title: Punctate pattern: A promising imaging marker for the diagnosis of natalizumab-associated PML.
abstract: OBJECTIVE
  To evaluate the usefulness of the punctate pattern (PP) for the diagnosis and follow-up of patients with progressive multifocal leukoencephalopathy (PML).
  
  
  METHODS
  A cohort of 20 consecutive patients with PML, related to natalizumab (NTZ) (n = 14) or not (n = 6), underwent 3T MRI (147 MRI examinations). MRI was available at presymptomatic (n = 9 patients), symptomatic (n = 15), immune reconstitution inflammatory syndrome (IRIS), and chronic stages (n = 20). A pathologic control group of patients without PML (n = 80), with clinically definitive multiple sclerosis or a clinically isolated syndrome suggestive of CNS demyelination, underwent the same MRI protocol. Number and appearance of punctate lesions were assessed by 3 blinded readers using T2-weighted, fluid-attenuated inversion recovery (FLAIR), and postcontrast T1-weighted images.
  
  
  RESULTS
  Interobserver agreement was good (κ = 0.79) (0.72-0.87). Of the 20 patients with PML, 18 had PP, including the 14 patients with NTZ-PML; none in the pathologic control group. Of the 9 presymptomatic patients with NTZ-PML, PP was observed in 7 (78% sensitive and 100% specific). Nonenhancing PP on T2-weighted/FLAIR images was detected in 13 patients with PML, exclusively at the presymptomatic or symptomatic stages (including 7 NTZ-PML), whereas enhancing PP occurred in 16 patients with PML, including 13 of the 14 patients with NTZ-PML at the IRIS stage.
  
  
  CONCLUSIONS
  PP is a highly specific feature of PML and may be the first imaging feature at the presymptomatic stage with potential implications in patient care.
  
  
  METHODS
  This study provides Class II evidence that a PP on MRI accurately identifies patients with NTZ-PML.
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France. Jerome.hodel@gmail.com.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Hodel
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Darchis
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Outteryck
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Verclytte
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Deramecourt
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lacour
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Zins
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pruvo
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vermersch
authors.affiliation: From the University of Lille, CHU Lille (J.H., C.D., O.O., V.D., A.L., J.P.P., P.V., X.L.), Lille, France; Departments of Neuroradiology (J.H., C.D., J.P.P., X.L.), Pathology (V.D.) and Neurology (O.O., A.L., P.V.), Hôpital Roger Salengro, Rue Emile Laine 59037 Lille, France; Department of Radiology (S.V.), Hôpital Saint Philibert, Lille, France; Department of Neuroradiology (J.H.), AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, France; Faculty of Medicine (J.H.), Université Paris Est Créteil, Créteil, France; and Department of Radiology (M.Z.), Hôpital Saint Joseph, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leclerc
mesh_terms: D000328:Adult; D000359:Aftercare; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D015331:Cohort Studies; D004279:DNA, Viral / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D007577:JC Virus; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000188:drug therapy; D000069442:Natalizumab / Q000009:adverse effects* / Q000627:therapeutic use; D015588:Observer Variation; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D004279:DNA, Viral; D007155:Immunologic Factors; D000069442:Natalizumab