and Friedreich ataxia...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29881971/-new-aspects-of-immunotherapy-in-multiple-sclerosis
#2
REVIEW
K Pape, F Zipp, S Bittner
The spectrum of therapeutic options for immunotherapy of multiple sclerosis is continuously broadening. After the approval of cladribine and ocrelizumab in Europe, two new drugs are now available with ocrelizumab being the first approved option for treatment of primary progressive multiple sclerosis; however, the increased use of highly effective therapies is accompanied by a rise in severe side effects. During recent months, special attention was paid to the new progressive multifocal leukoencephalopathy (PML) risk assessment in natalizumab-treated patients, cardiac side effects of fingolimod, cases of idiopathic thrombocytopenic purpura and listeria meningitis associated with alemtuzumab and cases of daclizumab-treated patients with liver failure or encephalitis...
June 7, 2018: Der Nervenarzt
https://www.readbyqxmd.com/read/29787494/-barbell-sign-a-diagnostic-imaging-finding-in-progressive-multifocal-leukoencephalopathy
#3
A Fourie Bezuidenhout, Savvas Andronikou, Christelle Ackermann, Anne-Marie Du Plessis, Derik Basson, Rafeeque A Bhadelia
The recently proposed diagnostic algorithm for progressive multifocal leukoencephalopathy underscores the importance of imaging and emphasizes the role of the radiologist in the diagnostic workup. We describe a case series of patients with visual symptoms and a typical pattern of brain involvement in definite progressive multifocal leukoencephalopathy, for which we have coined the term barbell sign.
May 21, 2018: Journal of Computer Assisted Tomography
https://www.readbyqxmd.com/read/29785581/anti-jc-virus-antibody-sera-positivity-and-index-value-among-patients-with-multiple-sclerosis-may-be-correlated-with-age-sex-and-area-of-residence
#4
Sogol Koolaji, Narges Sistany Allahabadi, Arash Ahmadi, Sharareh Eskandarieh, Abdorreza Naser Moghadasi, Amir Reza Azimi, Mohammad Ali Sahraian
Anti-JC virus (JCV) antibody index is the predictive factor of progressive multifocal leukoencephalopathy (PML) for multiple sclerosis (MS) patients treating with natalizumab. The aim of this study is to evaluate the prevalence of anti-JCV antibody positivity and index among Iranian patients who are the candidate for natalizumab and its correlation with their demographic data and previous therapies. A cross-sectional design was assessed for receiving anti-JCV antibody test results between January 2014 and December 2016...
May 21, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29774781/aging-and-lymphocyte-changes-by-immunomodulatory-therapies-impact-pml-risk-in-multiple-sclerosis-patients
#5
Elizabeth A Mills, Yang Mao-Draayer
New potent immunomodulatory therapies for multiple sclerosis (MS) are associated with increased risk for progressive multifocal leukoencephalopathy (PML). It is unclear why a subset of treated patients develops PML, but patient age has emerged as an important risk factor. PML is caused by the JC virus and aging is associated with immune senescence, which increases susceptibility to infection. With the goal of improving PML risk stratification, we here describe the lymphocyte changes that occur with disease-modifying therapies (DMTs) associated with high or moderate risk toward PML in MS patients, how these changes compare to immune aging, and which measures best correlate with risk...
May 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29754703/progression-of-a-series-of-patients-with-relapsing-remitting-multiple-sclerosis-treated-for-7-years-with-natalizumab-using-the-no-evidence-of-disease-activity-parameter
#6
A Pato Pato, E Costa Arpín, A Rodríguez Regal, I Rodríguez Constenla, I Cimas Hernando, I Muñoz Pousa, L Naya Ríos, J R Lorenzo González, M C Amigo Jorrín, J M Prieto González
INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters...
May 10, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/29740202/anti-integrin-therapy-for-inflammatory-bowel-disease
#7
REVIEW
Sung Chul Park, Yoon Tae Jeen
In inflammatory bowel disease (IBD), tumor necrosis factor plays an important role in mediating inflammation, but several other pathways are also involved in eliciting an inflammatory response. One such pathway is the invasion of the intestinal mucosa by leukocytes. Leukocytes within the systemic circulation move to sites of inflammation, and blocking this pathway could be an important treatment strategy for IBD. Anti-integrin therapy blocks the action of integrin on the surface of circulating immune cells and endothelial cell adhesion molecules, thereby inhibiting the interactions between leukocytes and intestinal blood vessels...
May 7, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29737503/a-programme-for-risk-assessment-and-minimisation-of-progressive-multifocal-leukoencephalopathy-developed-for-vedolizumab-clinical-trials
#8
Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H Lev, James M Provenzale, Jesse Shick, Mark Patti, Megan McAuliffe, Joseph R Berger, David B Clifford
INTRODUCTION: Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment...
May 8, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29725611/fingolimod-associated-pml-with-mild-iris-in-ms-a-clinicopathologic-study
#9
Shuhei Nishiyama, Tatsuro Misu, Yukiko Shishido-Hara, Kazuo Nakamichi, Masayuki Saijo, Yoshiki Takai, Kentarou Takei, Naoki Yamamoto, Hiroshi Kuroda, Ryuta Saito, Mika Watanabe, Teiji Tominaga, Ichiro Nakashima, Kazuo Fujihara, Masashi Aoki
Objective: To clarify the clinical, neuropathologic, and virologic characteristics of progressive multifocal leukoencephalopathy (PML) and its immune reconstitution inflammatory syndrome (IRIS) in a patient with fingolimod-treated MS. Methods: A case study. Results: A 34-year-old patient with MS using fingolimod for 4 years had a gradual progression of right hemiparesis and aphasia with a new subcortical white matter lesion in the precentral gyrus by initial MRI...
January 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29724903/natural-history-of-gata2-deficiency-in-a-survey-of-79-french-and-belgian-patients
#10
Jean Donadieu, Marie Lamant, Claire Fieschi, Flore Sicre de Fontbrune, Aurélie Caye, Marie Ouachee, Blandine Beaupain, Jacinta Bustamante, Hélène A Poirel, Bertrand Isidor, Eric Van Den Neste, Antoine Neel, Stanislas Nimubona, Fabienne Toutain, Vincent Barlogis, Nicolas Schleinitz, Thierry Leblanc, Pierre Rohrlich, Felipe Suarez, Dana Ranta, Wahid Abou Chahla, Bénédicte Bruno, Louis Terriou, Sylvie Francois, Bruno Lioure, Guido Ahle, Françoise Bachelerie, Claude Preudhomme, Eric Delabesse, Hélène Cavé, Christine Bellanné-Chantelot, Marlène Pasquet
Heterozygous germline GATA2 mutations strongly predispose to leukaemia, immunodeficiency, and/or lymphoedema. We now describe a series of 79 patients (53 families) diagnosed since 2011, compiling all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and haematological malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old...
May 3, 2018: Haematologica
https://www.readbyqxmd.com/read/29724377/editors-welcome-pregnancy-and-progressive-multifocal-leukoencephalopathy
#11
EDITORIAL
Michael Levy, Gavin Giovannoni, Chris Hawkes, Emmanuelle Waubant
No abstract text is available yet for this article.
April 2018: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29710027/-two-patients-with-progressive-multifocal-leukoencephalopathy-with-immune-response-against-jc-virus-showing-good-long-term-outcome-by-combination-therapy-of-mefloquine-mirtazapine-and-risperidone
#12
Yumi Akagawa, Akihiro Ueno, Junji Ikeda, Wataru Ishii, Yukiko Shishido-Hara, Yoshiki Sekijima
Patient 1 was a 59-year-old woman receiving prednisolone for idiopathic hypereosinophilia. Brain MRI of patient 1 disclosed slight gadolinium enhancement at lesions, indicating inflammation. Patient 2 was a 32-year-old woman with systemic lupus erythematosus under immunosuppressive therapy. Brain biopsy of patient 2 showed balanced infiltration of CD8+ and CD4+ T lymphocytes at the sites of lesions. Both subjects were diagnosed as having progressive multifocal leukoencephalopathy (PML) shortly after the onset of neurological symptoms and were treated with a combination of mefloquine, mirtazapine, and risperidone...
May 25, 2018: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/29709947/a-punctate-magnetic-resonance-imaging-pattern-in-a-patient-with-systemic-lupus-erythematosus-is-an-early-sign-of-progressive-multifocal-leukoencephalopathy-a-clinicopathological-study
#13
Junko Ishii, Yukiko Shishido-Hara, Michi Kawamoto, Satoru Fujiwara, Yukihiro Imai, Kazuo Nakamichi, Nobuo Kohara
A 37-year-old woman with systemic lupus erythematosus (SLE) presented with gait disturbance and cognitive dysfunction. Brain magnetic resonance imaging (MRI) revealed small, punctate, T2-/fluid-attenuated inversion recovery-hyperintense and T1-hypointense lesions without gadolinium enhancement, which is atypical for progressive multifocal leukoencephalopathy (PML). On a pathological examination of biopsied brain tissues, JC virus-infected cells were hardly detected via immunohistochemistry but were certainly detected via in situ hybridization, conclusively verifying the PML diagnosis...
April 27, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29709026/immunophenotypic-characterization-of-csf-b-cells-in-virus-associated-neuroinflammatory-diseases
#14
Yoshimi Enose-Akahata, Shila Azodi, Bryan R Smith, Bridgette Jeanne Billioux, Ashley Vellucci, Nyater Ngouth, Yuetsu Tanaka, Joan Ohayon, Irene Cortese, Avindra Nath, Steven Jacobson
Intrathecal antibody synthesis is a well-documented phenomenon in infectious neurological diseases as well as in demyelinating diseases, but little is known about the role of B cells in the central nervous systems. We examined B cell and T cell immunophenotypes in CSF of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) compared to healthy normal donors and subjects with the other chronic virus infection and/or neuroinflammatory diseases including HIV infection, multiple sclerosis (MS) and progressive multifocal leukoencephalopathy...
April 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29708072/a-review-on-clinical-pharmacokinetics-pharmacodynamics-and-pharmacogenomics-of-natalizumab-a-humanized-anti-%C3%AE-4-integrin-monoclonal-antibody
#15
Li Hao, Shi Fang-Hong, Huang Shi-Ying, Zhang Shun-Guo, Chen Min-Ling
Natalizumab (Tysabri®, Biogen-Idec Inc., NAT), a humanized anti-α4 integrin monoclonal antibody, binds in both α4β1 (Very Late Antigen 4, VLA-4) and α4β7 (lymphocytes Peyer's patch adhesion molecule 1, LPAM-1) integrins, is approved for the treatment of Multiple sclerosis (MS) and Crohn's disease (CD). NAT has been well tolerated in pivotal trials. Progressive multifocal leukoencephalopathy (PML) is an uncommon but serious complications resulting from NAT treatment. It is not confirmed that higher NAT concentration increases the risk of PML...
April 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29690814/concurrent-progressive-multifocal-leukoencephalopathy-and-central-nervous-system-infiltration-by-multiple-myeloma-a-case-report
#16
Yanira Ruiz-Heredia, Beatriz Sanchez-Vega, Santiago Barrio, María Linares, Inmaculada Rapado, Esteban Braggio, Keith Stewart, M Dolores Folgueira, Ana Ramos, Luis Collado, Juan Ruiz, Oscar Toldos, Aurelio Hernandez-Lain, Joaquin Martinez-Lopez
Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration. A 73-year-old woman with relapsed multiple myeloma was treated with 15 cycles of lenalidomide and dexamethasone, but therapy had to be stopped because of a hip fracture after a fall...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29687403/progressive-multifocal-leukoencephalopathy-in-idiopathic-cd4-lymphocytopenia
#17
Rajeswari Aghoram, Sunil K Narayan
Progressive multifocal leukoencephalopathy is a central nervous system demyelinating disease caused by infection with John Cunningham virus. It affects predominantly the subcortical white matter, producing progressive neurological deficits and large confluent white matter lesions on imaging. It is usually seen in immunodeficient individuals, such as those suffering from acquired immunodeficiency syndrome, those on treatment with monoclonal antibodies, and those following therapeutic bone marrow suppression...
April 23, 2018: Journal of Neurovirology
https://www.readbyqxmd.com/read/29686116/practice-guideline-recommendations-summary-disease-modifying-therapies-for-adults-with-multiple-sclerosis-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#18
Alexander Rae-Grant, Gregory S Day, Ruth Ann Marrie, Alejandro Rabinstein, Bruce A C Cree, Gary S Gronseth, Michael Haboubi, June Halper, Jonathan P Hosey, David E Jones, Robert Lisak, Daniel Pelletier, Sonja Potrebic, Cynthia Sitcov, Rick Sommers, Julie Stachowiak, Thomas S D Getchius, Shannon A Merillat, Tamara Pringsheim
OBJECTIVE: To develop recommendations for disease-modifying therapy (DMT) for multiple sclerosis (MS). METHODS: A multidisciplinary panel developed DMT recommendations, integrating findings from a systematic review; followed an Institute of Medicine-compliant process to ensure transparency and patient engagement; and developed modified Delphi consensus-based recommendations concerning starting, switching, and stopping DMTs pertinent to people with relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndromes of demyelination...
April 24, 2018: Neurology
https://www.readbyqxmd.com/read/29682547/jc-virus-dna-detection-is-associated-with-cd8-effector-accumulation-in-peripheral-blood-of-patients-with-multiple-sclerosis-under-natalizumab-treatment-independently-from-jc-virus-serostatus
#19
Maria A Zingaropoli, Marco Iannetta, Simona Pontecorvo, Elena Anzivino, Carla Prezioso, Donatella Maria Rodio, Manuela Morreale, Alessandra D'Abramo, Alessandra Oliva, Miriam Lichtner, Antonio Cortese, Marco Frontoni, Valeria Pietropaolo, Ada Francia, Claudio M Mastroianni, Vincenzo Vullo, Maria R Ciardi
Although natalizumab (anti- α 4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 ( N 0), 1-12 ( N 12), 13-24 ( N 24), 25-36 ( N 36), and over 36 ( N > 36) infusions...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29669908/progressive-multifocal-leukoencephalopathy-after-fingolimod-treatment
#20
Joseph R Berger, Bruce A Cree, Benjamin Greenberg, Bernhard Hemmer, Brian J Ward, Victor M Dong, Martin Merschhemke
OBJECTIVE: We describe the characteristics of the 15 patients with fingolimod-associated progressive multifocal leukoencephalopathy (PML) identified from the Novartis data safety base and provide risk estimates for the disorder. METHODS: The Novartis safety database was searched for PML cases with a data lock point of August 31, 2017. PML classification was based on previously published criteria. The risk and incidence were estimated using the 15 patients with confirmed PML and the overall population of patients treated with fingolimod...
May 15, 2018: Neurology
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