Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: a decade of lessons learned

Lancet Neurol. 2018 May;17(5):467-480. doi: 10.1016/S1474-4422(18)30040-1.


Progressive multifocal leukoencephalopathy (PML) is a rare, devastating demyelinating disease of the CNS caused by the JC virus (JCV) that occurs in patients with compromised immune systems. Detection of PML in systemically immunocompetent patients with multiple sclerosis treated with natalizumab points to a role for this drug in the pathophysiology of PML. Emerging knowledge of the cellular and molecular biology of JCV infection and the pathogenesis of PML-including interplay of this common virus with the human immune system and features of natalizumab that might contribute to PML pathogenesis-provides new opportunities to monitor viral status and predict risk of JCV-associated disease. In the absence of an effective treatment for PML, early detection of the disease in patients with multiple sclerosis who are receiving natalizumab or other immunomodulatory treatments is vital to minimize CNS injury and avoid severe disability. Frequent MRI, stratified along a clinical and virus-specific immune risk profile, can be used to detect presymptomatic PML. Improved approaches to PML risk stratification are needed to guide treatment choices and surveillance of patients with multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunologic Factors / adverse effects*
  • Leukoencephalopathy, Progressive Multifocal* / chemically induced
  • Leukoencephalopathy, Progressive Multifocal* / etiology
  • Leukoencephalopathy, Progressive Multifocal* / immunology
  • Leukoencephalopathy, Progressive Multifocal* / virology
  • Multiple Sclerosis / drug therapy*
  • Natalizumab / adverse effects*


  • Immunologic Factors
  • Natalizumab