Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients

Mult Scler. 2016 Aug;22(9):1174-83. doi: 10.1177/1352458515615225. Epub 2015 Nov 12.


Background: In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML).

Objective: To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability.

Methods: In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions (n = 21) or new MS lesions (n = 20) or no new lesions (n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated.

Results: Overall sensitivity and specificity for the detection of new lesions, regardless of the nature of the lesions, were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate.

Conclusion: The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate.

Keywords: Multiple sclerosis; magnetic resonance imaging (MRI); natalizumab; pharmacovigilance; progressive multifocal leukoencephalopathy (PML).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging*
  • Brain / drug effects*
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunocompromised Host
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Leukoencephalopathy, Progressive Multifocal / chemically induced
  • Leukoencephalopathy, Progressive Multifocal / diagnostic imaging*
  • Leukoencephalopathy, Progressive Multifocal / immunology
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Natalizumab / adverse effects
  • Natalizumab / therapeutic use*
  • Observer Variation
  • Opportunistic Infections / chemically induced
  • Opportunistic Infections / diagnostic imaging*
  • Opportunistic Infections / immunology
  • Pharmacovigilance*
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Immunologic Factors
  • Natalizumab