Punctate pattern: A promising imaging marker for the diagnosis of natalizumab-associated PML

Neurology. 2016 Apr 19;86(16):1516-23. doi: 10.1212/WNL.0000000000002586. Epub 2016 Mar 23.


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.

Classification of evidence: This study provides Class II evidence that a PP on MRI accurately identifies patients with NTZ-PML.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aftercare
  • Aged
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Cohort Studies
  • DNA, Viral / cerebrospinal fluid
  • Female
  • Humans
  • Immunologic Factors / adverse effects*
  • Immunologic Factors / therapeutic use
  • JC Virus
  • Leukoencephalopathy, Progressive Multifocal / cerebrospinal fluid
  • Leukoencephalopathy, Progressive Multifocal / diagnostic imaging*
  • Leukoencephalopathy, Progressive Multifocal / etiology*
  • Leukoencephalopathy, Progressive Multifocal / therapy
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Natalizumab / adverse effects*
  • Natalizumab / therapeutic use
  • Observer Variation
  • Retrospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index


  • DNA, Viral
  • Immunologic Factors
  • Natalizumab