Pub Date : 2026-01-02DOI: 10.1161/STROKEAHA.125.053704
Guangyu Han, Shuling Wan, Xunming Ji, Ran Meng, Da Zhou
Background: Genetic predisposition is increasingly recognized as an important contributor to cerebral venous thrombosis (CVT), yet findings from individual studies remain inconsistent. We conducted an updated meta-analysis to quantify associations between specific genetic variants and adult CVT.
Methods: We systematically searched PubMed, EMBASE, and Web of Science up to January 2025 for case-control studies comparing the prevalence of genetic variants in adults with CVT versus healthy controls. Pooled odds ratios (ORs) with 95% CIs were calculated using random-effects models in this meta-analysis.
Results: Sixty-one studies comprising 4106 patients with CVT and 12 323 controls were analyzed. Significant associations were identified for germline variants, including factor V Leiden (238/2753 [8.6%] versus 387/8747 [4.4%]; OR, 2.59 [95% CI, 2.06-3.26]; P<0.00001), prothrombin G20210A (290/2483 [11.7%] versus 235/8197 [2.9%]; OR, 6.05 [95% CI, 4.59-7.98]; P<0.00001), and inherited deficiencies of protein C (24/624 [3.8%] versus 7/2027 [0.3%]; OR, 10.30 [95% CI, 4.19-25.30]; P<0.00001), protein S (9/567 [1.6%] versus 1/1125 [0.1%]; OR, 6.86 [95% CI, 2.12-22.24]; P=0.001), and antithrombin (11/440 [2.5%] versus 3/989 [0.3%]; OR, 5.73 [95% CI, 1.98-16.55]; P=0.001). The somatic JAK-2 (Janus kinase-2) V617F mutation was likewise associated with increased risk (27/569 [4.7%] versus 13/1777 [0.7%]; OR, 9.17 [95% CI, 3.61-23.27]; P<0.00001). By contrast, MTHFR (methylenetetrahydrofolate reductase) C677T and PAI-1 (plasminogen activator inhibitor-1) 4G/5G polymorphisms showed no significant associations. Overall effect sizes were comparable to those reported in pediatric CVT but exceeded those in adult arterial ischemic stroke.
Conclusions: These findings support a genetic basis for adult CVT. Risk associations are broadly similar to pediatric CVT yet stronger than those reported for adult arterial ischemic stroke, highlighting distinct patterns of genetic susceptibility in venous stroke and the potential value of selective genetic testing for risk stratification and management.
{"title":"Genetic Susceptibility to Adult Cerebral Venous Thrombosis: An Updated Meta-Analysis of Candidate Gene Studies.","authors":"Guangyu Han, Shuling Wan, Xunming Ji, Ran Meng, Da Zhou","doi":"10.1161/STROKEAHA.125.053704","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.053704","url":null,"abstract":"<p><strong>Background: </strong>Genetic predisposition is increasingly recognized as an important contributor to cerebral venous thrombosis (CVT), yet findings from individual studies remain inconsistent. We conducted an updated meta-analysis to quantify associations between specific genetic variants and adult CVT.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, and Web of Science up to January 2025 for case-control studies comparing the prevalence of genetic variants in adults with CVT versus healthy controls. Pooled odds ratios (ORs) with 95% CIs were calculated using random-effects models in this meta-analysis.</p><p><strong>Results: </strong>Sixty-one studies comprising 4106 patients with CVT and 12 323 controls were analyzed. Significant associations were identified for germline variants, including factor V Leiden (238/2753 [8.6%] versus 387/8747 [4.4%]; OR, 2.59 [95% CI, 2.06-3.26]; <i>P</i><0.00001), prothrombin G20210A (290/2483 [11.7%] versus 235/8197 [2.9%]; OR, 6.05 [95% CI, 4.59-7.98]; <i>P</i><0.00001), and inherited deficiencies of protein C (24/624 [3.8%] versus 7/2027 [0.3%]; OR, 10.30 [95% CI, 4.19-25.30]; <i>P</i><0.00001), protein S (9/567 [1.6%] versus 1/1125 [0.1%]; OR, 6.86 [95% CI, 2.12-22.24]; <i>P</i>=0.001), and antithrombin (11/440 [2.5%] versus 3/989 [0.3%]; OR, 5.73 [95% CI, 1.98-16.55]; <i>P</i>=0.001). The somatic JAK-2 (Janus kinase-2) V617F mutation was likewise associated with increased risk (27/569 [4.7%] versus 13/1777 [0.7%]; OR, 9.17 [95% CI, 3.61-23.27]; <i>P</i><0.00001). By contrast, MTHFR (methylenetetrahydrofolate reductase) C677T and PAI-1 (plasminogen activator inhibitor-1) 4G/5G polymorphisms showed no significant associations. Overall effect sizes were comparable to those reported in pediatric CVT but exceeded those in adult arterial ischemic stroke.</p><p><strong>Conclusions: </strong>These findings support a genetic basis for adult CVT. Risk associations are broadly similar to pediatric CVT yet stronger than those reported for adult arterial ischemic stroke, highlighting distinct patterns of genetic susceptibility in venous stroke and the potential value of selective genetic testing for risk stratification and management.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1161/STROKEAHA.125.053343
Jaemin Shin, Keon-Joo Lee, Chi Kyung Kim, Kyumgmi Oh, Do Yeon Kim, Beom Joon Kim, Moon-Ku Han, Hyunsoo Kim, Joon-Tae Kim, Kang-Ho Choi, Dong-Ick Shin, Kyu Sun Yum, Jae-Kwan Cha, Dae-Hyun Kim, Dong-Eog Kim, Dong-Seok Gwak, Jong-Moo Park, Dongwhane Lee, Kyusik Kang, Soo Joo Lee, Jae Guk Kim, Kyung-Ho Yu, Mi-Sun Oh, Minwoo Lee, Keun-Sik Hong, Yong-Jin Cho, Hong-Kyun Park, Jay Chol Choi, Joong-Goo Kim, Tai Hwan Park, Sang-Soon Park, Jee-Hyun Kwon, Wook-Joo Kim, Jun Lee, Doo Hyuk Kwon, Sung-Il Sohn, Jeong-Ho Hong, Hyungjong Park, Kyungbok Lee, Jeong-Yoon Lee, Kwang-Yeol Park, Hae-Bong Jeong, Chulho Kim, Sang-Hwa Lee, Sung Hyuk Heo, Ho Geol Woo, Ji Sung Lee, Juneyoung Lee, Hee-Joon Bae
Background: Dual antiplatelet therapy (DAPT) is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack. However, the optimal timing for initiating DAPT remains unclear.
Methods: From a prospective multicenter cohort involving 20 stroke centers between January 2011 and April 2023, patients with minor noncardioembolic ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack who presented within 7 days of symptom onset were included. We evaluated outcomes based on in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a composite of recurrent stroke, myocardial infarction, and death within 90 days. Patients were grouped by time from symptom onset to hospital arrival: 0 to 24 hours, 24 to 72 hours, and >72 hours. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores. The adjusted models incorporated demographic factors, baseline clinical characteristics, vascular risk factors, stroke subtype, relevant arterial status, and prior antiplatelet use.
Results: Among the 41 530 patients (mean age, 66.3 years; 25 771 [62%] male), 25 112 (60.5%) received DAPT. The 90-day primary outcome occurred in 2663 (10.7%) of the DAPT group versus 1900 (11.6%) in the monotherapy group (hazard ratio, 0.82 [95% CI, 0.77-0.87]). The benefit of DAPT was most pronounced when initiated within 24 hours (hazard ratio, 0.74 [95% CI, 0.69-0.79]). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (hazard ratio, 1.00 [95% CI, 0.88-1.15]), and a higher risk was suggested for initiation beyond 72 hours (hazard ratio, 1.25 [95% CI, 1.01-1.55]). Time-dependent analysis showed a benefit crossing the null at ≈42 hours.
Conclusions: Early initiation of DAPT was associated with the greatest clinical benefit, consistent with current guideline recommendations. The therapeutic effect appeared to decline progressively beyond this period, with an estimated threshold around 42 hours.
{"title":"Timing of Initiation and Efficacy of Dual Antiplatelet Therapy in Minor Stroke or High-Risk TIA.","authors":"Jaemin Shin, Keon-Joo Lee, Chi Kyung Kim, Kyumgmi Oh, Do Yeon Kim, Beom Joon Kim, Moon-Ku Han, Hyunsoo Kim, Joon-Tae Kim, Kang-Ho Choi, Dong-Ick Shin, Kyu Sun Yum, Jae-Kwan Cha, Dae-Hyun Kim, Dong-Eog Kim, Dong-Seok Gwak, Jong-Moo Park, Dongwhane Lee, Kyusik Kang, Soo Joo Lee, Jae Guk Kim, Kyung-Ho Yu, Mi-Sun Oh, Minwoo Lee, Keun-Sik Hong, Yong-Jin Cho, Hong-Kyun Park, Jay Chol Choi, Joong-Goo Kim, Tai Hwan Park, Sang-Soon Park, Jee-Hyun Kwon, Wook-Joo Kim, Jun Lee, Doo Hyuk Kwon, Sung-Il Sohn, Jeong-Ho Hong, Hyungjong Park, Kyungbok Lee, Jeong-Yoon Lee, Kwang-Yeol Park, Hae-Bong Jeong, Chulho Kim, Sang-Hwa Lee, Sung Hyuk Heo, Ho Geol Woo, Ji Sung Lee, Juneyoung Lee, Hee-Joon Bae","doi":"10.1161/STROKEAHA.125.053343","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.053343","url":null,"abstract":"<p><strong>Background: </strong>Dual antiplatelet therapy (DAPT) is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack. However, the optimal timing for initiating DAPT remains unclear.</p><p><strong>Methods: </strong>From a prospective multicenter cohort involving 20 stroke centers between January 2011 and April 2023, patients with minor noncardioembolic ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack who presented within 7 days of symptom onset were included. We evaluated outcomes based on in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a composite of recurrent stroke, myocardial infarction, and death within 90 days. Patients were grouped by time from symptom onset to hospital arrival: 0 to 24 hours, 24 to 72 hours, and >72 hours. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores. The adjusted models incorporated demographic factors, baseline clinical characteristics, vascular risk factors, stroke subtype, relevant arterial status, and prior antiplatelet use.</p><p><strong>Results: </strong>Among the 41 530 patients (mean age, 66.3 years; 25 771 [62%] male), 25 112 (60.5%) received DAPT. The 90-day primary outcome occurred in 2663 (10.7%) of the DAPT group versus 1900 (11.6%) in the monotherapy group (hazard ratio, 0.82 [95% CI, 0.77-0.87]). The benefit of DAPT was most pronounced when initiated within 24 hours (hazard ratio, 0.74 [95% CI, 0.69-0.79]). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (hazard ratio, 1.00 [95% CI, 0.88-1.15]), and a higher risk was suggested for initiation beyond 72 hours (hazard ratio, 1.25 [95% CI, 1.01-1.55]). Time-dependent analysis showed a benefit crossing the null at ≈42 hours.</p><p><strong>Conclusions: </strong>Early initiation of DAPT was associated with the greatest clinical benefit, consistent with current guideline recommendations. The therapeutic effect appeared to decline progressively beyond this period, with an estimated threshold around 42 hours.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-14DOI: 10.1161/STROKEAHA.125.050399
Shiv Bhakta, John J McCabe, Jason M Tarkin, Mohammed M Chowdhury, Jessica Redgrave, James H F Rudd, Peter J Kelly, Elizabeth A Warburton, Nicholas R Evans
Carotid atherosclerosis is a significant cause of incident and recurrent ischemic stroke, with risk not solely related to the degree of luminal stenosis. Multimodal imaging approaches, including positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging, can provide anatomic and molecular evaluation of the atherosclerotic plaque in vivo. Plaque pathophysiology-including the key processes of inflammation and microcalcification-may help characterize stroke risk beyond conventional anatomic assessment alone. This review discusses the use of positron emission tomography in the investigation of carotid atherosclerosis, including methodological considerations, its contributions to our understanding of the underlying disease processes, and how imaging can be used in interventional trials. The clinical implications and potential future applications of positron emission tomography in the assessment and treatment of cerebrovascular disease are also examined.
{"title":"PET Imaging of Carotid Atherosclerosis: Methodology, Implications, and Applications in Neurovascular Disease.","authors":"Shiv Bhakta, John J McCabe, Jason M Tarkin, Mohammed M Chowdhury, Jessica Redgrave, James H F Rudd, Peter J Kelly, Elizabeth A Warburton, Nicholas R Evans","doi":"10.1161/STROKEAHA.125.050399","DOIUrl":"10.1161/STROKEAHA.125.050399","url":null,"abstract":"<p><p>Carotid atherosclerosis is a significant cause of incident and recurrent ischemic stroke, with risk not solely related to the degree of luminal stenosis. Multimodal imaging approaches, including positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging, can provide anatomic and molecular evaluation of the atherosclerotic plaque in vivo. Plaque pathophysiology-including the key processes of inflammation and microcalcification-may help characterize stroke risk beyond conventional anatomic assessment alone. This review discusses the use of positron emission tomography in the investigation of carotid atherosclerosis, including methodological considerations, its contributions to our understanding of the underlying disease processes, and how imaging can be used in interventional trials. The clinical implications and potential future applications of positron emission tomography in the assessment and treatment of cerebrovascular disease are also examined.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"254-264"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-30DOI: 10.1161/STR.0000000000000495
Renee Colsch, Wendy Dusenbury, Michelle Camicia, Ann Leonhardt-Caprio, Andrea King, Mulubrhan Mogos, Robert Moser, Jennifer Patterson, Stephanie Vaughn, Kori S Zachrison
Stroke remains a leading cause of morbidity and mortality in the United States, with rural-dwelling populations facing significant disparities in stroke prevalence, access to care, and outcomes. Rural-dwelling communities are particularly burdened by limited infrastructure and a higher prevalence of uncontrolled risk factors such as hypertension, diabetes, and obesity. Geographic isolation and long distances to medical facilities hinder timely access to acute stroke care. Nurses in rural settings are vital across the stroke care continuum, including prevention, acute management, and poststroke rehabilitation. They provide community-based education, conduct assessments, stabilize patients, and facilitate rehabilitation. However, rural-dwelling nurses face challenges, including limited access to specialized education, staffing shortages, and geographic barriers, that hinder the delivery of expert stroke care. Telemedicine and artificial intelligence-driven clinical support tools transform rural stroke care by enabling real-time specialist consultations and predictive analytics and enhancing decision-making capabilities. Despite its potential, telemedicine adoption in rural areas remains limited because of infrastructure constraints, resulting primarily from the high cost that low-volume facilities often cannot afford. This scientific statement explores the essential role of rural-dwelling nurses in stroke care and the barriers they face. Key initiatives are identified to enhance stroke care in rural areas, including telemedicine, artificial intelligence, innovative education models, and data-driven quality improvement efforts. Last, implications and resources for targeted nursing interventions to improve rural stroke outcomes, including promoting access to care through telehealth, ensuring ongoing education for rural-dwelling nurses, and advocating for the creation of stroke coordinator and champion roles in rural hospitals, are highlighted.
{"title":"Targeted Nursing Interventions for Improving Stroke Care and Outcomes in the Rural Setting: A Scientific Statement From the American Heart Association.","authors":"Renee Colsch, Wendy Dusenbury, Michelle Camicia, Ann Leonhardt-Caprio, Andrea King, Mulubrhan Mogos, Robert Moser, Jennifer Patterson, Stephanie Vaughn, Kori S Zachrison","doi":"10.1161/STR.0000000000000495","DOIUrl":"10.1161/STR.0000000000000495","url":null,"abstract":"<p><p>Stroke remains a leading cause of morbidity and mortality in the United States, with rural-dwelling populations facing significant disparities in stroke prevalence, access to care, and outcomes. Rural-dwelling communities are particularly burdened by limited infrastructure and a higher prevalence of uncontrolled risk factors such as hypertension, diabetes, and obesity. Geographic isolation and long distances to medical facilities hinder timely access to acute stroke care. Nurses in rural settings are vital across the stroke care continuum, including prevention, acute management, and poststroke rehabilitation. They provide community-based education, conduct assessments, stabilize patients, and facilitate rehabilitation. However, rural-dwelling nurses face challenges, including limited access to specialized education, staffing shortages, and geographic barriers, that hinder the delivery of expert stroke care. Telemedicine and artificial intelligence-driven clinical support tools transform rural stroke care by enabling real-time specialist consultations and predictive analytics and enhancing decision-making capabilities. Despite its potential, telemedicine adoption in rural areas remains limited because of infrastructure constraints, resulting primarily from the high cost that low-volume facilities often cannot afford. This scientific statement explores the essential role of rural-dwelling nurses in stroke care and the barriers they face. Key initiatives are identified to enhance stroke care in rural areas, including telemedicine, artificial intelligence, innovative education models, and data-driven quality improvement efforts. Last, implications and resources for targeted nursing interventions to improve rural stroke outcomes, including promoting access to care through telehealth, ensuring ongoing education for rural-dwelling nurses, and advocating for the creation of stroke coordinator and champion roles in rural hospitals, are highlighted.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"e45-e57"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-10-23DOI: 10.1161/STROKEAHA.125.053160
Shadi Yaghi, Farhan Khan, Skylar Lewis, Ava Stipanovich, Richard Choi, Richard Baker, Sami Al Kasab, Ahmad Abu Qdais, Sridhara S Yaddanapudi, Sabiha Sultana, Muhib Khan, Maarij Malik, James Klaas, Ekaterina Bakradze, Muhammad Aemaz Ur Rehman, Christopher Leon Guerrero, Hadley Walsh Ressler, Faddi G Saleh Velez, Cameron Owens, Camila Bonin Pinto, Margy McCullough-Hicks, Dawson Cooper, Abhiram Parameswaran Pillai, Praveen Hariharan, Shaista Alam, Morgan Mayer, Mirjam R Heldner, Irina Kugler, Kateryna Antonenko, William Almiri, Sheila Martins, Thais L Secchi, Gabriel Mantovani, Aaron Rothstein, Kelly Sloane, Balaji Krishnaiah, Linda Alfred, Cheran Elangovan, Venugopalan Y Vishnu, Meena Chandu, Ayush Agarwal, Michele Romoli, Nicola Marrone, Stefano Vozzi, Malik Ghannam, Mohamed Elshikh, Mahmoud Dibas, Yan Hou, Krithika Peshwe, Ajay Tunguturi, João Pedro Marto, Rui Duarte Armindo, Jennifer Frontera, Lindsey Kuohn, Mohammad AlMajali, Osama O Zaidat, Benan Barakat, Niha Khan, Alexis N Simpkins, Shayak Sen, Mariana Coelho, Joao Sargento Fritas, Joao Andre Sousa, Diana Aguiar de Sousa, Mafalda Soares, Amanda Cyntia Lima Fonseca Rodrigues, Aditya Jhaveri, Rami Z Morsi, James Siegler, Yasmin N Aziz, Pablo Harker, Sonia Bhati, Sophia Vassilopoulou, Argyro Tountopoulou, Adam de Havenon, Varsha Muddasani, Nils Henninger, Hieu Tran, Johanna Helenius, Mohammad Khasawneh, Ananth Vellimana, Ryan Apfel, Amir Molaie, Marina Mannino, Valeria Terruso, Tarek El Halabi, Mahasen Reda, Christel Tamer, Piers Klein, Liqi Shu, Pooja Khatri, Karen Furie, Thanh N Nguyen, David S Liebeskind, Shyam Prabhakaran
Background: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion-specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume-were associated with recurrent ischemic stroke within 90 days.
Methods: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%-99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at Tmax (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome (P<0.1).
Results: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02-1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03-3.28]).
Conclusions: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.
{"title":"Impaired Perfusion and Early Ischemic Stroke Recurrence in Symptomatic Intracranial Atherosclerosis: BIORISK ICAS Study.","authors":"Shadi Yaghi, Farhan Khan, Skylar Lewis, Ava Stipanovich, Richard Choi, Richard Baker, Sami Al Kasab, Ahmad Abu Qdais, Sridhara S Yaddanapudi, Sabiha Sultana, Muhib Khan, Maarij Malik, James Klaas, Ekaterina Bakradze, Muhammad Aemaz Ur Rehman, Christopher Leon Guerrero, Hadley Walsh Ressler, Faddi G Saleh Velez, Cameron Owens, Camila Bonin Pinto, Margy McCullough-Hicks, Dawson Cooper, Abhiram Parameswaran Pillai, Praveen Hariharan, Shaista Alam, Morgan Mayer, Mirjam R Heldner, Irina Kugler, Kateryna Antonenko, William Almiri, Sheila Martins, Thais L Secchi, Gabriel Mantovani, Aaron Rothstein, Kelly Sloane, Balaji Krishnaiah, Linda Alfred, Cheran Elangovan, Venugopalan Y Vishnu, Meena Chandu, Ayush Agarwal, Michele Romoli, Nicola Marrone, Stefano Vozzi, Malik Ghannam, Mohamed Elshikh, Mahmoud Dibas, Yan Hou, Krithika Peshwe, Ajay Tunguturi, João Pedro Marto, Rui Duarte Armindo, Jennifer Frontera, Lindsey Kuohn, Mohammad AlMajali, Osama O Zaidat, Benan Barakat, Niha Khan, Alexis N Simpkins, Shayak Sen, Mariana Coelho, Joao Sargento Fritas, Joao Andre Sousa, Diana Aguiar de Sousa, Mafalda Soares, Amanda Cyntia Lima Fonseca Rodrigues, Aditya Jhaveri, Rami Z Morsi, James Siegler, Yasmin N Aziz, Pablo Harker, Sonia Bhati, Sophia Vassilopoulou, Argyro Tountopoulou, Adam de Havenon, Varsha Muddasani, Nils Henninger, Hieu Tran, Johanna Helenius, Mohammad Khasawneh, Ananth Vellimana, Ryan Apfel, Amir Molaie, Marina Mannino, Valeria Terruso, Tarek El Halabi, Mahasen Reda, Christel Tamer, Piers Klein, Liqi Shu, Pooja Khatri, Karen Furie, Thanh N Nguyen, David S Liebeskind, Shyam Prabhakaran","doi":"10.1161/STROKEAHA.125.053160","DOIUrl":"10.1161/STROKEAHA.125.053160","url":null,"abstract":"<p><strong>Background: </strong>Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion-specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume-were associated with recurrent ischemic stroke within 90 days.</p><p><strong>Methods: </strong>The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%-99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T<sub>max</sub> (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome (<i>P</i><0.1).</p><p><strong>Results: </strong>Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02-1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03-3.28]).</p><p><strong>Conclusions: </strong>Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"96-106"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12616403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145347480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-09-30DOI: 10.1161/STROKEAHA.125.052146
Joseph P Broderick, Eva A Mistry, Paul M Wechsler, Mitchell S V Elkind, David S Liebeskind, George Harston, Jake Wolenberg, Jennifer A Frontera, W Taylor Kimberly, Christopher G Favilla, Johannes Boltze, Johanna Ospel, Edgar A Samaniego, Opeolu Adeoye, Scott E Kasner, Lee H Schwamm, Gregory W Albers
The Stroke Treatment Academic Industry Roundtable convened a workshop regarding artificial intelligence (AI) and innovative clinical trial designs during the Stroke Treatment Academic Industry Roundtable XIII meeting on March 28, 2025. This forum brought together stroke physicians and researchers, and industry representatives to discuss the current use and future opportunities for AI and novel trial designs in acute stroke trials. AI already plays a substantial role in the treatment of acute stroke with regards to imaging but is poised to have a much larger impact in clinical care and research trials over the coming years. The quality and understanding of the data are used to train the AI, the human element needed to ensure training is successful, and the clinician and trialist at the bedside, the humans "in the loop," will be necessary to maximize AI's effectiveness in clinical practice and trials. Platform trials address multiple scientific questions in an area of medicine simultaneously within the same trial structure by sharing controls across multiple interventions. While platform trials increase efficiency and potentially decrease the time needed to answer important clinical scientific questions, they also can introduce complexity to standard workflows. Future acute ischemic stroke clinical trials should incorporate elements of pragmatic and patient-centered trial design when possible. Pragmatic trials aim to assess the effectiveness of treatments when they are implemented into routine clinical care rather than under idealized conditions. AI models and platform, pragmatic, and patient-centered trial designs are new tools to answer important clinical questions, but understanding how they work, their best uses, and their limitations is critical for accelerating successful new treatments for stroke.
{"title":"Artificial Intelligence and Novel Trial Designs for Acute Ischemic Stroke: Opportunities and Challenges.","authors":"Joseph P Broderick, Eva A Mistry, Paul M Wechsler, Mitchell S V Elkind, David S Liebeskind, George Harston, Jake Wolenberg, Jennifer A Frontera, W Taylor Kimberly, Christopher G Favilla, Johannes Boltze, Johanna Ospel, Edgar A Samaniego, Opeolu Adeoye, Scott E Kasner, Lee H Schwamm, Gregory W Albers","doi":"10.1161/STROKEAHA.125.052146","DOIUrl":"10.1161/STROKEAHA.125.052146","url":null,"abstract":"<p><p>The Stroke Treatment Academic Industry Roundtable convened a workshop regarding artificial intelligence (AI) and innovative clinical trial designs during the Stroke Treatment Academic Industry Roundtable XIII meeting on March 28, 2025. This forum brought together stroke physicians and researchers, and industry representatives to discuss the current use and future opportunities for AI and novel trial designs in acute stroke trials. AI already plays a substantial role in the treatment of acute stroke with regards to imaging but is poised to have a much larger impact in clinical care and research trials over the coming years. The quality and understanding of the data are used to train the AI, the human element needed to ensure training is successful, and the clinician and trialist at the bedside, the humans \"in the loop,\" will be necessary to maximize AI's effectiveness in clinical practice and trials. Platform trials address multiple scientific questions in an area of medicine simultaneously within the same trial structure by sharing controls across multiple interventions. While platform trials increase efficiency and potentially decrease the time needed to answer important clinical scientific questions, they also can introduce complexity to standard workflows. Future acute ischemic stroke clinical trials should incorporate elements of pragmatic and patient-centered trial design when possible. Pragmatic trials aim to assess the effectiveness of treatments when they are implemented into routine clinical care rather than under idealized conditions. AI models and platform, pragmatic, and patient-centered trial designs are new tools to answer important clinical questions, but understanding how they work, their best uses, and their limitations is critical for accelerating successful new treatments for stroke.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"265-274"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12695146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-22DOI: 10.1161/STROKEAHA.125.052598
Oriane Paradas, Jennifer Boisgontier, Lelio Guida, Manoelle Kossorotoff, Nathalie Boddaert
{"title":"From Stroke to Silence: Akinetic Mutism in a Teenager With Bithalamic Infarction: Role of the Cerebello-Rubro-Thalamo-Cortical Pathway.","authors":"Oriane Paradas, Jennifer Boisgontier, Lelio Guida, Manoelle Kossorotoff, Nathalie Boddaert","doi":"10.1161/STROKEAHA.125.052598","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052598","url":null,"abstract":"","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"57 1","pages":"e4-e5"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-12-22DOI: 10.1161/STROKEAHA.125.053534
Anushika Raheja, Deidre Anne De Silva, Kaavya Narasimhalu
Stroke is a leading cause of death and disability globally, with Asia disproportionately affected. A critical barrier to effective secondary prevention is the high prevalence of CYP2C19 loss-of-function alleles, present in almost 75% of South and East Asians, which reduce clopidogrel efficacy. Evidence from trials, including CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), shows that genotype-guided alternatives, including ticagrelor and cilostazol, substantially lower recurrent stroke risk in loss-of-function carriers. Yet, clinical adoption remains limited by insufficient genetic testing infrastructure, cost, guideline gaps, and clinician training. Despite these challenges, genotype-guided therapy is both feasible and cost-effective, with the potential to reduce recurrent strokes, disability, and healthcare burden. Urgent action is required to implement precision antiplatelet strategies, update guidelines, and ensure equitable access, making pharmacogenomics a central component of stroke care in Asia.
{"title":"Why Genetics Can't Be Ignored in Secondary Stroke Prevention: The <i>CYP2C19</i> Challenge in Asia.","authors":"Anushika Raheja, Deidre Anne De Silva, Kaavya Narasimhalu","doi":"10.1161/STROKEAHA.125.053534","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.053534","url":null,"abstract":"<p><p>Stroke is a leading cause of death and disability globally, with Asia disproportionately affected. A critical barrier to effective secondary prevention is the high prevalence of CYP2C19 loss-of-function alleles, present in almost 75% of South and East Asians, which reduce clopidogrel efficacy. Evidence from trials, including CHANCE-2 (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), shows that genotype-guided alternatives, including ticagrelor and cilostazol, substantially lower recurrent stroke risk in loss-of-function carriers. Yet, clinical adoption remains limited by insufficient genetic testing infrastructure, cost, guideline gaps, and clinician training. Despite these challenges, genotype-guided therapy is both feasible and cost-effective, with the potential to reduce recurrent strokes, disability, and healthcare burden. Urgent action is required to implement precision antiplatelet strategies, update guidelines, and ensure equitable access, making pharmacogenomics a central component of stroke care in Asia.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":"57 1","pages":"285-289"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-09-30DOI: 10.1161/STROKEAHA.125.052545
Alexander Martin, Vivian Fu, Zamir Joya, Sajida Joya, Allie Eathorne, Mark Weatherall, Gabrielle Shortt, Alex Semprini, John Gommans, Harry McNaughton
Background: The Take Charge intervention-a conversation-based, community intervention to improve motivation, improved independence, and physical health 12 months after stroke in 2 randomized controlled trials with 572 participants. This article reports long-term outcomes for the 400 participants in the TaCAS study (Taking Charge After Stroke).
Methods: Follow-up study of a New Zealand multicenter, randomized, controlled, parallel-group trial. Outcomes were collected by postal questionnaire or telephone call. The TaCAS study recruited 400 participants discharged after stroke, randomized within 16 weeks to one of 3 groups: 1 session of the Take Charge intervention, 2 sessions 6 weeks apart, or no sessions (control). This study is of participants still alive and willing to answer a questionnaire 5 to 6 years after their index stroke, undertaken in 2022. The primary outcome was the Physical Component Summary of the Short Form 36, comparing the Take Charge intervention and control. Secondary outcomes were: Frenchay Activities Index; modified Rankin Scale (mRS); survival; and stroke recurrence. These outcomes were compared with those 12 months after stroke. Analysis was by ANOVA or logistic regression.
Results: Mortality data were available for all 400 participants, and functional data for 204/297 (69%) of survivors. The mean difference (95% CI) in Physical Component Summary between Take Charge and control groups was 2.8 (-0.8 to 6.5) units, P=0.12, and for independence (modified Rankin Scale score, 0-2) the odds ratio (95% CI) was 0.56 (0.28-1.16), P=0.11, both favoring Take Charge with similar point estimates to those after 12 months. Differences between Take Charge and control participants for Frenchay Activities Index scores, survival, and stroke recurrence were small and nonsignificant.
Conclusions: The clinically significant improvements in physical health and independence for Take Charge participants, observed at 12 months, were sustained 5 to 6 years after stroke, but no longer statistically significant.
{"title":"Long-Term Follow-Up of Participants in the Taking Charge After Stroke Randomized Controlled Trial.","authors":"Alexander Martin, Vivian Fu, Zamir Joya, Sajida Joya, Allie Eathorne, Mark Weatherall, Gabrielle Shortt, Alex Semprini, John Gommans, Harry McNaughton","doi":"10.1161/STROKEAHA.125.052545","DOIUrl":"10.1161/STROKEAHA.125.052545","url":null,"abstract":"<p><strong>Background: </strong>The Take Charge intervention-a conversation-based, community intervention to improve motivation, improved independence, and physical health 12 months after stroke in 2 randomized controlled trials with 572 participants. This article reports long-term outcomes for the 400 participants in the TaCAS study (Taking Charge After Stroke).</p><p><strong>Methods: </strong>Follow-up study of a New Zealand multicenter, randomized, controlled, parallel-group trial. Outcomes were collected by postal questionnaire or telephone call. The TaCAS study recruited 400 participants discharged after stroke, randomized within 16 weeks to one of 3 groups: 1 session of the Take Charge intervention, 2 sessions 6 weeks apart, or no sessions (control). This study is of participants still alive and willing to answer a questionnaire 5 to 6 years after their index stroke, undertaken in 2022. The primary outcome was the Physical Component Summary of the Short Form 36, comparing the Take Charge intervention and control. Secondary outcomes were: Frenchay Activities Index; modified Rankin Scale (mRS); survival; and stroke recurrence. These outcomes were compared with those 12 months after stroke. Analysis was by ANOVA or logistic regression.</p><p><strong>Results: </strong>Mortality data were available for all 400 participants, and functional data for 204/297 (69%) of survivors. The mean difference (95% CI) in Physical Component Summary between Take Charge and control groups was 2.8 (-0.8 to 6.5) units, <i>P</i>=0.12, and for independence (modified Rankin Scale score, 0-2) the odds ratio (95% CI) was 0.56 (0.28-1.16), <i>P</i>=0.11, both favoring Take Charge with similar point estimates to those after 12 months. Differences between Take Charge and control participants for Frenchay Activities Index scores, survival, and stroke recurrence were small and nonsignificant.</p><p><strong>Conclusions: </strong>The clinically significant improvements in physical health and independence for Take Charge participants, observed at 12 months, were sustained 5 to 6 years after stroke, but no longer statistically significant.</p><p><strong>Registration: </strong>URL: https://anzctr.org.au; Unique identifier: ACTRN12622000311752.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"20-26"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}