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

Mult Scler. 2018 Dec;24(14):1902-1908. doi: 10.1177/1352458517750765. Epub 2018 Jan 18.


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; diffusion-weighted imaging; immune reconstitution inflammatory syndrome; magnetic resonance imaging; natalizumab.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Brain / drug effects*
  • Brain / pathology
  • Female
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / drug therapy
  • Immune Reconstitution Inflammatory Syndrome / pathology
  • Leukoencephalopathy, Progressive Multifocal / diagnosis
  • Leukoencephalopathy, Progressive Multifocal / drug therapy*
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Natalizumab / pharmacology*


  • Antibodies, Monoclonal, Humanized
  • Natalizumab