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Juxtacortical susceptibility changes in progressive multifocal leukoencephalopathy at the gray-white matter junction

Kedar R Mahajan1, Moein Amin2, Matthew Poturalski3

  • 1Mellen Center for Multiple Sclerosis Treatment and Research, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA/Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|March 22, 2021
PubMed
Abstract

Insights

Magnetic resonance imaging (MRI) susceptibility changes, particularly along the gray-white matter junction, can indicate progressive multifocal leukoencephalopathy (PML) before other signs appear. These changes correlate with iron accumulation in macrophages.

Area of Science:

  • Neuroimaging
  • Neuropathology
  • Neuroradiology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare but serious demyelinating disease of the central nervous system.
  • Early detection of PML is crucial for timely intervention and improved patient outcomes.
  • Susceptibility-weighted imaging (SWI) and gradient echo (GRE) sequences are sensitive to magnetic susceptibility variations in the brain.

Purpose of the Study:

  • To describe magnetic resonance imaging (MRI) susceptibility changes in PML.
  • To identify neuropathological correlates of these MRI findings.
  • To assess the diagnostic utility of susceptibility changes for PML detection.

Main Methods:

  • Retrospective review of MRI brain scans (1.5 T, 3 T, and 7 T) from PML cases and controls with primary central nervous system lymphoma (PCNSL).
  • Correlation of MRI findings with neuropathological examination of fixed brain autopsy tissue in three PML subjects.
  • Analysis of susceptibility changes on MRI sequences prior to PML diagnosis.

Main Results:

  • Juxtacortical susceptibility changes were observed in a significant proportion of PML cases (63.6% on 1.5/3 T, 100% on 7 T), compared to PCNSL controls (12.0%).
  • These changes were significantly more frequent in PML (OR 12.83, p < 0.001).
  • Susceptibility changes preceded clinical diagnosis by an average of 2.7 months in 87.5% of cases and correlated with iron deposition in macrophages at the gray-white matter junction.

Conclusions:

  • Susceptibility changes on MRI, particularly at the gray-white matter junction, are characteristic of PML.
  • These findings can precede other MRI markers like FLAIR changes.
  • The observed susceptibility changes correlate with iron accumulation in macrophages, providing a neuropathological basis for the imaging findings.
Keywords:
7 T MRIPMLgray matterimmunohistochemistryironmacrophagepathologyprogressive multifocal leukoencephalopathysusceptibility changesu-fiber

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