Progressive multifocal leukoencephalopathy in a patient treated with natalizumab

N Engl J Med. 2005 Jul 28;353(4):375-81. doi: 10.1056/NEJMoa051847. Epub 2005 Jun 9.


We describe the clinical course of a patient with multiple sclerosis in whom progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the central nervous system, developed during treatment with interferon beta-1a and a selective adhesion-molecule blocker, natalizumab. The first PML lesion apparent on magnetic resonance imaging was indistinguishable from a multiple sclerosis lesion. Despite treatment with corticosteroids, cidofovir, and intravenous immune globulin, PML progressed rapidly, rendering the patient quadriparetic, globally aphasic, and minimally responsive. Three months after natalizumab therapy was discontinued, changes consistent with an immune-reconstitution inflammatory syndrome developed. The patient was treated with systemic cytarabine, and two months later, his condition had improved.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents / therapeutic use
  • Aphasia / chemically induced
  • Ataxia / chemically induced
  • Brain / pathology
  • Cytarabine / therapeutic use
  • Humans
  • Integrin alpha4 / immunology*
  • JC Virus* / isolation & purification
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Natalizumab
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / pathology
  • Paresis / chemically induced


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Natalizumab
  • Cytarabine
  • Integrin alpha4