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natalizumab PML diagnosis

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
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
Mike P Wattjes, Clemens Warnke
No abstract text is available yet for this article.
February 2016: Journal of Neurology, Neurosurgery, and Psychiatry
Justin M Honce, Lidia Nagae, Eric Nyberg
Natalizumab (Tysabri) is a monoclonal antibody (α4 integrin antagonist) approved for treatment of multiple sclerosis, both for patients who fail therapy with other disease modifying agents and for patients with aggressive disease. Natalizumab is highly effective, resulting in significant decreases in rates of both relapse and disability accumulation, as well as marked decrease in MRI evidence of disease activity. As such, utilization of natalizumab is increasing, and the presentation of its associated complications is increasing accordingly...
2015: Multiple Sclerosis International
C Carra-Dalliere, N Menjot de Champfleur, J Deverdun, X Ayrignac, E Nerrant, A Makinson, M L Casanova, P Labauge
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an opportunistic demyelinating encephalopathy related to JC virus. Its characteristics on conventional brain MRI are well known and are important for the diagnosis. OBJECTIVE: To analyze SWI hypointensities recently described in U-fibers and cortex adjacent to the white matter lesions of PML. METHODS: Prospective study including four patients with an history of definite diagnosis of PML...
February 2016: Journal of Neuroradiology. Journal de Neuroradiologie
Jérôme Hodel, Olivier Outteryck, Céline Dubron, Bastien Dutouquet, Mohamed Amine Benadjaoud, Emeline Duhin, Sébastien Verclytte, Marc Zins, Alain Luciani, Alain Rahmouni, Jean-Pierre Pruvo, Patrick Vermersch, Xavier Leclerc
PURPOSE: To determine diagnostic precision with magnetic resonance (MR) imaging of the brain, the most predictive MR imaging features, and the added value of comparison with previous data for the diagnosis of asymptomatic progressive multifocal leukoencephalopathy (PML) associated with natalizumab (NTZ). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and written informed consent was obtained. Eleven consecutive patients with multiple sclerosis (MS) who had received a definitive diagnosis of asymptomatic NTZ-associated PML (NTZ PML, 18 brain lesions) underwent 3-T MR imaging...
March 2016: Radiology
Mike P Wattjes, Martijn T Wijburg, Anke Vennegoor, Birgit I Witte, Marlieke de Vos, Nancy D Richert, Bernard M J Uitdehaag, Frederik Barkhof, Joep Killestein
OBJECTIVE: The early detection of MRI findings suggestive of immune reconstitution inflammatory syndrome (IRIS) in natalizumab-associated progressive multifocal leukoencephalopathy (PML) is of crucial clinical relevance in terms of treatment decision-making and clinical outcome. The aim of this study was to investigate the earliest imaging characteristics of PML-IRIS manifestation in natalizumab-treated patients with multiple sclerosis and describe an imaging pattern that might aid in the early and specific diagnosis...
August 2016: Journal of Neurology, Neurosurgery, and Psychiatry
J Hodel, O Outteryck, S Verclytte, V Deramecourt, A Lacour, J-P Pruvo, P Vermersch, X Leclerc
We investigated the brain magnetic susceptibility changes induced by natalizumab-associated progressive multifocal leukoencephalopathy. We retrospectively included 12 patients with natalizumab-progressive multifocal leukoencephalopathy, 5 with progressive multifocal leukoencephalopathy from other causes, and 55 patients with MS without progressive multifocal leukoencephalopathy for comparison. MR imaging examinations included T2* or SWI sequences in patients with progressive multifocal leukoencephalopathy (86 examinations) and SWI in all patients with MS without progressive multifocal leukoencephalopathy...
December 2015: AJNR. American Journal of Neuroradiology
P Mulero, M J Neri, M Rodriguez, J F Arenillas, N Téllez
Multiple sclerosis (MS) patients treated with natalizumab have a significant reduction in annualized relapse rate; in these patients, a relapse is uncommon but not unexpected. In contrast, the appearance of a severe exacerbation is striking and requires the differential diagnosis with progressive multifocal leukoencephalopathy. Here, we describe a case of a 22-year-old woman with relapsing-remitting MS who developed an unexpected response after the patient׳s fifth natalizumab infusion with an aggressive radiological and clinical evolution...
September 2014: Multiple Sclerosis and related Disorders
F Asztely, E Gilland, M P Wattjes, J Lycke
A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43 months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000 mg before a definite PML diagnosis was confirmed. Despite undetectable levels of B-cells, JC virus DNA became undetectable in the cerebrospinal fluid by quantitative polymerase chain reaction...
2015: Journal of the Neurological Sciences
R Alroughani, R Alroughani, A Almulla, S Lamdhade, A Thussu
BACKGROUND: Data on the mechanism of rebound activity post-withdrawal of fingolimod in multiple sclerosis (MS) patients is scarce. OBJECTIVES: To describe a patient with multiple sclerosis (MS) who developed severe reactivation after discontinuation of fingolimod. METHOD: Case report and review of literature. RESULTS: A 36-year old woman with aggressive MS since 1998 was switched to fingolimod due to JC virus seropositivity after receiving 24 infusions of natalizumab...
November 2014: Multiple Sclerosis and related Disorders
David B Clifford
PURPOSE OF REVIEW: This manuscript reviews current reports about clinical aspects of immune reconstitution inflammatory syndrome (IRIS), with a particular emphasis on IRIS in the setting of progressive multifocal leukoencephalopathy (PML) and to a lesser extent on cryptococcal meningitis and HIV. RECENT FINDINGS: PML prognosis has been radically improved, as it has become possible to provide immune reconstitution, although some remaining morbidity and mortality results from excess inflammation...
June 2015: Current Opinion in Neurology
Dimos D Mitsikostas, Vasileios Mastorodemos, Minas Tsagournizakis, Antonios Kodounis, Antonios Tsagkaropoulos, Spyridon Konitsiotis, Panagiotis Toulas, Alexandros Papadimitriou, Dimitra Papadimitriou, Antonios Tavernarakis, Dimitrios Papadopoulos
BACKGROUND & OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) may complicate natalizumab treatment in multiple sclerosis patients. We sought to characterize the clinical and laboratory features of natalizumab-related PML (NR-PML) cases from Greece. METHODS: Pharmaceutical industry, national drug authorities and all neurology departments within the Greek territory were asked to provide data for cases of NR-PML until October 2012. Collected cases were classified according to their level of diagnostic certainty using the five-level system introduced by Mentzer et al...
March 2014: Multiple Sclerosis and related Disorders
Robert L Carruthers, Joseph Berger
The natural history and clinical import of Progressive Multifocal Leukoencephalopathy has changed enormously in the last thirty years. After a resurgence of PML during the HIV/AIDS epidemic, advances in the treatment of multiple sclerosis created another group of 'at risk' patients. With a focus on issues pertaining to the multiple sclerosis patient population, this review covers pathophysiology of the JC virus, causes of PML, mechanisms by which natalizumab increases the risk of PML, determinants of PML risk in natalizumab-treated patients, risks of natalizumab discontinuation, PML prevention and surveillance, PML imaging features, PML diagnosis and stumbling blocks to making the diagnosis, PML and PML-Immune Reconstitution Inflammatory Syndrome (IRIS) treatment...
July 2014: Multiple Sclerosis and related Disorders
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