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. 2018 May;89(5):535-541.
doi: 10.1136/jnnp-2017-316886. Epub 2017 Nov 15.

Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS

Mike P Wattjes  1   2 , Martijn T Wijburg  2   3 , Jeroen van Eijk  4 , Stephan Frequin  5 , Bernard M J Uitdehaag  3 , Frederik Barkhof  2   6 , Clemens Warnke  7   8 , Joep Killestein  3 ; Dutch-Belgian Natalizumab-Associated PML Study Group
Collaborators, Affiliations

Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS

Mike P Wattjes et al. J Neurol Neurosurg Psychiatry. 2018 May.

Abstract

Background and objective: Natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) patients may show imaging signs suggestive of inflammation at diagnosis ('inflammatory PML'), reminiscent of PML-immune reconstitution inflammatory syndrome (PML-IRIS). We investigated the imaging characteristics of inflammatory NTZ-PML lesions and PML-IRIS to determine differentiating and overlapping features.

Methods: We scored the presence, localisation and pattern of imaging characteristics of inflammation on brain MRI scans of inflammatory NTZ-PML patients. The imaging characteristics were followed up until the occurrence of PML-IRIS.

Results: Ten out of the 44 NTZ-PML patients included showed signs suggestive of inflammation at the time of diagnosis. The inflammation pattern at diagnosis was similar to the pattern seen at PML-IRIS, with contrast enhancement representing the most frequent sign of inflammation (90% at diagnosis, 100% at PML-IRIS). However, the severity of inflammation differed, with absence of swelling and low frequency of perilesional oedema (10%) at diagnosis, as compared with the PML-IRIS stage (40%).

Conclusion: Patterns of inflammation at the time of PML diagnosis and at the PML-IRIS stage overlap but differ in their severity of inflammation. This supports histopathological evidence that the inflammation seen at both stages of the same disease shares a similar underlying pathophysiology, representing the immune response to the JC virus to a variable extend.

Keywords: magnetic resonance imaging; multiple sclerosis; natalizumab; progressive multifocal leukoencephalopathy.

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Conflict of interest statement

Competing interests: MPW has received consultancy fees from Biogen, Novartis and Roche. FB serves as a consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen, Teva, Novartis, Roche, Synthon BV, Genzyme and Jansen Research. JK has accepted consulting fees from Merck-Serono, TEVA, Biogen, Genzyme and Novartis. BMJU has received consultancy fees from Novartis, Merck Serono, Biogen and Danone Research. MTW does not report any competing interest. The VUmc has received financial support for research activities from Bayer Schering Pharma, Biogen, Glaxo Smith Kline, Merck Serono, Novartis and Teva. JE received consultancy fees and/or lecture fees from Biogen, Genzyme, Teva, Merck and Novartis. The authors had full editorial control of the manuscript and provided their final approval of all content.

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