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October 2020; 10 (5) Research

Cryptogenic stroke

Contemporary trends, treatments, and outcomes in the United States

Shyam Prabhakaran, Steven R. Messé, Dawn Kleindorfer, Eric E. Smith, Gregg C. Fonarow, Haolin Xu, Xin Zhao, Barbara Lytle, Joaquin Cigarroa, Lee H. Schwamm
First published September 26, 2019, DOI: https://doi.org/10.1212/CPJ.0000000000000736
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Article Information

vol. 10 no. 5 396-405
DOI: 
https://doi.org/10.1212/CPJ.0000000000000736
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
2163-0402
Online ISSN: 
2163-0933
History: 
  • Received March 19, 2019
  • Accepted August 21, 2019
  • First Published September 26, 2019.

Article Versions

Copyright & Usage: 
© 2019 American Academy of Neurology

Author Disclosures

    1. Shyam Prabhakaran, MD, MS,
    2. Steven R. Messé, MD,
    3. Dawn Kleindorfer, MD,
    4. Eric E. Smith, MD, MPH,
    5. Gregg C. Fonarow, MD,
    6. Haolin Xu, MS,
    7. Xin Zhao, PhD,
    8. Barbara Lytle, PhD,
    9. Joaquin Cigarroa, MD and
    10. Lee H. Schwamm, MD
  1. Shyam Prabhakaran, MD, MS,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Current Atherosclerosis Reports; Section editor; 2014- current

    Patents:

    1. NONE

    Publishing Royalties:

    1. Cryptogenic stroke, Uptodate, 2006-current

    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. NINDS: NS084288-01A1 (3/2014-present; co-PI); U24 NS107233 8/2018-present, PI) AHRQ: R18 HS025359 (7/2018-present, PI)

    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. Steven R. Messé, MD,
    3. Scientific Advisory Boards:

    1. (1) Yale University Cardiovascular Research Group, Clinical Event Committees for the REFLECT Trial and a left atrial appendage occluder registry.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. Dr. Messe has received funding from the American Academy of Neurology for travel to the Guideline Development Subcommittee meetings.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. Dr. Messe has received publishing royalties from Up To Date, Inc for articles on antiplatelets for secondary stroke prevention, coronary artery bypass graft surgery in patients with cerebrovascular disease, and patent foramen ovale (PFO) and stroke, over a period from 2006 - present.

    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) WL Gore, 2) Bayer, 3) Novartis, 4) Mallinkrodt, 5) Biogen

    Research Support, Government Entities:

    1. 1) NIH/NIDDK, U01-DK060990, endpoint adjudication committee, 2007 - present. 2) NIH/NHLBI UM1 HL088957-06, subinvestigator 2013 - 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

  3. Dawn Kleindorfer, MD,
    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. R01 NS30678 Kissela and Kleindorfer (PI) 4/1/2015 – 3/30/2020 3.60 cal mos NIH $7,578,621 Hemorrhagic and Ischemic Stroke Among Blacks and Whites (EPI) Role: Co-PI U01 NS041588 Howard (PI) – Kissela (Site PI) 09/24/2011 – 11/30/2017 3.00 cal mos Subaward w/Univ of Alabama Birmingham $116,286 “Etiology of Geographic and Racial Differences in Stroke (REGARDS)” U01NS086872 (Broderick) 09/30/2013 – 07/31/2018 2.40 cal mos NIH/NINDS $1,623,735 “NSTN National Clinical Coordinating Center”

    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. Eric E. Smith, MD, MPH,
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Assistant Editor for Stroke, 2011- present; Editorial Board for Neurology, 2016- present.

    Patents:

    1. NONE

    Publishing Royalties:

    1. UpToDate, royalties paid to me.

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. 1. Portola Pharmaceuticals, 2017-2018 2. Alnylam Phamraceuticals, 2018.

    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. Canadian Institutes of Health Research.

    Research Support, Academic Entities:

    1. Research services contracts with McMaster University and the Ottawa Heart Institute.

    Research Support, Foundations and Societies:

    1. 1. Brain Canada.

    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. Gregg C. Fonarow, MD,
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. JAMA Cardiology, Associate Editor, 2016 to present

    Patents:

    1. (1) Employee of the University of California, which holds a patent on retriever devices for stroke.

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. Serves as a member of the Get With the Guidelines (GWTG) steering committee

    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. Patient-Centered Outcomes Research Institute

    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. Haolin Xu, MS,
    7. 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

  7. Xin Zhao, 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. 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. Barbara Lytle, PhD,
    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. 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

  9. Joaquin Cigarroa, MD and
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. Associate Editor of CCI

    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. Lee H. Schwamm, MD
    11. Scientific Advisory Boards:

    1. Serve on the scientific advisory boards for (1) LifeImage (2) Medtronic clinical trial design for AF related stroke NCT02700945 (3) Penumbra MIND study DSMB NCT03342664, (4) Genentech TIMELESS study NCT03785678 Steering Committee, and expert advisory panel on late window thrombolysis, (5) Diffusion Pharma DSMB PHAST-TSC NCT03763929

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Medtronic Inc, cash, for coordination and moderating medical education satellite events for medtronic at the international stroke conference; Boehringer Ingleheim, cash, for speaking at ESOC 2018 on wakeup stroke

    Editorial Boards:

    1. Neurocritical Care, Editorial board (2007-2017) Stroke, editorial Board (2010-) Stroke and Vascular Neurology, Associate Editor (2017-) Frontiers in TeleNeurology, Editorial board (2010-2018) Circulation Cardiovascular Quality and Outcomes (2010-2017)

    Patents:

    1. Schwamm LH, Sorensen AG, inventors; The General Hospital Corporation assignee. Imaging system for obtaining quantitative perfusion indices. US Patent 6,542,769. 2003 Apr 1.

    Publishing Royalties:

    1. Acute Ischemic Stroke: Imaging and Intervention, 2nd Edition. Heidelberg, Germany: Springer-Verlag GmbH; 2011

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Serve on the scientific advisory boards for (1) LifeImage (2) Medtronic clinical trial design for AF related stroke (3) Mass Dept of Public Health on stroke systems of care, (4) Penumbra DSMB MIND trial, (5) Diffusion pharma DSMB

    Speakers' Bureaus:

    1. NONE

    Other activities:

    1. serving as chair of the AHA/ASA GWTG stroke systems of care advisory work group (volunteer) and chair of the ASA Advisory Committee

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Genentech; principal investigator of an investigator- initiated study of extended-window intravenous thrombolysis funded by the National Institutes of Neurological Disorders and Stroke (clinicaltrials.gov/show/NCT01282242) for which Genentech provides alteplase free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites

    Research Support, Government Entities:

    1. (1) NINDS, P50NS051343, PI of sub-R01, 2010-2016 principal investigator of an investigator- initiated study of extended-window intravenous thrombolysis funded by the National Institutes of Neurological Disorders and Stroke (clinicaltrials.gov/show/NCT01282242) for which Genentech provides alteplase free of charge to Massachusetts General Hospital as well as supplemental per-patient payments to participating sites (2) NIH-NINDS 5U01NS077179-02 (Cudkowicz, PI) 09/30/2011- 08/31/2018 Clinical Coordinating Center for the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) The long-term objective of the Network of Excellence in Neuroscience Clinical Trials (NEXT) initiative is to rapidly and efficiently translate advances n neuroscience into treatments for people with neurological disorders. Role: Investigator NINDS U10 NS086729 (Schwamm)10/01/2013 – 09/30/2018 1U24NS107243-01 (Schwamm, PD/PI) 8/01/2018 – 07/31/2023 New England Regional Coordinating Center for the NINDS Stroke Trials Network This is an integrated team of hospitals and EMS agencies in Boston and Western Massachusetts that will develop new translational science and successfully execute the NINDS Stroke Trials Network Phase 1,2 and 3 studies. Role: PD/PI PCORI IHS-1310-07420 (PI Reeves)10/01/2014 – 09/30/2017 Improving care transitions for acute stroke patients through a patient centered home based case management The major goals of this grant are to assemble relevant stroke stakeholders (stroke survivors and caregivers, stroke nurses, therapists, social workers, discharge planners, physiatrists, neurologists) to identify needs and barriers to improving transitions of care after stroke hospitalization, and to test two different interventions against usual care among 480 acute stroke patients in a pragmatic randomized, open clinical trial. Role: Consultant R-1609-35995, (Temel, PI) 12/01/17-11/30/22 Patient Centered Outcomes Research Institute Comparative Effectiveness of Early Integrated Telehealth Versus In-Person Palliative Care for Patients with Advanced Lung Cancer. The long-term objective of this multi-center randomized trial is to compare two delivery models of early integrated palliative and oncology care. Role: Lead TeleHealth Co-Investigator CDRN-1306-04608 (Mandl, PI – Harvard) 11/01/2015-09/30/18 Patient Centered Outcomes Research Institute Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS) The major goal of this project is to create a national-scale clinical data research network to support patient centered outcomes research Role: Co-Investigator 1R01NS111952-01 (Mehrotra, PI) 04/01/19 - 01/31/23 NIH-NINDS The Impact of Telestroke on Patterns of Care and Long-Term Outcomes The objective of this research project is to analyze the change in patterns of prehospital and hospital based care for patients with acute ischemic stroke after implementation of telestroke programs in the community Role: Co-Investigator 1R01AG062770-01 (Xian, PI) 04/01/19 - 03/31/24 NIH-NIA Antiplatelet in Stroke: Safety and Effectiveness in Seniors (ASSESS) The goal of this project is to conduct comparative effectiveness research of real world practices in antiplatelet prescribing patterns in elderly patients with non-cardioembolic ischemic stroke who are at increased risk for recurrent strokes, as well as bleeding complications. Role: Co-Investigator Stock/Stock Options, Medical Equipment & Materials: LifeImage, 2014

    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. University of Chicago (SP), Pritzker School of Medicine; University of Pennsylvania (SRM); University of Cincinnati (DK); Hotchkiss Brain Institute (EES), University of Calgary, Calgary, Alberta, Canada; Ahmanson Cardiomyopathy Center (GCF), UCLA, Los Angeles, CA; Duke Clinical Research Institute (HX, XZ, BL), Durham, NC; Knight Cardiovascular Institute (JC), Oregon Health and Sciences University; and Department of Neurology (LHS), Massachusetts General Hospital.
  1. Correspondence
    Dr. Prabhakaran shyam1{at}uchicago.edu

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