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January 2023; 10 (1) Diagnostic & Treatment ChallengesOpen Access

Recurrent Optic Neuritis and Perineuritis Followed by an Unexpected Discovery

From the National Multiple Sclerosis Society Case Conference Proceedings

Daniela A. Pimentel Maldonado, Robert Lisak, Steven Galetta, Laura Balcer, Thomas Varkey, Andrew Goodman, Jennifer Graves, Michael Racke, Scott S. Zamvil, Scott Newsome, Elliot M. Frohman, Teresa C. Frohman
First published November 10, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200051
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Article Information

vol. 10 no. 1 e200051
DOI: 
https://doi.org/10.1212/NXI.0000000000200051
PubMed: 
36357190
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received May 12, 2022
  • Accepted in final form September 12, 2022
  • First Published November 10, 2022.
Copyright & Usage: 
Copyright © 2022 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. Daniela A. Pimentel Maldonado, MD, MSCR,
    2. Robert Lisak, MD,
    3. Steven Galetta, MD,
    4. Laura Balcer, MD, MSCE,
    5. Thomas Varkey,
    6. Andrew Goodman, MD,
    7. Jennifer Graves, MD, PhD,
    8. Michael Racke, MD,
    9. Scott S. Zamvil, MD, PhD,
    10. Scott Newsome, DO*,
    11. Elliot M. Frohman, MD, PhD* and
    12. Teresa C. Frohman, MPAS, PA-C*
  1. Daniela A. Pimentel Maldonado, MD, MSCR,
    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. Robert Lisak, MD,
    3. Scientific Advisory Boards:

    1. 1) Advisory Board Commercial: Argenx, ; Mallinckrodt, Takeda, Alivant, ANI, MedDay, Horizon ;2) Advisory Board non-profit: National Multiple Sclerosis ;Society, ;Michigan Chapter, Clinical Advisory Committee; Myasthenia ;Gravis ;Foundation of America, Clinical Advisory Committee; ;Guillain-Barre Syndrome/CIDP Foundation, International, ;Global Medical Advisory Commmittee

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Section Editor for Neuroimmunology, Clinical ;Neuropharmacology, 2005-present; Editorial Board, ;Immunology Research, 1986-2021; Neuroimmunology Reports ;2020-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. International Neurology: A Clinical Approach, Blackwell, ;Oxford, 2009; 2017 (2nd edition) ;Neuroimmunology, Oxford University Press, 2019

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1)GLG Consulting; Insight Consulting; Alpha Sites ;Consulting; Argenx; Clearview Consulting, Guidepoint ;Consulting; Jupiter Consulting; Dedham, Triangle ;Insights, Horizon Pharmaceuticals, ALI, Alivar,Takeda, ;COUR (Data Safety Monitoring Board) ; ;and ACTHar Gel, Takeda consulting on autoimmune ;neurologic disorders, Janssen consulting on S1P receptor ;modulators

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. Health Advisory Committee; National Multiple ;Sclerosis Society, Michigan Chapter, Board of Governors; ;Research Grants Committee and Centers of Excellence ;Committee of the Medical Advisory Committee of the ;GBS/CIDP Foundation, International; Grants Committee of ;the Myasthenia Gravis Foundation of America ended-2020

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Alexion; Genentech, Novartis, ;Medimmune; Chugai, UCB/Ra Pharmaceuticals, Argenx, Takeda ;paid to Wayne State University for my participation in ;clinical trials ;MedDay as Chair of Adjudication Committee for study of ;biotin in progressive forms of MS

    Research Support, Government Entities:

    1. NINDS; 1R21NS118227-01; PI; 7/15/2020-06/30/2023

    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. Steven Galetta, MD,
    4. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. (1) Neurology, Editorial Board; ; ;(2) Journal of Neuro-ophthalmology, Editorial Board

    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

  4. Laura Balcer, MD, MSCE,
    5. Scientific Advisory Boards:

    1. Editor in Chief, Journal of Neuro-Ophthalmology, receive payments from the North American Neuro-Ophthalmology Society

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Journal of Neuro-Ophthalmology, Editor-in-Chief, 2019-present

    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. NIH

    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

  5. Thomas Varkey,
    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. Andrew Goodman, MD,
    7. Scientific Advisory Boards:

    1. IMCYSE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Received travel expenses and/or honoraria for lectures or ;educational activities not funded by industry from Americas Committee for Research and Treatment in MS; Guthy-Jackson Charitible Foundation; Race ;to Erase MS. ;Received travel expenses and/or honoraria for consuting ;from Genetech; Janssen: Lilly.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. Royalties:

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1 Adamas: consultant; SwanBio: consultant; Novartis: consultant; Janssen: consultant; Genentech:consultant; Lilly: consultant

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. 1.Biogen-Idec:research support ;2.Genzyme-sanofi:research support;3. Novartis: research ;support 3.Atara; research support4 . Roche:research ;support

    Research Support, Government Entities:

    1. 1. FUNDING AGENCY Mass Gen Hosp/NeuroNEXT (NINDS) Goodman (Site-PI NAME) Fox (PPI) ;DATES OF ACTIVE/PENDING AWARD 9/1/13-8/31/18 ANTIC ;TOTAL COSTS $151,880 PERCENT EFFORT 2% TITLE OF PROJECT (OR SUBPROJECT) A Randomized D-B, P-C ;Study to Evaluate the Safety, Tolerability & Activity of ;Ibudilast (MN-66) in Subjects with Progressive Multiple ;Sclerosis. ; ;2. FUNDING AGENCY John Hopkins University GRANT/CONTRACT NUMBER, (PI NAME) Andrew Goodman, MD ;DATES OF ACTIVE/PENDING AWARD : : 7/15/2011-3/31/2014 ANTIC TOTAL COSTS $0 PERCENT EFFORT ; 2% ;TITLE OF PROJECT (OR SUBPROJECT) A Randomized Controlled ;Trial of Vitamin D in Multiple Sclerosis ; ;3. UNIV/SUNY Buffalo:Establish NYS Multiple Sclerosis ;Consortium Currently Funded Grants/Contracts Andrew ;Goodman $0.00 $67,866.00 03/01/1995 10/31/2014 0% The ;goal of this study is to develop an ongoing, centralized, ;uniform database of MS patient information and specimens ;for member centers.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1. National 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. Acorda Therapeutics, expert witness for plaintiff

  7. Jennifer Graves, MD, PhD,
    8. Scientific Advisory Boards:

    1. Novartis, Genentech, Bayer

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Assistant editor for Neurology 2020-2021 ;Associate editor for ACTN 2019-2022

    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) Octave ;2) Biogen ;3) EMD Serono ;4) Sanofi

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. 1) National MS 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. NONE

  8. Michael Racke, MD,
    9. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Journal of Neuroimmunology, Editor-in-Chief, 2010-2020 ;Spouse has following editorial positions: ;Journal of Immunology- Section Editor ;Frontiers in Multiple Sclerosis and Neuroimmunology- ;Associate Editor ;Journal of Neuroimmunology-Deputy Editor- 2010-2020 ;Brain, Behavior, and Immunity-Editorial Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Quest Diagnostics, Medical Director for Neurology, 2 years

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Salary from Quest Diagnostics

    Research Support, Government Entities:

    1. Spouse has funding from NIH

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. None

    Stock/Stock Options/Board of Directors Compensation:

    1. Stock options from Quest Diagnostics

    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. Scott S. Zamvil, MD, PhD,
    10. Scientific Advisory Boards:

    1. Dr. Zamvil has received honoraria for serving on Data Safety ;Monitoring Boards for MS trials conducted by Opexa, BioMS, ;Teva Pharmaceuticals, Inc. and Eli Lilly and Co. ;Foundation.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1) Biogen - Speaker honoraria and advisory board meetings ;(2) Teva - Speaker honoraria and advisory board meetings ;(3) Alexion - Speaker honoraria and advisory board meetings ;(4) Novartis - Speaker honoraria and advisory board meetings

    Editorial Boards:

    1. (1) Neurology, Neuroimmunology and Neuroinflammation, ;Deputy Editor, 2014-present

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. SSZ has served as a consultant to Biogen Idec, Teva ;Neuroscience, EMD-Serono, Genzyme, Novartis and Roche.

    Speakers' Bureaus:

    1. Advanced Health Media, 2009-present ;Biogen, 2009-present ;Alexion, 2019-present ;Viela Bio, 2020

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Biogen - speaker and advisory board meetings ;(2) Teva - speaker and advisory board meetings ;(3) Genentech - advisory board meeting ;(4) Novartis - advisory board meetings ;(5) Genzyme - advisory board meetings ;(6) Alexion - advisory board meeting

    Research Support, Government Entities:

    1. NIH RO1 AI131624-O1A1 ;NIH R21 NS10815990-01

    Research Support, Academic Entities:

    1. NMSS RG 1701-26628 ;NMSS RG 1801-29861

    Research Support, Foundations and Societies:

    1. Alexander M. and June L. Maisin Foundation, PI

    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. Scott Newsome, DO*,
    11. Scientific Advisory Boards:

    1. Biogen Idec, scientific advisory board ;Genentech, scientific advisory board ;EMD Serono, scientific advisory board ;Bristol Myers Squibb, scientific advisory board ;Greenwich Biosciences, scientific advisory board ;Novartis, scientific advisory board ;Horizon Therapeutics, scientific advisory board ;medDay Pharmaceuticals, clinical adjudication committee ;member for a clinical trial

    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. Autobahn

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. study lead PI for a Roche clinical trial

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Biogen Idec; research support payed directly to my ;institution and not relevant to the submitted manuscript ;Genentech; research support payed directly to my ;institution and not relevant to the submitted manuscript ;Roche; research support payed directly to my ;institution and not relevant to the submitted manuscript

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National Multiple Sclerosis Society ;Department of Defense ;Patient Centered Outcomes Research Institute ;The Stiff Person Syndrome Research 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

  11. Elliot M. Frohman, MD, PhD* and
    12. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Genzyme-Speaker fees Novartis-Speaker fees Alexion-Speaker fees Janssen-Speaker fees

    Editorial Boards:

    1. J of Neurology-Editorial Board Frontiers in Neurology-Editorial Board J of the Neurological Sciences-Editorial Board Neuroimmunology Reports-Editorial Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. 1. Up To Date: i). Internuclear ophthalmoparesis ii). Multiple Sclerosis: Symptom management 2) Cambridge University Press Optical Coherence Tomography in Neurological Diseases

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. Genzyme Novartis Alexion Janssen

    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. National MS 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. NONE

  12. Teresa C. Frohman, MPAS, PA-C*
    13. Scientific Advisory Boards:

    1. spouse:Genzyme, Alexion, Novartis, JANSSEN- speaking and ;consulting

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Spouse: Genzyme, Alexion, Novartis

    Editorial Boards:

    1. self and spouse: ;Editor Neurology Reports ;Contributor: Up To Date ;NMSS Fellows Webinar Case Conference Proceedings

    Patents:

    1. NONE

    Publishing Royalties:

    1. Self: Up-To-Date ; ;Spouse: Up-To-Date

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Spouse: Genzyme, Alexion, Novartis, Janssen

    Speakers' Bureaus:

    1. Spouse:Genzyme, Alexion, Novartis, Janssen

    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

  1. From the Department of Neurology (D.A.P.M., S.N.), Johns Hopkins Hospital, Baltimore, MD; Department of Neurology (R.L.), Wayne State University, Detroit, MI; Departments of Neurology (S.G., L.B.), Population Health, and Ophthalmology, NYU Grossman School of Medicine; Department of Neurology (T.V.), Dell Medical School, The University of Texas at Austin; Department of Neurology (A.G.), University of Rochester, NY; Department of Neurosciences (J.G.), University of California at San Diego; Quest Diagnostics (M.R.), Secaucus, NJ; Department of Neurology and Program in Immunology (S.S.Z.), University of California San Francisco; and Distinguished Senior Fellows (Sabbatical) Neuroimmunology Laboratory of Professor Lawrence Steinman (E.M.F., T.C.F.), Stanford University School of Medicine, Palo Alto, CA.
  1. Correspondence
    Dr. Frohman elliot.frohman{at}austin.utexas.edu

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