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  • Clinical and paraclinical findings in natalizumab-associated infratentorial progressive multifocal leukoencephalopathy patients

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Letter
Clinical and paraclinical findings in natalizumab-associated infratentorial progressive multifocal leukoencephalopathy patients
  1. R Hoepner1,
  2. J Ahlbrecht2,
  3. S Faissner1,
  4. R Schneider1,
  5. S Dahlhaus1,
  6. O Adams3,
  7. P Raab4,
  8. C Lukas5,
  9. A Chan1,
  10. M Stangel2,
  11. R Gold1
  1. 1Department of Neurology, St. Josef Hospital Bochum, Ruhr University, Bochum, Germany
  2. 2Department of Neurology, Hannover Medical School, Hannover, Germany
  3. 3Department of Virology, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
  4. 4Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany
  5. 5Institute of Diagnostic and Interventional Neuroradiology, St. Josef Hospital Bochum, Ruhr University, Bochum, Germany
  1. Correspondence to Dr Robert Hoepner, Department of Neurology, St. Josef Hospital Bochum, Ruhr University, Gudrunstr. 56, Bochum 44791, Germany; roberthoepner{at}gmx.de

https://doi.org/10.1136/jnnp-2014-307582

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    Introduction

    Natalizumab (NAT)-treated relapsing remitting multiple sclerosis (RRMS) patients have a marked progressive multifocal leukoencephalopathy (PML) risk, with an overall incidence of 3.4 per 1000 NAT treated patients (95%− CI 3.08 to 3.74).1 In HIV-positive PML patients a supratentorial manifestation occurred in 93.8%. An infratentorial PML manifestation is less frequent, occurring in 11–58.3% of the HIV-positive PML patients.2 ,3 Within the infratentorial brain structures, the pons is most commonly affected.2 Irie et al reported a infratentorial PML manifestation in one patient with renal failure. They found an overall survival of ≤4 months after onset of infratentorial PML symptoms.4 Up to now no clinical studies regarding NAT-PML with a predominant infratentorial manifestation have been published. Our study aimed to investigate differences in clinical data and disease course between NAT-PML patients with or without initial infratentorial involvement.

    Methods

    NAT-PML patients treated in two German university hospitals (Bochum n=21, Hannover n=3,) until 1 November 2013 were included in this retrospective study (ethic committees: Bochum 4566–13, Hannover: 2100−2013). Treatment of NAT-PML was standardised including plasma exchange, mirtazapine and mefloquine treatment. Patients were followed for 14.6±12.4 months (mean±SD), basic characteristics and clinical data were collected by medical records. Extended Disability Status Scale (EDSS) and Karnofsky Index (KI) were performed at onset, after the immune reconstitution inflammatory syndrome (IRIS), and after 6 months post-NAT-PML diagnosis, 1,5-Tesla MRI scans were obtained. Compared with our preceding work,5 we focused on the speciality of infratentorial PML manifestations and included a larger patient population. Statistical analysis was performed using SPSS …

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    Footnotes

    • Contributors All authors reviewed and approved the final manuscript. RH: designed the investigation, acquired the data, performed statistical analyses, interpreted the data and wrote the first version of the manuscript. JA: designed the investigation, acquired the data, developed the structure of the arguments and critically reviewed the manuscript. SF: interpreted the data, developed the structure of the manuscript and reviewed the manuscript. RS collected the data and critically reviewed the manuscript. SD: interpreted and collected the data and reviewed the manuscript. OA: collected the data, developed the structure of the manuscript and critically reviewd it. PR: collected the data and reviewed the manuscript. CL: collected the data, interpreted the statistics and reviewed the manuscript. AC: developed the structure of the manuscript, interpreted the data and reviewed the manuscript critically. MS: collected the data, developed the design and the structure of the manuscript and critically reviewed it. RG: developed the design, interpreted the data and critically reviewed the statistics and the manuscript.

    • Competing interests RH received research and travel grants from Biogen-Idec and travel grants from Novartis. SF received a travel grant from Biogen-Idec. OA received consulting honoraria from Biogen-Idec. CL has received consulting and speaker's honoraria from Biogen-Idec, Bayer Schering, Novartis, Sanofi, Genzyme and TEVA, and has received research scientific grant support from Bayer Schering, TEVA and MerckSerono. AC has received personal compensation as a speaker or consultant for Bayer Schering, Biogen-Idec, Merck Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience and research support from the German Ministry for Education and Research (BMBF, “German Competence Network Multiple Sclerosis” [KKNMS], CONTROL MS, 01GI0914), Bayer Schering, Biogen Idec, Merck Serono, and Novartis. MS received speakers and consulting honoraria from Bayer Healthcare, Biogen-Idec, Baxter, CSL Behring, Grifols, Merck-Serono, Novartis, Sanofi-Aventis, and Teva. MS is also supported by the Niedersachsen Research Network on Neuroinfectiology (N-RENNT) of the Ministry of Science and Culture of Lower Saxony. His institution received research support from Bayer Healthcare, Biogen Idec, Merck-Serono, Novartis, and Teva. RG received speakers and consulting honoraria, scientific grant support from Baxter, Bayer Healthcare, Biogen-Idec, Merck-Serono, Novartis Pharma, Sanofi-Genzyme and Teva Pharma.

    • Ethics approval The research was approved by the local ethic committees of University Bochum and Hannover (no. 4566-13 (Bochum) & 2100-2013 (Hannover)).

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