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Multiple Sclerosis International
Volume 2015 (2015), Article ID 809252, 14 pages
Review Article

Neuroimaging of Natalizumab Complications in Multiple Sclerosis: PML and Other Associated Entities

Division of Neuroradiology, University of Colorado School of Medicine, 12700 E 19th Avenue Mail Stop C278, Aurora, CO 80045, USA

Received 12 June 2015; Revised 14 August 2015; Accepted 31 August 2015

Academic Editor: Martin Stangel

Copyright © 2015 Justin M. Honce et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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. This review focuses on the clinical and neuroimaging features of the major complications associated with natalizumab therapy, focusing on the rare but devastating progressive multifocal leukoencephalopathy (PML). Associated entities including PML associated immune reconstitution inflammatory syndrome (PML-IRIS) and the emerging phenomenon of rebound of MS disease activity after natalizumab discontinuation are also discussed. Early recognition of neuroimaging features associated with these processes is critical in order to facilitate prompt diagnosis, treatment, and/or modification of therapies to improve patient outcomes.