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

K.W. Krueger, P. Krueger, H.C. Lehmann, and M. Schroeter

View Article on Neurographics Website

Date of Activity Release: Dec. 1, 2016
Date of Activity Expiration: Dec. 1, 2019

Target Audience:
Intended for neuroradiologists and neuroradiology trainees with varying degrees of experience.

Learning Objectives:
Discuss the clinical and imaging features that suggest a diagnosis of progressive multifocal leukoencephalopathy in MS-patients during long-term treatment with monoclonal antibodies.

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 _1a. (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.

Commercial Support
No commercial support was received for this activity.

Credit Designation Statement

The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The American Society of Neuroradiology designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Method of Physician Participation:
Each participant will review the corresponding Neurographics article located at Upon completion, each physician will complete and pass a post-test with a score of at least 80% to receive a CME certificate.

Author Helmar C Lehmann has received research support and/or honoraria from Baxter, Celgene, CSL Behring, Grifols, Fresenius and Novartis. Author Michael Schroeter has received personal or institutional support by Baxalta, Bayer Healthcare, Biogen Idec, CSL, Behring, Genzyme, Grifols, Merck Serono, MIltenyi Biotec, Novartis and Teva. All other authors have no relevant financial relationships.

All individuals in control of content have disclosed the following relevant financial relationships. All of these relationships were treated as a conflict of interest, and have been resolved (C7 SCS 6.1-6.2, 6.5)





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Royalties, Lippincott Williams and Wilkins

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Associate Editor

Non-remunerative position, AUR6

Meng Law

Associate Editor

Stockholder, Clinical Imaging

Michele Johnson

Associate Editor

Consultant, Boston Scientific, Inc.

Edward Escott

Associate Editor

Grant, Atherysys, Inc.; Royalties, Thieme Medical Publishers

Scott Faro

Associate Editor

None, N/A

Tina Young Poussaint

Associate Editor

None, N/A

Dheeraj Ghandi

Associate Editor

Grant, Arstasis, Axera Inc.; Consultant, Covidien, EV3

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