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natalizumab PML diagnosis

Eric M L Williamson, Joseph R Berger
Progressive multifocal leukoencephalopathy (PML) is a rare, but serious, complication encountered in patients treated with a select number of disease-modifying therapies (DMTs) utilized in treating multiple sclerosis (MS). PML results from a viral infection in the brain for which the only demonstrated effective therapy is restoring the perturbed immune system-typically achieved in the patient with MS by removing the offending therapeutic agent or, in the case of HIV-associated PML, treatment with highly active antiretroviral therapies...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Giuseppe Pontillo, Sirio Cocozza, Roberta Lanzillo, Pasquale Borrelli, Anna De Rosa, Vincenzo Brescia Morra, Enrico Tedeschi, Giuseppe Palma
BACKGROUND: Brain MRI plays an essential role in both diagnosis and follow-up of the JC virus infection of the brain. Recently, MR studies with susceptibility-weighted imaging (SWI) sequences have shown hypointensities in U-fibers adjacent to white matter (WM) lesions of progressive multifocal leukoencephalopathy (PML). This finding has been confirmed with the use of quantitative susceptibility mapping (QSM), allowing to hypothesize a paramagnetic effect in these regions. Here, we report the first longitudinal assessment of QSM and R2* maps in natalizumab-associated PML to evaluate serial changes in susceptibility contrast images and their role in PML diagnosis and follow-up...
2017: Frontiers in Neurology
Ema Kantorová, Michal Bittšanský, Štefan Sivák, Eva Baranovičová, Petra Hnilicová, Vladimír Nosáľ, Daniel Čierny, Kamil Zeleňák, Wolfgang Brück, Egon Kurča
BACKGROUND: Co-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge. CASE PRESENTATION: We report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS...
June 19, 2017: BMC Cancer
Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Eva-Maria Kolb, Gisa Ellrichmann, Aiden Haghikia, Ralf Gold, Carsten Lukas
PURPOSE: Early diagnosis and treatment of multiple sclerosis-related progressive multifocal leukoencephalopathy (PML) significantly improve clinical outcomes. However, there is a lack of information regarding the restart of immunomodulatory therapy in the post-PML setting, when multiple sclerosis activity reappears. We aimed at the examination of metabolic differences using 1H-magnetic resonance spectroscopy (1H-MRS) in multiple sclerosis patients at various post-PML stages and at the exploration of differences according to their disease and JC virus (JCV) status...
2017: PloS One
Mark S Igra, David Paling, Mike P Wattjes, Daniel J A Connolly, Nigel Hoggard
MRI has long been established as the most sensitive in vivo technique for detecting multiple sclerosis (MS) lesions. The 2010 revisions of the McDonald Criteria have simplified imaging criteria, such that a diagnosis of MS can be made on a single contrast-enhanced MRI scan in the appropriate clinical context. New disease-modifying therapies have proven effective in reducing relapse rate and severity. Several of these therapies, most particularly natalizumab, but also dimethyl fumarate and fingolimod, have been associated with progressive multifocal leukoencephalopathy (PML)...
June 2017: British Journal of Radiology
Gaëlle Clavel, Antoine Moulignier, Luca Semerano
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood...
March 16, 2017: Joint, Bone, Spine: Revue du Rhumatisme
Doriana Landi, Nicola De Rossi, Sara Zagaglia, Cristina Scarpazza, Luca Prosperini, Maria Albanese, Fabio Buttari, Francesco Mori, Girolama Alessandra Marfia, Maria Pia Sormani, Ruggero Capra, Diego Centonze
OBJECTIVE: To examine retrospectively the effects of plasmapheresis (PLEX) on the survival and clinical outcomes of patients with multiple sclerosis (MS) and natalizumab (NTZ)-associated progressive multifocal leukoencephalopathy (PML). METHODS: The medical literature was searched for the terms natalizumab and progressive multifocal leukoencephalopathy. A total of 193 international and 34 Italian NTZ-PML cases were included. Clinical outcome was determined by comparing the patients' clinical status at PML diagnosis with status after PML resolution...
March 21, 2017: Neurology
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
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
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
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
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. Natalizumab is associated with the potentially fatal, rare, demyelinating, opportunistic brain infection, progressive multifocal leukoencephalopathy (PML). Prognosis and disability from PML are determined by early diagnosis. AIMS: 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...
February 2017: Internal Medicine Journal
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...
May 2017: Multiple Sclerosis: Clinical and Laboratory Research
Martijn T Wijburg, Birgit I Witte, Anke Vennegoor, Stefan D Roosendaal, Esther Sanchez, Yaou Liu, Carine O Martins Jarnalo, Bernard Mj Uitdehaag, Frederik Barkhof, Joep Killestein, Mike P Wattjes
OBJECTIVE: Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation. METHODS: Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters...
October 2016: Journal of Neurology, Neurosurgery, and Psychiatry
Jérôme Hodel, Christine Darchis, Olivier Outteryck, Sébastien Verclytte, Vincent Deramecourt, Arnaud Lacour, Marc Zins, Jean-Pierre Pruvo, Patrick Vermersch, Xavier Leclerc
OBJECTIVE: To evaluate the usefulness of the punctate pattern (PP) for the diagnosis and follow-up of patients with progressive multifocal leukoencephalopathy (PML). METHODS: A cohort of 20 consecutive patients with PML, related to natalizumab (NTZ) (n = 14) or not (n = 6), underwent 3T MRI (147 MRI examinations). MRI was available at presymptomatic (n = 9 patients), symptomatic (n = 15), immune reconstitution inflammatory syndrome (IRIS), and chronic stages (n = 20)...
April 19, 2016: Neurology
Martijn T Wijburg, Dorine Siepman, Jeroen J J van Eijk, Joep Killestein, Mike P Wattjes
Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN...
April 2016: Journal of Neurology
Martyn K White, Ilker K Sariyer, Jennifer Gordon, Serena Delbue, Valeria Pietropaolo, Joseph R Berger, Kamel Khalili
Progressive multifocal leukoencephalopathy (PML) is a devastating and often fatal demyelinating disease of the central nervous system for which effective therapies are lacking. It is caused by the replication of polyomavirus JC (JCV) in the oligodendrocytes and astrocytes leading to their cytolytic death and loss of myelin from the subcortical white matter. While the virus is very common in human populations worldwide, the incidence of the disease is very low and confined almost exclusively to individuals with some form of immunological dysfunction...
March 2016: Reviews in Medical Virology
Eric M L Williamson, Joseph R Berger
PURPOSE OF REVIEW: Serious central nervous system infections may occur in the setting of immunomodulatory drug use. It is important for neurologists to be aware of the incidence, diagnosis, management, and treatment of these infections. RECENT FINDINGS: Infectious disease has long been recognized as a complication of broad immunosuppression. However, the frequency with which infectious disease is observed appears to be lower and the spectrum of infectious complications narrower with immunomodulatory drugs, a class of agents having a more restricted effect on the immune system...
December 2015: Continuum: Lifelong Learning in Neurology
Tim Sinnecker, Jalal Othman, Marc Kühl, Ralf Mekle, Inga Selbig, Thoralf Niendorf, Annett Kunkel, Peter Wienecke, Peter Kern, Friedemann Paul, Juergen Faiss, Jens Wuerfel
OBJECTIVE: To assess the ability of ultra-high-field MRI to distinguish early progressive multifocal leukoencephalopathy (PML) from multiple sclerosis (MS) lesions in a rare case of simultaneous presentation of natalizumab-associated PML and ongoing MS activity. METHODS: Advanced neuroimaging including 1.5T, 3T, and 7T MRI with a spatial resolution of up to 0.08 mm(3) was performed. RESULTS: 7T MRI differentiated between PML-related and MS-related brain damage in vivo...
December 2015: Neurology® Neuroimmunology & Neuroinflammation
Marzena J Fabis-Pedrini, Wen Xu, Jason Burton, William M Carroll, Allan G Kermode
We report a case of asymptomatic progressive multifocal leukoencephalopathy (PML) detected on regular MRI screening in a 40-year-old patient with subsequent benign course with 12 months follow-up. The patient had a history of aggressive inflammatory multiple sclerosis, prior mitoxantrone therapy, Stratify John Cunningham Virus test positivity (Quest Diagnostics, Madison, NJ, USA), and 5 years of natalizumab monotherapy. The initial MRI detection of PML was both atypical and subtle. Early diagnosis and intervention, and pre-emptive treatment for immune reconstitution inflammatory syndrome with high dose steroids, as well as empirical mirtazapine and mefloquine, were associated with a benign PML disease course and outcome...
March 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
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