title: Asymptomatic Progressive Multifocal Leukoencephalopathy Associated with Natalizumab: Diagnostic Precision with MR Imaging.
abstract: OBJECTIVE
  To determine diagnostic precision with magnetic resonance (MR) imaging of the brain, the most predictive MR imaging features, and the added value of comparison with previous data for the diagnosis of asymptomatic progressive multifocal leukoencephalopathy (PML) associated with natalizumab (NTZ).
  
  
  METHODS
  This retrospective study was approved by the institutional review board, and written informed consent was obtained. Eleven consecutive patients with multiple sclerosis (MS) who had received a definitive diagnosis of asymptomatic NTZ-associated PML (NTZ PML, 18 brain lesions) underwent 3-T MR imaging. The control group included 40 patients with MS but without PML who were treated with NTZ. Three readers independently performed blinded analysis of MR images. First, the readers were asked to detect NTZ PML lesions without comparing current images with previously obtained MR imaging data by evaluating MR images for the following features: U fiber and/or cortex involvement, lesion signal intensity and borders, and occurrence of punctate lesions. Second, they reassessed NTZ PML lesions with all the previous MR imaging data available. Diagnostic precision with MR imaging was assessed with and without comparison with previously obtained data. Logistic regression analyses were performed to identify the association of MR imaging features with NTZ PML.
  
  
  RESULTS
  Overall interobserver agreement was good (κ = 0.76; 95% confidence interval [CI]: 0.71, 0.81). Hyperintensity on diffusion-weighted images and involvement of U fibers were the most predictive features (odds ratio, 33.7; 95% CI: 4.9, 229.7 [P < .0001] and odds ratio, 8.7; 95% CI: 1.2, 61.4 [P = .03], respectively), while punctate lesions were exclusively observed in patients with NTZ PML. Comparison with previous MR imaging data improved specificity of MR imaging for the detection of NTZ PML lesions (from 88% to 100%, P = .05).
  
  
  CONCLUSIONS
  Recognition of the most predictive imaging features and comparison with previous MR imaging data may facilitate the detection of asymptomatic NTZ PML.
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hodel
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Outteryck
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Céline
authors.initials: C
authors.lastname: Dubron
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Bastien
authors.initials: B
authors.lastname: Dutouquet
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Mohamed Amine
authors.initials: MA
authors.lastname: Benadjaoud
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Emeline
authors.initials: E
authors.lastname: Duhin
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Sébastien
authors.initials: S
authors.lastname: Verclytte
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Marc
authors.initials: M
authors.lastname: Zins
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Alain
authors.initials: A
authors.lastname: Luciani
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Alain
authors.initials: A
authors.lastname: Rahmouni
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pruvo
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Patrick
authors.initials: P
authors.lastname: Vermersch
authors.affiliation: From the University of Lille, CHU Lille (J.H., O.O., C.D., B.D., E.D., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., B.D., J.P.P., X.L.) and Neurology (O.O., E.D., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Departments of Neuroradiology (J.H.) and Medical Imaging (A.L., A.R.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine, Université Paris Est Créteil, Créteil, France (J.H., A.L., A.R.); Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Radiation Epidemiology Team, Villejuif, France (M.A.B.); Department of Radiology, Hôpital Saint Joseph, Paris, France (M.Z.).
authors.forename: Xavier
authors.initials: X
authors.lastname: Leclerc
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab