Progressive multifocal leukoencephalopathy after natalizumab monotherapy

N Engl J Med. 2009 Sep 10;361(11):1081-7. doi: 10.1056/NEJMoa0810316.


We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared after 14 monthly infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain-reaction (PCR) assay of cerebrospinal fluid. The patient's symptoms worsened, and the diagnosis of PML was established with a more sensitive quantitative PCR assay after 16 infusions of natalizumab. Plasma exchange was used to accelerate clearance of natalizumab. Approximately 3 weeks after plasma exchange, an immune-reconstitution inflammatory syndrome appeared. JC virus DNA was no longer detectable on quantitative PCR assay, and the patient's symptoms improved.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Brain / pathology
  • DNA, Viral / blood
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / etiology
  • Integrin alpha4 / immunology*
  • JC Virus* / genetics
  • JC Virus* / immunology
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / immunology
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Natalizumab
  • Polymerase Chain Reaction


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • DNA, Viral
  • Natalizumab
  • Integrin alpha4