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March 2020; 7 (2) ArticleOpen Access

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Tania Cellucci, Heather Van Mater, Francesc Graus, Eyal Muscal, William Gallentine, Marisa S. Klein-Gitelman, Susanne M. Benseler, Jennifer Frankovich, Mark P. Gorman, Keith Van Haren, Josep Dalmau, Russell C. Dale
First published January 17, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000663
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Article Information

vol. 7 no. 2 e663
DOI: 
https://doi.org/10.1212/NXI.0000000000000663
PubMed: 
31953309
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received July 31, 2019
  • Accepted in final form November 25, 2019
  • First Published January 17, 2020.
Copyright & Usage: 
Copyright © 2020 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. Tania Cellucci, MD, MScCH,
    2. Heather Van Mater, MD, MSc,
    3. Francesc Graus, MD, PhD,
    4. Eyal Muscal, MD, MS,
    5. William Gallentine, DO,
    6. Marisa S. Klein-Gitelman, MD, MPH,
    7. Susanne M. Benseler, MD, PhD,
    8. Jennifer Frankovich, MD, MS,
    9. Mark P. Gorman, MD,
    10. Keith Van Haren, MD,
    11. Josep Dalmau, MD, PhD and
    12. Russell C. Dale, MBChB, MSc, PhD
  1. Tania Cellucci, MD, MScCH,
    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. Heather Van Mater, MD, MSc,
    3. 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

  3. Francesc Graus, MD, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Assistant Editor MedLink Neurology

    Patents:

    1. licensing fee from Euroimmun for the use of IgLON5 as an autoantibody test

    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

  4. Eyal Muscal, MD, MS,
    5. 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. (1) Lupus Foundation of America

    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

  5. William Gallentine, DO,
    6. 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

  6. Marisa S. Klein-Gitelman, MD, MPH,
    7. Scientific Advisory Boards:

    1. GRAPPA (non-profit)

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. UpToDate 2011-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. UpToDate 2011- present Section Editor/Author pediatric rheumatology sections

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. Board Member, American College of Rheumatology

    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

  7. Susanne M. Benseler, MD, PhD,
    8. Scientific Advisory Boards:

    1. (1) The Arthritis Society, Autoimmune Encephalitis Alliance, Vasculitis Foundation (2) Novartis, Sobi

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) The Arthritis Society (travel, no honorarium) (2) Novartis, Sobi (travel, no honorarium)

    Editorial Boards:

    1. Neurology: Neuroimmunology & Neuroinflammation

    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

  8. Jennifer Frankovich, MD, MS,
    9. 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. (1)Yale University/NIH, GR106053, Site PI, 2 years

    Research Support, Academic Entities:

    1. Stanford SPARK Program Stanford Maternal and Child Health Research Institute

    Research Support, Foundations and Societies:

    1. PANS/PANDAS Physician Network PRAI Kids Global Lyme Alliance Lucile Packard Foundation for Children's Health Caudwell Children's 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

  9. Mark P. Gorman, MD,
    10. 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. (1) Pfizer, (2)Novartis, (3) Roche

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National Multiple Sclerosis Society (Grant numbers 70846, 73216)

    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. Keith Van Haren, MD,
    11. Scientific Advisory Boards:

    1. Scientific Advisory Board - The Myelin Project (unpaid)Board of Directors - ALD Connect (unpaid)DSMB for Phase I/II trial of NV1205 in ALD - Neurovia (paid)

    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. January 2017 - Due diligence review for ENSO Ventures regarding investment in NV1209June 2018 - Scientific consulting for Viking Pharma on ALD scientific program

    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. NIH K23NS087151 (PI, July 2015 - present)

    Research Support, Academic Entities:

    1. (1) Stanford University Dept of Neurology

    Research Support, Foundations and Societies:

    1. (1) Packard Foundation Sprague/McHugh Award for MS Research (June 2011 to present)(2) Child Neuorology Foundation - Scientific Award - Jan 2012 - June 2015)

    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

  11. Josep Dalmau, MD, PhD and
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Neurology, Neuroimmunology and Neuroinflammation Neurology UpToDate

    Patents:

    1. Patent for Ma2 autoantibody test: US 6,387,639; Issued May 14th, 2002. Patent for NMDA receptor autoantibody test: US 7,972,796 B2 July 5, 2011; European 2057466. Patent for GABAb receptor autoantibody test: US 8,685,656; European 2483417; Patents filed for GABA(A) receptor autoantibody test, DPPX autoantibody test, and IgLON5 autoantibody test.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Advance Medical

    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. -NIH, RO1NS077851, PI, 2011-2018 -Instituto Carlos III/FEDER (FIS, 14/00203 and CIBERER CB15/00010, and Proyectos Integrados de Excelencia, PIE 16/00014). -Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR), and CERCA Programme Generalitat de Catalunya -ERA-NET Neuron

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Safra Foundation Sage therapeutics Cellex Foundation La Caixa Health Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License fee payments, Technology or Inventions:

    1. NMDA receptor autoantibody test/Euroimmun GABA(B)R autoantibody test/Euroimmun GABA(A)R autoantibody test/Euroimmun DPPX autoantibody test/Euroimmun Iglon5 autoantibody test/Euroimmun

    Royalty Payments, Technology or Inventions:

    1. Patent Ma2 autoantibody test Patent NMDAR autoantibody test Patent GABA(B) receptor autoantibody test Patent application for the use of GABA(A) receptor, DPPX and IgLON5 autoantiboddy tests

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Russell C. Dale, MBChB, MSc, PhD
    13. Scientific Advisory Boards:

    1. National Blood Authority. Federal, not for profit

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. received an honoraria for lecturing from Biogen Idec and Bristol-Myers-Squibb

    Editorial Boards:

    1. Editorial advisory board member of MSARDEditorial board member of Neurology: Neuroimmunology and NeuroinflammationEditorial board member of European Journal of Paediatric Neurology

    Patents:

    1. NONE

    Publishing Royalties:

    1. Biogen Idec honoraria in 2008 and Bristol-Myers-Squibb in 2015

    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. NHMRC national grant in 2011 national grant for encephalitis studyNHMRC practitioner fellowship 2014-8NHMRC project grant 2015, 2018NHMRC partnership grant 2018

    Research Support, Academic Entities:

    1. Multiple Sclerosis Research Australia 2015

    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 Pediatrics (T.C.), McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada; Department of Pediatrics (H.V.M.), Duke University, Durham, NC; Neuroimmunology Program (F.G., J.D.), Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain; Department of Pediatrics (E.M.), Baylor College of Medicine, Houston, TX; Department of Neurology (W.G., K.V.H.), Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA; Division of Rheumatology (M.S.K.-G.), Ann & Robert H, Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, IL; Department of Pediatrics (S.M.B.), Alberta Children's Hospital, University of Calgary, Canada; Division of Pediatric Allergy, Immunology and Rheumatology (J.F.), Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA; Department of Neurology (M.P.G.), Boston Children's Hospital, Harvard University, MA; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; Catalan Institution for Research and Advanced Studies (ICREA) (J.D.); Neuroimmunology Group (R.C.D.), Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, New South Wales, Australia.
  1. Correspondence
    Dr. Dale Russell.dale{at}health.nsw.gov.au
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