Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS

Neurology. 2011 Dec 6;77(23):2010-6. doi: 10.1212/WNL.0b013e31823b9b27. Epub 2011 Nov 9.


Objective: To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab.

Results: Polyomavirus JC (JCV)-specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities.

Conclusions: This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / cerebrospinal fluid
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Biopsy
  • Brain / pathology*
  • Brain / virology
  • DNA, Viral / cerebrospinal fluid
  • Diagnosis, Differential
  • Female
  • Humans
  • JC Virus / genetics
  • JC Virus / immunology
  • JC Virus / metabolism*
  • Leukoencephalopathy, Progressive Multifocal / cerebrospinal fluid
  • Leukoencephalopathy, Progressive Multifocal / diagnosis*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Leukoencephalopathy, Progressive Multifocal / virology
  • Magnetic Resonance Imaging*
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / physiopathology
  • Natalizumab
  • Paresis / virology
  • Polymerase Chain Reaction
  • Treatment Outcome


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