Predictors of Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection

Predictors of Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Predictors of Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection View ORCID Profile Daniel M. Mandel , View ORCID Profile Liqi Shu , Christopher Chang , View ORCID Profile Naomi Jack , View ORCID Profile Christopher R. Leon Guerrero , View ORCID Profile Nils Henninger , View ORCID Profile Jayachandra Muppa , Muhammad Affan , Omair Ul Haq Lodhi , View ORCID Profile Mirjam R. Heldner , View ORCID Profile Kateryna Antonenko , View ORCID Profile David Seiffge , View ORCID Profile Marcel Arnold , View ORCID Profile Setareh Salehi Omran , View ORCID Profile Ross Crandall , Evan Lester , View ORCID Profile Diego Lopez Mena , View ORCID Profile Antonio Arauz , Ahmad Nehme , View ORCID Profile Marion Boulanger , View ORCID Profile Emmanuel Touze , View ORCID Profile Joao Andre Sousa , View ORCID Profile Joao Sargento-Freitas , View ORCID Profile Vasco Barata , View ORCID Profile Paulo Castro-Chaves , View ORCID Profile Maria Teresa Brito , View ORCID Profile Muhib Khan , Dania Mallick , View ORCID Profile Aaron Rothstein , View ORCID Profile Ossama Khazaal , View ORCID Profile Josefin E. Kaufman , View ORCID Profile Stefan T. Engelter , Christopher Traenka , View ORCID Profile Diana Aguiar de Sousa , View ORCID Profile Mafalda Soares , View ORCID Profile Sara Rosa , View ORCID Profile Lily W. Zhou , View ORCID Profile Preet Gandhi , View ORCID Profile Thalia S. Field , Steven Mancini , View ORCID Profile Issa Metanis , View ORCID Profile Ronen R. Leker , Kelly Pan , View ORCID Profile Vishnu Dantu , View ORCID Profile Karl Baumgartner , View ORCID Profile Tina Burton , View ORCID Profile Regina von Rennenberg , View ORCID Profile Christian H. Nolte , View ORCID Profile Richard Choi , View ORCID Profile Jason MacDonald , View ORCID Profile Reza Bavarsad Shahripour , View ORCID Profile Xiaofan Guo , View ORCID Profile Malik Ghannam , View ORCID Profile Mohammad Almajali , View ORCID Profile Edgar A. Samaniego , View ORCID Profile Sebastian Sanchez , View ORCID Profile Bastien Rioux , Faycal Zine-Eddine , View ORCID Profile Alexandre Poppe , View ORCID Profile Ana Catarina Fonseca , View ORCID Profile Maria Fortuna Baptista , View ORCID Profile Diana Cruz , View ORCID Profile Michele Romoli , Giovanna De Marco , View ORCID Profile Marco Longoni , View ORCID Profile Zafer Keser , View ORCID Profile Kim Griffin , View ORCID Profile Lindsey Kuohn , View ORCID Profile Jennifer Frontera , Jordan Amar , View ORCID Profile James Giles , View ORCID Profile Marialuisa Zedde , View ORCID Profile Rosario Pascarella , View ORCID Profile Ilaria Grisendi , View ORCID Profile Hipolito Nzwalo , View ORCID Profile David S. Liebeskind , View ORCID Profile Amir Molaie , Annie Cavalier , View ORCID Profile Wayneho Kam , View ORCID Profile Brian Mac Grory , View ORCID Profile Sami Al Kasab , View ORCID Profile Mohammad Anadani , View ORCID Profile Kimberly Kicielinski , View ORCID Profile Ali Eltatawy , View ORCID Profile Lina Chervak , Roberto Chulluncuy Rivas , View ORCID Profile Yasmin Aziz , View ORCID Profile Ekaterina Bakradze , Thanh Lam Tran , View ORCID Profile Marc Rodrigo Gisbert , View ORCID Profile Manuel Requena , View ORCID Profile Faddi Saleh Velez , View ORCID Profile Jorge Ortiz Gracia , View ORCID Profile Varsha Muddasani , View ORCID Profile Adam de Havenon , View ORCID Profile Venugopalan Y Vishnu , Sridhara Yaddanapudi , View ORCID Profile Latasha Adams , Abigail Browngoehl , View ORCID Profile Tamra Ranasinghe , Randy Dunston , Zachary Lynch , View ORCID Profile Mary Penckofer , View ORCID Profile James E. 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Morsi , View ORCID Profile Tareq Kass-Hout , View ORCID Profile Feina Shi , View ORCID Profile Jinhua Zhang , View ORCID Profile Dilraj Sokhi , Jamil Said , Newnex Mongare , View ORCID Profile Alexis Simpkins , Roberto Gomez , Shayak Sen , View ORCID Profile Mohammad Ghani , View ORCID Profile Marwa Elnazeir , View ORCID Profile Han Xiao , Narendra Kala , View ORCID Profile Farhan Khan , View ORCID Profile Christoph Stretz , Nahid Mohammadzadeh , View ORCID Profile Eric Goldstein , View ORCID Profile Karen Furie , View ORCID Profile Shadi Yaghi doi: https://doi.org/10.1101/2024.08.09.24311773 Daniel M. Mandel 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Daniel M. Mandel For correspondence: danielmmandel{at}gmail.com Liqi Shu 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Liqi Shu Christopher Chang 1 Department of Neurology, Brown Medical School , Providence, RI, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site Naomi Jack 1 Department of Neurology, Brown Medical School , Providence, RI, USA Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Naomi Jack Christopher R. Leon Guerrero 2 Department of Neurology, Atrium Health , Charlotte, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christopher R. Leon Guerrero Nils Henninger 3 Department of Neurology, University of Massachusetts, Chan Medical School , Worcester, MA, USA MD PhD Dr. Med Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Nils Henninger Jayachandra Muppa 3 Department of Neurology, University of Massachusetts, Chan Medical School , Worcester, MA, USA MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jayachandra Muppa Muhammad Affan 4 Department of Neurology, University of Minnesota , Minneapolis, MN, USA MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Omair Ul Haq Lodhi 4 Department of Neurology, University of Minnesota , Minneapolis, MN, USA MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mirjam R. Heldner 5 Department of Neurology, Inselspital, University of Bern , Bern, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mirjam R. Heldner Kateryna Antonenko 5 Department of Neurology, Inselspital, University of Bern , Bern, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kateryna Antonenko David Seiffge 5 Department of Neurology, Inselspital, University of Bern , Bern, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for David Seiffge Marcel Arnold 5 Department of Neurology, Inselspital, University of Bern , Bern, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marcel Arnold Setareh Salehi Omran 6 Department of Neurology, University of Colorado School of Medicine , Aurora, CO MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Setareh Salehi Omran Ross Crandall 6 Department of Neurology, University of Colorado School of Medicine , Aurora, CO MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ross Crandall Evan Lester 6 Department of Neurology, University of Colorado School of Medicine , Aurora, CO MD PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Diego Lopez Mena 7 Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez , Mexico City, Mexico MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Diego Lopez Mena Antonio Arauz 7 Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez , Mexico City, Mexico MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Antonio Arauz Ahmad Nehme 8 Service de Neurologie, Université Caen Normandie , CHU Caen Normandie, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marion Boulanger 8 Service de Neurologie, Université Caen Normandie , CHU Caen Normandie, France PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marion Boulanger Emmanuel Touze 8 Service de Neurologie, Université Caen Normandie , CHU Caen Normandie, France MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Emmanuel Touze Joao Andre Sousa 9 Department of Neurology, Coimbra University , Coimbra, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joao Andre Sousa Joao Sargento-Freitas 9 Department of Neurology, Coimbra University , Coimbra, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joao Sargento-Freitas Vasco Barata 9 Department of Neurology, Coimbra University , Coimbra, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vasco Barata Paulo Castro-Chaves 10 Department of Internal Medicine, São João University Hospital , Porto, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Paulo Castro-Chaves Maria Teresa Brito 10 Department of Internal Medicine, São João University Hospital , Porto, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Maria Teresa Brito Muhib Khan 11 Department of Neurology, Corewell Health , Grand Rapids, MI, USA 12 Department of Neurology, Mayo Clinic , Rochester, MN, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Muhib Khan Dania Mallick 11 Department of Neurology, Corewell Health , Grand Rapids, MI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aaron Rothstein 13 Department of Neurology, University of Pennsylvania , Philadelphia, PA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Aaron Rothstein Ossama Khazaal 13 Department of Neurology, University of Pennsylvania , Philadelphia, PA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ossama Khazaal Josefin E. Kaufman 14 Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, Department of Clinical Research, University of Basel, and University Hospital Basel , Basel, Switzerland MMed Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Josefin E. Kaufman Stefan T. Engelter 14 Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, Department of Clinical Research, University of Basel, and University Hospital Basel , Basel, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stefan T. Engelter Christopher Traenka 14 Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, Department of Clinical Research, University of Basel, and University Hospital Basel , Basel, Switzerland MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Diana Aguiar de Sousa 15 Stroke Center, Centro Hospitalar Universitário Lisboa Central, and Institute of Anatomy, Faculdade de Medicina da Universidade de Lisboa , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Diana Aguiar de Sousa Mafalda Soares 16 Department of Neurology, Centro Hospitalar Universitário Lisboa Central , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mafalda Soares Sara Rosa 17 Department of Neuroradiology, Centro Hospitalar Universitário Lisboa Central , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sara Rosa Lily W. Zhou 18 Vancouver Stroke Program, Division of Neurology, University of British Columbia , Vancouver, British Columbia, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lily W. Zhou Preet Gandhi 18 Vancouver Stroke Program, Division of Neurology, University of British Columbia , Vancouver, British Columbia, Canada MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Preet Gandhi Thalia S. Field 18 Vancouver Stroke Program, Division of Neurology, University of British Columbia , Vancouver, British Columbia, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thalia S. Field Steven Mancini 18 Vancouver Stroke Program, Division of Neurology, University of British Columbia , Vancouver, British Columbia, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Issa Metanis 19 Department of Neurology, Hadassah-Hebrew University Medical Center , Jerusalem, Israel MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Issa Metanis Ronen R. Leker 19 Department of Neurology, Hadassah-Hebrew University Medical Center , Jerusalem, Israel MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ronen R. Leker Kelly Pan 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vishnu Dantu 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vishnu Dantu Karl Baumgartner 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Karl Baumgartner Tina Burton 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tina Burton Regina von Rennenberg 20 Department of Neurology with Experimental Neurology, Charite Universitätsmedizin-Berlin and Center for Stroke Research (CSB) , Berlin, Germany MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Regina von Rennenberg Christian H. Nolte 20 Department of Neurology with Experimental Neurology, Charite Universitätsmedizin-Berlin and Center for Stroke Research (CSB) , Berlin, Germany MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christian H. Nolte Richard Choi 21 Department of Neurosciences , ChristianaCare, Newark, DE, USA DO Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Richard Choi Jason MacDonald 21 Department of Neurosciences , ChristianaCare, Newark, DE, USA NP Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jason MacDonald Reza Bavarsad Shahripour 22 Department of Neurology, University of California at San Diego , San Diego, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Reza Bavarsad Shahripour Xiaofan Guo 23 Department of Neurology, Loma Linda University , Loma Linda, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Xiaofan Guo Malik Ghannam 24 Department of Neurology, University of Iowa , Iowa City, IA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Malik Ghannam Mohammad Almajali 24 Department of Neurology, University of Iowa , Iowa City, IA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohammad Almajali Edgar A. Samaniego 24 Department of Neurology, University of Iowa , Iowa City, IA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Edgar A. Samaniego Sebastian Sanchez 24 Department of Neurology, University of Iowa , Iowa City, IA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sebastian Sanchez Bastien Rioux 25 Department of Neurosciences, Université de Montréal , Montreal, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Bastien Rioux Faycal Zine-Eddine 25 Department of Neurosciences, Université de Montréal , Montreal, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexandre Poppe 25 Department of Neurosciences, Université de Montréal , Montreal, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alexandre Poppe Ana Catarina Fonseca 26 Department of Neurology, Hospital de Santa Maria, Centro de Estudos Egas Moniz, Faculdade de Medicina da Universidade de Lisboa , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ana Catarina Fonseca Maria Fortuna Baptista 26 Department of Neurology, Hospital de Santa Maria, Centro de Estudos Egas Moniz, Faculdade de Medicina da Universidade de Lisboa , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Maria Fortuna Baptista Diana Cruz 26 Department of Neurology, Hospital de Santa Maria, Centro de Estudos Egas Moniz, Faculdade de Medicina da Universidade de Lisboa , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Diana Cruz Michele Romoli 27 Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital , Cesena, Italy MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michele Romoli Giovanna De Marco 27 Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital , Cesena, Italy MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marco Longoni 27 Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital , Cesena, Italy MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marco Longoni Zafer Keser 12 Department of Neurology, Mayo Clinic , Rochester, MN, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Zafer Keser Kim Griffin 12 Department of Neurology, Mayo Clinic , Rochester, MN, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kim Griffin Lindsey Kuohn 28 Department of Neurology, NYU Langone Health , New York, NY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lindsey Kuohn Jennifer Frontera 28 Department of Neurology, NYU Langone Health , New York, NY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jennifer Frontera Jordan Amar 29 Department of Neurology, Washington University , Saint Louis, MO, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site James Giles 29 Department of Neurology, Washington University , Saint Louis, MO, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for James Giles Marialuisa Zedde 30 Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marialuisa Zedde Rosario Pascarella 31 Neuroradiology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rosario Pascarella Ilaria Grisendi 30 Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ilaria Grisendi Hipolito Nzwalo 32 Department of Internal Medicine, Centro Hospital Universitario do Algarve , Faro, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Hipolito Nzwalo David S. Liebeskind 33 Department of Neurology, University of California at Los Angeles , Los Angeles, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for David S. Liebeskind Amir Molaie 33 Department of Neurology, University of California at Los Angeles , Los Angeles, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Amir Molaie Annie Cavalier 34 Department of Neurology, Duke University , Durham, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Wayneho Kam 35 Department of Neurology, University of North Carolina Health Rex , Raleigh, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Wayneho Kam Brian Mac Grory 34 Department of Neurology, Duke University , Durham, NC, USA MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Brian Mac Grory Sami Al Kasab 36 Department of Neurology, Medical University of South Carolina , Charleston, SC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sami Al Kasab Mohammad Anadani 36 Department of Neurology, Medical University of South Carolina , Charleston, SC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohammad Anadani Kimberly Kicielinski 37 Department of Neurosurgery, Medical University of South Carolina , Charleston, SC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kimberly Kicielinski Ali Eltatawy 38 Department of Neurology, University of Cincinnati Medical Center , Cincinnati, OH, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ali Eltatawy Lina Chervak 38 Department of Neurology, University of Cincinnati Medical Center , Cincinnati, OH, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lina Chervak Roberto Chulluncuy Rivas 38 Department of Neurology, University of Cincinnati Medical Center , Cincinnati, OH, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yasmin Aziz 38 Department of Neurology, University of Cincinnati Medical Center , Cincinnati, OH, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yasmin Aziz Ekaterina Bakradze 39 Department of Neurology, University of Alabama at Birmingham , Birmingham, AL, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ekaterina Bakradze Thanh Lam Tran 39 Department of Neurology, University of Alabama at Birmingham , Birmingham, AL, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marc Rodrigo Gisbert 40 Department of Neurology, University Hospital Vall d’Hebron , Barcelona, Spain MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marc Rodrigo Gisbert Manuel Requena 40 Department of Neurology, University Hospital Vall d’Hebron , Barcelona, Spain MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Manuel Requena Faddi Saleh Velez 41 Department of Neurology, University of Oklahoma , Oklahoma, OK, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Faddi Saleh Velez Jorge Ortiz Gracia 41 Department of Neurology, University of Oklahoma , Oklahoma, OK, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jorge Ortiz Gracia Varsha Muddasani 42 Department of Neurology, Einstein-Jefferson Healthcare Network , Philadelphia, PA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Varsha Muddasani Adam de Havenon 43 Department of Neurology, Yale New Haven Hospital , New Haven, CT, USA 44 Department of Neurology, University of Utah , Salt Lake City, UT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Adam de Havenon Venugopalan Y Vishnu 45 Department of Neurology, All India Medical School , New Delhi, India MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Venugopalan Y Vishnu Sridhara Yaddanapudi 46 Department of Neurology, Thomas Jefferson University , Philadelphia, PA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Latasha Adams 46 Department of Neurology, Thomas Jefferson University , Philadelphia, PA MBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Latasha Adams Abigail Browngoehl 46 Department of Neurology, Thomas Jefferson University , Philadelphia, PA MPH Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tamra Ranasinghe 47 Department of Neurology, Wake Forest Medical Center , Wake Forest, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tamra Ranasinghe Randy Dunston 47 Department of Neurology, Wake Forest Medical Center , Wake Forest, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Zachary Lynch 47 Department of Neurology, Wake Forest Medical Center , Wake Forest, NC, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mary Penckofer 48 Department of Neurology, Cooper University , Camden, NJ, USA BA Find this author on Google Scholar Find 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Siegler 48 Department of Neurology, Cooper University , Camden, NJ, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for James E. Siegler Silvia Mayer 49 Department of Neurology, Columbia University Medical Center , New York, NY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Silvia Mayer Joshua Willey 49 Department of Neurology, Columbia University Medical Center , New York, NY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joshua Willey Adeel Zubair 43 Department of Neurology, Yale New Haven Hospital , New Haven, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Adeel Zubair Yee Kuang Cheng 43 Department of Neurology, Yale New Haven Hospital , New Haven, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Yee Kuang Cheng Richa Sharma 43 Department of Neurology, Yale New Haven Hospital , New Haven, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Richa Sharma João Pedro Marto 50 Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for João Pedro Marto Vítor Mendes Ferreira 50 Department of Neurology, Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental , Lisbon, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vítor Mendes Ferreira Piers Klein 51 Department of Neurology, Boston Medical Center , Boston, MA, USA MA Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Piers Klein Thanh N. Nguyen 51 Department of Neurology, Boston Medical Center , Boston, MA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thanh N. Nguyen Syed Daniyal Asad 52 Department of Neurology, Hartford Hospital , Hartford, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Syed Daniyal Asad Zoha Sarwat 52 Department of Neurology, Hartford Hospital , Hartford, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Anvesh Balabhadra 52 Department of Neurology, Hartford Hospital , Hartford, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Anvesh Balabhadra Shivam Patel 52 Department of Neurology, Hartford Hospital , Hartford, CT, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Thais Secchi 53 Department of Neurology, Hospital Moinhos de Vento , Porto Alegre, Brazil MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sheila Martins 54 Department of Neurology, Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sheila Martins Gabriel Mantovani 54 Department of Neurology, Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gabriel Mantovani Young Dae Kim 55 Department of Neurology, Yonsei University , Seoul, South Korea MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Young Dae Kim Balaji Krishnaiah 56 Department of Neurology, University of Tennessee at Memphis , Memphis, TN, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Balaji Krishnaiah Cheran Elangovan 56 Department of Neurology, University of Tennessee at Memphis , Memphis, TN, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Cheran Elangovan Sivani Lingam 57 Department of Neurology, Kansas University Medical Center , Kansas City, KS, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abid Quereshi 57 Department of Neurology, Kansas University Medical Center , Kansas City, KS, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Abid Quereshi Sebastian Fridman 58 Department of Neurology, Western Ontario University , London, ON, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sebastian Fridman Alonso Alvarado 58 Department of Neurology, Western Ontario University , London, ON, Canada MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alonso Alvarado Farid Khasiyev 59 Department of Neurology, Saint Louis University , Saint Louis, MO, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Farid Khasiyev Guillermo Linares 59 Department of Neurology, Saint Louis University , Saint Louis, MO, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Guillermo Linares Marina Mannino 60 Department of Neurology and Stroke Unit , AOOR Villa Sofia-V. 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Cervello, Palermo, Italy MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Valeria Terruso Sofia Vassilopoulou 61 1st Department of Neurology, National and Kapodistrian University of Athens , Athens, Greece MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sofia Vassilopoulou Vasilis Tentolouris 61 1st Department of Neurology, National and Kapodistrian University of Athens , Athens, Greece MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vasilis Tentolouris Manuel Martinez Marino 62 Department of Neurology, Centro Médico Nacional Siglo XXI IMSS. , México City, Mexico MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Manuel Martinez Marino Victor Carrasco Wall 62 Department of Neurology, Centro Médico Nacional Siglo XXI IMSS. , México City, Mexico MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Victor Carrasco Wall Fransisca Indraswari 63 Department of Neurology, The Miriam Hospital , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Fransisca Indraswari Sleiman El Jamal 63 Department of Neurology, The Miriam Hospital , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sleiman El Jamal Shilin Liu 64 Department of Neurocritical Care Unit, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui, China MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shilin Liu Muhammad Alvi 65 Department of Neurology, West Virginia University , WV, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Farman Ali 65 Department of Neurology, West Virginia University , WV, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mohammed Sarvath 65 Department of Neurology, West Virginia University , WV, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohammed Sarvath Rami Z. Morsi 66 Department of Neurology, University of Chicago , Chicago, IL, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rami Z. Morsi Tareq Kass-Hout 66 Department of Neurology, University of Chicago , Chicago, IL, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Tareq Kass-Hout Feina Shi 67 Department of Neurology, Sir Run Run Shaw Hospital of Zhejiang University Medical School , Hangzhou, China MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Feina Shi Jinhua Zhang 67 Department of Neurology, Sir Run Run Shaw Hospital of Zhejiang University Medical School , Hangzhou, China MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jinhua Zhang Dilraj Sokhi 68 Department of Neurology, Aga Khan University , Nairobi, Kenya MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Dilraj Sokhi Jamil Said 68 Department of Neurology, Aga Khan University , Nairobi, Kenya MBBS Find this author on Google Scholar Find this author on PubMed Search for this author on this site Newnex Mongare 68 Department of Neurology, Aga Khan University , Nairobi, Kenya MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alexis Simpkins 69 Department of Neurology, Cedars Sinai Medical Center , Los Angeles, CA, USA MD, PhD, MSCR Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Alexis Simpkins Roberto Gomez 69 Department of Neurology, Cedars Sinai Medical Center , Los Angeles, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shayak Sen 69 Department of Neurology, Cedars Sinai Medical Center , Los Angeles, CA, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Mohammad Ghani 70 Department of Neurology, University of Louisville , Louisville, KY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Mohammad Ghani Marwa Elnazeir 70 Department of Neurology, University of Louisville , Louisville, KY, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marwa Elnazeir Han Xiao 71 Department of Economics, University of California Santa Barbara , Santa Barbara, CA, USA MS Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Han Xiao Narendra Kala 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Farhan Khan 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Farhan Khan Christoph Stretz 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Christoph Stretz Nahid Mohammadzadeh 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eric Goldstein 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eric Goldstein Karen Furie 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Karen Furie Shadi Yaghi 1 Department of Neurology, Brown Medical School , Providence, RI, USA MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Shadi Yaghi Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Objective Patients with cervical artery dissection (CAD) are at increased ischemic stroke risk. We aimed to identify characteristics that are associated with increased risk of ischemic stroke following initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. Methods This was a secondary analysis of the Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study, a multicenter retrospective observational study. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Patient characteristics were compared between those with vs. without subsequent ischemic stroke. Significant predictors were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type in high-risk patients were explored using adjusted Cox regression. Results 4,023 patients (mean age 47.4 years; 44.5% were women) were included. By day 180, 5.3% experienced a subsequent ischemic stroke. In adjusted Cox regression, factors associated with increased subsequent ischemic stroke risk were prior ischemic stroke (aHR 7.31, 95% CI 1.61-33.13, p=0.010), presentation within seven days from symptoms, (aHR 3.04, 95% CI 1.04-8.91, p=0.043), infarct on imaging (aHR 9.85, 95% CI 3.65-26.58, p<0.001), and occlusive dissection (aHR 2.34, 95% CI 1.03-5.34, p=0.043). Only patients with occlusive dissection had reduced subsequent ischemic stroke risk with anticoagulation versus antiplatelets (HR 0.37; 95% CI 0.15-0.89, p=0.03). Interpretation This study identified several predictors of subsequent ischemic stroke among patients with CAD but only patients with occlusive dissection demonstrated a benefit from anticoagulation. These findings require validation by meta-analyses of prior studies. Introduction Cervical artery dissection (CAD) accounts for approximately 2% of all ischemic strokes but emerges as the second-leading cause of stroke in young adults under 45 years of age. 1 - 3 The main mechanisms of ischemic stroke after CAD relate to vessel wall injury, which promotes the formation of an intraluminal thrombus or steno-occlusion. 4 CAD may also cause local symptoms (e.g. neck pain and headache) without ischemic stroke. The risk of subsequent ischemic stroke is up to 3.5% in randomized clinical trials but as high as 8.7% in observational studies. 5 - 10 Moreover, the risk of clinically covert infarcts is substantial, with one study showing that new ischemic brain lesions on MR-imaging occurred in one-quarter of patients in the early phase after diagnosis of CAD. 11 Antithrombotic treatment (antiplatelets or anticoagulation) is an important aspect of stroke prevention in the management of patients with CAD. 12 Randomized clinical trials and meta-analyses of observational data have yielded conflicting results regarding the relative effectiveness and safety of anticoagulation compared to antiplatelet treatment. 5 - 7 , 13 The primary results from the recent study, “Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD)”, showed no significant difference in ischemic stroke risk between anticoagulation versus antiplatelet therapies. Conversely, treatment with anticoagulation up to day 180 significantly increased the risk of major hemorrhage. Nevertheless, exploratory subgroup analyses from the STOP-CAD study found a significant association between anticoagulation use and a lower risk of subsequent ischemic stroke in patients with occlusive dissection. 14 Identifying patients at higher risk for subsequent ischemic stroke could pinpoint subgroups that may benefit from anticoagulation. In addition, optimizing the triage of these patients to intensified monitoring could potentially influence patient outcomes. A recent subgroup analysis of the “Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD)” trial explored whether high-risk clinical features influenced the effects of antithrombotic treatment on the risk of subsequent stroke. The study’s conclusions are constrained by its relatively small sample size and by the use of composite outcomes—both imaging and clinical—instead of exclusively focusing on subsequent ischemic strokes, which limits the specificity of its findings. 15 Risk factors identified from several observational studies are comparable with those from TREAT-CAD but are similarly limited by sample size. 9 , 10 , 16 Therefore, this study sought to identify clinical features associated with subsequent ischemic stroke (“high risk features”) in CAD patients using a large, contemporary multi-national database, and to evaluate if treatment with anticoagulation was associated with a decreased risk of stroke compared to antiplatelets. Methods Institutional review board approval This analysis was conducted in accordance with the ethical guidelines of the original STOP-CAD study, which received Institutional Review Board (IRB) approval. As this is a secondary analysis of de-identified data, additional IRB approval was waived by the Lifespan IRB. Aggregate data will be shared upon reasonable request to the STOP-CAD principal investigator. Study design and patient population We conducted a pre-planned secondary analysis of the STOP-CAD study. The STOP-CAD study was a multicenter international retrospective observational study of patients with non-major trauma-related CAD. Methodological details from STOP-CAD have been previously described. 14 The STOP-CAD study aimed to compare the safety and efficacy of antiplatelets to anticoagulation. All patients from the STOP-CAD study were included in this analysis. Study variables Selected variables reported for the STOP-CAD study were used; further details are provided in the main paper. 14 For the present study, we collected the following co-variates: Demographics age, biological sex, race (White, Black, Asian, Other/Unknown), and ethnicity (Hispanic vs. non-Hispanic). Clinical variables history of migraine, history of hypertension, history of diabetes, history of hyperlipidemia, active smoking, known history of connective tissue disease, a history of prior ischemic stroke, time from first symptoms to dissection diagnosis (0-7 days vs. > 7 days), and recent history of non-major neck trauma. Imaging variables infarct on baseline imaging (CT or MRI), intracranial dissection or extension, location of dissection (carotid, vertebral, multivessel, other/undetermined), partially occlusive intraluminal thrombus at or distal to the dissection site, intracranial large vessel occlusion, occlusive dissection (defined as complete occlusion at the dissected artery), and pseudoaneurysm. Treatment arms antiplatelet (single or dual) and anticoagulation (therapeutic parenteral anticoagulation with heparin or low molecular weight heparin or oral anticoagulation with direct oral anticoagulation or vitamin K antagonist). Study Outcome The study outcome was subsequent ischemic stroke by day 180 after initial diagnosis. Subsequent ischemic stroke was defined as new or worsening neurologic symptoms referable to the territory of the dissected artery and either (1) lasting for at least 24 hours or (2) with imaging evidence of new or enlarging acute infarction. Analytical Plan The patient cohort was divided into two groups based on the occurrence of a subsequent ischemic stroke by day 180 after diagnosis. Patient demographic, clinical, and imaging variables were compared between groups to identify potential predictors of subsequent stroke. Chi-square test, Fisher exact test, Wilcoxon Rank Sum, and Student t-test were conducted as appropriate. Univariable analyses were performed to preliminarily assess each variable’s association with the incidence of subsequent ischemic stroke, applying a p-value cutoff of <0.2 to select variables for further multivariable stepwise Cox regression. Lasso regression was executed to confirm the most important predictors. In further analysis, adjusted Cox regression models were used to explore the impact of anticoagulation versus antiplatelet therapy on patients with high-risk predictors that reached statistical significance in the preceding multivariable stepwise Cox regression. Kaplan-Meier curves were constructed to depict event rates across treatment arms for each high-risk subgroup. In these models, patients were categorized based on the initial treatment they received—either anticoagulation or antiplatelet—and the follow-up period started on the day of dissection diagnosis. Censoring was applied at the occurrence of a subsequent ischemic stroke, at the last known follow-up until day 180, upon death, upon switching between anticoagulation and antiplatelet treatments or cessation of therapy, or after stent placement at dissection site. Outcomes counted towards the treatment the patient was on at the time of occurrence. Data were analyzed using StataSE 18. Results The analysis included 4,023 patients with an average age of 47.4 years and 44.5% of the population were women. The rate of subsequent ischemic stroke was 5.3% (214/4023) by 180 days. The rate of subsequent ischemic stroke that occurred by day 7, day 15, and day 30 was 3.0% (122/4023), 4.0% (160/4023), and 4.6% (187/4023), respectively. Factors associated with subsequent ischemic stroke risk in univariable analyses In univariable analyses, factors associated with an increased risk of subsequent ischemic stroke were older age (mean age: 49 vs. 46 years old, p=0.042), hyperlipidemia (29.0% vs. 22.6%, p=0.030), prior history of ischemic stroke (7.5% vs. 4.2%, p=0.024), presentation within seven days from symptom onset (83.6% vs. 75.8%, p=0.009), acute infarct on baseline imaging (77.1% vs. 57.0%, p<0.001), occlusive dissection (47.2% vs. 35.8%, p=0.001), and intracranial large vessel occlusion (34.1% vs. 23.6%, p<0.001; Table 1 ). View this table: View inline View popup Table 1. Univariable Analysis of Preselected Variables Across Patients With or Without Subsequent Ischemic Stroke. Predictors of subsequent ischemic stroke in stepwise multivariable Cox regression In the stepwise multivariable Cox regression analysis, which included variables with a p-value <0.2 from univariate analyses, factors associated with a higher risk of subsequent ischemic stroke were prior history of ischemic stroke (aHR 7.31, 95% CI 1.61-33.13, p=0.010), presentation within 7 days from symptom onset (aHR 3.04, 95% CI 1.04-8.91, p=0.043), acute infarct on baseline imaging (aHR 9.85, 95% CI 3.65-26.58, p<0.001), and occlusive dissection (aHR 2.34, 95% CI 1.03-5.34, p=0.043; Table 2 ). The Lasso regression suggested that the presence of infarct on imaging was the most contributing predictor in the multivariable model. View this table: View inline View popup Download powerpoint Table 2. Unadjusted and Adjusted Cox Regression Comparing Hazard Ratios for Statistically Significant Variables Identified in Multivariable Stepwise Cox Regression The benefit of anticoagulation based on factors associated with ischemic stroke Among patients with the high-risk features above, those with occlusive dissection had a significantly lower risk of subsequent ischemic stroke with anticoagulation compared to antiplatelet treatment (HR 0.37, 95% CI 0.15-0.89, p=0.03; Figure 1a ). This was not the case with the other predictors of subsequent ischemic stroke: prior history of ischemic stroke (HR 1.78, 95% CI 0.46-6.85, p=0.40; Figure 1b ), presentation within seven days of symptom onset (HR 0.79, 95% CI 0.38-1.64, p=0.53; Figure 1c ), and acute infarct on baseline brain imaging (HR 0.85, 95% CI 0.41-1.78, p=0.67; Figure 1d ). Download figure Open in new tab Download figure Open in new tab Download figure Open in new tab Download figure Open in new tab Figures 1a-d. Kaplan-Meier Estimates comparing subsequent ischemic stroke event rates with anticoagulation versus antiplatelets in high-risk subgroups. Discussion This post-hoc analysis of the STOP-CAD study found that among patients diagnosed with acute non-major trauma-related CAD, high-risk features for a subsequent stroke following the index presentation included a prior history of ischemic stroke, presentation within seven days of dissection symptom onset, acute infarct on initial imaging, and occlusive dissection. Among these high-risk features, acute infarct on initial imaging was identified as the most important factor associated with subsequent ischemic stroke, in keeping with prior studies. 4 , 7 Several studies have investigated predictors of subsequent ischemic stroke after initial diagnosis of CAD. 5 - 10 , 15 The TREAT-CAD trial found that the risk of stroke was highest within two weeks of randomization. 7 Other observational studies showed that multivessel dissection, early recurrent dissection, occlusive dissection, and cerebrovascular ischemia on presentation were associated with increased risk of ischemic stroke. 8 - 10 , 16 Recently, the American Heart Association published a scientific statement regarding the treatment for CAD. 12 In this article, the predictors of ischemic stroke present in greater than one reviewed study included male sex, current smoking, vertebral artery involvement, multiple dissections, early recurrent dissection, high-grade stenosis or occlusion, and intraluminal thrombus. 12 Consistent with several of the aforementioned observations, the current study found that early presentation, cerebrovascular ischemia, and occlusive dissection were associated with increased risk of subsequent ischemic stroke. In contrast, male sex, smoking, vertebral artery involvement, multivessel dissections, and presence of an intraluminal thrombus were not significantly associated with an increased risk of subsequent ischemic stroke. Occlusive dissection is a variable of particular interest in this study given the implications for a particular therapeutic strategy. This study found that patients with occlusive dissection who were treated with anticoagulation had a decreased risk of subsequent ischemic stroke compared to those treated with antiplatelets. This was not the case for other high-risk predictive factors identified in this study. Prior studies suggested a benefit of anticoagulation over antiplatelet in patients with carotid occlusion, 17 possibly related to reducing further thrombosis and stump embolization which frequently occurs in the early phase following index presentation. 18 Likewise, the current study illustrates the benefit of anticoagulation in patients with occlusive CAD, which may lower the risk of subsequent ischemic stroke by a similar mechanism. Other predictors of subsequent ischemic stroke in this study do not seem to have a plausible mechanistic benefit from anticoagulation. In the present study, there was no association between intraluminal thrombus and subsequent ischemic stroke risk. In the STOP-CAD study, patients with intraluminal thrombus were more likely to be treated with anticoagulation, 14 potentially reducing their risk. Additionally, the limited number of patients with intraluminal thrombus precluded definitive conclusions about the relative risk this predictor poses or the efficacy of anticoagulation compared to antiplatelet therapy in this specific group. Although this study showed a marginally increased risk of subsequent ischemic stroke in patients with intraluminal thrombus (13.1%) versus those without (10.0%), the difference was not statistically significant (p = 0.147; Table 1 ), possibly reflecting the small sample size of patients with this feature. Thus, larger studies or meta-analyses of existing studies are needed to further explore this finding. Notably, results from the recently published subgroup analysis of the TREAT-CAD trial suggested that anticoagulation might be a more effective treatment in CAD patients with non-occlusive dissection. This conclusion was supported by the finding that patients without occlusion had decreased odds of the study’s combined clinical and radiographic outcomes when treated with anticoagulation compared to those treated with aspirin. 15 The noticeable divergence between the current study’s findings and those from the TREAT-CAD study could arise from the current study’s exclusive focus on ischemic stroke as the primary endpoint, in contrast to the TREAT-CAD study, which evaluated a composite of clinical and radiographic outcomes, encompassing both ischemic and hemorrhagic events. Accordingly, when isolating clinically-apparent ischemic stroke outcomes in the TREAT-CAD subgroup analysis, subsequent ischemic strokes were numerically higher in the antiplatelet group among those with occlusive dissection (3/32; 9.4%) compared to those with non-occlusive dissection (4/58; 6.8%). No ischemic strokes occurred in the vitamin K antagonist group among those with occlusive dissection (0/23) and non-occlusive dissection (0/59). 15 Despite the limited sample size in the TREAT-CAD subgroup analysis, the clinical outcome data suggests that the beneficial effect of anticoagulation is at least numerically more pronounced in those with occlusive dissection versus non-occlusive dissection. It is within this framework that the seemingly disparate findings from the two studies can be reconciled. This study has several limitations. First, the retrospective and observational nature of the STOP-CAD study may affect the findings through confounding by indication, particularly when comparing antiplatelet to anticoagulation across high-risk sub-groups, although it is conceivable that the assumed influence would bias against anticoagulation and likely result in a reduced treatment effect of anticoagulation in high-risk sub-groups. This is particularly the case in patients with partially occlusive intraluminal thrombus where anticoagulation is generally preferred. Second, the patient cohort, primarily drawn from tertiary care centers at major academic institutions with high rates of mechanical thrombectomy, might not represent the full spectrum of stroke severity. Therefore, the findings from the present study may not fully extend to individuals with milder strokes or localized symptoms or to patients managed in smaller, non-academic healthcare settings. Third, the inclusion of the variable ‘prior history of ischemic stroke’ in this analysis has interpretive limitations, as the specific causes and timing of previous strokes were not determined. Fourth, the comparisons of anticoagulants and antiplatelets within certain high-risk subgroups had limited statistical power due to small numbers of patients and events, potentially obscuring any statistically significant differences. Larger studies or an individual patient data meta-analysis may help address these limitations. Finally, this study did not have a central adjudication of radiographic imaging and relied on the individual reporting of each center, which might have led to an inaccurate assessment of dissection features such as degree of stenosis or presence of intraluminal thrombus in some patients. Conclusion In this post-hoc analysis of the STOP-CAD study, early presentation from first dissection symptom onset, acute infarct on baseline imaging, occlusive dissection, and prior history of ischemic stroke were identified as factors associated with a lower risk of subsequent ischemic stroke among patients with CAD. Among these high-risk subgroups, patients with occlusive dissection demonstrated a reduced stroke risk from anticoagulation. These findings can inform the design of future randomized trials and meta-analyses in order to validate the effectiveness of anticoagulants versus antiplatelets in reducing the risk of subsequent strokes in CAD patients, particularly those with occlusive dissection. Data Availability This analysis was conducted in accordance with the ethical guidelines of the original STOP-CAD study, which received Institutional Review Board (IRB) approval. As this is a secondary analysis of de-identified data, additional IRB approval was waived by the Lifespan IRB. Aggregate data will be shared upon reasonable request to the STOP-CAD principal investigator. Author Contributions Daniel Mandel, Liqi Shu, and Shadi Yaghi wrote the first draft of the manuscript, and all the authors reviewed and contributed to subsequent versions. Conflicts of Interest CHN received funding from German Center for cardiovascular Research (DZHK) and German Center for neurodegenerative diseases (DZNE). CHN reports honoraria for lectures and/or speakers bureau from Abbott, Alexion, Astra Zeneca, BMS, Daiichi Sankyo, Novartis, Pfizer, Portola and Takeda. TNN reports advisory board for Brainomix, Aruna Bio; Associate Editor of Stroke. Acknowledgements None. This study was not funded. References 1. ↵ Bejot Y , Daubail B , Debette S , Durier J , Giroud M. Incidence and outcome of cerebrovascular events related to cervical artery dissection: the Dijon Stroke Registry . Int J Stroke . Oct 2014 ; 9 ( 7 ): 879 – 82 . doi: 10.1111/ijs.12154 OpenUrl CrossRef PubMed 2. Putaala J , Metso AJ , Metso TM , et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry . Stroke . Apr 2009 ; 40 ( 4 ): 1195 – 203 . doi: 10.1161/STROKEAHA.108.529883 OpenUrl Abstract / FREE Full Text 3. ↵ Ekker MS , Verhoeven JI , Schellekens MMI , et al. Risk Factors and Causes of Ischemic Stroke in 1322 Young Adults . Stroke . 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Heldner , Kateryna Antonenko , David Seiffge , Marcel Arnold , Setareh Salehi Omran , Ross Crandall , Evan Lester , Diego Lopez Mena , Antonio Arauz , Ahmad Nehme , Marion Boulanger , Emmanuel Touze , Joao Andre Sousa , Joao Sargento-Freitas , Vasco Barata , Paulo Castro-Chaves , Maria Teresa Brito , Muhib Khan , Dania Mallick , Aaron Rothstein , Ossama Khazaal , Josefin E. Kaufman , Stefan T. Engelter , Christopher Traenka , Diana Aguiar de Sousa , Mafalda Soares , Sara Rosa , Lily W. Zhou , Preet Gandhi , Thalia S. Field , Steven Mancini , Issa Metanis , Ronen R. Leker , Kelly Pan , Vishnu Dantu , Karl Baumgartner , Tina Burton , Regina von Rennenberg , Christian H. Nolte , Richard Choi , Jason MacDonald , Reza Bavarsad Shahripour , Xiaofan Guo , Malik Ghannam , Mohammad Almajali , Edgar A. Samaniego , Sebastian Sanchez , Bastien Rioux , Faycal Zine-Eddine , Alexandre Poppe , Ana Catarina Fonseca , Maria Fortuna Baptista , Diana Cruz , Michele Romoli , Giovanna De Marco , Marco Longoni , Zafer Keser , Kim Griffin , Lindsey Kuohn , Jennifer Frontera , Jordan Amar , James Giles , Marialuisa Zedde , Rosario Pascarella , Ilaria Grisendi , Hipolito Nzwalo , David S. Liebeskind , Amir Molaie , Annie Cavalier , Wayneho Kam , Brian Mac Grory , Sami Al Kasab , Mohammad Anadani , Kimberly Kicielinski , Ali Eltatawy , Lina Chervak , Roberto Chulluncuy Rivas , Yasmin Aziz , Ekaterina Bakradze , Thanh Lam Tran , Marc Rodrigo Gisbert , Manuel Requena , Faddi Saleh Velez , Jorge Ortiz Gracia , Varsha Muddasani , Adam de Havenon , Venugopalan Y Vishnu , Sridhara Yaddanapudi , Latasha Adams , Abigail Browngoehl , Tamra Ranasinghe , Randy Dunston , Zachary Lynch , Mary Penckofer , James E. Siegler , Silvia Mayer , Joshua Willey , Adeel Zubair , Yee Kuang Cheng , Richa Sharma , João Pedro Marto , Vítor Mendes Ferreira , Piers Klein , Thanh N. Nguyen , Syed Daniyal Asad , Zoha Sarwat , Anvesh Balabhadra , Shivam Patel , Thais Secchi , Sheila Martins , Gabriel Mantovani , Young Dae Kim , Balaji Krishnaiah , Cheran Elangovan , Sivani Lingam , Abid Quereshi , Sebastian Fridman , Alonso Alvarado , Farid Khasiyev , Guillermo Linares , Marina Mannino , Valeria Terruso , Sofia Vassilopoulou , Vasilis Tentolouris , Manuel Martinez Marino , Victor Carrasco Wall , Fransisca Indraswari , Sleiman El Jamal , Shilin Liu , Muhammad Alvi , Farman Ali , Mohammed Sarvath , Rami Z. 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