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Research paper
MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance
  1. Martijn T Wijburg1,2,
  2. Birgit I Witte3,
  3. Anke Vennegoor1,
  4. Stefan D Roosendaal2,4,
  5. Esther Sanchez2,
  6. Yaou Liu2,5,
  7. Carine O Martins Jarnalo2,6,
  8. Bernard MJ Uitdehaag1,
  9. Frederik Barkhof2,
  10. Joep Killestein1,
  11. Mike P Wattjes2
  1. 1Department of Neurology, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, VUmc MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  3. 3Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  4. 4Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands
  5. 5Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, P. R. China
  6. 6Department of Radiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands
  1. Correspondence to Martijn T Wijburg, Department of Neurology, Neuroscience Amsterdam, VUmc MS center Amsterdam, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands; m.wijburg{at}vumc.nl

Abstract

Objective Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation.

Methods Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters. We tested the association with PML for each characteristic and constructed a multivariable prediction model which we analysed using a receiver operating characteristic (ROC) curve.

Results Presence of punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localisation were associated with new MS lesions. In the multivariable model, punctate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localisation predict for new MS lesions (area under the curve: 0.988, 95% CI 0.977 to 1.0, sensitivity: 100%, specificity: 80.6%).

Interpretation The MRI characteristics of asymptomatic natalizumab-associated PML lesions proved to differ from new MS lesions. This led to a prediction model with a high discriminating power. Careful assessment of the presence of punctate T2 lesions, cortical grey matter involvement, focal lesion appearance and periventricular localisation allows for an early diagnosis of PML.

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