Journal of NeuroVirology

, Volume 25, Issue 1, pp 133–136 | Cite as

Quantitative electroencephalography supports diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy

  • G. Classen
  • C. Classen
  • C. Bernasconi
  • C. Brandt
  • R. Gold
  • A. Chan
  • R. HoepnerEmail author
Case Report


Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.


EEG Multiple sclerosis Natalizumab John Cunningham virus encephalopathy Screening Pharmacovigilance 



We like to thank F. Zubler, A. Salmen, S. Dahlhaus, R. Schneider, I. Kleiter and R. Schneider-Gold for their valuable contributions to this work.


  1. Berger JR, Aksamit AJ, Clifford DB, Davis L, Koralnik IJ, Sejvar JJ, Bartt R, Major EO, Nath A (2013) PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology 80:1430–1438CrossRefGoogle Scholar
  2. Biogen (2017). Manufacture information. Accessed 10 Dec 2017
  3. Bräu H, Ulrich G (1990) Electroencephalographic vigilance dynamics in multiple sclerosis during an acute episode and after remission. Eur Arch Psychiatry Neurol Sci 239:320–324CrossRefGoogle Scholar
  4. Cinque P, Scarpellini P, Vago L, Linde A, Lazzarin A (1997) Diagnosis of central nervous system complications in HIV-infected patients: cerebrospinal fluid analysis by the polymerase chain reaction. AIDS 11:1–17CrossRefGoogle Scholar
  5. Frigo, M. and Johnson, S. G. (1997). The fastest Fourier transform in the West. Massachusetts Institute of Technology, MIT-LCS-TR-728Google Scholar
  6. Kleiter I, Schröder M, Lürding R, Schuierer G, Clifford DB, Bogdahn U, Steinbrecher A, Pöschl P (2010) Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy. Mult Scler 16:749–753CrossRefGoogle Scholar
  7. Koralnik IJ (2006) Progressive multifocal leukoencephalopathy revisited: has the disease outgrown its name? Ann Neurol 60:162–173CrossRefGoogle Scholar
  8. Vermersch P, Kappos L, Gold R, Foley JF, Olsson T, Cadavid D, Bozic C, Richman S (2011) Clinical outcomes of natalizumab-associated progressive multifocal leukoencephalopathy. Neurology 76:1697–1704CrossRefGoogle Scholar
  9. Warnke C, von Geldern G, Markwerth P, Dehmel T, Hoepner R, Gold R, Pawlita M, Kümpfel T, Mäurer M, Stangel M, Wegner F, Hohlfeld R, Straeten V, Limmroth V, Weber T, Hermsen D, Kleinschnitz C, Hartung H-P, Wattjes MP, Svenningson A, Major E, Olsson T, Kieseier BC, Adams O (2014) Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy. Ann Neurol 76:792–801CrossRefGoogle Scholar
  10. Wattjes MP, Wijburg MT, Vennegoor A, Witte BI, Roosendaal SD, Sanchez E, Liu Y, Martins Jarnalo CO, Richert ND, Uitdehaag BM, Barkhof F, Killestein J (2016) Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients. Mult Scler 22:1174–1183CrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2018

Authors and Affiliations

  • G. Classen
    • 1
  • C. Classen
    • 2
  • C. Bernasconi
    • 3
  • C. Brandt
    • 4
  • R. Gold
    • 5
  • A. Chan
    • 5
    • 6
  • R. Hoepner
    • 5
    • 6
    Email author
  1. 1.Department of Paediatric NeurologyEvangelisches Klinikum BethelBielefeldGermany
  2. 2.Department of Computer ScienceTU Dortmund UniversityDortmundGermany
  3. 3.Clinical Trial Unit, Neurocentre BernBern University Hospital, University of BernBernSwitzerland
  4. 4.Department of General EpileptologyBethel Epilepsy CentreBielefeldGermany
  5. 5.Department of Neurology, St. Josef HospitalRuhr University BochumBochumGermany
  6. 6.Department of Neurology, InselspitalBern University Hospital, University of BernBernSwitzerland

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