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May 2019; 6 (3) Clinical/Scientific NotesOpen Access

A case of CLIPPERS syndrome responsive to tocilizumab

Torge Rempe, Jos Steffen Becktepe, Imke Metz, Wolfgang Brück, Klarissa Hanja Stürner, Günther Deuschl, Daniela Berg, Ralf Baron, Rainald Zeuner, Frank Leypoldt
First published February 4, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000545
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Article Information

vol. 6 no. 3 e545
DOI: 
https://doi.org/10.1212/NXI.0000000000000545
PubMed: 
30882019
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received September 11, 2018
  • Accepted in final form January 8, 2019
  • First Published February 4, 2019.
Copyright & Usage: 
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Torge Rempe, MD,
    2. Jos Steffen Becktepe, MD,
    3. Imke Metz, MD,
    4. Wolfgang Brück, MD,
    5. Klarissa Hanja Stürner, MD,
    6. Günther Deuschl, MD,
    7. Daniela Berg, MD,
    8. Ralf Baron, MD,
    9. Rainald Zeuner, MD and
    10. Frank Leypoldt, MD
  1. Torge Rempe, MD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Jos Steffen Becktepe, MD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Ipsen Pharma GmbH, travel funding

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Imke Metz, MD,
    4. Scientific Advisory Boards:

    1. 1) commercial: advisory board for Roche.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. 1)commercial: speaker honoraria, travel grants from BiogenIdec, Bayer Healthcare, TEVA, Serono, Novartis, Genzyme.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. research grant from BiogenIdec.

    Research Support, Government Entities:

    1. grants from German Ministry for Education and Research (BMBF, ??German Competence Network Multiple Sclerosis?? (KKNMS), Pattern MS/NMO);

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Wolfgang Brück, MD,
    5. Scientific Advisory Boards:

    1. I serve on the advisory boards of Genzyme, Novartis, Medday, Biogen and Teva Pharma.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. I received honoraria for oral presentations from Teva, Sanofi, Genzyme, Novartis, Merck-Serono, Biogen, Roche and Bayer in the last 2 years.

    Editorial Boards:

    1. I am editorial board member of Therapeutic Advances in Neurological disorders, Multiple Sclerosis International and Neuropathology and Applied Neurobiology

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Teva Pharma, (2) Novartis, (3) Biogen, (4) Genzyme, (5) Medday

    Research Support, Government Entities:

    1. (1) German Research foundation (DFG SFB TR43): The brain as a target of inflammatory processes, 2008-2015 German ministry for science and education: Competence network multiple sclerosis, 2010-2018 (2) German Ministry for Education and Research: Competence Network Multiple Sclerosis, 2009-2018 (3)German Ministry for Education and Research: 3D-Patho, 2017-2020

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Tschira Foundation German Multiple Sclerosis Society

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. Teva Pharma, expert witness, 2015-2018

  5. Klarissa Hanja Stürner, MD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Klarissa St?rner reports travel grants and speaker honoraria Biogen Idec, Merck, Roche and Sanofi Genzyme outside the submitted work.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) BiogenIdec (IIT Grant)

    Research Support, Government Entities:

    1. (1) BMBF,0315610?0315620, Investigator,2015

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Günther Deuschl, MD,
    7. Scientific Advisory Boards:

    1. Medtronic, Boston Scientific

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Boston Scientific

    Editorial Boards:

    1. Movement Disorders, editor 2004-2010 Aktuelle Neurologie, co-editor 1994-now

    Patents:

    1. NONE

    Publishing Royalties:

    1. Thieme publishers

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Medtronic

    Research Support, Government Entities:

    1. German Ministry of Education and Research

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Daniela Berg, MD,
    8. Scientific Advisory Boards:

    1. (1) Biogen, (2) BIAL, (3) Lundbeck, (4) UCB Pharma GmbH

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1)Desitin, travel and speaker honoraria (2)Pfizer, travel (3)Lundbeck, travel and speaker honoraria (4)Boehringer Ingelheim Pharma GmbH, travel (5)Coppenrath Stiftung, travel (6)Gr?nenthal GmbH, travel (7)JPND Research, travel (8)Apothekenwirtschaftsdienst GmbH, travel and speaker honoraria (9) Asklepios Kliniken Hamburg GmbH, travel and speaker honoraria (10)Bayer Vital GmbH, travel and speaker honoraria (11)BIAl Deutschland GmbH, travel and speaker honoraria (12)J. Weser GmbH (Zambon), travel and spaeker honoraria (13)AbbVie Deutschland GmbH, travel and Speaker honoraria (14)TEVA GmbH, travel and Speaker honoraria (15)Dekanat der CAU, travel (16)?rztekammer Schleswig-Holstein,travel and Speaker honoraria (17) Deutsche Parkinson Vereinigung (DPV), travel and Speaker honoraria (18)Jansen Neuroscience Network, travel and Speaker honoraria (19)Uniklinik RWTH Aachen, travel (20)Humanitas Research Hospital Mailand, travel (21)Universit?tsmedizin Rostock, travel (22)Deutsche Gesellschaft f?r Neurologie (DGN), travel (23)Universit?tsklinik T?bingen, travel (24)Aklepios-Klinik Altona, travel and Speaker honoraria (25)NDR-Fernsehen, travel and Speaker honoraria (26)Segeberger Kliniken, travel (27)Deutsche Parkinson Gesellschaft (DPG), travel (28)Scandinavian Movement Disorder Society, travel (29)International Parkinson and Movement Disorder Society, travel and speaker honoraria

    Editorial Boards:

    1. (1) DGNeurologie, Funding-Co-Editor, (2) Movement Disorders Clinical Practice Journal, Editorial Board, (3) Neurological Research and Practice, Editorial Board (4) Journal of Parkinsons's Disease, Associate Editor (5) Der Nervenarzt, Member of the Scientific Advisory Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Biogen (2) BIAL (3) Lundbeck (4) UCB Pharma GmbH

    Speakers' Bureaus:

    1. (1)AbbVie (2)Biogen (3)BIAL (4)Lundbeck (5)UCB Pharma GmbH

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1)Janssen Pharmaceutica N.V. (2)UCB Pharma GmbH (3)TEVA Pharma GmbH (4)Novartis Pharma GmbH (5)Lundbeck

    Research Support, Government Entities:

    1. (1)BMWi (2)EU

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. (1)Michael J.Fox Foundation (2)German Parkinson Disease Society (dPG) (3)Damp foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Ralf Baron, MD,
    9. Scientific Advisory Boards:

    1. Abbvie, Allergan, Astellas, AstraZeneca, Bayer-Schering, Biogenidec, Biotest, AG, Bohringer, Ingelheim, Pharma, GmbH, &, Co., KG, Bristol-Meyers, Squibb, Celegene, Daiichi, Sankyo, Desitin, Eisai, Co., Ltd., Galapagos, NV, Genentech, Genzyme, GmbH, Glenmark, Pharmaceuticals, Gr?nenthal, GmbH, Kyowa, Kirin, GmbH, Lilly, GmbH, Medtronic, Merck, MSD, GmbH, Mundipharma, Novartis, Pfizer, Sanofi, Pasteur, Sequirus, TAD, Pharma, GmbH, Teva, Pharma, Theranexus, Vertex, Pharmaceuticals, Inc.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Pfizer, Genzyme GmbH, Gr?nenthal GmbH, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai Co.Ltd., Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Desitin, Teva Pharma, Bayer- Schering, MSD GmbH, Seqirus, Novartis, TAD Pharma GmbH

    Editorial Boards:

    1. Nature Reviews Neurology (Advisory Board), European Journal of Pain

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Pfizer, Genzyme GmbH, Gr?nenthal GmbH, Mundipharma, Allergan, Sanofi Pasteur, Medtronic, Eisai, Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Novartis, Bristol-Myers Squibb, Biogenidec, AstraZeneca, Merck, Abbvie, Daiichi Sankyo, Glenmark Pharmaceuticals, Seqirus, Teva Pharma, Genentech, Galapagos NV, Kyowa Kirin GmbH, Vertex Pharmaceuticals Inc., Biotest AG, Celgene, Desitin, Theranexus

    Speakers' Bureaus:

    1. Pfizer, Genzyme GmbH, Gr?nenthal GmbH, Mundipharma, Sanofi Pasteur, Medtronic Inc. Neuromodulation, Eisai Co.Ltd., Lilly GmbH, Boehringer Ingelheim Pharma GmbH&Co.KG, Astellas, Desitin, Teva Pharma, Bayer- Schering, MSD GmbH, Seqirus, Novartis, TAD Pharma GmbH

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Abbvie, Allergan, Astellas, AstraZeneca, Bayer-Schering, Biogenidec, Biotest, AG, Bohringer, Ingelheim, Pharma, GmbH, &, Co., KG, Bristol-Meyers, Squibb, Celegene, Daiichi, Sankyo, Desitin, Eisai, Co., Ltd., Galapagos, NV, Genentech, Genzyme, GmbH, Glenmark, Pharmaceuticals, Gr?nenthal, GmbH, Kyowa, Kirin, GmbH, Lilly, GmbH, Medtronic, Merck, MSD, GmbH, Mundipharma, Novartis, Pfizer, Sanofi, Pasteur, Sequirus, TAD, Pharma, GmbH, Teva, Pharma, Theranexus, Vertex, Pharmaceuticals, Inc.

    Research Support, Government Entities:

    1. Member of the IMI ?Europain? collaboration and industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB- Pharma, Sanofi Aventis, Gr?nenthal GmbH, Eli Lilly and Boehringer Ingelheim Pharma GmbH&Co.KG ,German Federal Ministry of Education and Research (BMBF): Member of the ERA_NET NEURON / IM-PAIN Project (01EW1503), German Research Network on Neuropathic Pain (01EM0903), NoPain system biology (0316177C), Member of the EU Project No 633491: DOLORisk, EU: IMI 2 Paincare

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License fee payments, Technology or Inventions:

    1. Copyrights, Pfizer

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Rainald Zeuner, MD and
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Roche: Speaker and travel honoraria

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Frank Leypoldt, MD
    11. Scientific Advisory Boards:

    1. (1) Roche, Biogen

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Grifols (2) Teva (3) Biogen (4) Fresenius (5) Bayer (6) Novartis (7) Merck (8) Roche

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical procedures or imaging studies:

    1. Institute of Laboratory Medicine, University Hospital Schleswig- Holstein Campus Kiel, Germany, commercial antibody testing service, 20%

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Neurology (T.R., J.S.B., K.H.S., G.D., D.B., R.B., F.L.), Department of Rheumatology (R.Z.), and Neuroimmunology, Institute of Clinical Chemistry (F.L.), Division of Neurological Pain Research and Therapy (R.B.), University Hospital of Schleswig-Holstein, Kiel, Germany; Department of Neurology (T.R.), University of Florida, Gainesville, FL; and Institute of Neuropathology (I.M., W.B.), University Hospital Göttingen, Germany.
  1. Correspondence
    Dr. Leypoldt frank.leypoldt{at}uksh.de
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