Neurological Sciences

, Volume 40, Issue 10, pp 2119–2124 | Cite as

Four cases of natalizumab-related PML: a less severe course in extended interval dosing?

  • Cristina ScarpazzaEmail author
  • Nicola De Rossi
  • Giulietta Tabiadon
  • Maria Vittoria Turrini
  • Simonetta Gerevini
  • Ruggero CapraEmail author
Original Article



Progressive multifocal leukoencephalopathy (PML) is a severe adverse event of natalizumab (NTZ). The administration of NTZ with extended interval dosing (EID) has been proposed as a strategy to potentially reduce the incidence of PML while maintaining its therapeutic efficacy.


In the current paper, we describe 4 cases of NTZ-PML in EID included in the Italian PML cohort.


The patients developed PML after at least 38 NTZ infusions. Their John Cunningham virus (JCv) index was > 1.5, and patients had not previously used immunosuppressant. Two patients were asymptomatic at PML onset, while two had mild motor impairment of the right hand and anomia, respectively. All of them had undetectable viral load but one (37 JCv copies/ml). In all patients, MRI revealed unilobar lesions with deferred contrast enhancement suggestive of immune reconstitution. The clinical course ended with a favorable clinical outcome (ΔEDSS up to 1).


Although PML in EID seems to occur less frequently than in conventional dosing regimen, strict monitoring of high-risk patients contributed to the indolent course observed in the four described cases, characterized by a prolonged pre-symptomatic phase, paucisymptomatic onset, low JCv load, less severe functional impairment during immune reconstitution, and a mild disability burden.


Multiple sclerosis Progressive multifocal leukoencephalopathy Extended doses regimen Natalizumab Early diagnosis 


Authors’ contributions

Conceived the study: CS, RC. Collected the data: CS, GT, NDR, MVT. Analyzed the data: CS, SG, RC. Critically reviewed the data: GT, NDR, MVT. Drafted the manuscript: CS, RC. Critically reviewed the manuscript: GT, NDR, MVT. All the authors approved the final version of the manuscript.

Compliance with ethical standards

Ethical standards

This study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Patients provided written informed consent for the publication of data. Retrospective analysis of patients’ data was approved by the ethical committee of the Spedali Civili of Brescia.

Conflict of interest

Dr. Scarpazza, Dr. Tabiadon, and Dr. Turrini have no conflicts of interest. Dr. De Rossi received consulting fees from Biogen, Merk-Serono, and Genzyme. Dr. Gerevini declares consulting fees or honorarium from Novartis and Biogen and payment for lectures including service on speaker bureaus from Novartis and Biogen. Dr. Capra received payment for lectures from Novartis, Biogen, and Genzyme.


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Regional Multiple Sclerosis CenterASST - Spedali Civili di BresciaMontichiariItaly
  2. 2.Department of General PsychologyUniversity of PadovaPadovaItaly
  3. 3.Department of NeurologyRegional General HospitalBolzanoItaly
  4. 4.Department of Neuroradiology, San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilanItaly

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