Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis

N Engl J Med. 2005 Jul 28;353(4):369-74. doi: 10.1056/NEJMoa051782. Epub 2005 Jun 9.


A 46-year-old woman with relapsing-remitting multiple sclerosis died from progressive multifocal leukoencephalopathy (PML) after having received 37 doses of natalizumab (300 mg every four weeks) as part of a clinical trial of natalizumab and interferon beta-1a. PML was diagnosed on the basis of the finding of JC viral DNA in cerebrospinal fluid on polymerase-chain-reaction assay and was confirmed at autopsy. Nearly every tissue section from bilateral cerebral hemispheres contained either macroscopic or microscopic PML lesions. There was extensive tissue destruction and cavitation in the left frontoparietal area, large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes, which were positive for JC virus DNA on in situ hybridization.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Brain / pathology
  • Cerebrospinal Fluid / virology
  • Fatal Outcome
  • Female
  • Humans
  • Integrin alpha4 / immunology*
  • Interferon beta-1a
  • Interferon-beta / adverse effects*
  • Interferon-beta / therapeutic use
  • JC Virus* / isolation & purification
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Magnetic Resonance Imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Natalizumab
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / pathology


  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Natalizumab
  • Integrin alpha4
  • Interferon-beta
  • Interferon beta-1a