PML MRI Patterns in MS Patients Treated with Natalizumab: An Update of Natalizumab PML-MRI Guidelines (P07.057)

Abstract

Objective: To update existing guidelines for early diagnosis of progressive multifocal leukoencephalopathy (PML) with magnetic resonance imaging (MRI) based on common characteristics of PML and PML-related immune reconstitution inflammatory syndrome (IRIS) in natalizumab-treated multiple sclerosis (MS) patients. Background Natalizumab is an efficient treatment in MS patients that is associated with a small but devastating risk of PML. Guidelines were published in 2006 to improve early diagnosis of PML using MRI. However, owing to the small number of MS patients initially diagnosed with PML, the imaging criteria could only be derived from PML lesions in HIV patients. There is therefore an urgent need to assess the MR characteristics of PML in MS patients and to update the existing guidelines accordingly. Design/Methods: In the postmarketing phase, the first 40 cases of PML in natalizumab-treated MS patients were identified, of whom 22 (7 with IRIS) fulfilled the inclusion criteria for this study. The MR images were analyzed according to predefined criteria by 5 independent readers. Results: The most frequent lesion pattern in early PML patients was that of large (>3 cm, 15/18), subcortical (18/18), T2 or FLAIR hyperintense (18/18), T1 hypointense (17/18), and diffusion hyperintense (15/15) lesions, with a sharp border towards the grey matter and an ill-defined border towards the white matter (18/18) on T2 weighted images. We could detect contrast enhancement in 59% (10/17) of the cases on the first scan at clinical presentation. Conclusions: For the purpose of screening and early diagnosis of PML in MS patients treated with natalizumab, attention to characteristic MRI patterns, especially the presence of frequent, punctate/rim-like contrast enhancement and the subcortical location, is critical. Supported by: Biogen Idec and Elan. Disclosure: Dr. Yousry has received personal compensation in an editorial capacity for European Radiology Journal. Dr. Yousry has received compensation for serving on the board of Biogen Idec, Bristol-Myers Squibb, and UCB Pharma. Dr. Yousry has received research support from Biogen Idec, British Heart Foundation, GlaxoSmithKline, Inc., Medical Research Council, MS Society of Great Britain and Northern Ireland, NIHR Comprehensive Biomedical Research Centre, Novartis, PSP Association, Stroke Association, and Wellcome Trust. Dr. Pelletier has received personal compensation for activities with Teva Neuroscience, Genetech, Biogen-Idec, Bayer, and Synarc Inc. Dr. Pelletier has received research support from Biogen Idec. Dr. Cadavid has received personal compensation for activities with Biogen Idec as an employee. Dr. Cadavid holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Cadavid was involved as an investigator. Dr. Cadavid has received research support from Biogen Idec. Dr. Gass has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck & Co., and Teva Neuroscience as a consultant, speaker and participant on an advisory board. Dr. Richert has received personal compensation for activities with Biogen Idec as an employee.Dr. Richert holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Richert was involved as an investigator. Dr. Radue has received personal compensation for activities with AIM, Biogen Idec, and Novartis as a consultant.Dr. Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Merck Serono, and Novartis. Dr. Filippi has received personal compensation for activities with ECTRIMS, MSIF, MS Ireland, US NMSS, Bayer-Schering, Biogen-Dompe AG, Genmab, Merck Serono, Pepgen Corporation, Teva, and Sanofi-Aventis. Dr. Filippi has received research support from Teva, Bayer-Schering and Genmab.