Magnetic resonance imaging changes following natalizumab discontinuation in multiple sclerosis patients with progressive multifocal leukoencephalopathy

Abstract

Background:

Detecting early progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant.

Objective:

Evaluating magnetic resonance imaging (MRI) changes following natalizumab (NTZ) discontinuation and preceding PML-IRIS.

Methods:

MRIs (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were performed every week following PML diagnosis in 11 consecutive NTZ-PML patients. PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were evaluated on each MRI sequence, following NTZ discontinuation.

Results:

PML-IRIS occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR imaging (p < 0.003). Two DWI features (marked PML expansion, punctate lesions) systematically preceded contrast-enhancement.

Conclusion:

Subtle changes may occur on DWI preceding contrast-enhancement.

Keywords

Multiple sclerosis natalizumab immune reconstitution inflammatory syndrome magnetic resonance imaging diffusion-weighted imaging

Get full access to this article

View all access options for this article.

References

Tan

McArthur

Clifford

et al . Immune reconstitution inflammatory syndrome in natalizumab-associated PML. Neurology 2011; 77: 1061–1067.

Wattjes

Wijburg

Vennegoor

et al . MRI characteristics of early PML-IRIS after natalizumab treatment in patients with MS. J Neurol Neurosurg Psychiatry 2016; 87: 879–884.

Berger

Aksamit

Clifford

et al . PML diagnostic criteria: Consensus statement from the AAN neuroinfectious disease section. Neurology 2013; 80: 1430–1438.

Yousry

Pelletier

Cadavid

et al . Magnetic resonance imaging pattern in natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 2012; 72: 779–787.

Wattjes

Richert

Killestein

et al . The chameleon of neuroinflammation: Magnetic resonance imaging characteristics of natalizumab-associated progressive multifocal leukoencephalopathy. Mult Scler 2013; 19: 1826–1840.

Kuker

Mader

Nagele

et al . Progressive multifocal leukoencephalopathy: value of diffusion-weighted and contrast-enhanced magnetic resonance imaging for diagnosis and treatment control. Eur J Neurol 2006; 13: 819–826.

Buckle

Castillo

. Use of diffusion-weighted imaging to evaluate the initial response of progressive multifocal leukoencephalopathy to highly active antiretroviral therapy: Early experience. Am J Neuroradiol 2010; 31: 1031–1035.

Hodel

Darchis

Outteryck

et al . Punctate pattern: A promising imaging marker for the diagnosis of natalizumab-associated PML. Neurology 2016; 86: 1516–1523.

Kleinschmidt-DeMasters

Miravalle

Schowinsky

et al . Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J Neuropathol Exp Neurol 2012; 71: 604–617.

10.

Wattjes

Verhoeff

Zentjens

et al . Punctate lesion pattern suggestive of perivascular inflammation in acute natalizumab-associated progressive multifocal leukoencephalopathy: Productive JC virus infection or preclinical PML-IRIS manifestation? J Neurol Neurosurg Psychiatry 2013; 84: 1176–1177.