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Free Content Therapy-Associated Progressive Multifocal Leukoencephalopathy During Disease-Modifying Treatment of Multiple Sclerosis

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During the past 10 years, therapy-associated progressive multifocal leukoencephalopathy has gained an inglorious relevance, particularly among patients with MS who are on long-term treatment with natalizumab. More than 500 cases of this serious therapy complication have been reported worldwide until 2015, and, recently, progressive multifocal leukoencephalopathy has also been described in patients with MS who received monotherapy with dimethyl fumarate, fingolimod, and interferon β1a. (The neuroimmunologic features of this case and some of the MR images have recently been published elsewhere by the authors.) Finally, therapy-associated progressive multifocal leukoencephalopathy can also occur in patients without MS during disease-modifying immunotherapy with monoclonal antibodies other than natalizumab. As we still lack reliable predictive factors of this adverse event and although its risk factors are under intense debate, all of us must apparently learn to live with this “uninvited guest.” The objective of this article was to share and contribute some clinical experience and neuroradiologic features to further meet the diagnostic and therapeutic challenges of this potentially fatal therapy complication. Besides a review of the literature, we presented specific clinical and imaging data of 4 patients with relapsing-remitting MS who developed therapy-associated progressive multifocal leukoencephalopathy. We included results from patient-specific databases on continuous magnetization-transfer ratio monitoring before, during, and after the onset of therapy-associated progressive multifocal leukoencephalopathy and immune-reconstitution-inflammatory syndrome in 3 patients. They might be of additional benefit given the urgent need of further diagnostic tools to better assess the progressive multifocal leukoencephalopathy risk and its course in individual patients with MS during disease-modifying immunotherapy.

Learning Objective: Discuss the clinical and imaging features that suggest a diagnosis of progressive multifocal leukoencephalopathy in MS-patients during long-term treatment with monoclonal antibodies.
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Keywords: ANOVA = analysis of variance; CE = contrast-enhancement, contrast-enhanced; CSF = cerebrospinal fluid; DMT = disease modifying immunotherapy; DWI = diffusion-weighted imaging; FFE = fast field echo (gradient echo); FLAIR = fluid attenuated inversion recovery; FSE = fast spin-echo; HAART = high active antiretroviral therapy; IFN-β1a = Interferon beta-1a; IRIS = immune-reconstitution-inflammatory-syndrome; JCV = John-Cunningham-virus (human Polyomavirus); MS = multiple sclerosis; MTC = magnetization-transfer-contrast; MTR = magnetization-transfer ratio; NTZ = Natalizumab; NTZ-PML = Natalizumab-associated PML; PML = progressive multifocal leukoencephalopathy; ROI = region of interest; SE = spin-echo; T1-W IR = T1-weighted inversion-recovery

Document Type: Research Article

Publication date: 2016-11-01

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  • Neurographics is the peer-reviewed, quarterly educational journal of the American Society of Neuroradiology. The journal comprises mainly articles created from select scientific exhibits at the ASNR Annual Meeting. Neurographics will also publish other high-quality submissions that are primarily educational and have a high emphasis on a pictorial approach. Articles are available free online, and a print-on-demand edition can be ordered from the Neurographics site.

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