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Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis

Chen S Tan1, Igor J Koralnik

  • 1Division of Viral Pathogenesis, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

The Lancet. Neurology
|March 20, 2010
PubMed

Insights

Progressive multifocal leukoencephalopathy (PML), a fatal brain disease from JC virus reactivation, is increasingly linked to new therapies. Understanding JC virus pathogenesis is crucial due to diverse at-risk populations and novel neurological disorders.

Area of Science:

  • Neuroscience
  • Virology
  • Immunology

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, fatal brain disease caused by JC polyomavirus reactivation.
  • PML understanding evolved with HIV treatment and immune reconstitution inflammatory syndrome (IRIS).
  • Monoclonal antibodies (natalizumab, efalizumab, rituximab) are newly associated with PML risk.

Purpose of the Study:

  • To reappraise JC virus pathogenesis in the central nervous system (CNS).
  • To highlight novel JC virus-associated neurological disorders.
  • To address the expanding population at risk for PML and related conditions.

Main Methods:

  • Review of recent literature on PML, JC virus, and associated therapies.
  • Analysis of epidemiological data linking monoclonal antibodies to PML.
  • Examination of emerging JC virus-related neurological conditions.

Main Results:

  • JC virus reactivation causes PML, with increased incidence linked to certain therapies.
  • JC virus is associated with granule cell neuronopathy, encephalopathy, and meningitis.
  • JC virus presence in grey matter necessitates a broader understanding of its CNS impact.

Conclusions:

  • The spectrum of JC virus-related CNS diseases is expanding.
  • Diverse patient populations are now at risk for PML and novel neurological disorders.
  • Reappraisal of JC virus pathogenesis is essential given new clinical associations and viral localization.

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