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August 11, 2020; 95 (6) Article

Neurofilament light as a biomarker in traumatic brain injury

Pashtun Shahim, Adam Politis, Andre van der Merwe, Brian Moore, Yi-Yu Chou, Dzung L. Pham, John A. Butman, Ramon Diaz-Arrastia, Jessica M. Gill, David L. Brody, Henrik Zetterberg, Kaj Blennow, Leighton Chan
First published July 8, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009983
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Article Information

vol. 95 no. 6 e610-e622
DOI: 
https://doi.org/10.1212/WNL.0000000000009983
PubMed: 
32641538
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received August 29, 2019
  • Accepted in final form January 7, 2020
  • First Published July 8, 2020.

Article Versions

Copyright & Usage: 
© 2020 American Academy of Neurology

Author Disclosures

    1. Pashtun Shahim, MD, PhD,
    2. Adam Politis, MS,
    3. Andre van der Merwe, BS,
    4. Brian Moore, PA-C, MPH,
    5. Yi-Yu Chou, MS,
    6. Dzung L. Pham, PhD,
    7. John A. Butman, MD, PhD,
    8. Ramon Diaz-Arrastia, MD, PhD,
    9. Jessica M. Gill, PhD,
    10. David L. Brody, MD, PhD,
    11. Henrik Zetterberg, MD, PhD,
    12. Kaj Blennow, MD, PhD and
    13. Leighton Chan, MD, MPH
  1. Pashtun Shahim, MD, PhD,
    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. Adam Politis, MS,
    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. Andre van der Merwe, BS,
    4. 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. Department of Defense (Center for Neuroscience and Regenerative Medicine) and the National Institutes of Health Intramural Research Program (Award Number: 63326), sponsor, 10 years

    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. Brian Moore, PA-C, MPH,
    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. Henry M. Jackson Foundation for the Advancement of Military Medicine, physician assistant,3 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. 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

  5. Yi-Yu Chou, MS,
    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. Dzung L. Pham, PhD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. PLOS ONE, 5 years

    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. CNRM/Uniformed Services University, “CNRM Image Processing Core”, HU0001-09-2-0004, , Role: Core Director, 04/22/09- 06/30/20 CNRM/Uniformed Services University, “Characterizing Microhemorrhages from Magnetic Resonance Imaging”, 307513- 5.01-60855, Role: Co-I, 04/01/15-03/31/20 NIH/NINDS, R56-NS055951, “In Vivo Measurement of Brain Biomechanics,” Role: Subaward PI, 09/01/18-08/31/20 NIH/NINDS, “MRI Measurement of the Mechanical Vulnerability of the Brain,” U01-NS112120, Role: Subaward PI, 04/01/19- 09/30/24 CDMRP, “Determining the Role of Tau and Amyloid in Chronic Symptoms and Deficits in Military Personnel Following TBIs through PET Imaging,” W81XWH1810691, Role: Co- investigator, 09/15/18-09/14/21,

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National MS Society, “Imaging Biomarker Discovery With Advanced Brain Segmentation Algorithms”, RG-1507-05243, Role: PI, 04/01/16-03/31/20

    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. John A. Butman, MD, PhD,
    8. 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. I am employed by the National Institutes of Health Stock/Stock Options, Medical Equipment & Materials: Medtronic > 10 years

    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. Ramon Diaz-Arrastia, MD, PhD,
    9. Scientific Advisory Boards:

    1. NeuralAnalytics, Inc BrainBox Solutions, Inc FloTBI Pinteon Therapeutics MesoScale Discoveries

    Gifts:

    1. BrainBox Solutions, Inc. Pinteon Therapeutics

    Funding for travel or speaker honoraria:

    1. Quanterix, Inc

    Editorial Boards:

    1. Journal of Neurotrauma Frontiers of Neuroscience

    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. BrainBox Solutions, Inc

    Research Support, Government Entities:

    1. NIH/NINDS U01 NS086090 09/01/2013-08/30/2018 co-PI NIH/NINDS Project Title: “Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK TBI)” DoD/USAMRAA Diaz-Arrastia (Co-PI) (Manley-PI) 09/01/2014- 08/31/2018 Project Title: “TBI Endpoints Development (TED)” NIH/NINDS U01 NS099046 (Diaz-Arrastiaco-PI) 8/1/2018 – 7/31/2023 2.4 $32,532,017 Project Title: Brain Oxygen Optimization in Severe TBI—Phase 3 (BOOST-3) NIH/NINDS U24 NS107199 (R. Diaz-Arrastia, contact PI) 9/1/2018 – 8/31/2023 Project title: Penn Center for Excellence in Neuroscience Clinical Trials (Penn NeuroNEXT) NIH/NINDS U01 NS114140 (R.Diaz-Arrastia, PI) 12/1/2019 – 11/30/2024 Project Title: Clinical validation of serum neurofilament light as a biomarker of traumatic axonal injury US Dept. of Defense BA170613 (R. Diaz-Arrastia, PI) 9/1/2019 – 8/30/2023 Project Title: Biomarkers of Brain Oxygen Optimization in Severe TBI Trial (Bio-BOOST) US Department of Defense EP180013 (R. Diaz-Arrastia, PI) 9/1/2019 – 8/30/2023 Project Title: TRACK-TBI Epileptogenesis Project

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. Neural Analytics, Inc BrainBox Solutions, Inc Stock/Stock Options, Medical Equipment & Materials: Neural Analytics, Inc

    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. Jessica M. Gill, PhD,
    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. NONE

    Research Support, Government Entities:

    1. NIH intramural research, year 2012-current

    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. David L. Brody, MD, PhD,
    11. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. 1) Acta Neuropathologica, editorial board, 2014-present 1) Journal of Neurotrauma, editorial board, 2013-present

    Patents:

    1. Intracranial hemorrhage detection and treatment device for prolonged field care

    Publishing Royalties:

    1. Concussion Care Manual, Oxford University Press, 2018

    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) NIH intramural research program, PI, 2017-present 2) USUHS, PI and center director, 2017-present

    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

  11. Henrik Zetterberg, MD, PhD,
    12. Scientific Advisory Boards:

    1. HZ has served at advisory boards for Roche Diagnostics, Samumed, CogRx and Wave.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Journal of Alzheimer's Disease, Associate Editor Alzheimer's & Dementia, Associate Editor DADM, Associate Senior Editor Molecular and Cellular Neuroscience, Editor Scandinavian Journal of Clinical and Laboratory Investigation, Editor

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. HZ is co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg.

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. (1) The European Research Council (#681712), (2) Swedish State Support for Clinical Research (#ALFGBG-720931), and (3) the Knut and Alice Wallenberg Foundation.

    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

  12. Kaj Blennow, MD, PhD and
    13. Scientific Advisory Boards:

    1. Dr Blennow has served as a consultant or at advisory boards for Abcam, Azon Neuroscience, Biogen, Eli Lilly, MagQu, Novartis, and Roche Diagnostics

    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. Co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Lundbeck, MagQu, UCB Pharma, Roche Diagnostics

    Research Support, Government Entities:

    1. LUA/ALF project, Västra Götalandsregionen, Sweden (project # ALFGBG- 11019)

    Research Support, Academic Entities:

    1. Dr. Blennow holds the Torsten Söderberg professorship in Medicine.

    Research Support, Foundations and Societies:

    1. The Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences, the Alzheimer Foundation, Sweden, the Stiftelsen för Gamla Tjänarinnor, Stockholm, Sweden and Hjärnfonden, Sweden.

    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. Leighton Chan, MD, MPH
    14. Scientific Advisory Boards:

    1. I serve on a DSMB for a NIH funded clinical trial. There is no compensation

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Archives of Physical Medicine and Rehabilitation, Co- Editor in Chief. 2013- 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. I work for the the NIH Intramural Research Program 2007- present

    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 NIH (P.S., A.P., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); Center for Neuroscience and Regenerative Medicine (P.S., A.v.d.M., B.M., Y.-Y.C., D.L.P., J.A.B., J.M.G., D.L.B., L.C.); The Henry M. Jackson Foundation for the Advancement of Military Medicine (P.S., A.v.d.M., B.M., J.M.G., D.L.B.), Bethesda, MD; Department of Psychiatry and Neurochemistry (P.S., H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Uniformed Services University of the Health Sciences (D.L.B.), Bethesda, MD; Department of Neurology (R.D.-A.), University of Pennsylvania, Philadelphia; UK Dementia Research Institute at UCL (H.Z.); and Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London, UK.
  1. Correspondence
    Dr. Shahim pashtun-poh.shahim{at}nih.gov
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