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September 2019; 6 (5) ArticleOpen Access

Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS

Chenyu Wang, Michael H. Barnett, Con Yiannikas, Joshua Barton, John Parratt, Yuyi You, Stuart L. Graham, Alexander Klistorner
First published July 16, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000593
Chenyu Wang
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Michael H. Barnett
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Con Yiannikas
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Joshua Barton
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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John Parratt
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Yuyi You
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Stuart L. Graham
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Alexander Klistorner
From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
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Full PDF
Citation
Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS
Chenyu Wang, Michael H. Barnett, Con Yiannikas, Joshua Barton, John Parratt, Yuyi You, Stuart L. Graham, Alexander Klistorner
Neurol Neuroimmunol Neuroinflamm Sep 2019, 6 (5) e593; DOI: 10.1212/NXI.0000000000000593

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Article Information

vol. 6 no. 5 e593
DOI: 
https://doi.org/10.1212/NXI.0000000000000593
PubMed: 
31454773

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received November 27, 2018
  • Accepted in final form May 7, 2019
  • First Published July 16, 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. Chenyu Wang, PhD,
    2. Michael H. Barnett, PhD,
    3. Con Yiannikas, FRACP,
    4. Joshua Barton, FRACP,
    5. John Parratt, FRACP,
    6. Yuyi You, PhD,
    7. Stuart L. Graham, PhD and
    8. Alexander Klistorner, PhD
  1. Chenyu Wang, PhD,
  2. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. Novartis, Travel support attending ECTRIMS2018 conference

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. Sydney Neuroimaging Analysis Centre, Director of Operations, 0.4 years

    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. Multiple Sclerosis Research Australia, 18-0461, MSRA fellowship, 3 years

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. Nerve 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

  3. Michael H. Barnett, PhD,
  4. Scientific Advisory Boards:
    1. 1.Novartis, scientific advisory board 2.Genzyme-Sanofi, scientific advisory board

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. 1. Teva, Conference Travel (2016 ECTRIMS)

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. 1. Sydney Neuroimaging Analysis Centre

    Speakers' Bureaus:
    1. NONE

    Other activities:
    1. Consultant, Medical Safety Systems / RxMx.

    Clinical Procedures or Imaging Studies:
    1. NONE

    Research Support, Commercial Entities:
    1. 1. Novartis, Research Grant support 2. Genzyme-Sanofi, Research Grant Support 3. Bio-CSL, Research Grant Support 4. Biogen, Research Grant Support

    Research Support, Government Entities:
    1. 1. Australian Government, CRC-P Grant: "New Smarts for the Medical Imaging Industry", Partner Investigator, 2018-2021

    Research Support, Academic Entities:
    1. 1. MS Research Australia, Project Grant: "Does somatic mutation in the brain drive progressive MS?", Co- Investigator 2018-2021 2. MS Research Australia, Project Grant: "Understanding the induction of disease quiescence by immunomodulating drugs in multiple sclerosis", Co-Investigator, 2018-2021. 3. The University of Sydney. SOAR Research accelerator Fellowship, CI, 2018-2019.

    Research Support, Foundations and Societies:
    1. Nerve Research Foundation, The University of Sydney

    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. Con Yiannikas, FRACP,
  6. Scientific Advisory Boards:
    1. Teva advisory board for migraine.

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. Commercial- Ipsen-Travel to Int Movement disorders meeting 2018 Biogen speaker 2019 CSL speaker 2019

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. Consultant-Allergan, Ipsen

    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

  7. Joshua Barton, FRACP,
  8. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. (1) Teva, educational travel support (2) Novartis, educational travel support (3) Sanofi-Genzyme, educational travel support, speaker honoraria (4) Merck, educational travel support, speaker honoraria (5) Biogen, educational travel support

    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. Multiple Sclerosis Research Australia- postgraduate scholarship

    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. John Parratt, FRACP,
  10. Scientific Advisory Boards:
    1. 1. Commercial - Genzyme scientific advisory board 2. Commercial - Novartis scientific advisory board 3. Biogen advisory board

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. 1. Commercial - Honoraria from Biogen for educational meetings 2. Commercial - Honoraria from Genzyme/Sanofi for educational meetings 3. Commercial - Honoraria from Merck Serono for educational meetings.

    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. Multiple sclerosis research Australia Neil and Norma Hill inaugural junior practitioner fellowship

    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. Yuyi You, PhD,
  12. 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) National Health and Medical Research Council (NHMRC), #1089853, CI, 2015-2018 (2) The Ophthalmic Research Institute of Australia (ORIA), CI, 2017,2019 (3) Sydney Medical School, CI, 2016

    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

  13. Stuart L. Graham, PhD and
  14. Scientific Advisory Boards:
    1. (1)Allergan Australia

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. (1) Allergan Australia - conference support 2)Novartis Australia - invited lecturer

    Editorial Boards:
    1. (1)Clin Exp Ophthalmol - Glaucoma Section editor

    Patents:
    1. (1)US Patent for multifocal VEP electrode positioning and signal scaling

    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)Novartis - research support (2)Allergan Australia - research fellowship support

    Research Support, Government Entities:
    1. (1 ) NHMRC grants CIA x2 Perpetual Hillcrest Foundation grant CIA Ophthalmic Research Institute Australia Grant CIA

    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

  15. Alexander Klistorner, PhD
  16. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. NONE

    Editorial Boards:
    1. NONE

    Patents:
    1. 1. "Electrophysiological visual field measurement" Klistorner and Graham 1999, PCT/AU99/00340. 2. "Method and apparatus for objective electrophysiological assessment of visual function" Klistorner and Graham 2001, PCT/AU01/00423. 3. ?Stimulus Method for Multifocal Visual Evoked Potential? Klistorner and Graham (Australian Patent Application No 2007900803). 4. ?Flexible electrode assembly and apparatus for measuring electrophysiological signals? Cheng, Klistorner, Graham (Australian Provisional Patent # 2006904755). 5. ?Apparatus for measuring electrophysiological signals? Cheng, Klistorner, Dyer - Australian Design No. 310666. 6. ? Flexible printed circuit board electrode assembly? Cheng, Klistorner, Dyer - Australian Design No. 311943.

    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. Sydney University Foundation for Medical Research. 2. Sydney eye hospital 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

  1. From the Brain and Mind Centre (C.W., M.H.B., J.B.), Sydney Medical School, University of Sydney; Sydney Neuroimaging Analysis Centre (C.W., M.H.B.); Royal North Shore Hospital (C.Y., J.P.); Save Sight Institute (Y.Y., A.K.), Sydney Medical School, University of Sydney; and Faculty of Medicine and Health Sciences (S.L.G., A.K.), Macquarie University, Sydney, NSW, Australia.
  1. Correspondence
    Dr. Klistorner sasha{at}eye.usyd.edu.au
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