Stroke

Fouzi Bala, Ilaria Casetta, Stefania Nannoni, Darragh Herlihy, Mayank Goyal, Enrico Fainardi, Patrik Michel, John Thornton, Sarah Power, Valentina Saia, Aidan Hegarty, Giovanni Pracucci, Andrew Demchuk, Salvatore Mangiafico, Karl Boyle, Michael D. Hill, Danilo Toni, Sean Murphy, Ayoola Ademola, Beom Joon Kim, Bijoy K. Menon and Mohammed A. Almekhlafi

doi : 10.1161/STROKEAHA.121.037127

Stroke. 2022;53:311–318

Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window.

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Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk?

Michelle H. Leppert, James F. Burke, Lynda D. Lisabeth, Tracy E. Madsen, Dawn O. Kleindorfer, Stefan Sillau, Lee H. Schwamm, Stacie L. Daugherty, Cathy J. Bradley, P. Michael Ho and Sharon N. Poisson

doi : 10.1161/STROKEAHA.121.037117

Stroke. 2022;53:319–327

Recent evidence suggests that young women (18–45 years) may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among young adults with ischemic strokes.

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Infertility, Miscarriage, Stillbirth, and the Risk of Stroke Among Women: A Systematic Review and Meta-Analysis

Chen Liang, Hsin-Fang Chung, Annette J. Dobson and Gita D. Mishra

doi : 10.1161/STROKEAHA.121.036271

Stroke. 2022;53:328–337

Stroke is one of the leading causes of mortality, and women are impacted more from stroke than men in terms of their absolute number and in having worse outcomes. A growing number of studies have explored the association between pregnancy complications, pregnancy outcomes, and stroke. Limited studies, however, have investigated links involving infertility, miscarriage, and stillbirth, which could plausibly be associated via a background of endocrine conditions, endothelial dysfunction, and chronic systematic inflammation. This review aims to summarize current evidence and provide up-to-date information on the associations of infertility, miscarriage, and stillbirth, with stroke incidence.

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Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time

Shih-Kai Hung, Moon-Sing Lee, Hon-Yi Lin, Liang-Cheng Chen, Chi-Jou Chuang, Chia-Hui Chew, Ben-Hui Yu, Hsuan-Ju Yang, Feng-Chun Hsu and Wen-Yen Chiou

doi : 10.1161/STROKEAHA.121.034109

Stroke. 2022;53:338–344

Hypertensive disorders of pregnancy (HDP) comprise 4 subtypes. Previous studies have not investigated the relationship between stroke risk, different HDP subtypes, and follow-up time, which was the purpose of this study.

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Sex Differences in Presentation of Stroke: A Systematic Review and Meta-Analysis

Mariam Ali, Hendrikus J.A. van Os, Nelleke van der Weerd, Jan W. Schoones, Martijn W. Heymans, Nyika D. Kruyt, Marieke C. Visser and Marieke J.H. Wermer

doi : 10.1161/STROKEAHA.120.034040

Stroke. 2022;53:345–354

Women have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack.

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Health Screening Program to Enhance Enrollment of Women and Minorities in CREST-2

Brajesh K. Lal, James F. Meschia, Michael Jones, Herbert D. Aronow, Angelica Lackey, Rachel Lake, George Howard and Thomas G. Brott

doi : 10.1161/STROKEAHA.120.033226

Stroke. 2022;53:355–361

The CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) consists of 2 parallel randomized stroke prevention trials in patients with asymptomatic high-grade stenosis of the cervical carotid artery. The purpose of this report is to detail the outcomes of a health screening effort to increase trial enrollment of women and minorities.

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Sex Difference and Rupture Rate of Intracranial Aneurysms: An Individual Patient Data Meta-Analysis

Charlotte C.M. Zuurbier, Rob Molenberg, Liselore A. Mensing, Marieke J.H. Wermer, Seppo Juvela, Antti E. Lindgren, Juha E. Jääskeläinen, Timo Koivisto, Tomosato Yamazaki, Maarten Uyttenboogaart, J. Marc C. van Dijk, Marlien W. Aalbers, Akio Morita, Shinjiro Tominari, Hajime Arai, Kazuhiko Nozaki, Yuichi Murayama, Toshihiro Ishibashi, Hiroyuki Takao, Renato Gondar, Philippe Bijlenga, Gabriel J.E. Rinkel, Jacoba P. Greving and Ynte M. Ruigrok

doi : 10.1161/STROKEAHA.121.035187

Stroke. 2022;53:362–369

In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture.

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Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis

Dianne H.K. van Dam-Nolen, Nina C.M. van Egmond, Kristine Dilba, Kelly Nies, Anja G. van der Kolk, Madieke I. Liem, M. Eline Kooi, Jeroen Hendrikse, Paul J. Nederkoorn, Peter J. Koudstaal, Aad van der Lugt and Daniel Bos

doi : 10.1161/STROKEAHA.121.036564

Stroke. 2022;53:370–378

Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes.

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Sex and Carotid Disease

Leo Bonati

doi : 10.1161/STROKEAHA.121.037638

Stroke. 2022;53:379–380

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Regulatory T Cells Contribute to Sexual Dimorphism in Neonatal Hypoxic-Ischemic Brain Injury

Lucia Beckmann, Stefanie Obst, Nicole Labusek, Hanna Abberger, Christian Köster, Ludger Klein-Hitpass, Sven Schumann, Christoph Kleinschnitz, Dirk M. Hermann, Ursula Felderhoff-Müser, Ivo Bendix, Wiebke Hansen and Josephine Herz

doi : 10.1161/STROKEAHA.121.037537

Stroke. 2022;53:381–390

Neonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of death and disability in newborns. Clinical and experimental studies suggest a sexual dimorphism in HI-induced brain injury and therapy responses. A major hallmark of HI pathophysiology is the infiltration of peripheral immune cells into the injured brain. However, the specific role of regulatory T cells (Tregs) in neonatal HI is still unknown.

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Vascular Contributions to Brain Health: Cross-Cutting Themes

Steven M. Greenberg

doi : 10.1161/STROKEAHA.121.034921

Stroke. 2022;53:391–393

As life expectancy grows, brain health is increasingly seen as central to what we mean by successful aging—and vascular brain health as central to overall brain health. Cerebrovascular pathologies are highly prevalent independent contributors to age-related cognitive impairment and at least partly modifiable with available treatments. The current Focused Update addresses vascular brain health from multiple angles, ranging from pathophysiologic mechanisms and neuroimaging features to epidemiologic risk factors, social determinants, and candidate treatments. Here we highlight some of the shared themes that cut across these distinct perspectives: (1) the lifetime course of vascular brain injury pathogenesis and progression; (2) the scientific and ethical imperative to extend vascular brain health research in non-White and non-affluent populations; (3) the need for improved tools to study the cerebral small vessels themselves; (4) the potential role for brain recovery mechanisms in determining vascular brain health and resilience; and (5) the cross-pathway mechanisms by which vascular and neurodegenerative processes may interact. The diverse perspectives featured in this Focused Update offer a sense of the multidisciplinary approaches and collaborations that will be required to launch our populations towards improved brain health and successful aging.

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Risk Factors, Lifestyle Behaviors, and Vascular Brain Health

Rebecca F. Gottesman and Sudha Seshadri

doi : 10.1161/STROKEAHA.121.032610

Stroke. 2022;53:394–403

Although a relationship between traditional cardiovascular risk factors and stroke has long been recognized, these risk factors likely play a role in other aspects of brain health. Clinical stroke is only the tip of the iceberg of vascular brain injury that includes covert infarcts, white matter hyperintensities, and microbleeds. Furthermore, an individual’s risk for not only stroke but poor brain health includes not only these traditional vascular risk factors but also lifestyle and genetic factors. The purpose of this narrative review is to summarize the state of the evidence on traditional and nontraditional vascular risk factors and their contributions to brain health. Additionally, we will review important modifiers that interact with these risk factors to increase, or, in some cases, reduce risk of adverse brain health outcomes, with an emphasis on genes and biomarkers associated with Alzheimer disease. Finally, we will consider the importance of social determinants of health in brain health outcomes.

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Neuropathology of Vascular Brain Health: Insights From Ex Vivo Magnetic Resonance Imaging–Histopathology Studies in Cerebral Small Vessel Disease

Susanne J. van Veluw, Konstantinos Arfanakis and Julie A. Schneider

doi : 10.1161/STROKEAHA.121.032608

Stroke. 2022;53:404–415

Sporadic cerebral small vessel disease (SVD) is a major contributor to vascular cognitive impairment and dementia in the aging human brain. On neuropathology, sporadic SVD is characterized by abnormalities to the small vessels of the brain predominantly in the form of cerebral amyloid angiopathy and arteriolosclerosis. These pathologies frequently coexist with Alzheimer disease changes, such as plaques and tangles, in a single brain. Conversely, during life, magnetic resonance imaging (MRI) only captures the larger manifestations of SVD in the form of parenchymal brain abnormalities. There appears to be a major knowledge gap regarding the underlying neuropathology of individual MRI-detectable SVD abnormalities. Ex vivo MRI in postmortem human brain tissue is a powerful tool to bridge this gap. This review summarizes current insights into the histopathologic correlations of MRI manifestations of SVD, their underlying cause, presumed pathophysiology, and associated secondary tissue injury. Moreover, we discuss the advantages and limitations of ex vivo MRI-guided histopathologic investigations and make recommendations for future studies.

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Imaging Markers of Vascular Brain Health: Quantification, Clinical Implications, and Future Directions

Prashanthi Vemuri, Charles Decarli and Marco Duering

doi : 10.1161/STROKEAHA.120.032611

Stroke. 2022;53:416–426

Cerebrovascular disease (CVD) manifests through a broad spectrum of mechanisms that negatively impact brain and cognitive health. Oftentimes, CVD changes (excluding acute stroke) are insufficiently considered in aging and dementia studies which can lead to an incomplete picture of the etiologies contributing to the burden of cognitive impairment. Our goal with this focused review is 3-fold. First, we provide a research update on the current magnetic resonance imaging methods that can measure CVD lesions as well as early CVD-related brain injury specifically related to small vessel disease. Second, we discuss the clinical implications and relevance of these CVD imaging markers for cognitive decline, incident dementia, and disease progression in Alzheimer disease, and Alzheimer-related dementias. Finally, we present our perspective on the outlook and challenges that remain in the field. With the increased research interest in this area, we believe that reliable CVD imaging biomarkers for aging and dementia studies are on the horizon.

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Inflammation and the Link to Vascular Brain Health: Timing Is Brain

Katherine T. Mun and Jason D. Hinman

doi : 10.1161/STROKEAHA.121.032613

Stroke. 2022;53:427–436

Inflammation and its myriad pathways are now recognized to play both causal and consequential roles in vascular brain health. From acting as a trigger for vascular brain injury, as evidenced by the COVID-19 pandemic, to steadily increasing the risk for chronic cerebrovascular disease, distinct inflammatory cascades play differential roles in varying states of cerebrovascular injury. New evidence is regularly emerging that characterizes the role of specific inflammatory pathways in these varying states including those at risk for stroke and chronic cerebrovascular injury as well as during the acute, subacute, and repair phases of stroke. Here, we aim to highlight recent basic science and clinical evidence for many distinct inflammatory cascades active in these varying states of cerebrovascular injury. The role of cerebrovascular infections, spotlighted by the severe acute respiratory syndrome coronavirus 2 pandemic, and its association with increased stroke risk is also reviewed. Rather than converging on a shared mechanism, these emerging studies implicate varied and distinct inflammatory processes in vascular brain injury and repair. Recognition of the phasic nature of inflammatory cascades on varying states of cerebrovascular disease is likely essential to the development and implementation of an anti-inflammatory strategy in the prevention, treatment, and repair of vascular brain injury. Although advances in revascularization have taught us that time is brain, targeting inflammation for the treatment of cerebrovascular disease will undoubtedly show us that timing is brain.

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Epidemiologic Trends, Social Determinants, and Brain Health: The Role of Life Course Inequalities

Saima Hilal and Carol Brayne

doi : 10.1161/STROKEAHA.121.032609

Stroke. 2022;53:437–443

Brain health as expressed in our mental health and occurrence of specific disorders such as dementia and stroke is vitally important to quality of life, functional independence, and risk of institutionalization. Maintaining brain health is, therefore, a societal imperative, and public health challenge, from prevention of acquisition of brain disorders, through protection and risk reduction to supporting those with such disorders through effective societal and system approaches. To identify possible mechanisms that explain the differential effect of potentially modifiable risk factors, and factors that may mitigate risk, a life course approach is needed. This is key to understanding how poor health can accumulate from the earliest life stages. It also allows us to integrate and investigate key material, behavioral, and psychological factors that generate health inequalities within and across communities and societies. This review provides a narrative on how brain health is intimately linked to wider health determinants, thus importance for clinicians and societies alike. There is compelling evidence accumulated from research over decades that socioeconomic status, higher education, and healthy lifestyle extend life and compress major morbidities into later life. Brain health is part of this, but collective action has been limited, partly because of the separation of disciplines and focus on highly reductionist approaches in that clinicians and associated research have focused more on mitigation and early detection of specific diseases. However, clinicians could be part of the drive for better brain health for all society to support life courses that have more protection and less risk. There is evidence of change in such risks for conditions such as stroke and dementia across generations. The evidence points to the importance of starting with parental health and life course inequalities as a central focus.

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Trials and Treatments for Vascular Brain Health: Risk Factor Modification and Cognitive Outcomes

Miia Kivipelto, Katie Palmer, Tina D. Hoang and Kristine Yaffe

doi : 10.1161/STROKEAHA.121.032614

Stroke. 2022;53:444–456

There is robust evidence linking vascular health to brain health, cognition, and dementia. In this article, we present evidence from trials of vascular risk factor treatment on cognitive outcomes. We summarize findings from randomized controlled trials of antihypertensives, lipid-lowering medications, diabetes treatments (including antidiabetic drugs versus placebo, and intensive versus standard glycemic control), and multidomain interventions (that target several domains simultaneously such as control of vascular and metabolic factors, nutrition, physical activity, and cognitive stimulation etc). We report that evidence on the efficacy of vascular risk reduction interventions is promising, but not yet conclusive, and several methodological limitations hamper interpretation. Evidence mainly comes from high-income countries and, as cognition and dementia have not been the primary outcomes of many trials, evaluation of cognitive changes have often been limited. As the cognitive aging process occurs over decades, it is unclear whether treatment during the late-life window is optimal for dementia prevention, yet older individuals have been the target of most trials thus far. Further, many trials have not been powered to explore interactions with modifiers such as age, race, and apolipoprotein E, even though sub-analyses from some trials indicate that the success of interventions differs depending on patient characteristics. Due to the complex multifactorial etiology of dementia, and variations in risk factors between individuals, multidomain interventions targeting several risk factors and mechanisms are likely to be needed and the long-term sustainability of preventive interventions will require personalized approaches that could be facilitated by digital health tools. This is especially relevant during the COVID-19 pandemic, where intervention strategies will need to be adapted to the new normal, when face-to-face engagement with participants is limited and public health measures may create changes in lifestyle that affect individuals’ vascular risk profiles and subsequent risk of cognitive decline.

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Intracranial Hemorrhage in the TST Trial

Pierre Amarenco, Jong S. Kim, Julien Labreuche, Hugo Charles, Maurice Giroud, Philippa C. Lavallée, Byung-Chul Lee, Marie-Hélène Mahagne, Elena Meseguer, Norbert Nighoghossian, Philippe Gabriel Steg, Éric Vicaut and Eric Bruckert

doi : 10.1161/STROKEAHA.121.035846

Stroke. 2022;53:457–462

Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH.

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Lowering Cholesterol and Intracerebral Hemorrhage: There Won’t Be Blood!

Seemant Chaturvedi

doi : 10.1161/STROKEAHA.121.037523

Stroke. 2022;53:463–464

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Application of Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping Score for Efficacy of Clopidogrel: Secondary Analysis of the CHANCE Trial

Liye Dai, Jie Xu, Hongyi Yan, Zimo Chen, Yuesong Pan, Xia Meng, Hao Li and Yongjun Wang

doi : 10.1161/STROKEAHA.120.033049

Stroke. 2022;53:465–472

The age, body mass index, chronic kidney disease, diabetes, and genotyping (ABCD-GENE) score is a validated risk score integrating CYP2C19 genotypes with clinical risk factors influencing clopidogrel response that would allow the more precise identification of subjects at risk for high platelet reactivity and adverse clinical outcomes. Our objective was to further verify application of the ABCD-GENE score and investigate appropriate cutoff value in patients with minor stroke or transient ischemic attack.

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The Stockholm Stroke Triage Project: Outcomes of Endovascular Thrombectomy Before and After Triage Implementation

Boris Keselman, Annika Berglund, Niaz Ahmed, Matteo Bottai, Mia von Euler, Staffan Holmin, Ann-Charlotte Laska, Jan M. Mathé, Christina Sjöstrand, Einar E. Eriksson and Michael V. Mazya

doi : 10.1161/STROKEAHA.121.034195

Stroke. 2022;53:473–481

The Stockholm Stroke Triage System (SSTS) is a prehospital algorithm for detection of endovascular thrombectomy (EVT)-eligible patients, combining symptom severity assessment and ambulance-to-hospital teleconsultation, leading to a decision on primary stroke center bypass. In the Stockholm Region (6 primary stroke centers, 1 EVT center), SSTS implementation in October 2017 reduced onset-to-EVT time by 69 minutes. We compared clinical outcomes before and after implementation of SSTS in an observational study.

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Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke

Jose G. Romano, Hannah Gardener, Eric E. Smith, Iszet Campo-Bustillo, Yosef Khan, Sofie Tai, Nikesha Riley, Ralph L. Sacco, Pooja Khatri, Heather M. Alger, Brian Mac Grory, Deepak Gulati, Navdeep S. Sangha, Karin E. Olds, Curtis G. Benesch, Adam G. Kelly, Scott S. Brehaut, Amit C. Kansara and Lee H. Schwamm

doi : 10.1161/STROKEAHA.121.034124

Stroke. 2022;53:482–487

Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized.

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Long-Term Impact of Urgent Secondary Prevention After Transient Ischemic Attack and Minor Stroke: Ten-Year Follow-Up of the EXPRESS Study

Ramon Luengo-Fernandez, Linxin Li, Louise Silver, Sergei Gutnikov, Nicola C. Beddows and Peter M. Rothwell

doi : 10.1161/STROKEAHA.121.034279

Stroke. 2022;53:488–496

Urgent assessment aimed at reducing stroke risk after transient ischemic attack or minor stroke is cost-effective over the short-term. However, it is unclear if the short-term impact is lost on long-term follow-up, with recurrent events being delayed rather than prevented. By 10-year follow-up of the EXPRESS study (Early Use of Existing Preventive Strategies for Stroke), previously showing urgent assessment reduced 90-day stroke risk by 80%, we determined whether that early benefit was still evident long-term for stroke risk, disability, and costs.

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Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation

Laurent Fauchier, Arnaud Bisson, Alexandre Bodin, Julien Herbert, Pascal Spiesser, Bertrand Pierre, Nicolas Clementy, Anne Bernard, Dominique Babuty and Gregory Y.H. Lip

doi : 10.1161/STROKEAHA.121.034213

Stroke. 2022;53:497–504

Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not.

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Impact of Delirium on Outcomes After Intracerebral Hemorrhage

Michael E. Reznik, Seth A. Margolis, Ali Mahta, Linda C. Wendell, Bradford B. Thompson, Christoph Stretz, James L. Rudolph, Olga Boukrina, A.M. Barrett, Lori A. Daiello, Richard N. Jones and Karen L. Furie

doi : 10.1161/STROKEAHA.120.034023

Stroke. 2022;53:505–513

Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site.

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Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants

Alexander Humberg, Mark Dzietko, Sören Schulz, Ursula Felderhoff-Müser, Britta Hüning, Anja Stein, Mats I. Fortmann, Janina Marissen, Tanja K. Rausch, Egbert Herting, Christoph Härtel, Wolfgang Göpel and German Neonatal Network (GNN)

doi : 10.1161/STROKEAHA.120.033432

Stroke. 2022;53:514–522

Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-?4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age.

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Cerebral Small Vessel Disease and Depression Among Intracerebral Hemorrhage Survivors

Juan Pablo Castello, Marco Pasi, Patryk Kubiszewski, Jessica R. Abramson, Andreas Charidimou, Christina Kourkoulis, Zora DiPucchio, Kristin Schwab, Christopher D. Anderson, M. Edip Gurol, Steven M. Greenberg, Jonathan Rosand, Anand Viswanathan and Alessandro Biffi

doi : 10.1161/STROKEAHA.121.035488

Stroke. 2022;53:523–531

Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment.

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Hematoma Expansion and Clinical Outcomes in Patients With Factor-Xa Inhibitor–Related Atraumatic Intracerebral Hemorrhage Treated Within the ANNEXA-4 Trial Versus Real-World Usual Care

Hagen B. Huttner, Stefan T. Gerner, Joji B. Kuramatsu, Stuart J. Connolly, Jan Beyer-Westendorf, Andrew M. Demchuk, Saskia Middeldorp, Elena Zotova, Julia Altevers, Frank Andersohn, Mary J. Christoph, Patrick Yue, Leonhard Stross and Stefan Schwab

doi : 10.1161/STROKEAHA.121.034572

Stroke. 2022;53:532–543

It is unestablished whether andexanet alfa, compared with guideline-based usual care including prothrombin complex concentrates, is associated with reduced hematoma expansion (HE) and mortality in patients with factor-Xa inhibitor–related intracerebral hemorrhage (ICH). We compared the occurrence of HE and clinical outcomes in patients treated either with andexanet alfa or with usual care during the acute phase of factor-Xa inhibitor–related ICH.

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Relation Between the Corticospinal Tract State and Activities of Daily Living in Patients With Intracerebral Hemorrhage

Sung Ho Jang and Eun Bi Choi

doi : 10.1161/STROKEAHA.121.034939

Stroke. 2022;53:544–551

We investigated the relation between the ipsilesional corticospinal tract (CST) state and activity of daily living independence in patients with chronic intracerebral hemorrhage.

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Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy

Emma A. Koemans, Sabine Voigt, Ingeborg Rasing, Thijs W. van Harten, Wilmar M.T. Jolink, Floris H.B.M. Schreuder, Erik W. van Zwet, Mark A. van Buchem, Matthias J.P. van Osch, Gisela M. Terwindt, Catharina J.M. Klijn, Marianne A.A. van Walderveen and Marieke J.H. Wermer

doi : 10.1161/STROKEAHA.121.035019

Stroke. 2022;53:552–557

Although evidence accumulates that the cerebellum is involved in cerebral amyloid angiopathy (CAA), cerebellar superficial siderosis is not considered to be a disease marker. The objective of this study is to investigate cerebellar superficial siderosis frequency and its relation to hemorrhagic magnetic resonance imaging markers in patients with sporadic and Dutch-type hereditary CAA and patients with deep perforating arteriopathy–related intracerebral hemorrhage.

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Phenotypes of Chronic Covert Brain Infarction in Patients With First-Ever Ischemic Stroke: A Cohort Study

Jan Vynckier, Johannes Kaesmacher, Joanna Marguerite Wardlaw, Laurent Roten, Morin Beyeler, Nebiyat Filate Belachew, Lorenz Grunder, David Julian Seiffge, Simon Jung, Jan Gralla, Tomas Dobrocky, Mirjam Rachel Heldner, Ulrike Prange, Martina Béatrice Goeldlin, Marcel Arnold, Urs Fischer and Thomas Raphael Meinel

doi : 10.1161/STROKEAHA.121.034347

Stroke. 2022;53:558–568

The aim of this study was to assess the rate of chronic covert brain infarctions (CBIs) in patients with acute ischemic stroke (AIS) and to describe their phenotypes and diagnostic value.

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Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging

Anke Wouters, David Robben, Soren Christensen, Henk A. Marquering, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Diederik W.J. Dippel, Charles B.L.M. Majoie, Wouter J. Schonewille, Aad van der Lugt, Maarten Lansberg, Gregory W. Albers, Paul Suetens and Robin Lemmens

doi : 10.1161/STROKEAHA.121.034444

Stroke. 2022;53:569–577

Computed tomography perfusion imaging allows estimation of tissue status in patients with acute ischemic stroke. We aimed to improve prediction of the final infarct and individual infarct growth rates using a deep learning approach.

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Fast Outcome Categorization of the Upper Limb After Stroke

Harry T. Jordan, Joia Che, Winston D. Byblow and Cathy M. Stinear

doi : 10.1161/STROKEAHA.121.035170

Stroke. 2022;53:578–585

The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The COVID-19 pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks.

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Subacute AMD3100 Treatment Is Not Efficient in Neonatal Hypoxic-Ischemic Rats

Daiane Aparecida Spiess, Raquel Maria Pereira Campos, Luciana Conde, Nadine Didwischus, Johannes Boltze, Rosalia Mendez-Otero and Pedro Moreno Pimentel-Coelho

doi : 10.1161/STROKEAHA.120.033768

Stroke. 2022;53:586–594

Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE.

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Imaging High-Risk Atherothrombosis Using a Novel Fibrin-Binding Positron Emission Tomography Probe

David Izquierdo-Garcia, Himashinie Diyabalanage, Ian A. Ramsay, Nicholas J. Rotile, Adam Mauskapf, Ji-Kyung Choi, Thomas Witzel, Valerie Humblet, Farouc A. Jaffer, Anna-Liisa Brownell, Ahmed Tawakol, Ciprian Catana, Mark F. Conrad, Peter Caravan and Ilknur Ay

doi : 10.1161/STROKEAHA.121.035638

Stroke. 2022;53:595–604

High-risk atherosclerosis is an underlying cause of cardiovascular events, yet identifying the specific patient population at immediate risk is still challenging. Here, we used a rabbit model of atherosclerotic plaque rupture and human carotid endarterectomy specimens to describe the potential of molecular fibrin imaging as a tool to identify thrombotic plaques.

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First Pass Effect With Neurothrombectomy for Acute Ischemic Stroke: Analysis of the Systematic Evaluation of Patients Treated With Stroke Devices for Acute Ischemic Stroke Registry

Ashutosh P. Jadhav, Shashvat M. Desai, Osama O. Zaidat, Raul G. Nogueira, Tudor G. Jovin, Diogo C. Haussen, Nils Mueller-Kronast and David S. Liebeskind

doi : 10.1161/STROKEAHA.121.035457

Stroke. 2022;53:e30–e32

Achieving complete revascularization after a single pass of a mechanical thrombectomy device (first pass effect [FPE]) is associated with good clinical outcomes in patients with acute ischemic stroke due to large vessel occlusion. We assessed patient characteristics, outcomes, and predictors of FPE among a large real-world cohort of patients (Systematic Evaluation of Patients Treated with Stroke Devices for Acute Ischemic Stroke registry).

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Carotid Web Phenotype Is Uncommonly Associated With Classic Fibromuscular Dysplasia: A Retrospective Observational Study

Vera Sharashidze, Raul G. Nogueira, Alhamza R. Al-Bayati, Nirav Bhatt, Fadi B Nahab, Johanna Yun, Jason W. Allen, Michael Frankel and Diogo C Haussen

doi : 10.1161/STROKEAHA.121.036188

Stroke. 2022;53:e33–e36

Carotid web (CaW) is an intimal form of fibromuscular dysplasia (FMD) involving the carotid bulb which has been increasingly recognized as a potential cause of recurrent ischemic strokes. It is overlooked as a separate entity and often dismissed if no coexistent signs of classic FMD changes are observed. We aim to evaluate the frequency of classic FMD in high-yield vascular territories in patients with symptomatic CaW.

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Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice

Saif Ahmad, Seth Truran, Nina Karamanova, Adam Kindelin, Maria Lozoya, Volkmar Weissig, Hannah Emerson, Daniel R. Griffiths, Tyler Vail, Jonathan Lifshitz, Andrew F. Ducruet and Raymond Q. Migrino

doi : 10.1161/STROKEAHA.121.037120

Stroke. 2022;53:e37–e41

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phosphatidylcholine, cholesterol, and monosialogangliosides (nanoliposomes) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that nanoliposomes will preserve human neuroblastoma (SH-SY5Y) and human brain microvascular endothelial cells viability following oxygen-glucose deprivation (OGD)–reoxygenation and will reduce injury in mice following middle cerebral artery occlusion.

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Cannabis Use and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Joshua S. Catapano, Kavelin Rumalla, Visish M. Srinivasan, Mohamed A. Labib, Candice L. Nguyen, Caleb Rutledge, Redi Rahmani, Jacob F. Baranoski, Tyler S. Cole, Ashutosh P. Jadhav, Andrew F. Ducruet, Joseph M. Zabramski, Felipe C. Albuquerque and Michael T. Lawton

doi : 10.1161/STROKEAHA.121.035650

Stroke. 2022;53:e42–e43

Growing evidence links cannabis use to cerebrovascular disease, including aneurysmal subarachnoid hemorrhage (aSAH)1 and acute ischemic stroke.2 In a population-based study, the aSAH incidence was twice as high in cannabis users as in nonusers in a younger age group.3 The pathophysiology of this association is unknown, but research suggests that multifocal intracranial stenosis, oxidative stress, and cerebral mitochondrial dysfunction are contributors. Given the popularization of cannabis use in the United States, it is essential to continue evaluating the associated risks and benefits. This study investigates the effects of cannabis on delayed cerebral ischemia (DCI) and other outcomes of patients with aSAH.

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Can Marijuana Use Lead to Cerebral Ischemia?

Feras Akbik and Ofer Sadan

doi : 10.1161/STROKEAHA.121.037791

Stroke. 2022;53:e44–e46

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International Study of Intracranial Aneurysm Treatment Using Woven EndoBridge: Results of the WorldWideWEB Consortium

Adam A. Dmytriw, Jose Danilo Bengzon Diestro, Mahmoud Dibas, Kevin Phan, Ahmad Sweid, Hugo H. Cuellar-Saenz, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Ali Al Balushi, Sri Hari Sundararajan, Joseph Carnevale, Guillaume Saliou, Markus Möhlenbruch, Justin E. Vranic, Pablo Harker, James D. Rabinov, Ivan Lylyk, Paul M. Foreman, Jay A. Vachhani, Vedran Župan?i?, Muhammad U. Hafeez, Caleb Rutledge, Muhammad Waqas, Vincent M. Tutino, Rawad Abbas, Yasuaki Inoue, Carolina Capirossi, Yifan Ren, Clemens M. Schirmer, Mariangela Piano, Anna Luisa Kühn, Caterina Michelozzi, Stéphanie Elens, Robert W. Regenhardt, Sherief Ghozy, Naif M. Alotaibi, Stavropoula Tjoumakaris, Robert M. Starke, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Christoph J. Griessenauer, Christian Ulfert, Hamed Asadi, Mark Brooks, Julian Maingard, Ashu Jhamb, Adnan Siddiqui, Andrew F. Ducruet, Felipe C. Albuquerque, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Amey Savardekar, Srikanth Boddu, Jared Knopman, Nicola Limbucci, Karen S. Chen, Mohammad A. Aziz-Sultan, Christopher J. Stapleton, Pascal Jabbour, Christophe Cognard, Aman B. Patel and Nimer Adeeb

doi : 10.1161/STROKEAHA.121.037609

Stroke. 2022;53:e47–e49

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Higher Risk of Ischemic Stroke After an Intracerebral Hemorrhage Than in General Population: A Cohort Study From the United Kingdom

David Gaist, Antonio Gonzáléz-Pérez, Stine Munk Hald and Luis Alberto García Rodríguez

doi : 10.1161/STROKEAHA.121.037633

Stroke. 2022;53:e50–e52

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Advances in Stroke: Stroke in Women

Cheryl D. Bushnell and Moira K. Kapral

doi : 10.1161/STROKEAHA.121.036975

Stroke. 2022;53:605–607

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Advances in Stroke: Treatments-Preventive

Else Charlotte Sandset and Larry B. Goldstein

doi : 10.1161/STROKEAHA.121.036977

Stroke. 2022;53:608–610

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Carotid Interventions for Women: The Hazards and Benefits

Caron Rockman, Valeria Caso and Peter A. Schneider

doi : 10.1161/STROKEAHA.121.035386

Stroke. 2022;53:611–623

The goal of the current review is to examine the hazards and benefits of carotid interventions in women and to provide recommendations for the indications for carotid intervention in female patients. Stroke and cerebrovascular disease are prevalent in women. There are inherent biological and other differences in men and women, which affect the manifestations and outcome of stroke, with women experiencing worse disability and higher mortality following ischemic stroke than men. Due to the underrepresentation of female patients in most clinical trials, the ability to make firm but alternative recommendations for women specifically on the management of carotid stenosis is challenging. Although some data suggest that women might have worse periprocedural outcomes as compared to men following all carotid revascularization procedures, there is also an abundance of data to support a similar risk for carotid procedures in men and women, especially with carotid endarterectomy and transcarotid artery revascularization. Therefore, the indications for carotid revascularization are the same in women as they are in men. The choice of a carotid revascularization procedure in women is based upon the same factors as in men and requires careful evaluation of a particular patient’s risk profile, anatomic criteria, plaque morphology, and medical comorbidities that might favor one technique over the other. When performing carotid revascularization procedures in women, tailored techniques and procedures to address the small diameter of the female artery are warranted.

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Sex Differences in Cerebral Aneurysms and Subarachnoid Hemorrhage

Angelica M. Fuentes, Laura Stone McGuire and Sepideh Amin-Hanjani

doi : 10.1161/STROKEAHA.121.037147

Stroke. 2022;53:624–633

Sex differences in cerebral aneurysm occurrence and characteristics have been well described. Although sex differences in outcomes following ischemic stroke have been identified, the effect of sex on outcomes following hemorrhagic stroke, and in particular, aneurysm treatment has been less studied. We describe the current state of knowledge regarding the impact of sex on treatment and outcomes of cerebral aneurysms. Although prior studies suggest that aneurysm prevalence and progression may be related to sex, we did not find clear evidence that outcomes following subarachnoid hemorrhage vary based on sex. Last, we identify areas for future research that could enhance understanding of the role sex plays in this context.

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