title: Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martijn T
authors.initials: MT
authors.lastname: Wijburg
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Vennegoor
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Roosendaal
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China.
authors.forename: Yaou
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands/Department of Radiology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Carine O
authors.initials: CO
authors.lastname: Martins Jarnalo
authors.affiliation: Multiple Sclerosis Clinical Development Group, Biogen, Cambridge, MA, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Richert
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard Mj
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Radiology and Nuclear Medicine, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D015588:Observer Variation; D009894:Opportunistic Infections / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000276:immunology; D060735:Pharmacovigilance; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab
keywords: Multiple sclerosis; magnetic resonance imaging (MRI); natalizumab; pharmacovigilance; progressive multifocal leukoencephalopathy (PML)