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

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.