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3D Modeling of the Lateral Ventricles and Histological Characterization of Periventricular Tissue in Humans and Mouse
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Progressive multifocal leukoencephalopathy: why gray and white matter.

Sarah Gheuens1, Christian Wüthrich, Igor J Koralnik

  • 1Division of Neurovirology and Departments of Neurology and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. sgheuens@bidmc.harvard.edu

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Progressive multifocal leukoencephalopathy (PML), a brain disease caused by JC virus (JCV), now affects more people and presents differently than previously thought. Understanding JCV

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Area of Science:

  • Neurology
  • Virology
  • Immunology

Background:

  • Progressive multifocal leukoencephalopathy (PML) was historically viewed as a fatal, noninflammatory demyelinating disease affecting immunosuppressed individuals.
  • PML was primarily associated with oligodendrocytes and astrocytes in the brain's white matter.

Purpose of the Study:

  • To update the understanding of PML's evolution, presentation, and pathology.
  • To highlight the expanding spectrum of affected individuals and the broader impact of JC virus (JCV).

Main Methods:

  • Review of historical and contemporary literature on PML.
  • Analysis of evolving clinical presentations and pathological findings.

Main Results:

  • PML is now recognized in immune reconstitution inflammatory syndrome and in patients with minimal immunosuppression or on novel immunomodulatory drugs.
  • JC virus (JCV) infection extends beyond white matter, affecting gray matter and glial cells at the gray-white matter junction.
  • JCV variants can infect neurons, leading to JCV granule cell neuronopathy and JCV encephalopathy.

Conclusions:

  • PML is a dynamic disease with evolving clinical and pathological characteristics.
  • The understanding of PML has expanded to include a wider patient population and broader neuropathological manifestations.
  • JCV's neurotropic capabilities are more diverse than previously understood, impacting both glial and neuronal cells.