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September 2021 Stroke Highlights
José Rafael Romero
doi : 10.1161/STROKEAHA.121.036674
Stroke. 2021;52:2735
Effect of Operator’s Experience on Proficiency in Mechanical Thrombectomy: A Multicenter Study
François Zhu, MD, MSc Wagih Ben Hassen, MD Nicolas Bricout, MD Basile Kerleroux, MD Kevin Janot, MD Benjamin Gory, MD, PhD René Anxionnat, MD, PhD Sébastien Richard, MD, PhD Adrien Marchal, MD Raphael Blanc, MD Michel Piotin, MD Arturo Consoli, MD, MSc Denis Trystram, MD Christine Rodriguez Regent, MD Jean-Philippe Desilles, MD David Weisenburger-Lile, MD Simon Escalard, MD Denis Herbreteau, MD, PhD Heloise Ifergan, MD Igor Lima Maldonado, MD Julien Labreuche, BST Hilde Henon, MD Olivier Naggara, MD, PhD Bertrand Lapergue, MD, PhD Grégoire Boulouis, MD, PhDon behalf of the ETIS Registry and Study Collaborators* Redjem Hocine, , Ciccio Gabriele, , Smajda Stanislas, , Maier Benjamin, , Mazighi Mikael, , Obadia Mikael, , Sabben Candice, , Peres Roxanne, , Corabianu Ovide, , De Broucker Thomas, , Smadja Didier, , Alamowitch Sonia, , Ille Olivier, , Manchon Eric, , Garcia Pierre-Yves, , Taylor Guillaume, , Ben Maacha Malek, , Wang Adrien, , Evrard Serge, , Tchikviladze Maya, , Ajili Nadia, , Gorza Lucas, , Buard Géraldine, , Coskun Oguzhan, , Di Maria Federico, , Rodesh Georges, , Zimatore Sergio, , Leguen Morgan, , Gratieux Julie, , Pico Fernando, , Rakotoharinandrasana Haja, , Tassan Philippe, , Poll Roxanna, , Marinier Sylvie, , Nighoghossian Norbert, , Riva Roberto, , Eker Omer, , Turjman Francis, , Derex Laurent, , Cho Tae-Hee, , Mechtouff Laura, , Claire Lukaszewicz Anne, , Philippeau Frédéric, , Cakmak Serkan, , Blanc-Lasserre Karine, , Vallet Anne-Evelyne, , Marnat Gaultier, , Gariel Florent, , Barreau Xavier, , Berge Jérôme, , Menegon Patrice, Sibon Igor, , Liegey Sebastien, , Olindo Stéphane, , Renou Pauline, , Sagnier Sharmila, , Poli Mathilde, , Debruxelles Sabrina, , Pangon Nicolas, , Bourcier Romain, , Detraz Lili, , Daumas-Duport Benjamin, , Alexandre Pierre-Louis, , Roy Monica, , Lenoble Cédric, , L’allinec Vincent, , Girot Jean-Baptiste, , Desal Hubert, , Bracard Serge, , Braun Marc, , Derelle Anne-Laure, , Tonnelet Romain, , Liao Liang, , Muszynski Patricio, , Schmitt Emmanuelle, , Planel Sophie, , Humbertjean Lisa, , Mione Gioia, , Lacour Jean-Christophe, , Riou-Comte Nolwenn, , Audibert Gérard, , Voicu Marcela, , Alb Ionel, , Reitter Marie, , Brezeanu Madalina, , Masson Agnès, , Tabarna Adriana, Podar Ioana, , Macian-Montoro Francisco, , Saleme Suzanna, , Mounayer Charbel, , Rouchaud Aymeric, , Costalat Vincent, , Arquizan Caroline, , Dargazanli Cyril, , Gascou Grégory, , Lefèvre Pierre-Henri, , Derraz Imad, , Riquelme Carlos, , Gaillard Nicolas, , Mourand Isabelle, , Corti Lucas, , Francois Eugene, , Vannier Stéphane, , Ferre Jean-Christophe, , Raoult Helene, , Ronziere Thomas, , Lassale Maria, , Paya Christophe, , Gauvrit Jean-Yves, , Tracol Clément, , Langnier-Lemercier Sophie, , Samson Yves, , Rosso Charlotte, , Leger Anne, , Deltour Sandrine, , Clarencon Frederic, , Shotar Eimad, , Spelle Laurent, , Denier Christian, , Chassin Olivier, , Chalumeau Vanessa, , Caroff Jildaz, , Chassin Olivier, , Venditti Laura, , Turc Guillaume, , Seners Pierre, , Domigo Valérie, , Lamy Catherine, , Birchenall Julia, , Isabel Clothilde, , Viguier Alain, , Cognard Christophe, , Christine Januel Anne, , Olivot Jean-Marc, , Raposo Nicolas, , Bonneville Fabrice, , François Albucher Jean, , Calviere Lionel, , Touze Emmanuel, , Barbier Charlotte, , Schneckenburger Romain, , Boulanger Marion, , Cogez Julien, , Guettier Sophie, , Timsit Serge, , Gentric Jean-Christophe, , Ognard Julien, , Mathias Merrien Francois, , Ozkul Wermester Ozlem, , Massardier Evelyne, , Papagiannaki Chrysanthi, , Bourdain Frédéric, , Patricia Bernady, , Lagoarde-Segot Laurent, , Cailliez Hélène, , Veunac Louis, , Higue David, , Wolff Valérie, , Pop Raoul, , Beaujeux Rémi, , Mihoc Dan-Sorin, , Manisor Monica, , Le Bras Anthony, , Evain Sarah, , Le Guen Arnaud, , Richter Sebastian, , Hubrecht Regis, , Demasles Stéphanie, , Barroso Bruno, , Zuber Mathieu, , Farhat Wassim, , Alias Quentin, , Lun François, , Stenvenoot Delphine, , Heinzlef Olivier, , Godon Hardy Sylvie, , Bohotin Valentin, , Grimaud Jérôme,
doi : 10.1161/STROKEAHA.120.031940
Stroke. 2021;52:2736–2742
We aimed to evaluate among trained interventional neuroradiologist, whether increasing individual experience was associated with an improvement in mechanical thrombectomy (MT) procedural performance metrics.
When More Is Better…
Shelagh B. Coutts, MD Diogo C. HaussenMD
doi : 10.1161/STROKEAHA.121.035303
Stroke. 2021;52:2743–2745
Reasons for Not Performing Mechanical Thrombectomy: A Population-Based Study of Stroke Codes
Daniel Guisado-Alonso, MD Alejandro Martínez-Domeño, MD Luis Prats-Sánchez, MD, PhD Raquel Delgado-Mederos, MD, PhD Pol Camps-Renom, MD Sònia Abilleira, MD, PhD Natalia Pérez de la Ossa, MD, PhD Anna Ramos-Pachón, MD Pere Cardona, MD, PhD Ana Rodríguez-Campello, MD, PhD Carlos A. Molina, MD, PhD Salvatore Rudilosso, MD, PhD Joan Martí-Fàbregas, MD, PhDon behalf of the Catalan Stroke Code and Reperfusion Consortium (Cat-SCR) Rebeca Marín, Francisco Purroy, Joaquín Serena, David Canovas, Manuel Gómez- Choco, Xavier Ustrell, Josep Zaragoza, Jerzy Krupinski, Natalia Mas Sala, Ernest Palomeras, Dolors Cocho, Josep Maria Aragonés, Núria López, Eduard Sanjurjo, Dolors Carrión Duch, Mercè López, M.Cruz Almendros Rivas, Jordi Monedero Boado, Esther Catena, Esther Catena, Maria Rybyeba, Gloria Diaz
doi : 10.1161/STROKEAHA.120.032648
Stroke. 2021;52:2746–2753
Mechanical thrombectomy (MT) is effective for acute ischemic stroke (AIS) in selected patients with large intracranial vessel occlusion. A minority of patients with AIS receive MT. We aimed to describe the reasons for excluding patients with AIS for MT.
Treat or Retreat: Reasons for Deferral of Endovascular Therapy for Large Vessel Occlusion Stroke
Erica Camargo, MD, MMSc, PhD Ashutosh P. JadhavMD, PhD
doi : 10.1161/STROKEAHA.121.034361
Stroke. 2021;52:2754–2756
Lack of Reperfusion Rather Than Number of Passes Defines Futility in Stroke Thrombectomy: A Matched Case-Control Study
Mahmoud H. Mohammaden, MD, MSc Diogo C. Haussen, MD Leonardo Pisani, MD Alhamza R. Al-Bayati, MD Nicolas Bianchi, MD Bernardo Liberato, MD Nirav Bhatt, MD Dinesh Jillella, MD Michael R. Frankel, MD Raul G. NogueiraMD
doi : 10.1161/STROKEAHA.120.033539
Stroke. 2021;52:2757–2763
There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ?6 passes with those of failed reperfusion.
Prediction of Outcome and Endovascular Treatment Benefit: Validation and Update of the MR PREDICTS Decision Tool
Esmee Venema, MD Bob Roozenbeek, MD Maxim J.H.L. Mulder, MD Scott Brown, PhD Charles B.L.M. Majoie, MD Ewout W. Steyerberg, PhD Andrew M. Demchuk, MD Keith W. Muir, MD Antoni Dávalos, MD Peter J. Mitchell, MD Serge Bracard, MD Olvert A. Berkhemer, MD Geert J. Lycklama à Nijeholt, PhD Robert J. van Oostenbrugge, MD Yvo B.W.E.M. Roos, MD Wim H. van Zwam, MD Aad van der Lugt, PhD Michael D. Hill, MD Philip White, MD Bruce C.V. Campbell, PhD Francis Guillemin, PhD Jeffrey L. Saver, MD Tudor G. Jovin, MD Mayank Goyal, MD Diederik W.J. Dippel, MD Hester F. Lingsma, PhDon behalf of the HERMES collaborators and MR CLEAN Registry Investigators* Aad van der Lugt, Jelis Boiten, Jan Albert Vos, Ivo G.H. Jansen, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Adriaan C.G.M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Jan Albert Vos, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Jelis Boiten, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Tomas Bulut, Paul J.A.M. Brouwers, Marianne A.A. van Walderveen, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Adriaan C.G.M. van Es, Bart J. Emmer, Jasper M. Martens, Lonneke S.F. Yo, Jan Albert Vos, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Reinoud P.H. Bokkers, Marc P. van Proosdij, G. Menno Krietemeijer, Jo P. Peluso, Hieronymus D. Boogaarts, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, Jelis Boiten, Jan Albert Vos, Wouter J. Schonewille, Jeannette Hofmeijer, Jasper M. Martens, H. Bart van der Worp, Rob H. Lo, Jeannette Hofmeijer, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte- Terreros, Lucas A. Ramos
doi : 10.1161/STROKEAHA.120.032935
Stroke. 2021;52:2764–2772
Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice.
Detection of Atrial Fibrillation After Central Retinal Artery Occlusion
Brian Mac Grory, MB BCh BAO, MRCP Sean R. Landman, PhD Paul D. Ziegler, MS Chantal J. Boisvert, MD Shane P. Flood, MB BCh BAO Christoph Stretz, MD Tracy E. Madsen, MD, ScM Michael E. Reznik, MD Shawna Cutting, MD, MS Elizabeth E. Moore, BS Hunter Hewitt, BS James B. Closser, BS Jose Torres, MD Patrick J. Lavin, MB BCh BAO, MRCPI Karen L. Furie, MD, MPH Ying Xian, MD, PhD Wayne Feng, MD, MSc Valérie Biousse, MD Matthew Schrag, MD, PhD Shadi YaghiMD
doi : 10.1161/STROKEAHA.120.033934
Stroke. 2021;52:2773–2781
Central retinal artery occlusion (CRAO) causes sudden, irreversible blindness and is a form of acute ischemic stroke. In this study, we sought to determine the proportion of patients in whom atrial fibrillation (AF) is detected by extended cardiac monitoring after CRAO.
Anticonvulsant Primary and Secondary Prophylaxis for Acute Ischemic Stroke Patients: A Decision Analysis
Felipe J.S. Jones, MD Paula R. Sanches, MD Jason R. Smith, BA Sahar F. Zafar, MBBS Sonia Hernandez-Diaz, MD, DrPH Deborah Blacker, MD, ScD John Hsu, MD, MBA, MSCE Lee H. Schwamm, MD Michael B. Westover, MD, PhD Lidia M.V.R. MouraMD, MPH
doi : 10.1161/STROKEAHA.120.033299
Stroke. 2021;52:2782–2791
We examined the impact of 3 anticonvulsant prophylaxis strategies on quality-adjusted life-years (QALYs) among patients with an incident acute ischemic stroke.
Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression
Morsaleh Ganji, MD Valentina Nardi, MD Megha Prasad, MD Kyra L. Jordan, Melanie C. Bois, MD Federico Franchi, PhD Xiang Y. Zhu, MD, PhD Hui Tang, MD, PhD Melissa D. Young, PhD Lilach O. Lerman, MD, PhD Amir LermanMD
doi : 10.1161/STROKEAHA.120.032964
Stroke. 2021;52:2792–2801
XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors.
Risk of Fractures in Stroke Patients Treated With a Selective Serotonin Reuptake Inhibitor: A Systematic Review and Meta-Analysis
Joshua S. Jones, BPharm Rina Kimata, MPharm Osvaldo P. Almeida, PhD Graeme J. HankeyMD
doi : 10.1161/STROKEAHA.120.032973
Stroke. 2021;52:2802–2808
Stroke survivors have an increased risk of depression and bone fractures. Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures in observational studies. Several randomized controlled trials (RCTs) reporting the effect of SSRIs on the risk of fractures in stroke survivors have been published recently but have not been subject to a meta-analysis. We aimed to determine the risk of fractures associated with the use of SSRIs, and the risk of falls, seizures, and recurrent strokes as possible mediators of fractures, in stroke survivors.
Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events
Alexandra Bálint, MD Dániel Tornyos, MD Oumaima El Alaoui El Abdallaoui, MS Péter Kupó, MD András KomócsiMD, DSc
doi : 10.1161/STROKEAHA.120.032670
Stroke. 2021;52:2809–2816
Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease.
Compliance With Preferred Reporting Items for Systematic Review and Meta-Analysis Individual Participant Data Statement for Meta-Analyses Published for Stroke Studies
Fareed Jumah, MD Silky Chotai, MD Omar Ashraf, BS Michael S. Rallo, BS Bharath Raju, MD Arjun Gadhiya, MD Hai Sun, MD, PhD Vinayak Narayan, MD Gaurav Gupta, MD Anil NandaMD, MPH
doi : 10.1161/STROKEAHA.120.033288
Stroke. 2021;52:2817–2826
Individual-participant data meta-analyses (IPD-MA) are powerful evidence synthesis studies which are considered the gold-standard of MA. The quality of reporting in these studies is guided by the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis of Individual Participant Data (PRISMA-IPD) guidelines. The growing number of IPD-MA published for stroke studies calls for an assessment of the compliance of these studies with the PRISMA-IPD statement.
Residual Inflammatory Risk Predicts Poor Prognosis in Acute Ischemic Stroke or Transient Ischemic Attack Patients
Jiejie Li, MD, PhD Yuesong Pan, PhD Jie Xu, MD, PhD Shiyu Li, MD, PhD Mengxing Wang, PhD Kehua Quan, MD, PhD Xia Meng, MD, PhD Hao Li, PhD Jinxi Lin, MD, PhD Yilong Wang, MD, PhD Xingquan Zhao, MD, PhD Liping Liu, MD, PhD Yongjun Wang, MD and on behalf of the CNSR-III Investigators
doi : 10.1161/STROKEAHA.120.033152
Stroke. 2021;52:2827–2836
It is still unclear whether the residual cholesterol and inflammatory risk in the acute phase is associated with prognosis of stroke. We aimed to investigate the proportion and relative contribution of residual cholesterol and inflammatory risk, determined by baseline low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP) levels, to the risk of recurrent stroke and poor functional outcome at 1 year.
Inflammation, Cholesterol, and Stroke Risk: Building Evidence for a Dual Target Strategy for Secondary Prevention
John J. McCabe, MB Peter J. KellyMD
doi : 10.1161/STROKEAHA.121.035676
Stroke. 2021;52:2837–2838
Comparing the Prognostic Impact of Age and Baseline National Institutes of Health Stroke Scale in Acute Stroke due to Large Vessel Occlusion
Johanna Maria Ospel, MD Scott Brown, PhD Manon Kappelhof, MD Wim van Zwam, MD, PhD Tudor Jovin, MD Daniel Roy, MD Bruce C.V. Campbell, MD, PhD Peter Mitchell, MD Yvo Roos, MD, PhD Francis Guillemin, MD, PhD Brian Buck, MD Keith Muir, MD, PhD Serge Bracard, MD, PhD Phil White, MD, PhD Richard du Mesnil de Rochemont, MD, PhD Mayank Goyal, MD, PhD and for the HERMES Investigators
doi : 10.1161/STROKEAHA.120.032364
Stroke. 2021;52:2839–2845
Little is known about the combined effect of age and National Institutes of Health Stroke Scale (NIHSS) in endovascular treatment (EVT) for acute ischemic stroke due to large vessel occlusion, and it is not clear how the effects of baseline age and NIHSS on outcome compare to each other. The previously described Stroke Prognostication Using Age and NIHSS (SPAN) index adds up NIHSS and age to a 1:1 combined prognostic index. We added a weighting factor to the NIHSS/age SPAN index to compare the relative prognostic impact of NIHSS and age and assessed EVT effect based on weighted age and NIHSS.
Relative Effect of Stroke Severity and Age on Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke
Maria Bres-Bullrich, MD Sebastian Fridman, MD, MPH Luciano A. SposatoMD, MBA
doi : 10.1161/STROKEAHA.121.034946
Stroke. 2021;52:2846–2848
White Matter Lesions and Outcomes After Endovascular Treatment for Acute Ischemic Stroke: MR CLEAN Registry Results
Simone M. Uniken Venema, MD Alida A. Postma, MD, PhD Ido R. van den Wijngaard, MD, PhD Jan Albert Vos, MD, PhD Hester F. Lingsma, PhD Reinoud P.H. Bokkers, MD, PhD Jeannette Hofmeijer, MD, PhD Diederik W.J. Dippel, MD, PhD Charles B. Majoie, MD, PhD H. Bart van der Worp, MD, PhDon behalf of the MR CLEAN Registry Investigators* Aad van der Lugt, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Jelis Boiten, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Bob Roozenbeek, Aad van der Lugt, Adriaan C.G.M. van Es, Yvo B.W.E.M. Roos, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Robert J. van Oostenbrugge, Wim H. van Zwam, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Jelis Boiten, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Paul J.A.M. Brouwers, Wim H. van Zwam, Aad van der Lugt, Geert J. Lycklama à Nijeholt, Marianne A.A. van Walderveen, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Stefan D. Roosendaal, Bas F.W. van der Kallen, Adriaan C.G.M. van Es, Bart J. Emmer, Jasper M. Martens, Lonneke S.F. Yo, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Jo P. Peluso, Hieronymus D. Boogaarts, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, Aad van der Lugt, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Geert J. Lycklama à Nijeholt, Jelis Boiten, Wouter J. Schonewille, Jasper M. Martens, Rob H. Lo, Robert J. van Oostenbrugge, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A. Ramos
doi : 10.1161/STROKEAHA.120.033334
Stroke. 2021;52:2849–2857
Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice.
Correlations Between Physician and Hospital Stroke Thrombectomy Volumes and Outcomes: A Nationwide Analysis
Laura K. Stein, MD, MPH J Mocco, MD, MS Johanna Fifi, MD Nathalie Jette, MD, MSc Stanley Tuhrim, MD Mandip S. DhamoonMD, DrPH
doi : 10.1161/STROKEAHA.120.033312
Stroke. 2021;52:2858–2865
Despite the Joint Commission’s certification requirement of ?15 stroke thrombectomy (ST) cases per center and proceduralist annually, the relationship between ST case volumes and outcomes is uncertain. We sought to determine whether a proceduralist or hospital volume threshold exists that is associated with better outcomes among Medicare beneficiaries.
Digital Peripheral Arterial Tonometry and Cardiovascular Disease Events: The Framingham Heart Study
Leroy L. Cooper, PhD, MPH Na Wang, MA Alexa S. Beiser, PhD José Rafael Romero, MD Hugo J. Aparicio, MD, MPH Vasileios-Arsenios Lioutas, MD Emelia J. Benjamin, MD, ScM Martin G. Larson, ScD Ramachandran S. Vasan, MD Gary F. Mitchell, MD Sudha Seshadri, MD Naomi M. HamburgMD, MS
doi : 10.1161/STROKEAHA.120.031102
Stroke. 2021;52:2866–2873
Novel noninvasive measures of vascular function are emerging as subclinical markers for cardiovascular disease (CVD) and may be useful to predict CVD events. The purpose of our prospective study was to assess associations between digital peripheral arterial tonometry (PAT) measures and first-onset major CVD events in a sample of FHS (Framingham Heart Study) participants.
Utility of the Hospital Frailty Risk Score Derived From Administrative Data and the Association With Stroke Outcomes
Monique F. Kilkenny, PhD Hoang T. Phan, PhD Richard I. Lindley, MD Joosup Kim, PhD Derrick Lopez, PhD Lachlan L. Dalli, BBiomedSc Rohan Grimley, MBBS Vijaya Sundararajan, MD Amanda G. Thrift, PhD Nadine E. Andrew, PhD Geoffrey A. Donnan, PhD Dominique A. Cadilhac, PhDon behalf of the Stroke123 Investigators and the AuSCR Consortium Craig Anderson, PhD Julie Bernhardt, PhD Paul Bew, MPhty Christopher Bladin, MD, MBBS, FRACP Greg Cadigan, BN Helen Castley, MBBS Andrew Lee, MBBS FRACP Mark Mackay, MBBS, FRACP Sandra Martyn, , John McNeil, PhD Sandy Middleton, PhD Michael Pollack, MBBS, FAFRM (RACP), FACRM, FFPM (ANZCA), MMedSci (Clin Epi) Mark Simcocks, BSc Frances Simmonds, MSc(Med) Helen Dewey, PhD Steven Faux, FAFRM (RACP) Kelvin Hill, BAppSci Christopher Levi, PhD Christopher Price, BSocW, BSc Pradeep Bambery, MD, FRCP(G), FRACP Tim Bates, MBBS, FRACP Carolyn Beltrame, RN (Div1) David Blacker, MBBS, FRACP Ernie Butler, MBBS FRACP Sean Butler, FIMLS, BM Hons, MRCP(UK), FRACP Douglas Crompton, MA, PhD, MBBS, FRACP Vanessa Crosby, Dip Physio Carolyn De Wytt, MRCP (UK), MB BCH DUBL, FRACP David Douglas, MBBS, M Admin, FRACGP, FAFRM (RACP) Martin Dunlop, MBBS, FACRM Paula Easton, BPhty (Hons) Sharan Ermel, RN (Div1) Nisal Gange, MBBS, AMC CERT Richard Geraghty, MBBS, FRACP Melissa Gill, BAppSc (SpPath) Graham Hall, MBBS, FRACP Peter Hand, MBBS, MD, FRACP Geoffrey Herkes, MBBS, PhD, FRACP Karen Hines, BHIM Francis Hishon, RN James Hughes, BMed, FRACP Joel Iedema, MBBS, FRACP Martin Jude, MBBS, FRACP Thomas Kraemer, , Paul Laird, MBBS, FRACP Johanna Madden, BPhysio Graham Mahaffey, RN Suzana Milosevic, MD, FRACP, AMC CERT Peter O’Brien, MBBS, DIP RANZCOG, FRACMA, FACRRM Stephen Read, MBBS, PhD, FRACP Kristen Rowe, BNurs, Cert NeuroSci Nurs Fiona Ryan, BAppSc (SpPath), MHlthSc Arman Sabet, MD, FRACP, BSc Noel Saines, MBBS, FRACP Eva Salud, MD, AMC CERT Amanda Siller, MBBS, FRACP Christopher Staples, MD Richard White, MD, FRCP, FRACP Andrew Wong, MBBS, PhD Robin Armstrong, Leonid Churilov, Alison Dias, Adele Gibbs, Brenda Grabsch, Francis Kung, Joyce Lim, Karen Moss, Kate Paice, Enna Salama, Sabrina Small, Renee Stojanovic, Steven Street, Emma Tod, Kasey Wallis
doi : 10.1161/STROKEAHA.120.033648
Stroke. 2021;52:2874–2881
Conditions associated with frailty are common in people experiencing stroke and may explain differences in outcomes. We assessed associations between a published, generic frailty risk score, derived from administrative data, and patient outcomes following stroke/transient ischemic attack; and its accuracy for stroke in predicting mortality compared with other measures of clinical status using coded data.
Predictive Performance of a Polygenic Risk Score for Incident Ischemic Stroke in a Healthy Older Population
Johannes T. Neumann, Moeen Riaz, Andrew Bakshi, Galina Polekhina, Le T.P. Thao, Mark R. Nelson, Robyn L. Woods, Gad Abraham, Michael Inouye, Christopher M. Reid, Andrew M. Tonkin, Jeff D. Williamson, Geoffrey A. Donnan, Amy Brodtmann, Geoffrey C. Cloud, John J. McNeil, Paul Lacaze
doi : 10.1161/STROKEAHA.120.033670
Stroke. 2021;52:2882–2891
Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur.
Combined Omic Analyzes of Cerebral Thrombi: A New Molecular Approach to Identify Cardioembolic Stroke Origin
Laurent Suissa, Jean-Marie Guigonis, Fanny Graslin, Emmanuelle Robinet-Borgomano, Yves Chau, Jacques Sedat, Sabine Lindenthal, Thierry Pourcher
doi : 10.1161/STROKEAHA.120.032129
Stroke. 2021;52:2892–2901
The diagnosis of cardioembolic stroke can be challenging for patient management in secondary stroke prevention, particularly in the case of covert paroxysmal atrial fibrillation. The molecular composition of a cerebral thrombus is related to its origin. Therefore, proteomic and metabolomic analyses of the retrieved thrombotic material should allow the identification of biomarkers or signatures to improve the etiological diagnosis of stroke.
Computed Tomography Angiography Spot Sign, Hematoma Expansion, and Functional Outcome in Spontaneous Cerebellar Intracerebral Hemorrhage
Sanjula D. Singh, Marco Pasi, Floris H.B.M. Schreuder, Andrea Morotti, Jasper R. Senff, Andrew D. Warren, Brenna N. McKaig, Kristin Schwab, M. Edip Gurol, Jonathan Rosand, Steven M. Greenberg, Anand Viswanathan, Catharina J.M. Klijn, Gabriel J.E. Rinkel, Joshua N. Goldstein, H. Bart Brouwers
doi : 10.1161/STROKEAHA.120.033297
Stroke. 2021;52:2902–2909
The computed tomography angiography spot sign is associated with hematoma expansion, case fatality, and poor functional outcome in spontaneous supratentorial intracerebral hemorrhage (ICH). However, no data are available on the spot sign in spontaneous cerebellar ICH.
Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke
Chia-Lin Koh, Chun-Hung Yeh, Xiaoyun Liang, Rishma Vidyasagar, Rüdiger J. Seitz, Michael Nilsson, Alan Connelly, Leeanne M. Carey
doi : 10.1161/STROKEAHA.120.031520
Stroke. 2021;52:2910–2920
Changes in connectivity of white matter fibers remote to a stroke lesion, suggestive of structural connectional diaschisis, may impact on clinical impairment and recovery after stroke. However, until recently, we have not had tract-specific techniques to map changes in white matter tracts in vivo in humans to enable investigation of potential mechanisms and clinical impact of such remote changes. Our aim was to identify and quantify white matter tracts that are affected remote from a stroke lesion and to investigate the associations between reductions in tract-specific connectivity and impaired touch discrimination function after stroke.
Association of Lesion Pattern and Dysphagia in Acute Intracerebral Hemorrhage
Felix Hess, Christian Foerch, Fee Keil, Alexander Seiler, Sriramya Lapa
doi : 10.1161/STROKEAHA.120.032615
Stroke. 2021;52:2921–2929
Dysphagia is a common and severe symptom of acute stroke. Although intracerebral hemorrhages (ICHs) account for 10% to 15% of all strokes, the occurrence of dysphagia in this subtype of stroke has not been widely investigated. The aim of this study was to evaluate the overall frequency and associated lesion locations and clinical predictors of dysphagia in patients with acute ICH.
Anterior Cerebral Artery Stroke: Role of Collateral Systems on Infarct Topography
Tharani Thirugnanachandran, Richard Beare, Melissa Mitchell, Chloe Wong, Jason Vuong, Shaloo Singhal, Lee-Anne Slater, James Hilton, Mathew Sinnott, Velandai Srikanth, Henry Ma, Thanh Phan
doi : 10.1161/STROKEAHA.120.032867
Stroke. 2021;52:2930–2938
The circle of Willis (CoW) and leptomeningeal anastomoses play an important role in transforming infarct topography following middle cerebral artery occlusion. Their role in infarct topography following anterior cerebral artery occlusion is not well understood. The aim of this study was to evaluate the role of the CoW and leptomeningeal anastomoses in modifying regional variation in infarct topography following occlusion of the anterior cerebral artery and its branches.
Central Nervous System-Infiltrating T Lymphocytes in Stroke Are Activated via Their TCR (T-Cell Receptor) but Lack CD25 Expression
Juliane Schulze, Juliane Gellrich, Michael Kirsch, Alexander Dressel, Antje Vogelgesang
doi : 10.1161/STROKEAHA.120.032763
Stroke. 2021;52:2939–2947
T lymphocytes contribute to secondary brain damage after stroke. It has not been fully investigated whether this contribution is caused by antigen-specific or antigen-nonspecific activation of T lymphocytes. Lymphocytes from Nur77GFP transgenic mice express a fluorescent protein upon activation via the TCR (T-cell receptor), allowing the differentiation of activation mode in a natural repertoire of immune cells and antigens.
Translating Functional Connectivity After Stroke: Functional Magnetic Resonance Imaging Detects Comparable Network Changes in Mice and Humans
Stefan J. Blaschke, Lukas Hensel, Anuka Minassian, Susan Vlachakis, Caroline Tscherpel, Sabine U. Vay, Monika Rabenstein, Michael Schroeter, Gereon R. Fink, Mathias Hoehn, Christian Grefkes, Maria A. Rueger
doi : 10.1161/STROKEAHA.120.032511
Stroke. 2021;52:2948–2960
The translational roadblock has long impeded the implementation of experimental therapeutic approaches for stroke into clinical routine. Considerable interspecies differences, for example, in brain anatomy and function, render comparisons between rodents and humans tricky, especially concerning brain reorganization and recovery of function. We tested whether stroke-evoked changes in neural networks follow similar patterns in mice and patients using a systems-level perspective.
Functional Connectivity Change in Response to Stroke Is Comparable Across Species: From Mouse to Man
Gerard R. Hall, Marcus Kaiser, Tracy D. Farr
doi : 10.1161/STROKEAHA.121.034097
Stroke. 2021;52:2961–2963
Mobile Interventional Stroke Teams Improve Outcomes in the Early Time Window for Large Vessel Occlusion Stroke
Jacob R. Morey, Xiangnan Zhang, Naoum Fares Marayati, Stavros Matsoukas, Emily Fiano, Thomas Oxley, Neha Dangayach, Laura K. Stein, Michael G. Fara, Maryna Skliut, Christopher Kellner, Reade De Leacy, J Mocco, Stanley Tuhrim, Johanna T. Fifi
doi : 10.1161/STROKEAHA.121.034222
Stroke. 2021;52:e527–e530
Endovascular thrombectomy for large vessel occlusion stroke is a time-sensitive intervention. The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes, as compared with the drip-and-ship (DS) model. The effect of the MIST model stratified by time of presentation has yet to be studied. We hypothesize that patients who present in the early window (last known well of ?6 hours) will have better clinical outcomes in the MIST model.
Rapid Assessment of Blood Pressure Variability and Outcome After Successful Thrombectomy
Pedro Castro, Francisca Ferreira, Cindy K. Nguyen, Seyedmehdi Payabvash, Can Ozan Tan, Farzaneh Sorond, Elsa Azevedo, Nils Petersen
doi : 10.1161/STROKEAHA.121.034291
Stroke. 2021;52:e531–e535
High blood pressure (BP) variability after endovascular stroke therapy is associated with poor outcome. Conventional BP variability measures require long recordings, limiting their utility as a risk assessment tool to guide clinical decision-making. Here, we performed rapid assessment of BP variability by spectral analysis and evaluated its association with early clinical improvement and long-term functional outcomes.
Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency
Benjamin Maïer, Erwan Robichon, Romain Bourcier, Cyril Dargazanli, Julien Labreuche, Laurie-Anne Thion, Morgan Leguen, Romuald Riem, Jean-Philippe Desilles, Grégoire Boulouis, François Delvoye, Solène Hebert, Hocine Redjem, Stanislas Smajda, Simon Escalard, Raphaël Blanc, Michel Piotin, Bertrand Lapergue, Mikael Mazighi,and on behalf of the ASTER Trial†
doi : 10.1161/STROKEAHA.121.034542
Stroke. 2021;52:2964–2967
Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency.
Time to Evacuation and Functional Outcome After Minimally Invasive Endoscopic Intracerebral Hemorrhage Evacuation
Christopher P. Kellner, Rui Song, Muhammad Ali, Dominic A. Nistal, Milan Samarage, Neha S. Dangayach, John Liang, Ian McNeill, Xiangnan Zhang, Joshua B. Bederson, J Mocco
doi : 10.1161/STROKEAHA.121.034392
Stroke. 2021;52:e536–e539
We present a retrospective analysis of patients who underwent minimally invasive endoscopic intracerebral hemorrhage (ICH) evacuation to identify variables that were associated with long-term outcome.
Association of Proportional Recovery After Stroke With Health-Related Quality of Life
Chen Lin, Kimberly Martin, Yurany A. Arevalo, Richard L. Harvey, Shyam Prabhakaran
doi : 10.1161/STROKEAHA.120.033672
Stroke. 2021;52:2968–2971
No data exists on whether proportional recovery (PR) is associated with health-related quality of life (HRQOL) domains. We evaluated whether PR was associated with domain-specific HRQOL scores at 3 months after ischemic stroke.
Role of Rare Genetic Variants Found in Families With Intracranial Aneurysms in the General Dutch and UK Population
Mark K. Bakker, Roos A. Ettema, Maxime Klostermann, Gabriël J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok
doi : 10.1161/STROKEAHA.121.035492
Stroke. 2021;52:e540–e541
Angiography Suite Cone-Beam Computed Tomography Perfusion Imaging in Large-Vessel Occlusion Patients Using RAPID Software: A Pilot Study
Darko Quispe-Orozco, Mudassir Farooqui, Cynthia Zevallos, Sebastian Schafer, Alan Mendez-Ruiz, Gregory Albers, Nils Petersen, Santiago Ortega-Gutierrez
doi : 10.1161/STROKEAHA.121.035992
Stroke. 2021;52:e542–e544
PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Inhibition in Hyperglycemic Mice Increases the Risk of Hemorrhagic Transformation of Ischemic Stroke
Brice Nativel, Stéphane Ramin-Mangata, David Couret, Cynthia Planesse, Mathias Roche, Antonio Gallo, Olivier Meilhac, Gilles Lambert, Steeve Bourane
doi : 10.1161/STROKEAHA.121.035677
Stroke. 2021;52:e545–e547
Health Equity
Lewis B. Morgenstern, Amytis Towfighi
doi : 10.1161/STROKEAHA.121.033939
Stroke. 2021;52:2972–2973
Stroke Genetics: Turning Discoveries into Clinical Applications
Martin Dichgans, Nathalie Beaufort, Stephanie Debette, Christopher D. Anderson
doi : 10.1161/STROKEAHA.121.032616
Stroke. 2021;52:2974–2982
The field of medical and population genetics in stroke is moving at a rapid pace and has led to unanticipated opportunities for discovery and clinical applications. Genome-wide association studies have highlighted the role of specific pathways relevant to etiologically defined subtypes of stroke and to stroke as a whole. They have further offered starting points for the exploration of novel pathways and pharmacological strategies in experimental systems. Mendelian randomization studies continue to provide insights in the causal relationships between exposures and outcomes and have become a useful tool for predicting the efficacy and side effects of drugs. Additional applications that have emerged from recent discoveries include risk prediction based on polygenic risk scores and pharmacogenomics. Among the topics currently moving into focus is the genetics of stroke outcome. While still at its infancy, this field is expected to boost the development of neuroprotective agents. We provide a brief overview on recent progress in these areas.
Risk Prediction Using Polygenic Risk Scores for Prevention of Stroke and Other Cardiovascular Diseases
Gad Abraham, Loes Rutten-Jacobs, Michael Inouye
doi : 10.1161/STROKEAHA.120.032619
Stroke. 2021;52:2983–2991
Early prediction of risk of cardiovascular disease (CVD), including stroke, is a cornerstone of disease prevention. Clinical risk scores have been widely used for predicting CVD risk from known risk factors. Most CVDs have a substantial genetic component, which also has been confirmed for stroke in recent gene discovery efforts. However, the role of genetics in prediction of risk of CVD, including stroke, has been limited to testing for highly penetrant monogenic disorders. In contrast, the importance of polygenic variation, the aggregated effect of many common genetic variants across the genome with individually small effects, has become more apparent in the last 5 to 10 years, and powerful polygenic risk scores for CVD have been developed. Here we review the current state of the field of polygenic risk scores for CVD including stroke, and their potential to improve CVD risk prediction. We present findings and lessons from diseases such as coronary artery disease as these will likely be useful to inform future research in stroke polygenic risk prediction.
Mendelian Randomization Studies in Stroke: Exploration of Risk Factors and Drug Targets With Human Genetic Data
Marios K. Georgakis, Dipender Gill
doi : 10.1161/STROKEAHA.120.032617
Stroke. 2021;52:2992–3003
Elucidating the causes of stroke is key to developing effective preventive strategies. The Mendelian randomization approach leverages genetic variants related to an exposure of interest to investigate the effects of varying that exposure on disease risk. The random allocation of genetic variants at conception reduces confounding from environmental factors and thus strengthens causal inference, analogous to treatment allocation in a randomized controlled trial. With the recent explosion in the availability of human genetic data, Mendelian randomization has proven a valuable tool for studying risk factors for stroke. In this review, we provide an overview of recent developments in the application of Mendelian randomization to unravel the pathophysiology of stroke subtypes and identify therapeutic targets for clinical translation. The approach has offered novel insight into the differential effects of risk factors and antihypertensive, lipid-lowering, and anticoagulant drug classes on risk of stroke subtypes. Analyses have further facilitated the prioritization of novel drug targets, such as for inflammatory pathways underlying large artery atherosclerotic stroke and for the coagulation cascade that contributes to cardioembolic stroke. With continued methodological advances coupled with the rapidly increasing availability of genetic data related to a broad range of stroke phenotypes, the potential for Mendelian randomization in this context is expanding exponentially.
Genetics of Intracranial Aneurysms
Mark K. Bakker, Ynte M. Ruigrok
doi : 10.1161/STROKEAHA.120.032621
Stroke. 2021;52:3004–3012
Rupture of an intracranial aneurysm leads to aneurysmal subarachnoid hemorrhage, a severe type of stroke which is, in part, driven by genetic variation. In the past 10 years, genetic studies of IA have boosted the number of known genetic risk factors and improved our understanding of the disease. In this review, we provide an overview of the current status of the field and highlight the latest findings of family based, sequencing, and genome-wide association studies. We further describe opportunities of genetic analyses for understanding, prevention, and treatment of the disease.
Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome: From Early Brain Injury to Long-Term Recovery
Jin-Moo Lee, Israel Fernandez-Cadenas, Arne G. Lindgren
doi : 10.1161/STROKEAHA.121.032622
Stroke. 2021;52:3013–3024
There is a critical need to elucidate molecular mechanisms underlying brain injury, repair, and recovery following ischemic stroke—a global health problem with major social and economic impact. Despite 5 decades of intensive research, there are no widely accepted neuroprotective drugs that mitigate ischemic brain injury, or neuroreparative drugs, or personalized approaches that guide therapies to enhance recovery. We here explore novel reverse translational approaches that will complement traditional forward translational methods in identifying mechanisms relevant to human stroke outcome. Although genome-wide association studies have yielded over 30 genetic loci that influence ischemic stroke risk, only a few genome-wide association studies have been performed for stroke outcome. We discuss important considerations for genetic studies of ischemic stroke outcome—including carefully designed phenotypes that capture injury/recovery mechanisms, anchored in time to stroke onset. We also address recent genome-wide association studies that provide insight into mechanisms underlying brain injury and repair. There are several ongoing initiatives exploring genomic associations with novel phenotypes related to stroke outcome. To improve the understanding of the genetic architecture of ischemic stroke outcome, larger studies using standardized phenotypes, preferably embedded in standard-of-care measures, are needed. Novel techniques beyond genome-wide association studies—including exploiting informatics, multi-omics, and novel analytics—promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.
Hereditary Cerebral Small Vessel Diseases and Stroke: A Guide for Diagnosis and Management
Stéphanie Guey, Saskia A.J. Lesnik Oberstein, Elisabeth Tournier-Lasserve, Hugues Chabriat
doi : 10.1161/STROKEAHA.121.032620
Stroke. 2021;52:3025–3032
Cerebral small vessel diseases represent a frequent cause of stroke and cognitive or motor disability in adults. A small proportion of cerebral small vessel diseases is attributable to monogenic conditions. Since the characterization in the late 1990s of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, several other monogenic conditions leading to adult-onset ischemic or hemorrhagic stroke have been described. In this practical guide, we summarize the key features that should elicit the differential diagnosis of a hereditary cerebral small vessel diseases in adult stroke patients, describe the main clinical and imaging characteristics of the major hereditary cerebral small vessel diseases that can manifest as stroke, and provide general recommendations for the clinical management of affected patients and their relatives.
Cerebroprotection for Acute Ischemic Stroke: Looking Ahead
Patrick D. Lyden
doi : 10.1161/STROKEAHA.121.032241
Stroke. 2021;52:3033–3044
We search for ischemic stroke treatment knowing we have failed—intensely and often—to translate mechanistic knowledge into treatments that alleviate our patients’ functional impairments. Lessons can be derived from our shared failures that may point to new directions and new strategies. First, the principle criticisms of both preclinical and clinical assessments are summarized. Next, previous efforts to develop single-mechanism treatments are reviewed. Finally, new definitions, novel approaches, and different directions are presented. In previous development efforts, the basic science and preclinical assessment of candidate treatments often lacked rigor and sufficiency; the clinical trials may have lacked power, rigor, or rectitude; or most likely both preclinical and clinical investigations were flawed. Single-target agents directed against specific molecular mechanisms proved unsuccessful. The term neuroprotection should be replaced as it has become ambiguous: protection of the entire neurovascular unit may be called cerebral cytoprotection or cerebroprotection. Success in developing cerebroprotection—either as an adjunct to recanalization or as stand-alone treatment—will require new definitions that recognize the importance of differential vulnerability in the neurovascular unit. Recent focus on pleiotropic multi-target agents that act via multiple mechanisms of action to interrupt ischemia at multiple steps may be more fruitful. Examples of pleiotropic treatments include therapeutic hypothermia and 3K3A-APC (activated protein C). Alternatively, the single-target drug NA-1 triggers multiple downstream signaling events. Renewed commitment to scientific rigor is essential, and funding agencies and journals may enforce quality principles of rigor in preclinical science. Appropriate animal models should be selected that are suited to the purpose of the investigation. Before clinical trials, preclinical assessment could include subjects that are aged, of both sexes, and harbor comorbid conditions such as diabetes or hypertension. With these new definitions, novel approaches, and renewed attention to rigor, the prospect for successful cerebroprotective therapy should improve.
Cerebral Vein Thrombosis With Vaccine-Induced Immune Thrombotic Thrombocytopenia
James E. Siegler, Piers Klein, Shadi Yaghi, Nicholas Vigilante, Mohamad Abdalkader, Jonathan M. Coutinho, Feras Abdul Khalek, Thanh N. Nguyen
doi : 10.1161/STROKEAHA.121.035613
Stroke. 2021;52:3045–3053
In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150?000 ChAdOx1 recipients and 1:470?000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.
Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI
Jeffrey L. Saver, Napasri Chaisinanunkul, Bruce C.V. Campbell, James C. Grotta, Michael D. Hill, Pooja Khatri, Jaren Landen, Maarten G. Lansberg, Chitra Venkatasubramanian, Gregory W. Albers, and on behalf of the XIth Stroke Treatment Academic Industry Roundtable
doi : 10.1161/STROKEAHA.121.034480
Stroke. 2021;52:3054–3062
The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale’s original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.
Top Priorities for Cerebroprotective Studies—A Paradigm Shift: Report From STAIR XI
Patrick Lyden, Alastair Buchan, Johannes Boltze, Marc Fisher,and on behalf of the STAIR XI Consortium*
doi : 10.1161/STROKEAHA.121.034947
Stroke. 2021;52:3063–3071
Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke treatments. At STAIR XI, participants in workshop no. 1 Top Priorities for Neuroprotection sought to redefine the neuroprotection paradigm and given the paucity of evidence underlying preclinical assessment, offer consensus-based recommendations. STAIR proposes the term brain cytoprotection or cerebroprotection to replace the term neuroprotection when the intention of an investigation is to demonstrate that a new, candidate treatment benefits the entire brain. Although “time is still brain,” tissue imaging techniques have been developed to identify patients with both predicted core injury and penumbral, salvageable brain tissue, regardless of time after stroke symptom onset. STAIR XI workshop participants called this imaging approach a tissue window to select patients for recanalization. Elements of the neurovascular unit show differential vulnerability evolving over differing time scales in different brain regions. STAIR proposes the term target window to suggest therapies that target the different elements of the neurovascular unit at different times. Based on contemporary principles of rigor and transparency, the workshop updated, revised, and enhanced the STAIR preclinical recommendations for developing new treatments in 2 phases: an exploratory qualification phase and a definitive validation phase. For new, putative treatments, investigators should carefully characterize the mechanism of action, the pharmacokinetics/pharmacodynamics, demonstrate target engagement, and confirm penetration through the blood-brain barrier. Before clinical trials, testing of candidate molecules in stroke models could proceed in a comprehensive manner using animals of both sexes and to include significant variables such as age and comorbid conditions. Comprehensive preclinical assessment might include multicenter, collaborative testing, for example, network trials. In the absence of a proven cerebroprotective agent to use as a gold standard, however, it remains speculative whether such comprehensive preclinical assessment can effectively predict clinical outcome.
Improving Outcomes After Stroke: From Stroke Units to Mobile Stroke Units
Andrei V. Alexandrov, Yongchai Nilanont
doi : 10.1161/STROKEAHA.121.034616
Stroke. 2021;52:3072–3074
A proactive clinical approach to stroke care improved functional outcomes with implementation of specialized in-hospital stroke units, urgently delivered systemic thrombolysis, mechanical thrombectomy and most recently with mobile stroke units deployed in the field. An 18% absolute difference in outcomes as a shift across all modified Rankin Scale strata at 3 months in the recent Berlin study may not be explained by just 8.8% more patients treated within the golden hour for thrombolytic treatment from symptom onset. These findings parallel the findings in the largest controlled multi-center BEST-MSU trial (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit) to date. A shortcoming in blinding of the investigators to the mode of transportation is similar to blinding to the endovascular treatment in PROBE (Prospective Randomized Open, Blinded End-Point) design used in thrombectomy trials. A faster access to stroke experts and brain imaging in the field for all patients suspect of stroke regardless symptom nature, severity, duration or resolution delivered by mobile stroke units is likely the reason for improved outcomes akin the impact observed in the initial multidisciplinary approach to in-hospital stroke units and reperfusion therapies delivery.
Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?
Jukka Putaala, Jeffrey L. Saver, May Nour, Dawn Kleindorfer, Mollie McDermott, Markku Kaste
doi : 10.1161/STROKEAHA.121.034244
Stroke. 2021;52:3075–3080
Interventions for Spatial Neglect After Stroke or Nonprogressive Brain Injury: A Cochrane Systematic Review
Verity Longley, Christine Hazelton, Calvin Heal, Alex Pollock, Kate Woodward-Nutt, Claire Mitchell, Gorana Pobric, Andy Vail, Audrey Bowen
doi : 10.1161/STROKEAHA.121.036590
Stroke. 2021;52:e548–e549
Exposure to Neurointervention During Neurology Training
Kaustubh Limaye, Santiago Ortega-Gutierrez, Maxim Mokin, Amanda Jagolino, Sunil A. Sheth, Ashutosh P. Jadhav
doi : 10.1161/STROKEAHA.121.036026
Stroke. 2021;52:e550–e553
There is an urgent need to include a dedicated neurointerventional rotation in the curriculum of neurology residency and vascular neurology fellowship based on the paradigm shift in recent years of stroke workflow. The recent changes coupled with growing body of evidence about lack of neurointerventional exposure in current curriculum makes it imperative for us to restructure the training for future neurologists. The exposure will prepare the neurology house-staff for the contemporary management of cerebrovascular diseases and will lead to high quality, patient-centric care.
Cerebral Venous Thrombosis and Hypercoagulability Associated With In Vitro Fertilization
Amreen B. Farooqui, Meghan L. Humbert, Mary Stewart Montague, Sylvain Doré, Alexis N. Simpkins
doi : 10.1161/STROKEAHA.121.035962
Stroke. 2021;52:e554–e557
Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association
Walter N. Kernan, Anthony J. Viera, Sandra A. Billinger, Dawn M. Bravata, Susan L. Stark, Scott E. Kasner, Louis Kuritzky, Amytis Towfighi, and on behalf of the American Heart Association Stroke Council; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease
doi : 10.1161/STR.0000000000000382
Stroke. 2021;52:e558–e571
Primary care teams provide the majority of poststroke care. When optimally configured, these teams provide patient-centered care to prevent recurrent stroke, maximize function, prevent late complications, and optimize quality of life. Patient-centered primary care after stroke begins with establishing the foundation for poststroke management while engaging caregivers and family members in support of the patient. Screening for complications (eg, depression, cognitive impairment, and fall risk) and unmet needs is both a short-term and long-term component of poststroke care. Patients with ongoing functional impairments may benefit from referral to appropriate services. Ongoing care consists of managing risk factors such as high blood pressure, atrial fibrillation, diabetes, carotid stenosis, and dyslipidemia. Recommendations to reduce risk of recurrent stroke also include lifestyle modifications such as healthy diet and exercise. At the system level, primary care practices can use quality improvement strategies and available resources to enhance the delivery of evidence-based care and optimize outcomes.
Correction to: Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency
doi : 10.1161/STR.0000000000000389
Stroke. 2021;52:e572
Correction to: Activation of Dopamine D2 Receptor Suppresses Neuroinflammation Through ?B-Crystalline by Inhibition of NF-?B Nuclear Translocation in Experimental ICH Mice Model
doi : 10.1161/STR.0000000000000390
Stroke. 2021;52:e573
