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Neuroinfectious Diseases
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Jeremy D. Young, Jesica A. Herrick, Scott Borgetti
JC virus infection is ubiquitous and usually acquired in childhood, with approximately 70–85% of adults in the United States possessing antibodies to the virus.1,2 PML was once quite rare, but the HIV pandemic has changed the epidemiology dramatically. PML was seen occasionally in patients with hematologic malignancies,3,4 steroid use,5 or the rare patient of advanced age. It has also been reported in presumably immunocompetent individuals. However, PML is currently considered a disease of the immunocompromised, particularly those with AIDS, and patients receiving cytotoxic chemotherapy or other immunosuppressive agents. More than 50% of all deaths from PML occur in HIV-infected individuals, and it is estimated that 1–4% of patients with HIV will develop PML.6
Oncological effects on the central nervous system
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
The symptoms of PML involve a progressive loss of mental function, with an initial onset of confusion, then development of focal neurological deficits, loss of motor coordination, and visual/speech/ataxic changes. The progression occurs gradually, usually over weeks to months, with mortality as high as 90%.
Multiple Sclerosis, Transverse Myelitis, Tropical Spastic Paraparesis, Progressive Multifocal Leukoencephalopathy, Lyme Disease
Published in Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg, Essentials of the Adult Neurogenic Bladder, 2020
Michele Fascelli, Howard B. Goldman
Progressive multifocal leukoencephalopathy (PML) is an infectious demyelinating brain disease caused by JC virus (JCV), which is associated with significant morbidity and mortality in the immunosuppressed (IS) host. Considered a rare opportunistic infection of the CNS, PML has recently been associated with select IS patients with MS, particularly those treated with natalizumab.85
An update on the safety of treating relapsing-remitting multiple sclerosis
Published in Expert Opinion on Drug Safety, 2019
Clara G. Chisari, Simona Toscano, Emanuele D’Amico, Salvatore Lo Fermo, Aurora Zanghì, Sebastiano Arena, Mario Zappia, Francesco Patti
On 2005 the manufacturer voluntary suspended NTZ from the market and on March 2006 a new post-marketing study was conducted with the aim to estimate the risk of PML following NTZ exposure. It was reintroduced in 2006 with a Boxed Warning for PML and a restricted distribution program, Tysabri® Outreach: Unified Commitment to Health (TOUCH) [128]. As of March 2019, there have been 814 confirmed PML cases (811 MS, 3 Crohn’s Disease), 221 in the USA, 507 in Europe, 86 in the rest of the world [129]. Based on follow-up data for at least 6 months after PML diagnosis, 76.0% of patients were alive with varying levels of disability. The duration of NTZ dosing prior to PML diagnosis ranged from 8 to 144 doses [130]. Based on analysis of pooled data from post-marketing sources, clinical studies, and an independent Swedish registry, the risk was found to increase with JCV seropositivity, increasing treatment duration (particularly beyond 2 years), and prior immunosuppressant use (even if remote and with a relatively mild immunosuppressant such as azathioprine or methotrexate) [131].
Brentuximab vedotin in T-cell lymphoma
Published in Expert Review of Hematology, 2019
Carrie Van Der Weyden, Michael Dickinson, James Whisstock, H. Miles Prince
Progressive multifocal leukoencephalopathy (PML) is a progressive, debilitating and commonly fatal inflammatory condition of the central nervous system, which occurs in association with the JC virus [108,109]. A case series reported the development of PML in five patients, with median onset of seven weeks after BV initiation (range 3–34 weeks); the condition was fatal in four patients [110]. While immunocompromised states and lymphoid malignancies have been postulated as risk factors for the development of PML, two of the cases in this series occurred in patients with CTCL, in whom significant immunosuppression, either de novo or attributable to previous therapy, would be unusual. The rapidity of symptom onset after BV initiation is also different to the pattern seen in association with PML in patients with HIV or in association with other immunomodulatory therapies.
Cost-effectiveness of alemtuzumab and natalizumab for relapsing-remitting multiple sclerosis treatment in Iran: decision analysis based on an indirect comparison
Published in Journal of Medical Economics, 2019
Saeed Taheri, Mohammad Ali Sahraian, Nazila Yousefi
The cost of PML was considered within the model, including diagnosis (a gadolinium-enhanced MRI scan and a cerebrospinal fluid analysis for JCV) and treatment. There is no consensus on how to treat PML; the most common approach is to restore the host adaptive immune response77. However, based upon limited observational data found in the literature, a course of plasma exchange every other day for a total of five treatments, accompanied by oral mirtazapine for 3–5 weeks, is recommended78. The survival rate in MS patients who developed NTZ-associated PML is more than 80% at 1 year after PML diagnosis, but almost all survivors have moderate-to-severe disability79,80. Thus, the mortality rate of 20% for patients who develop PML was included in the model. NTZ therapy will also be discontinued and patients will be switched to “RRMS Off Treatment”.