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Abstract

Objective:

We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.

Methods:

Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.

Results:

Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%–26%) in those with 0 to 3 points to 73% (95% CI: 66%–79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%–28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%–4%) in the highest.

Conclusion:

Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

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Information & Authors

Information

Published In

Neurology®
Volume 81Number 7August 13, 2013
Pages: 619-625
PubMed: 23864310

Publication History

Received: December 12, 2012
Accepted: April 29, 2013
Published online: July 17, 2013
Published in print: August 13, 2013

Permissions

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Disclosure

D. Kent has consulted for W.L. Gore Associates. R. Ruthazer, J. Mas, J. Serena, S. Homma, E. Di Angelantonio, M. Di Tullio, J. Lutz, M. Elkind, J. Griffith, C. Jaigobin, H. Mattle, P. Michel, M. Mono, K. Nedeltchev, and F. Papetti report no disclosures. D. Thaler is a consultant to AGA Medical Corporation and has consulted for W.L. Gore Associates. Go to Neurology.org for full disclosures.

Study Funding

Supported by NIH (UL1 RR025752, R01 NS062153).

Authors

Affiliations & Disclosures

David M. Kent, MD, CM, MSc
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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.
WL Gore Associates
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 Institute of Health (NIH), R21 NS079826, Principal Investigator, 2012 to 2014 (2) National Institute of Health (NIH), R01 NS062153, Principal Investigator, 2009 to 2014 (3)Patient Centered Outcomes Research Institute (PCORI) 1IP2PI000722, Principal Investigator, 2012 to 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
Robin Ruthazer, MPH
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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/NINDS R01 NS062153 The Risk of Paradoxical Embolism (RoPE) Study [PI=Kent] My role: Statistician/Programmer 03/06/09-02/28/14
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
Christian Weimar, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
(1) Bayer Schering (2) Bristol-Myers Squib (3) Sanofi Aventis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Sanofi Aventis, travel and speaker honoraria (2) Arbeitsgemeinschaft Neurologische Intensivmedizin, funding for travel (3) Deutsche Gesellschaft für Neurologie, funding for travel (4) Biogen Idec, funding for travel (5) Teva, funding for travel (6) Boehringer Ingelheim, funding for travel
Editorial Boards:
1.
(1) Cerebrovascular Diseases, editorial board member, 2008-ongoing (2) Stroke News, editorial office 2006- ongoing
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Consultant, University hospital Essen
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
(1) Sanofi Aventis (2) Boehringer Ingelheim
Other Activities:
1.
participation in clinical trials by (1) Brainsgate, (2) D-Pharm (3) PhotoThera (4) Portola (5) Pierre Fabre
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Johnson & Johnson
Research Support, Government Entities:
1.
(1) German Research Council, 2010-ongoing, WE 2858/3-1 (2) TeBiKom.Ruhr, 2012-ongoing, 005-GW02-067E
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
Jean-Louis Mas, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
(1) Astra-Zeneca (2) Boehringer-Ingelheim (3) BMS (4) Daiichi-Sankyo (5) Sanofi Aventis
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1) Boehringer-Ingelheim, honoraria, 2) Sanofi Aventis, honoraria, 3) Servier, honoraria
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) French Ministry of Health, 1 grant, coordination of a randomized clinical trial, ongoing, (2) INSERM Institut National Scientifique Et de la Recherche Medicale, financing a Stroke Research Unit, ongoing
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
Joaquín Serena, MD, PhD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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
Shunichi Homma, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
St Judes - Medical Consultant Pfizer - Pharmaceutical Consultant/Advisory Bd Tekeda - Pharmaceutical Consultant/Advisory Bd BMS - Pharmaceutical Consultant/Advisory Bd
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 WARCEF Study, NIH-NINDS, U01 NS043975
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
Emanuele Di Angelantonio, MD, MSc
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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
Marco R. Di Tullio, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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/NINDS R01 NS36286-11 PI Years:2005-2012
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
Jennifer S. Lutz, MS
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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
Mitchell S.V. Elkind, MD, MS
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
(1) Jarvik Heart, Clinical Events Committee member, adjudicating events in clinical trial of artificial heart (2008-present); (2) Biogen IDEC, scientific advisory board, stroke trial design
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
(1) Neurology, Resident and Fellow Section editor, published by American Academy of Neurology (2007-present)
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
Columbia University
Consultancies:
1.
(1) BMS-Pfizer Partnership, consultant regarding antithrombotics for stroke
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) diaDexus, Inc: funding for biomarker research; (2) BMS-Sanofi Pharmaceutical Partnership: funding for biomarker research
Research Support, Government Entities:
1.
(1) NIH/NINDS P50 NS049060, Project PI, 2004-2013;(2) NIH/NINDS R37 NS029993, Co-PI, 2008-2013; (3) NIH/NINDS 1R25 NS070697, PI, 2010-2015
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) American Heart Association Founders Affiliate Board of Directors)(2008-present); (2) American Heart Association NY City Board of Directors (2011-present)
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.
(1) GSK, Avandia and stroke litigation, 2009-2011;(2) Organon/Merck, NuvaRing and stroke litigation, 2009-present;(3) Novartis, aliskiren and stroke litigation, 2013-present
John Griffith, PhD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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.
Northeastern University, Bouve College Associate Dean of Research
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) Boston Public Health Commission. Biostatistician, 2011- 2013 (2) NIH, P50HL105185, Biostatistician, 2010-2015 (3) NIH, R01NS062153, Biostatistician, 2009-2014 (4) NIH, R01MH096707, Biostatistician, 2012-2015
Research Support, Academic Entities:
1.
Tufts Medical Center, Biostatistician -2012
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
Cheryl Jaigobin, MD, MSc
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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.
Honoria at speaking engagements sponsored by Boeringer- Ingelheim and Sanofi Aventis June 2008, June 2009
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
Heinrich P. Mattle, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
Servier, St. Jude Medical
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Servier, Sanofi, Bayer, Biogen, Böhringer-Ingelheim, Merck, MSD, Teva, St. Jude Medical, Novartis, Pfizer
Editorial Boards:
1.
Stroke, International Journal of Stroke, Swiss Medical Weekly, Practical Neurology
Patents:
1.
NONE
Publishing Royalties:
1.
Neurologie, Kurzlehrbuch Neurologie, Neurology, Fundamentals of Neurology, DGN Leitlinien, all Thieme Publisher, Stuttgart
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Servier, Sanofi, Bayer, Biogen, Genzyme, Merck, MSD, Pfizer, Teva, AGA Medical, Novartis, Pfizer
Speakers' Bureaus:
1.
Servier, Sanofi, Bayer, Biogen, Merck, Teva, St. Jude Medical, Novartis, Böhringer-Ingelheim
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Servier, Sanofi, Bayer, Biogen, Merck, Teva, St. Jude Medical, Novartis, Pfizer
Research Support, Government Entities:
1.
Swiss Science Foundation
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Swiss Heart 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
Patrik Michel, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
Bayer, Pfizer
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Bayer, Boehringer-Ingelheim
Editorial Boards:
1.
International Journal of Stroke.
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Pierre-Fabre
Speakers' Bureaus:
1.
Boehringer-Ingelheim, Bayer
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Lundbeck
Research Support, Government Entities:
1.
Swiss National Science Foundation
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Swiss Cardiology 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
Marie-Louise Mono, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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
Krassen Nedeltchev, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
Served on a scientific advisory board for Bayer (Schweiz) AG, Pfizer, Boehringer-Ingelheim, Teva Pharmaceuticals, Genzyme
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.
Consultancies for “Innovative Technologies-Invatec” in 2007.
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.
Sponsor/Funding source: The Swiss National Research Foundation, Grant Nr 32003B_120522; 3 years
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Swiss Heart 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
Federica Papetti, MD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
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
David E. Thaler, MD, PhD
From the Institute for Clinical Research and Health Policy Studies (D.M.K., R.R., J.S.L., J.G.) and Department of Neurology (D.M.K., D.E.T.), Tufts Medical Center/Tufts University School of Medicine, Boston, MA; Department of Neurology (C.W.), University of Duisburg-Essen, Germany; Department of Neurology (J.-L.M.), Hôpital Sainte-Anne, Paris-Descartes University, France; Department of Neurology (J.S.), Hospital Universitari Doctor Josep Trueta Institut d'Investigació Biomèdica de Girona, Spain; Division of Cardiology (S.H., M.R.D.) and Departments of Neurology (M.S.V.E.) and Epidemiology (M.S.V.E.), Columbia University, New York, NY; Department of Public Health and Primary Care (E.D.), Cambridge University, UK; Department of Neurology (C.J.), University of Toronto, Canada; Department of Neurology (H.P.M., M.-L.M.), Inselspital, University of Bern; Centre Hospitalier Universitaire de Lausanne (P.M.); Department of Neurology (K.N.), Triemli Municipal Hospital, Switzerland; and Department of Cardiology (F.P.), Sapienza University of Rome, Italy.
Disclosure
Scientific Advisory Boards:
1.
Lantheus Medical Imaging, DSMB
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.
St Jude Medical (AGA Medical); WL Gore Associates
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, Risk of Paradoxical Embolism (RoPE) Study, co-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

Notes

Correspondence to Dr. Kent: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

D.K.: designed and conceptualized the study, analyzed and interpreted data in the study, drafted the manuscript, revised, reviewed, and approved the manuscript. D.T.: designed and conceptualized the study, analyzed and interpreted data in the study, contributed study data, and revised, reviewed, and approved the manuscript. R.R.: analyzed and interpreted data in the study, supervised database management, revised, reviewed, and approved the manuscript. M.E., P.M., C.W.: contributed study data, analyzed and interpreted data in the study, revised, reviewed, and approved the manuscript. J.M., J.S., S.H., E.D., M.D., C.J., H.M., M.M., K.N., F.P.: contributed study data, revised, reviewed, and approved the manuscript. J.G., J.L.: revised, reviewed, and approved the manuscript.

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    Abstract
  8. A novel NODAL variant in a young embolic stroke patient with visceral heterotaxy, BMC Neurology, 24, 1, (2024).https://doi.org/10.1186/s12883-024-03619-x
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