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Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple

Eugene O Major1, Tarek A Yousry2, David B Clifford3

  • 1Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

The Lancet. Neurology
|April 17, 2018
PubMed

Insights

Progressive multifocal leukoencephalopathy (PML), a rare CNS disease caused by JC virus (JCV), can affect multiple sclerosis patients on natalizumab. Early detection via MRI and risk profiling is crucial for managing this devastating condition.

Area of Science:

  • Neuroimmunology
  • Viral Pathogenesis
  • Demyelinating Diseases

Background:

  • Progressive multifocal leukoencephalopathy (PML) is a rare, severe demyelinating disease of the central nervous system (CNS).
  • PML is caused by the JC virus (JCV) and typically affects immunocompromised individuals.
  • Natalizumab treatment for multiple sclerosis has been linked to PML development, even in immunocompetent patients.

Purpose of the Study:

  • To explore the role of natalizumab in PML pathogenesis.
  • To identify new strategies for monitoring JCV status and predicting PML risk.
  • To emphasize the importance of early PML detection in multiple sclerosis patients undergoing immunomodulatory therapy.

Main Methods:

  • Review of emerging knowledge on JCV infection, immune system interplay, and natalizumab's properties.
  • Discussion of using frequent MRI for presymptomatic PML detection.
  • Stratification of patients based on clinical and virus-specific immune risk profiles.

Main Results:

  • Natalizumab may contribute to PML pathogenesis in multiple sclerosis patients.
  • Understanding JCV biology and immune interactions offers opportunities for risk prediction.
  • Presymptomatic PML detection is possible through frequent MRI and risk stratification.

Conclusions:

  • Early detection of PML is vital for minimizing CNS injury and disability in multiple sclerosis patients on natalizumab or similar treatments.
  • Improved risk stratification approaches are needed to guide treatment decisions and surveillance.
  • Further research into JCV pathogenesis and natalizumab's effects is warranted.

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