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Punctate lesion pattern suggestive of perivascular inflammation in acute natalizumab-associated progressive multifocal leukoencephalopathy: productive JC virus infection or preclinical PML-IRIS manifestation?
  1. Mike P Wattjes1,
  2. Lonneke Verhoeff2,
  3. Willemijn Zentjens2,
  4. Joep Killestein3,
  5. Erik T van Munster2,
  6. Frederik Barkhof1,
  7. Jeroen J J van Eijk2
  1. 1Department of Radiology, Nuclear Medicine & PET research, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Neurology, Jeroen Bosch Ziekenhuis, Den Bosch, The Netherlands
  3. 3Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
  1. Correspondence to Dr Mike P Wattjes, Department of Radiology, Nuclear Medicine & PET research, MS Center Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands; m.wattjes{at}

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Natalizumab (Tysabri, Biogen-Idec Inc, Cambridge, Massachusetts, USA) is an effective drug for the treatment of multiple sclerosis (MS). Patients treated with natalizumab are at higher risk of developing progressive multifocal leukoencephalopathy (PML). MRI has become crucial in the drug surveillance in terms of an early (preferably presymptomatic) detection and monitoring of natalizumab-associated PML with special regard to the occurrence of an immune reconstitution inflammatory syndrome (IRIS).1

Natalizumab-associated PML is characterised by rather heterogeneous imaging findings particularly in the early disease course. Recently, a rare PML imaging pattern with punctiform enhancing lesions has been described in a patient with an asymptomatic course of natalizumab-associated PML.2 It remains unclear what this inflammation pattern in acute PML represents regarding the underlying histopathology and possible consequences of the disease progression or PML-IRIS development. In this case report, we describe a patient with acute natalizumab-associated PML presenting with punctate enhancing lesions suggestive of perivascular inflammation and discuss the importance of correctly interpreting this imaging finding in terms of differentiating productive JC virus infection from early presymptomatic PML-IRIS manifestation.

Case report

A 45-year-old female with relapsing-remitting MS (5 years disease duration, EDSS 2.0) complained of subacute slurred speech and mild ataxia of her right arm after completing 51 infusions of natalizumab. Natalizumab treatment was immediately discontinued. She had tested positive for serum antibodies against JC virus 6 months earlier. MRI showed multifocal classical PML lesions in the cerebellum and supratentorial brain. In addition, a group of small punctate T2-/FLAIR-hyperintense and contrast-enhancing lesions was identified in the deep white matter of the left parietal lobe, suggesting a perivascular distribution pattern with …

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  • Contributors MPW and JJE contributed to the conception, design, analysis and interpretation of the data and drafting the article. LV, WZ, JK, EvM and FB contributed to the interpretation of the data and drafting the article. All authors approved the final version of the manuscript.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Since this was an observational case study with permission from the patient, a formal review by the Institutional Review Board at our institution was not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.