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1. Antithrombotic Treatment for Cervical Artery Dissection: A Systematic Review and Individual Patient Data Meta-Analysis

Author: Kaufmann, Josefin E., Harshfield, Eric L., Gensicke, Henrik, Wegener, Susanne, Michel, Patrik, Kägi, Georg, Nedeltchev, Krassen, Kellert, Lars, Rosenbaum, Sverre, Nolte, Christian H., Christensen, Hanne, Arnold, Marcel, Lyrer, Philippe, Levi, Christopher, Bath, Philip M., Engelter, Stefan T., Traenka, Christopher, and Markus, Hugh S.
Abstract: IMPORTANCE: Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. OBJECTIVE: To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. DATA SOURCES: PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. STUDY SELECTION: Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. DATA EXTRACTION/SYNTHESIS: Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. RESULTS: Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). CONCLUSIONS AND RELEVANCE: This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.
Published: 2024
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2. The risk of stroke recurrence in patients with atrial fibrillation and reduced ejection fraction

Author: Paciaroni, Maurizio, Agnelli, Giancarlo, Caso, Valeria, Becattini, Cecilia, Mosconi, Maria Giulia, Giustozzi, Michela, Tsivgoulis, Georgios, Seiffge, David Julian, Engelter, Stefan T., Lyrer, Philippe, Polymeris, Alexandros A., Dittrich, Tolga, Zietz, Annaelle, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna M., Yperzeele, Laetitia, Loos, Caroline M.J., Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil H., Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Mac Grory, Brian, Jayaraman, Mahesh, Yaghi, Shadi, Furie, Karen L., Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Lotti, Enrico Maria, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, De Magistris, Ilaria Leone, Cancelloni, Virginia, Kargiotis, Odysseas, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Moci, Marco, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D’Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrios, Giannopoulos, Sotirios, Kosmidou, Maria, Ntais, Evangelos, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Saggese, Carlo Emanuele, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Morotti, Andrea, Magoni, Mauro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Caselli, Maria Chiara, Ulivi, Leonardo, Giannini, Nicola, Vadikolias, Kostantinos, Liantinioti, Chrysoula, Chondrogianni, Maria, Carletti, Monica, Karagkiozi, Efstathia, Athanasakis, George, Makaritsis, Kostantinos, Lanari, Alessia, Tatlisumak, Turgut, Acciarresi, Monica, Vannucchi, Vieri, Lorenzini, Gianni, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Sohn, Sung-Il, Mumoli, Nicola, Tadi, Prasanna, Letteri, Federica, Maccarrone, Miriam, Galati, Franco, Tiseo, Cindy, Gourbali, Vanessa, Halvatsiotis, Panagiotis, Orlandi, Giovanni, Giuntini, Martina, Corea, Francesco, Bellesini, Marta, Baronello, Mario Maimone, Karapanayiotides, Theodore, Rueckert, Christina, Csiba, Laszló, Szabó, Lilla, Rigatelli, Alberto, Imberti, Davide, Zabzuni, Dorjan, Pieroni, Alessio, Barlinn, Kristian, Pallesen, Lars-Peder, Barlinn, Jessica, Doronin, Boris, Volodina, Vera, Deleu, Dirk, Bonetti, Bruno, Porta, Cesare, Gentile, Luana, Eskandari, Ashraf, and De Marchis, Gian Marco
Abstract: Background: Atrial fibrillation (AF) and congestive heart failure often coexist due to their shared risk factors leading to potential worse outcome, particularly cerebrovascular events. The aims of this study were to calculate the rates of ischemic and severe bleeding events in ischemic stroke patients having both AF and reduced ejection fraction (rEF) (⩽40%), compared to ischemic stroke patients with AF but without rEF.Methods: We performed a retrospective analysis that drew data from prospective studies. The primary outcome was the composite of either ischemic (stroke or systemic embolism), or hemorrhagic events (symptomatic intracranial bleeding and severe extracranial bleeding).Results: The cohort for this analysis comprised 3477 patients with ischemic stroke and AF, of which, 643 (18.3%) had also rEF. After a mean follow-up of 7.5 ± 9.1 months, 375 (10.8%) patients had 382 recorded outcome events, for an annual rate of 18.0%. While the number of primary outcome events in patients with rEF was 86 (13.4%), compared to 289 (10.2%) for the patients without rEF; on multivariable analysis rEF was not associated with the primary outcome (OR 1.25; 95% CI 0.84–1.88). At the end of follow-up, 321 (49.9%) patients with rEF were deceased or disabled (mRS ⩾3), compared with 1145 (40.4%) of those without rEF; on multivariable analysis, rEF was correlated with mortality or disability (OR 1.35; 95% CI 1.03–1.77).Conclusions: In patients with ischemic stroke and AF, the presence of rEF was not associated with the composite outcome of ischemic or hemorrhagic events over short-term follow-up but was associated with increased mortality or disability.
Published: 2023
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3. The impact of competing stroke etiologies in patients with atrial fibrillation

Author: Zietz, Annaelle, Polymeris, Alexandros A, Helfenstein, Fabrice, Schaedelin, Sabine, Hert, Lisa, Wagner, Benjamin, Seiffge, David J, Traenka, Christopher, Altersberger, Valerian L, Dittrich, Tolga, Kaufmann, Josefin, Ravanelli, Flavia, Fladt, Joachim, Fisch, Urs, Thilemann, Sebastian, De Marchis, Gian Marco, Gensicke, Henrik, Bonati, Leo H, Katan, Mira, Fischer, Urs, Lyrer, Philippe, Engelter, Stefan T, and Peters, Nils
Abstract: Background: Data on the impact of competing stroke etiologies in stroke patients with atrial fibrillation (AF) are scarce.Methods: We used prospectively obtained data from an observational registry (Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-(NOACISP)-LONGTERM) of consecutive AF-stroke patients treated with oral anticoagulants. We compared the frequency of (i) the composite outcome of recurrent ischemic stroke (IS), intracerebral hemorrhage (ICH) or all-cause death as well as (ii) recurrent IS alone among AF-stroke patients with versus without competing stroke etiologies according to the TOAST classification. We performed cox proportional hazards regression modeling adjusted for potential confounders. Furthermore, the etiology of recurrent IS was assessed.Results: Among 907 patients (median age 81, 45.6% female), 184 patients (20.3%) had competing etiologies, while 723 (79.7%) had cardioembolism as the only plausible etiology. During 1587 patient-years of follow-up, patients with additional large-artery atherosclerosis had higher rates of the composite outcome (adjusted HR [95% CI] 1.64 [1.11, 2.40], p= 0.017) and recurrent IS (aHR 2.96 [1.65, 5.35 ], p< 0.001), compared to patients with cardioembolism as the only plausible etiology. Overall 71 patients had recurrent IS (7.8%) of whom 26.7% had a different etiology than the index IS with large-artery-atherosclerosis (19.7%) being the most common non-cardioembolic cause.Conclusion: In stroke patients with AF, causes other than cardioembolism as competing etiologies were common in index or recurrent IS. Concomitant presence of large-artery-atherosclerosis seems to indicate an increased risk for recurrences suggesting that stroke preventive means might be more effective if they also address competing stroke etiologies in AF-stroke patients.Clinical Trial Registration: NCT 03826927
Published: 2023
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4. Risk of recurrent stroke in patients with atrial fibrillation treated with oral anticoagulants alone or in combination with anti-platelet therapy

Author: Caliandro, Pietro, Cancelloni, Virginia, Marco, Moci, Reale, Giuseppe, Zauli, Aurelia, Agnelli, Giancarlo, Caso, Valeria, Becattini, Cecilia, Calabresi, Paolo, Giulia Mosconi, Maria, Giustozzi, Michela, Tsivgoulis, Georgios, Julian Seiffge, David, Engelter, Stefan T., Lyrer, Philippe, Polymeris, Alexandros A., Dittrich, Tolga, Zietz, Annaelle, Marco De Marchis, Gian, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna, Yperzeele, Laetitia, Loos, Caroline M.J., Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil, Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Mac Grory, Brian, Jayaraman, Mahesh, McTaggart, Ryan, Yaghi, Shadi, Furie, Karen L., Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Maria Lotti, Enrico, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, Leone De Magistris, Ilaria, Kargiotis, Odysseas, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D’Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrios, Giannopoulos, Sotirios, Kosmidou, Maria, Ntais, Evangelos, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Emanuele Saggese, Carlo, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Chiara Caselli, Maria, Ulivi, Leonardo, Giannini, Nicola, Vadikolias, Kostantinos, Liantinioti, Chrysoula, Chondrogianni, Maria, Halvatsiotis, Panagiotis, Carletti, Monica, Karagkiozi, Efstathia, Athanasakis, George, Makaritsis, Kostantinos, Lanari, Alessia, Tatlisumak, Turgut, Acciarresi, Monica, Vannucchi, Vieri, Lorenzini, Gianni, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Sohn, Sung-Il, Mumoli, Nicola, Tadi, Prasanna, Letteri, Federica, Maccarrone, Miriam, Poli, Loris, Magoni, Mauro, Galati, Franco, Tiseo, Cindy, Gourbali, Vanessa, Orlandi, Giovanni, Giuntini, Martina, Corea, Francesco, Bellesini, Marta, Girardi, Laura, Maimone Baronello, Mario, Karapanayiotides, Theodore, Rueckert, Christina, Csiba, Laszló, Szabó, Lilla, Rigatelli, Alberto, Imberti, Davide, Zabzuni, Dorjan, Pieroni, Alessio, Barlinn, Kristian, Pallesen, Lars-Peder, Barlinn, Jessica, Doronin, Boris, Volodina, Vera, Deleu, Dirk, Bonetti, Bruno, Porta, Cesare, Gentile, Luana, Eskandari, Ashraf, and Paciaroni, Maurizio
Abstract: Introduction: Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke.Patients and methods: We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM).Results: During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01–1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48–3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02–2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19–3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01–1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06–4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23–4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35–2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45–2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06–3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05–2.74]).Discussion: Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort.Conclusion: Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation.
Published: 2023
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5. Apical pulmonary lesions suspected of malignancy visible on neck CT angiography performed for acute stroke: Prevalence, treatment, and clinical implications – the PLEURA study

Author: Dittrich, Tolga D, Aujesky, Mara, Rudin, Salome, Zietz, Annaelle, Wagner, Benjamin, Polymeris, Alexandros, Altersberger, Valerian L, Sinnecker, Tim, Gensicke, Henrik, Engelter, Stefan T, Lyrer, Philippe, Hess, Viviane, Sutter, Raoul, Nickel, Christian H, Bonati, Leo H, Fischer, Urs, Psychogios, Marios, Katan, Mira, and De Marchis, Gian Marco
Abstract: Background: Computed tomography angiography (CTA) of the supraaortic arteries is commonly used for acute stroke workup and may reveal apical pulmonary lesions (APL).Aim: To determine the prevalence, follow-up algorithms, and in-hospital outcomes of stroke patients with APL on CTA.Methods: We retrospectively included consecutive adult patients with ischemic stroke, transient ischemic attack, or intracerebral hemorrhage and available CTA at a tertiary hospital between January 2014 and May 2021. We reviewed all CTA reports for the presence of APL. APL were classified as malignancy suspicious or benign appearing based on radiological-morphological criteria. We performed regression analyses to investigate the impact of malignancy suspicious APL on different in-hospital outcome parameters.Results: Among 2715 patients, APL on CTA were found in 161 patients (5.9% [95%CI: 5.1–6.9]; 161/2715). Suspicion of malignancy was present in one third of patients with APL (36.0% [95%CI: 29.0–43.7]; 58/161), 42 of whom (72.4% [95%CI: 60.0–82.2]; 42/58) had no history of lung cancer or metastases. When performed, further investigations confirmed primary or secondary pulmonary malignancy in three-quarters (75.0% [95%CI: 50.5–89.8]; 12/16), with two patients (16.7% [95%CI: 4.7–44.8]; 2/12) receiving de novo oncologic therapy. In multivariable regression, the presence of radiologically malignancy suspicious APL was associated with higher NIHSS scores at 24 h (beta = 0.67, 95%CI: 0.28–1.06, p= 0.001) and all-cause in-hospital mortality (aOR = 3.83, 95%CI: 1.29–9.94, p= 0.01).Conclusions: One in seventeen patients shows APL on CTA, of which one-third is malignancy suspicious. Further work-up confirmed pulmonary malignancy in a substantial number of patients triggering potentially life-saving oncologic therapy.
Published: 2023
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6. Stroke Risk and Antithrombotic Treatment During Follow-up of Patients With Ischemic Stroke and Cortical Superficial Siderosis

Author: Martí-Fàbregas, Joan, Camps-Renom, Pol, Best, Jonathan G., Ramos-Pachon, Anna, Guasch-Jiménez, Marina, Martinez-Domeño, Alejandro, Guisado-Alonso, Daniel, Gómez-Ansón, Beatriz M., Ambler, Gareth, Wilson, Duncan, Lee, Keon-Joo, Lim, Jae-Sung, Bae, Hee-Joon, Shiozawa, Masayuki, Koga, Masatoshi, Toyoda, Kazunori, Hennerici, Michael G., Chabriat, Hugues, Jouvent, Eric, Wong, Debbie Yuen Kwun, Mak, Henry, Lau, Kui Kai, Kim, Young Dae, Song, Tae-Jin, Heo, Ji-Hoe, Eppinger, Sebastian, Gattringer, Thomas, Uysal, Ender, Demirelli, Derya Selçuk, Bornstein, Natan, Ben Assayag, Einor, Hallevi, Hen, Molad, Jeremy A., Nishihara, Masashi, Tanaka, Jun, Hara, Hideo, Yakushiji, Yusuke, Coutts, Shelagh B., Smith, Eric, Polymeris, Alexandros A., Wagner, Benjamin, Seiffge, David, Lyrer, Philippe A., Peters, Nils, Engelter, Stefan T., Al-Shahi Salman, Rustam, Jäger, Hans Rudolf, Lip, Gregory Y.H., Goeldlin, Martina, Panos, Leonidas, Karayiannis, Christopher Charles, Phan, Thanh G., Srikanth, Velandai K., Christ, Nicolas, Gunkel, Sarah, Fluri, Felix, Leung, Thomas W., Soo, Yannie O.Y., Chu, Winnie, Abrigo, Jill, Barbato, Carmen, Browning, Simone, Simister, Robert, Mendyk, Anne-Marie, Bordet, Régis, Hilal, Saima, Gyanwali, Bibek, Chen, Christopher, Jung, Simon, Necioglu Orken, Dilek, Werring, David, and Prats-Sanchez, Luis
Published: 2023
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7. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author: Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui
Published: 2023
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8. Mechanical Thrombectomy Versus Best Medical Treatment in the Late Time Window in Non-DEFUSE-Non-DAWN Patients: A Multicenter Cohort Study

Author: Dittrich, Tolga D., Sporns, Peter B., Kriemler, Lilian F., Rudin, Salome, Nguyen, Anh, Zietz, Annaelle, Polymeris, Alexandros A., Tränka, Christopher, Thilemann, Sebastian, Wagner, Benjamin, Altersberger, Valerian L., Piot, Ines, Barinka, Filip, Müller, Susanne, Hänsel, Martin, Gensicke, Henrik, Engelter, Stefan T., Lyrer, Philippe A., Sutter, Raoul, Nickel, Christian H., Katan, Mira, Peters, Nils, Kulcsár, Zsolt, Karwacki, Grzegorz M., Pileggi, Marco, Cereda, Carlo, Wegener, Susanne, Bonati, Leo H., Fischer, Urs, Psychogios, Marios, and De Marchis, Gian Marco
Published: 2023
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9. Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration

Author: Altersberger, Valerian L., Rusche, Norman, Martinez-Majander, Nicolas, Hametner, Christian, Scheitz, Jan F., Henon, Hilde, Dell’Acqua, Maria Luisa, Strambo, Davide, Stolp, Jeffrey, Heldner, Mirjam R., Grisendi, Ilaria, Jovanovic, Dejana R., Bejot, Yannick, Pezzini, Alessandro, Leker, Ronen R., Kägi, Georg, Wegener, Susanne, Cereda, Carlo W., Lindgren, Erik, Ntaios, George, Piot, Ines, Polymeris, Alexandros A., Lyrer, Philippe A., Räty, Silja, Sibolt, Gerli, Tiainen, Marjaana, Heyse, Miriam, Erdur, Hebun, Kaaouana, Olfa, Padjen, Visnja, Zedde, Marialuisa, Arnold, Marcel, Nederkoorn, Paul J., Michel, Patrik, Bigliardi, Guido, Zini, Andrea, Cordonnier, Charlotte, Nolte, Christian H., Ringleb, Peter A., Curtze, Sami, Engelter, Stefan T., and Gensicke, Henrik
Published: 2022
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10. Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Author: Paciaroni, Maurizio, Caso, Valeria, Agnelli, Giancarlo, Mosconi, Maria Giulia, Giustozzi, Michela, Seiffge, David Julian, Engelter, Stefan T., Lyrer, Philippe, Polymeris, Alexandros A., Kriemler, Lilian, Zietz, Annaelle, Putaala, Jukka, Strbian, Daniel, Tomppo, Liisa, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Remillard, Suzette, Buehrer, Manuela, Bavaud, Odessa, Vanacker, Peter, Zuurbier, Susanna, Yperzeele, Laetitia, Loos, Caroline M.J., Cappellari, Manuel, Emiliani, Andrea, Zedde, Marialuisa, Abdul-Rahim, Azmil, Dawson, Jesse, Cronshaw, Robert, Schirinzi, Erika, Del Sette, Massimo, Stretz, Christoph, Kala, Narendra, Reznik, Michael, Schomer, Ashley, Grory, Brian Mac, Jayaraman, Mahesh, McTaggart, Ryan, Yaghi, Shadi, Furie, Karen L., Masotti, Luca, Grifoni, Elisa, Toni, Danilo, Risitano, Angela, Falcou, Anne, Petraglia, Luca, Lotti, Enrico Maria, Padroni, Marina, Pavolucci, Lucia, Lochner, Piergiorgio, Silvestrelli, Giorgio, Ciccone, Alfonso, Alberti, Andrea, Venti, Michele, Traballi, Laura, Urbini, Chiara, Kargiotis, Odysseas, Rocco, Alessandro, Diomedi, Marina, Marcheselli, Simona, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Antonenko, Kateryna, Rota, Eugenia, Tassinari, Tiziana, Saia, Valentina, Palmerini, Francesco, Aridon, Paolo, Arnao, Valentina, Monaco, Serena, Cottone, Salvatore, Baldi, Antonio, D’Amore, Cataldo, Ageno, Walter, Pegoraro, Samuela, Ntaios, George, Sagris, Dimitrios, Giannopoulos, Sotirios, Kosmidou, Maria, Ntais, Evangelos, Romoli, Michele, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Chiti, Alberto, Canavero, Isabella, Saggese, Carlo Emanuele, Plocco, Maurizio, Giorli, Elisa, Palaiodimou, Lina, Bakola, Eleni, Tsivgoulis, Georgios, Bandini, Fabio, Gasparro, Antonio, Terruso, Valeria, Mannino, Marina, Pezzini, Alessandro, Ornello, Raffaele, Sacco, Simona, Popovic, Nemanja, Scoditti, Umberto, Genovese, Antonio, Denti, Licia, Flomin, Yuriy, Mancuso, Michelangelo, Ferrari, Elena, Caselli, Maria Chiara, Ulivi, Leonardo, Giannini, Nicola, and De Marchis, Gian Marco
Published: 2022
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11. Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison

Author: Wagner, Benjamin, Lorscheider, Johannes, Wiencierz, Andrea, Blackham, Kristine, Psychogios, Marios, Bolliger, Daniel, De Marchis, Gian Marco, Engelter, Stefan T., Lyrer, Philippe, Wright, Patrick R., Fischer, Urs, Mordasini, Pasquale, Nannoni, Stefania, Puccinelli, Francesco, Kahles, Timo, Bianco, Giovanni, Carrera, Emmanuel, Luft, Andreas R., Cereda, Carlo W., Kägi, Georg, Weber, Johannes, Nedeltchev, Krassen, Michel, Patrik, Gralla, Jan, Arnold, Marcel, and Bonati, Leo H.
Published: 2022
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12. Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial

Author: Law, Zhe Kang, Appleton, Jason P., Scutt, Polly, Roberts, Ian, Al-Shahi Salman, Rustam, England, Timothy J., Werring, David J., Robinson, Thompson, Krishnan, Kailash, Dineen, Robert A., Laska, Ann Charlotte, Lyrer, Philippe A., Egea-Guerrero, Juan Jose, Karlinski, Michal, Christensen, Hanne, Roffe, Christine, Bereczki, Daniel, Ozturk, Serefnur, Thanabalan, Jegan, Collins, Ronan, Beridze, Maia, Ciccone, Alfonso, Duley, Lelia, Shone, Angela, Bath, Philip M., and Sprigg, Nikola
Published: 2022
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13. Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation

Author: Polymeris, Alexandros A, Meinel, Thomas R, Oehler, Hannah, Ho¨lscher, Kyra, Zietz, Annaelle, Scheitz, Jan F, Nolte, Christian H, Stretz, Christoph, Yaghi, Shadi, Stoll, Svenja, Wang, Ruihao, Ha¨usler, Karl Georg, Hellwig, Simon, Klammer, Markus G, Litmeier, Simon, Leon Guerrero, Christopher R, Moeini-Naghani, Iman, Michel, Patrik, Strambo, Davide, Salerno, Alexander, Bianco, Giovanni, Cereda, Carlo, Uphaus, Timo, Gro¨schel, Klaus, Katan, Mira, Wegener, Susanne, Peters, Nils, Engelter, Stefan T, Lyrer, Philippe A, Bonati, Leo H, Grunder, Lorenz, Ringleb, Peter Arthur, Fischer, Urs, Kallmu¨nzer, Bernd, Purrucker, Jan C, and Seiffge, David J
Abstract: ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.
Published: 2022
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14. Early versus late start of direct oral anticoagulants after acute ischaemic stroke linked to atrial fibrillation: an observational study and individual patient data pooled analysis

Author: De Marchis, Gian Marco, Seiffge, David J., Schaedelin, Sabine, Wilson, Duncan, Caso, Valeria, Acciarresi, Monica, Tsivgoulis, Georgios, Koga, Masatoshi, Yoshimura, Sohei, Toyoda, Kazunori, Cappellari, Manuel, Bonetti, Bruno, Macha, Kosmas, Kallmu¨nzer, Bernd, Cereda, Carlo W., Lyrer, Philippe, Bonati, Leo H., Paciaroni, Maurizio, Engelter, Stefan T., and Werring, David J.
Abstract: ObjectiveThe optimal timing to start direct oral anticoagulants (DOACs) after an acute ischaemic stroke (AIS) related to atrial fibrillation (AF) remains unclear. We aimed to compare early (≤5 days of AIS) versus late (>5 days of AIS) DOAC-start.MethodsThis is an individual patient data pooled analysis of eight prospective European and Japanese cohort studies. We included patients with AIS related to non-valvular AF where a DOAC was started within 30 days. Primary endpoints were 30-day rates of recurrent AIS and ICH.ResultsA total of 2550 patients were included. DOACs were started early in 1362 (53%) patients, late in 1188 (47%). During 212 patient-years, 37 patients had a recurrent AIS (1.5%), 16 (43%) before a DOAC was started; 6 patients (0.2%) had an ICH, all after DOAC-start. In the early DOAC-start group, 23 patients (1.7%) suffered from a recurrent AIS, while 2 patients (0.1%) had an ICH. In the late DOAC-start group, 14 patients (1.2%) suffered from a recurrent AIS; 4 patients (0.3%) suffered from ICH. In the propensity score-adjusted comparison of late versus early DOAC-start groups, there was no statistically significant difference in the hazard of recurrent AIS (aHR=1.2, 95% CI 0.5 to 2.9, p=0.69), ICH (aHR=6.0, 95% CI 0.6 to 56.3, p=0.12) or any stroke.ConclusionsOur results do not corroborate concerns that an early DOAC-start might excessively increase the risk of ICH. The sevenfold higher risk of recurrent AIS than ICH suggests that an early DOAC-start might be reasonable, supporting enrolment into randomised trials comparing an early versus late DOAC-start.
Published: 2022
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15. Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source: An Analysis of the RE-SPECT ESUS Trial

Author: Bahit, Maria Cecilia, Sacco, Ralph L., Easton, J. Donald, Meyerhoff, Juliane, Cronin, Lisa, Kleine, Eva, Grauer, Claudia, Brueckmann, Martina, Diener, Hans-Christoph, Lopes, Renato D., Brainin, Michael, Lyrer, Phillippe, Wachter, Rolf, Segura, Tomas, and Granger, Christopher B.
Abstract: Supplemental Digital Content is available in the text.
Published: 2021
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16. Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others

Author: Meya, Louisa, Polymeris, Alexandros A., Schaedelin, Sabine, Schaub, Fabian, Altersberger, Valerian L., Traenka, Christopher, Thilemann, Sebastian, Wagner, Benjamin, Fladt, Joachim, Hert, Lisa, Yoshimura, Sohei, Koga, Masatoshi, Zietz, Annaelle, Dittrich, Tolga, Fisch, Urs, Toyoda, Kazunori, Seiffge, David J., Peters, Nils, De Marchis, Gian Marco, Gensicke, Henrik, Bonati, Leo H., Lyrer, Philippe A., and Engelter, Stefan T.
Abstract: Supplemental Digital Content is available in the text.
Published: 2021
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17. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author: Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Chester, Johanna, Cradduck-Bamford, Andrea, Peto, Richard, Pan, Hongchao, Halliday, Alison, Bulbulia, Richard, Bonati, Leo H, Peto, Richard, Pan, Hongchao, Potter, John, Henning Eckstein, Hans, Farrell, Barbara, Flather, Marcus, Mansfield, Averil, Mihaylova, Boby, Rahimi, Kazim, Simpson, David, Thomas, Dafydd, Sandercock, Peter, Gray, Richard, Molyneux, Andrew, Shearman, Cliff P, Rothwell, Peter, Belli, Anna, Herrington, Will, Judge, Parminder, Leopold, Peter, Mafham, Marion, Gough, Michael, Cao, Piergiorgio, MacDonald, Sumaira, Bari, Vasha, Berry, Clive, Bradshaw, S, Brudlo, Wojciech, Clarke, Alison, Chester, Johanna, Cox, Robin, Cradduck-Bamford, Andrea, Fathers, Susan, Gaba, Kamran, Gray, Mo, Hayter, Elizabeth, Holliday, Constance, Kurien, Rijo, Lay, Michael, le Conte, Steffi, McManus, Jessica, Madgwick, Zahra, Morris, Dylan, Munday, Andrew, Pickworth, Sandra, Ostasz, Wiktor, Poorthuis, Michiel, Richards, Sue, Teixeira, Louisa, Tochlin, Sergey, Tully, Lynda, Wallis, Carol, Willet, Monique, Young, Alan, Casana, Renato, Malloggi, Chiara, Odero Jr, Andrea, Silani, Vincenzo, Parati, Gianfranco, Malchiodi, Giuseppe, Malferrari, Giovanni, Strozzi, Francesco, Tusini, Nicola, Vecchiati, Enrico, Coppi, Gioacchino, Lauricella, Antonio, Moratto, Roberto, Silingardi, Roberto, Veronesi, Jessica, Zini, Andrea, Ferrero, Emanuele, Ferri, Michelangelo, Gaggiano, Andrea, Labate, Carmelo, Nessi, Franco, Psacharopulo, Daniele, Viazzo, Andrea, Malacrida, Giovanni, Mazzaccaro, Daniela, Meola, Giovanni, Modafferi, Alfredo, Nano, Giovanni, Occhiuto, Maria Teresa, Righini, Paolo, Stegher, Silvia, Chiarandini, Stefano, Griselli, Filippo, Lepidi, Sandro, Pozzi Mucelli, Fabio, Naccarato, Marcello, D'Oria, Mario, Ziani, Barbara, Stella, Andrea, Dieng, Mortalla, Faggioli, Gianluca, Gargiulo, Mauro, Palermo, Sergio, Pini, Rodolfo, Puddu, Giovanni Maria, Vacirca, Andrea, Angiletta, Domenico, Desantis, Claudio, Marinazzo, Davide, Mastrangelo, Giovanni, Regina, Guido, Pulli, Raffaele, Bianchi, Paolo, Cireni, Lea, Coppi, Elisabetta, Pizzirusso, Rocco, Scalise, Filippo, Sorropago, Giovanni, Tolva, Valerio, Caso, Valeria, Cieri, Enrico, DeRango, Paola, Farchioni, Luca, Isernia, Giacomo, Lenti, Massimo, Parlani, Gian Battista, Pupo, Guglielmo, Pula, Grazia, Simonte, Gioele, Verzini, Fabio, Carimati, Federico, Delodovici, Maria Luisa, Fontana, Federico, Piffaretti, Gabriele, Tozzi, Matteo, Civilini, Efrem, Poletto, Giorgio, Reimers, Bernhard, Praquin, Barbara, Ronchey, Sonia, Capoccia, Laura, Mansour, Wassim, Sbarigia, Enrico, Speziale, Francesco, Sirignano, Pasqualino, Toni, Danilo, Galeotti, Roberto, Gasbarro, Vincenzo, Mascoli, Francesco, Rocca, Tiberio, Tsolaki, Elpiniki, Bernardini, Giulia, DeMarco, Ester, Giaquinta, Alessia, Patti, Francesco, Veroux, Massimiliano, Veroux, Pierfrancesco, Virgilio, Carla, Mangialardi, Nicola, Orrico, Matteo, Di Lazzaro, Vincenzo, Montelione, Nunzio, Spinelli, Francesco, Stilo, Francesco, Cernetti, Carlo, Irsara, Sandro, Maccarrone, Giuseppe, Tonello, Diego, Visonà, Adriana, Zalunardo, Beniamino, Chisci, Emiliano, Michelagnoli, Stefano, Troisi, Nicola, Masato, Maela, Dei Negri, Massimo, Pacchioni, Andrea, Saccà, Salvatore, Amatucci, Giovanni, Cannizzaro, Alfredo, Accrocca, Federico, Ambrogi, Cesare, Barbazza, Renzo, Marcucci, Giustino, Siani, Andrea, Bajardi, Guido, Savettieri, Giovanni, Argentieri, Angelo, Corbetta, Riccardo, Odero, Attilio, Quaretti, Pietro, Thyrion, Federico Z, Cappelli, Alessandro, Benevento, Domenico, De Donato, Gianmarco, Mele, Maria Agnese, Palasciano, Giancarlo, Pieragalli, Daniela, Rossi, Alessandro, Setacci, Carlo, Setacci, Francesco, Palombo, Domenico, Perfumo, Maria Cecilia, Martelli, Edoardo, Paolucci, Aldo, Trimarchi, Santi, Grassi, Viviana, Grimaldi, Luigi, La Rosa, Giuliana, Mirabella, Domenico, Scialabba, Matteo, Sichel, Leonildo, D'Angelo, Costantino L, Fadda, Gian Franco, Kasemi, Holta, Marino, Mario, Burzotta, Francesco, Codispoti, Francesco Alberto, Ferrante, Angela, Tinelli, Giovanni, Tshomba, Yamume, Vincenzoni, Claudio, Amis, Deborah, Anderson, Dawn, Catterson, Martin, Clarke, Mike, Davis, Michelle, Dixit, Anand, Dyker, Alexander, Ford, Gary, Jackson, Ralph, Kappadath, Sreevalsan, Lambert, David, Lees, Tim, Louw, Stephen, McCaslin, James, Parr, Noala, Robson, Rebecca, Stansby, Gerard, Wales, Lucy, Wealleans, Vera, Wilson, Lesley, Wyatt, Michael, Baht, Hardeep, Balogun, Ibrahim, Burger, Ilse, Cosier, Tracy, Cowie, Linda, Gunathilagan, Gunaratnam, Hargroves, David, Insall, Robert, Jones, Sally, Rudenko, Hannah, Schumacher, Natasha, Senaratne, Jawaharlal, Thomas, George, Thomson, Audrey, Webb, Tom, Brown, Ellen, Esisi, Bernard, Mehrzad, Ali, MacSweeney, Shane, McConachie, Norman, Southam, Alison, Sunman, Wayne, Abdul-Hamiq, Ahmed, Bryce, Jenny, Chetter, Ian, Ettles, Duncan, Lakshminarayan, Raghuram, Mitchelson, Kim, Rhymes, Christopher, Robinson, Graham, Scott, Paul, Vickers, Alison, Ashleigh, Ray, Butterfield, Stephen, Gamble, Ed, Ghosh, Jonathan, McCollum, Charles N, Welch, Mark, Welsh, Sarah, Wolowczyk, Leszek, Donnelly, Mary, D'Souza, Stephen, Egun, Anselm A, Gregary, Bindu, Joseph, Thomas, Kelly, Christine, Punekar, Shuja, Rahi, M Asad, Raj, Sonia, Seriki, Dare, Thomson, George, Brown, James, Durairajan, Ragunath, Grunwald, Iris, Guyler, Paul, Harman, Paula, Jakeways, Matthew, Khuoge, Christopher, Kundu, Ashish, Loganathan, Thayalini, Menon, Nisha, Prabakaran, Raji O, Sinha, Devesh, Thompson, Vicky, Tysoe, Sharon, Briley, Dennis, Darby, Chris, Hands, Linda, Howard, Dominic, Kuker, Wilhelm, Schulz, Ursula, Teal, Rachel, Barer, David, Brown, Andrew, Crawford, Susan, Dunlop, Paul, Krishnamurthy, Ramesh, Majmudar, Nikhil, Mitchell, Duncan, Myint, Min P, O'Brien, Richard, O'Connell, Janice, Sattar, Naweed, Vetrivel, Shanmugam, Beard, Jonathan, Cleveland, Trevor, Gaines, Peter, Humphreys, John, Jenkins, Alison, King, Craig, Kusuma, Daniel, Lindert, Ralph, Lonsdale, Robbie, Nair, Raj, Nawaz, Shah, Okhuoya, Faith, Turner, Douglas, Venables, Graham, Dorman, Paul, Hughes, Andrea, Jones, Deborah, Mendelow, David, Rodgers, Helen, Raudoniitis, Aidas, Enevoldson, Peter, Nahser, Hans, O'Brien, Imelda, Torella, Francesco, Watling, Dave, White, Richard, Brown, Pauline, Dutta, Dipankar, Emerson, Lorraine, Hilltout, Paula, Kulkarni, Sachin, Morrison, Jackie, Poskitt, Keith, Slim, Fiona, Smith, Sarah, Tyler, Amanda, Waldron, Joanne, Whyman, Mark, Bajoriene, Milda, Baker, Lucy, Colston, Amanda, Eliot-Jones, Bekky, Gramizadeh, Gita, Lewis-Clarke, Catherine, McCafferty, Laura, Oliver, Deborah, Palmer, Debbie, Patil, Abhijeet, Pegler, Suzannah, Ramadurai, Gopi, Roberts, Aisling, Sargent, Tracey, Siddegowda, Shivaprasad, Singh-Ranger, Ravi, Williams, Akintunde, Williams, Lucy, Windebank, Steve, Zuromskis, Tadas, Alwis, Lanka, Angus, Jane, Asokanathan, Asaipillai, Fornolles, Caroline, Hardy, Diana, Hunte, Sophy, Justin, Frances, Phiri, Duke, Mitabouana-Kibou, Marie, Sekaran, Lakshmanan, Sethuraman, Sakthivel, Tate, Margaret L, Akyea-Mensah, Joyce, Ball, Stephen, Chrisopoulou, Angela, Keene, Elizabeth, Phair, Alison, Rogers, Steven, Smyth, John V, Bicknell, Colin, Chataway, Jeremy, Cheshire, Nicholas, Clifton, Andrew, Eley, Caroline, Gibbs, Richard, Hamady, Mohammad, Hazel, Beth, James, Alex, Jenkins, Michael, Khanom, Nyma, Lacey, Austin, Mireskandari, Maz, O'Reilly, Joanna, Pereira, Antony, Sachs, Tina, Wolfe, John, Brown, Ellen, Davey, Philip, Rogers, Gill, Smith, Gemma, Tervit, Gareth, Nichol, Ian, Parry, Andrew, Young, Gavin, Ashley, Simon, Barwell, James, Dix, Francis, Nor, Azlisham M, Parry, Chris, Birt, Angela, Davies, Paul, George, Jim, Graham, Anne, Jonker, Leon, Joseph, Thomas, Kelsall, Nicci, Potts, Caroline, Wilson, Toni, Clifton, Andrew, Crinnion, Jamie, Cuenoud, Larissa, Aleksic, Nikola, Babic, Srdan, Ilijevski, Nenad, Radak, Đorde, Sagic, Dragan, Tanaskovic, Slobodan, Colic, Momcilo, Cvetic, Vladimir, Davidovic, Lazar, Jovanovic, Dejana R, Koncar, Igor, Mutavdžic, Perica, Sladojevic, Miloš, Tomic, Ivan, Debus, Eike S, Grzyska, Ulrich, Otto, Dagmar, Thomalla, Götz, Barlinn, Jessica, Gerber, Johannes, Haase, Kathrin, Hartmann, Christian, Ludwig, Stefan, Pütz, Volker, Reeps, Christian, Schmidt, Christine, Weiss, Norbert, Werth, Sebastian, Winzer, Simon, Gemper, Janine, Günther, Albrecht, Heiling, Bianka, Jochmann, Elisabeth, Karvouniari, Panagiota, Klingner, Carsten, Mayer, Thomas, Schubert, Julia, Schulze-Hartung, Friederike, Zanow, Jürgen, Bausback, Yvonne, Borger, Franka, Botsios, Spiridon, Branzan, Daniela, Bräunlich, Sven, Hölzer, Henryk, Lenzer, Janin, Piorkowski, Christopher, Richter, Nadine, Schuster, Johannes, Scheinert, Dierk, Schmidt, Andrej, Staab, Holger, Ulrich, Matthias, Werner, Martin, Berger, Hermann, Biró, Gábor, Eckstein, Hans-Henning, Kallmayer, Michael, Kreiser, Kornelia, Zimmermann, Alexander, Berekoven, Bärbel, Frerker, Klaus, Gordon, Vera, Torsello, Giovanni, Arnold, Sebastian, Dienel, Cora, Storck, Martin, Biermaier, Bernhard, Gissler, Hans Martin, Klötzsch, Christof, Pfeiffer, Tomas, Schneider, Ralph, Söhl, Leander, Wennrich, Michael, Alonso, Angelika, Keese, Michael, Groden, Christoph, Cöster, Andreas, Engelhardt, Andreas, Ratusinski, Christoph-Maria, Berg, Bengt, Delle, Martin, Formgren, Johan, Gillgren, Peter, Jarl, Lotta, Kall, Torbjörn B, Konrad, Peter, Nyman, Niklas, Skiöldebrand, Claes, Steuer, Johnny, Takolander, Rabbe, Malmstedt, Jonas, Acosta, Stefan, Björses, Katarina, Brandt, Kerstin, Dias, Nuno, Gottsäter, Anders, Holst, Jan, Kristmundsson, Thorarinn, Kühme, Tobias, Kölbel, Tilo, Lindblad, Bengt, Lindh, Mats, Malina, Martin, Ohrlander, Tomas, Resch, Tim, Rönnle, Viola, Sonesson, Björn, Warvsten, Margareta, Zdanowski, Zbigniew, Campbell, Erik, Kjellin, Per, Lindgren, Hans, Nyberg, Johan, Petersen, Björn, Plate, Gunnar, Pärsson, Håkan, Qvarfordt, Peter, Ignatenko, Pavel, Karpenko, Andrey, Starodubtsev, Vladimir, Chernyavsky, Mikhail A, Golovkova, Maria S, Komakha, Boris B, Zherdev, Nikolay N, Belyasnik, Andrey, Chechulov, Pavel, Kandyba, Dmitry, Stepanishchev, Igor, Csobay-Novák, Csaba, Dósa, Edit, Entz, László, Nemes, Balázs, Szeberin, Zoltán, Barzó, Pál, Bodosi, Mihaly, Fákó, Eniko, Fülöp, Béla, Németh, Tamás, Pazdernyik, Szilárd, Skoba, Krisztina, Vörös, Erika, Chatzinikou, Eleni, Giannoukas, Athanasios, Karathanos, Christos, Koutsias, Stylianos, Kouvelos, Georgios, Matsagkas, Miltiadis, Ralli, Styliani, Rountas, Christos, Rousas, Nikolaos, Spanos, Konstantinos, Brountzos, Elias, Kakisis, John D, Lazaris, Andreas, Moulakakis, Konstantinos G, Stefanis, Leonidas, Tsivgoulis, Georgios, Vasdekis, Spyros, Antonopoulos, Constantine N, Bellenis, Ion, Maras, Dimitrios, Polydorou, Antonios, Polydorou, Victoria, Tavernarakis, Antonios, Ioannou, Nikolaos, Terzoudi, Maria, Lazarides, Miltos, Mantatzis, Michalis, Vadikolias, Kostas, Dzieciuchowicz, Lukasz, Gabriel, Marcin, Krasinski, Zbigniew, Oszkinis, Grzegorz, Pukacki, Fryderyk, Slowinski, Maciej, Stanišic, Michal-Goran, Staniszewski, Ryszard, Tomczak, Jolanta, Zielinski, Maciej, Myrcha, Piotr, Rózanski, Dorota, Drelichowski, Stanislaw, Iwanowski, Wojciech, Koncewicz, Katarzyna, Bialek, Pawel, Biejat, Zbigniew, Czepel, Wojciech, Czlonkowska, Anna, Dowzenko, Anatol, Jedrzejewska, Julia, Kobayashi, Adam, Leszczynski, Jerzy, Malek, Andrzej, Polanski, Jerzy, Proczka, Robert, Skorski, Maciej, Szostek, Mieczyslaw, Andziak, Piotr, Dratwicki, Maciej, Gil, Robert, Nowicki, Miroslaw, Pniewski, Jaroslaw, Rzezak, Jaroslaw, Seweryniak, Piotr, Dabek, Pawel, Juszynski, Michal, Madycki, Grzegorz, Pacewski, Bartosz, Raciborski, Witold, Slowinski, Piotr, Staszkiewicz, Walerian, Bombic, Martin, Chlouba, Vladimír, Fiedler, Jirí, Hes, Karel, Koštál, Petr, Sova, Jindrich, Kríž, Zdenek, Prívara, Mojmír, Reif, Michal, Staffa, Robert, Vlachovský, Robert, Vojtíšek, Bohuslav, Hrbác, Tomáš, Kuliha, Martin, Procházka, Václav, Roubec, Martin, Školoudík, David, Netuka, David, Šteklácová, Anna, Beneš III, Vladimír, Buchvald, Pavel, Endrych, Ladislav, Šercl, Miroslav, Campos Jr, Walter, Casella, Ivan B, de Luccia, Nelson, Estenssoro, André E V, Presti, Calógero, Puech-Leão, Pedro, Neves, Celso R B, da Silva, Erasmo S, Sitrângulo Jr, Cid J, Monteiro, José A T, Tinone, Gisela, Bellini Dalio, Marcelo, Joviliano, Edwaldo E, Pontes Neto, Octávio M, Serra Ribeiro, Mauricio, Cras, Patrick, Hendriks, Jeroen M H, Hoppenbrouwers, Mieke, Lauwers, Patrick, Loos, Caroline, Yperzeele, Laetitia, Geenens, Mia, Hemelsoet, Dimitri, van Herzeele, Isabelle, Vermassen, Frank, Astarci, Parla, Hammer, Frank, Lacroix, Valérie, Peeters, André, Verhelst, Robert, Cirelli, Silvana, Dormal, Pol, Grimonprez, Annelies, Lambrecht, Bart, Lerut, Philipe, Thues, Eddy, De Koster, Guy, Desiron, Quentin, Maertens de Noordhout, Alain, Malmendier, Danielle, Massoz, Mireille, Saad, Georges, Bosiers, Marc, Callaert, Joren, Deloose, Koen, Blanco Cañibano, Estrella, García Fresnillo, Beatriz, Guerra Requena, Mercedes, Morata Barrado, Pilar C, Muela Méndez, Miguel, Yusta Izquierdo, Antonio, Aparici Robles, Fernando, Blanes Orti, Paula, García Dominguez, Luis, Martínez López, Rafael, Miralles Hernández, Manuel, Tembl Ferrairo, José I, Chamorro, Ángel, Macho, Juan, Obach, Víctor, Riambau, Vincent, San Román, Luis, Ahlhelm, Frank J, Blackham, Kristine, Engelter, Stefan, Eugster, Thomas, Gensicke, Henrik, Gürke, Lorenz, Lyrer, Philippe, Mariani, Luigi, Maurer, Marina, Mujagic, Edin, Müller, Mandy, Psychogios, Marios, Stierli, Peter, Stippich, Christoph, Traenka, Christopher, Wolff, Thomas, Wagner, Benjamin, Wiegert, Martina M, Clarke, Sandra, Diepers, Michael, Gröchenig, Ernst, Gürke, Lorenz, Gruber, Philipp, Isaak, Andrej, Kahles, Timo, Marti, Regula, Nedeltchev, Krassen, Remonda, Luca, Stierli, Peter, Tissira, Nadir, Valença Falcão, Martina, de Borst, Gert J, Lo, Rob H, Moll, Frans L, Toorop, Raechel, van der Worp, Bart H, Vonken, Evert J, Kappelle, Jaap L, Jahrome, Ommid, Vos, Floris, Schuiling, Wouter, van Overhagen, Hendrik, Keunen, Rudolf W M, Knippenberg, Bob, Wever, Jan J, Lardenoije, Jan W, Reijnen, Michel, Smeets, Luuk, van Sterkenburg, Steven, Fraedrich, Gustav, Gizewski, Elke, Gruber, Ingrid, Knoflach, Michael, Kiechl, Stefan, Rantner, Barbara, Abdulamit, Timur, Bergeron, Patrice, Padovani, Raymond, Trastour, Jean-Christophe, Cardon, Jean-Marie, Le Gallou-Wittenberg, Anne, Allaire, Eric, Becquemin, Jean-Pierre, Cochennec-Paliwoda, Frédéric, Desgranges, Pascal, Hosseini, Hassan, Kobeiter, Hicham, Marzelle, Jean, Almekhlafi, Mohammed A, Bal, Simerpreet, Barber, Phillip A, Coutts, Shelagh B, Demchuk, Andrew M, Eesa, Muneer, Gillies, Michelle, Goyal, Mayank, Hill, Michael D, Hudon, Mark E, Jambula, Anitha, Kenney, Carol, Klein, Gary, McClelland, Marie, Mitha, Alim, Menon, Bijoy K, Morrish, William F, Peters, Steven, Ryckborst, Karla J, Samis, Greg, Save, Supriya, Smith, Eric E, Stys, Peter, Subramaniam, Suresh, Sutherland, Garnette R, Watson, Tim, Wong, John H, Zimmel, L, Flis, Vojko, Matela, Jože, Miksic, Kazimir, Milotic, Franko, Mrdja, Božidar, Stirn, Barbara, Tetickovic, Erih, Gasparini, Mladen, Grad, Anton, Kompara, Ingrid, Miloševic, Zoren, Palmiste, Veronika, Toomsoo, Toomas, Aidashova, Balzhan, Kospanov, Nursultan, Lyssenko, Roman, Mussagaliev, Daulet, Beyar, Rafi, Hoffman, Aaron, Karram, Tony, Kerner, Arthur, Nikolsky, Eugenia, Nitecki, Samy, Andonova, Silva, Bachvarov, Chavdar, Petrov, Vesko, Cvjetko, Ivan, Vidjak, Vinko, Halužan, Damir, Petrunic, Mladen, Liu, Bao, Liu, Chang-Wei, Bartko, Daniel, Beno, Peter, Rusnák, František, Zelenák, Kamil, Ezura, Masayuki, Inoue, Takashi, Kimura, Naoto, Kondo, Ryushi, Matsumoto, Yasushi, Shimizu, Hiroaki, Endo, Hidenori, Furui, Eisuke, Bakke, Søren, Krohg-Sørensen, Kristen, Nome, Terje, Skjelland, Mona, Tennøe, Bjørn, Albuquerque e Castro, João, Alves, Gonçalo, Bastos Gonçalves, Frederico, de Aragão Morais, José, Garcia, Ana C, Valentim, Hugo, Vasconcelos, Leonor, Belcastro, Fernando, Cura, Fernando, Zaefferer, Patricio, Abd-Allah, Foad, Eldessoki, Mohamed H, Heshmat Kassem, Hussein, Soliman Gharieb, Haytham, Colgan, Mary P, Haider, Syed N, Harbison, Joe, Madhavan, Prakash, Moore, Dermot, Shanik, Gregor, Kazan, Viviane, Nazzal, Munier, and Ramsey-Williams, Vicki
Abstract: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.
Published: 2021
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18. Biomarkers and antithrombotic treatment in cervical artery dissection – Design of the TREAT-CAD randomised trial

Author: Traenka, Christopher, Gensicke, Henrik, Schaedelin, Sabine, Luft, Andreas, Arnold, Marcel, Michel, Patrik, Kägi, Georg, Kahles, Timo, Nolte, Christian H, Kellert, Lars, Rosenbaum, Sverre, Sztaizel, Roman, Brehm, Alex, Stippich, Christoph, Psychogios, Marios, Lyrer, Philippe, and Engelter, Stefan T
Abstract: Introduction The type of antithrombotic treatment in cervical artery dissection patients is still a matter of debate. Most physicians prefer anticoagulants over antiplatelet agents for stroke prevention. However, this approach is not evidence-based and antiplatelets might be as safe and as effective. The ‘Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection’ (‘TREAT-CAD’) trial (clinicaltrials.gov: NCT02046460) compares Aspirin to oral anticoagulants (vitamin K antagonists) with regard to efficacy and safety by using both clinical and imaging surrogate outcome measures. TREAT-CAD tests the hypothesis, that aspirin is as safe and effective as vitamin K antagonists.Patients and methods TREAD-CAD is a Prospective, Randomised controlled, Open-labelled, multicentre, non-inferiority trial with Blinded assessment of outcome Events (PROBE-design). Key eligibility criteria are (i) clinical symptoms attributable to cervical artery dissection and (ii) verification of the cervical artery dissection diagnosis by established magnetic resonance imaging criteria. Patients are randomised to receive either Aspirin 300 mg daily or vitamin K antagonists for 90 days.Results Primary outcomes are assessed at 14 ± 10 days (magnetic resonance imaging and clinical examination) and at 90 ± 30 days (clinical examinations). The primary endpoint is a composite outcome measure – labelled Cerebrovascular Ischemia, major Hemorrhagic events or Death (CIHD) – and includes (i) occurrence of any stroke (including retinal infarction), (ii) new ischaemic lesions on diffusion-weighted magnetic resonance imaging, (iii) any major extracranial haemorrhage, (iv) any symptomatic intracranial haemorrhage, (v) any new haemorrhagic lesion visible on paramagnetic-susceptible sequences and (vi) death.Discussion After database closure, (i) central verification of cervical artery dissection diagnosis will be done by two experienced raters, (ii) adjudication of outcome events will be performed by independent adjudication committees, separately for clinical and imaging outcomes. The primary analysis will be done on the per protocol data set. The targeted sample size consists of 169 evaluable patients in the per protocol data set.Conclusion TREAT-CAD is testing the non-inferiority of Aspirin versus vitamin K antagonists treatment in patients with symptomatic cervical artery dissection by combined clinical and magnetic resonance imaging outcomes.
Published: 2020
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19. Antithrombotic Treatment of Embolic Stroke of Undetermined Source

Author: Diener, Hans-Christoph, Sacco, Ralph L., Easton, J. Donald, Granger, Christopher B., Bar, Michal, Bernstein, Richard A., Brainin, Michael, Brueckmann, Martina, Cronin, Lisa, Donnan, Geoffrey, Gdovinová, Zuzana, Grauer, Claudia, Kleine, Eva, Kleinig, Timothy J., Lyrer, Philippe, Martins, Sheila, Meyerhoff, Juliane, Milling, Truman, Pfeilschifter, Waltraud, Poli, Sven, Reif, Michal, Rose, David Z., Šaňák, Daniel, and Schäbitz, Wolf-Rüdiger
Abstract: Supplemental Digital Content is available in the text.
Published: 2020
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20. Effect of haemoglobin levels on outcome in intravenous thrombolysis-treated stroke patients

Author: Altersberger, Valerian L, Kellert, Lars, Al Sultan, Abdulaziz S, Martinez-Majander, Nicolas, Hametner, Christian, Eskandari, Ashraf, Heldner, Mirjam R, van den Berg, Sophie A, Zini, Andrea, Padjen, Visnja, Kägi, Georg, Pezzini, Alessandro, Polymeris, Alexandros, DeMarchis, Gian M, Tiainen, Marjaana, Räty, Silja, Nannoni, Stefania, Jung, Simon, Zonneveld, Thomas P, Maffei, Stefania, Bonati, Leo, Lyrer, Philippe, Sibolt, Gerli, Ringleb, Peter A, Arnold, Marcel, Michel, Patrik, Curtze, Sami, Nederkoorn, Paul J, Engelter, Stefan T, and Gensicke, Henrik
Abstract: Introduction Alterations in haemoglobin levels are frequent in stroke patients. The prognostic meaning of anaemia and polyglobulia on outcomes in patients treated with intravenous thrombolysis is ambiguous.Patients and methods In this prospective multicentre, intravenous thrombolysis register-based study, we compared haemoglobin levels on hospital admission with three-month poor outcome (modified Rankin Scale 3–6), mortality and symptomatic intracranial haemorrhage (European Cooperative Acute Stroke Study II-criteria (ECASS-II-criteria)). Haemoglobin level was used as continuous and categorical variable distinguishing anaemia (female: <12 g/dl; male: <13 g/dl) and polyglobulia (female: >15.5 g/dl; male: >17 g/dl). Anaemia was subdivided into mild and moderate/severe (female/male: <11 g/dl). Normal haemoglobin level (female: 12.0–15.5 g/dl, male: 13.0–17.0 g/dl) served as reference group. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated with logistic regression models.Results Among 6866 intravenous thrombolysis-treated stroke patients, 5448 (79.3%) had normal haemoglobin level, 1232 (17.9%) anaemia – of those 903 (13.2%) had mild and 329 (4.8%) moderate/severe anaemia – and 186 (2.7%) polyglobulia. Anaemia was associated with poor outcome (ORadjusted1.25 (1.05–1.48)) and mortality (ORadjusted1.58 (1.27–1.95)). In anaemia subgroups, both mild and moderate/severe anaemia independently predicted poor outcome (ORadjusted1.29 (1.07–1.55) and 1.48 (1.09–2.02)) and mortality (ORadjusted1.45 (1.15–1.84) and ORadjusted2.00 (1.46–2.75)). Each haemoglobin level decrease by 1 g/dl independently increased the risk of poor outcome (ORadjusted1.07 (1.02–1.11)) and mortality (ORadjusted1.08 (1.02–1.15)). Anaemia was not associated with occurrence of symptomatic intracranial haemorrhage. Polyglobulia did not change any outcome.Discussion The more severe the anaemia, the higher the probability of poor outcome and death. Severe anaemia might be a target for interventions in hyperacute stroke.Conclusion Anaemia on admission, but not polyglobulia, is a strong and independent predictor of poor outcome and mortality in intravenous thrombolysis-treated stroke patients.
Published: 2020
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21. Small vessel disease is associated with an unfavourable outcome in stroke patients on oral anticoagulation

Author: Hert, Lisa, Polymeris, Alexandros A., Schaedelin, Sabine, Lieb, Johanna, Seiffge, David J., Traenka, Christopher, Fladt, Joachim, Thilemann, Sebastian, Gensicke, Henrik, De Marchis, Gian Marco, Bonati, Leo, Lyrer, Philippe, Engelter, Stefan T., and Peters, Nils
Abstract: Introduction Cerebral small vessel disease is an important cause for both ischaemic stroke and intracranial haemorrhage. To date, knowledge on the impact of small vessel disease on the clinical course in stroke patients treated with oral anticoagulation for atrial fibrillation is limited.Patients and Methods Registry-based prospective observational study of 320 patients (aged 78.2 ± 9.2 years) treated with anticoagulation following atrial fibrillation stroke. Patients underwent standardised magnetic-resonance-imaging assessing measures of small vessel disease, including cerebral microbleeds and white matter hyperintensities. Median follow-up was 754 (interquartile range = [708–828]) days. Using adjusted logistic and Cox regression, we assessed the association of imaging measures with clinical outcome including recurrent ischaemic stroke, intracranial haemorrhage and death and assessed disability (modified Rankin Scale).Results Overall, recurrent ischaemic stroke was more common than intracranial haemorrhage (22 versus 8, respectively). Cerebral microbleeds were related to an increased risk of the composite endpoint (ischaemic stroke, intracranial haemorrhage, death: odds ratio (OR) 2.05, 95% confidence interval (CI) 1.27–3.31; P= 0.003), as were white matter hyperintensities (OR 2.00, 95%CI 1.23–3.27, P= 0.005). This was also true in time-to-event analysis (cerebral microbleeds: HR 2.31, 95%CI 1.39–3.52; P< 0.001; white matter hyperintensities: HR 1.99, 95%CI 1.20–3.17; P= 0.007). Both measures were associated with an increased risk for recurrent ischaemic stroke (cerebral microbleeds: HR 4.42, 95%CI 1.07–18.20; P= 0.04; white matter hyperintensities: HR 5.27, 95%CI 1.08–25.79, P= 0.04) and intracranial haemorrhage (cerebral microbleeds: HR 2.43, 95%CI 1.04–5.69; P= 0.04; white matter hyperintensities: HR 2.57, 95%CI 1.11–5.98, P= 0.03). Furthermore, confluent white matter hyperintensities were associated with increased disability (OR 4.03; 95%CI 2.16–7.52; P< 0.001) and mortality (HR 1.81, 95%CI 1.04–3.14, P= 0.04).Discussion and conclusion In atrial fibrillation stroke patients treated with oral anticoagulation, small vessel disease is associated with an unfavourable outcome. The presence of microbleeds indicated a risk higher for recurrent ischaemic stroke than for intracranial haemorrhage.
Published: 2020
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22. Rare genetic variants in patients with cervical artery dissection

Author: Traenka, Christopher, Kloss, Manja, Strom, Tim, Lyrer, Philippe, Brandt, Tobias, Bonati, Leo H, Grond-Ginsbach, Caspar, and Engelter, Stefan
Abstract: Introduction The potential role of genetic alterations in cervical artery dissection (CeAD) pathogenesis is poorly understood. We aimed to identify pathogenic genetic variants associated with cervical artery dissection by using whole exome sequencing.Patients and methods CeAD-patients with either a family history of cervical artery dissection (f-CeAD) or recurrent cervical artery dissection (r-CeAD) from the CeAD-databases of two experienced stroke centres were analysed by whole exome sequencing. Variants with allele frequency <0.05 and classified as pathogenic by predicting algorithms (SIFT or Polyphen-2) or the ClinVar database were explored. First, we analysed a panel of 30 candidate genes associated with arterial dissection (any site) or aneurysm according to the OMIM (online Mendelian Inheritance of Men) database. Second, we performed a genome-wide search for pathogenic variants causing other vascular phenotypes possibly related to cervical artery dissection. Findings were classified as CeAD-causing (pathogenic variants in genes from the arterial dissection or aneurysm panel) or suggestive (pathogenic variants in genes associated with other vascular phenotypes and variants of unknown significance in genes from the arterial dissection or aneurysm panel). All other variants were classified as benign/uncertain.Results Among 43 CeAD-patients, 28 patients (17 pedigrees) had f-CeAD and 15 had r-CeAD. No CeAD-causing variants were identified in r-CeAD patients. Among f-CeAD-patients, 5/17 pedigrees carried CeAD-causing variants in COL3A1, COL4A1, COL4A3, COL4A4, COL5A1, COL5A2 and FBN1. Suggestive variants in ABCC6, COL3A1, COL5A2, MEF2A, and RNF213 were detected in three pedigrees with f-CeAD and six patients with r-CeAD. Discussion and conclusion:CeAD-causing variants were rare and exclusively found in f-CeAD-patients, suggesting differences between the genetic architectures of f-CeAD and r-CeAD. The identified variants indicate a high genetic heterogeneity of the study sample.
Published: 2019
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23. Stent Design, Restenosis and Recurrent Stroke After Carotid Artery Stenting in the International Carotid Stenting Study

Author: Müller, Mandy D., Gregson, John, McCabe, Dominick J.H., Nederkoorn, Paul J., van der Worp, H. Bart, de Borst, Gert J., Cleveland, Trevor, Wolff, Thomas, Engelter, Stefan T., Lyrer, Philippe A., Brown, Martin M., and Bonati, Leo H.
Published: 2019
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24. Atherosclerosis in patients with cervical artery dissection

Author: Brunner, Eveline, Kaufmann, Josefin E, Fischer, Sandro, Gensicke, Henrik, Zietz, Annaelle, Polymeris, Alexandros A, Altersberger, Valerian L, Lyrer, Philippe A, Traenka, Christopher, and Engelter, Stefan T
Abstract: Introduction: Cervical artery dissection (CeAD) is considered a non-atherosclerotic arteriopathy, but atherosclerosis of the cervical arteries may co-exist. We explored the frequency and clinical importance of co-existent atherosclerosis in patients with CeAD.Patients and methods: Single-center exploratory study from the Stroke Center Basel, Switzerland. We re-reviewed duplex ultrasound images at (i) baseline and (ii) last follow-up visit for the presence versus absence of the following atherosclerotic manifestations in the carotid arteries: (i) abnormal carotid intima-media thickness, (ii) plaques, and (iii) atherosclerotic stenosis. We investigated whether CeAD patients with versus without co-existing atherosclerosis differ regarding (a) recurrence of CeAD and (b) occurrence of vascular events (myocardial infarction, peripheral artery disease, or ischemic stroke) using logistic regression with adjustment for age and follow-up time.Results: Among 294 CeAD patients (median age 46 [IQR 37–53], 41.8% women), 35 (12%) had any atherosclerotic signs at baseline. Among 196 patients with available follow-up, another 21/196 (11%) patients developed atherosclerosis during a median follow-up of 55.7 months. Patients with atherosclerosis had decreased odds of recurrent CeADs when compared to patients without atherosclerosis (OR 0.03, 95% CI = 0.00-0.30). During follow-up, 6 (15%) vascular events occurred among 40 CeAD patients with atherosclerosis and 13 (8.5%) among 153 patients without atherosclerosis (OR 1.38, 95% CI = 0.39-4.55, data for 3 patients were missing).Discussion and conclusion: Signs of atherosclerosis in the carotid artery were detectable in 12% of CeAD patient at baseline. Additionally, 11% of CeAD patients developed new signs of atherosclerosis within the following 5 years. The presence of atherosclerosis may suggest a lower risk for recurrent CeAD. Whether it might indicate an increased risk for late clinical vascular events deserves further studies.
Published: 2024
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25. Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial

Author: Zietz, Annaelle, Kaufmann, Josefin E, Wiesner, Karin, Fischer, Sandro Kevin, Wiegert, Martina, Verhagen-Kamerbeek, Wilma DJ, Rottenberger, Yannik, Schwarz, Anne, Peters, Nils, Gensicke, Henrik, Medlin, Friedrich, Möller, Jens Carsten, Bujan, Bartosz, Bonati, Leo H, Arnold, Marcel, Schaedelin, Sabine, Müri, René M., Hemkens, Lars G, Michel, Patrik, Lyrer, Philippe A, Held, Jeremia P, Ford, Gary A, Luft, Andreas R, Traenka, Christopher, and Engelter, Stefan T
Abstract: Rationale: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery.Aim and hypothesis: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo.Design: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial.Participants: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living.Intervention: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset.Comparison: Matching placebo plus standardized rehabilitation.Outcomes: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events.Conclusion: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.
Published: 2024
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26. Combined Transcriptomic and Proteomic Analyses of Cerebral Frontal Lobe Tissue Identified RNA Metabolism Dysregulation as One Potential Pathogenic Mechanism in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Author: Ritz, Marie-Françoise, Jenoe, Paul, Bonati, Leo, Engelter, Stefan, Lyrer, Philippe, and Peters, Nils
Abstract: Background: Cerebral small vessel disease (SVD) is an important cause of stroke and vascular cognitive impairment (VCI), leading to subcortical ischemic vascular dementia. As a hereditary form of SVD with early onset, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) represents a pure form of SVD and may thus serve as a model disease for SVD. To date, underlying molecular mechanisms linking vascular pathology and subsequent neuronal damage in SVD are incompletely understood. Objective: We performed comparative transcriptional profiling microarray and proteomic analyses on post-mortem frontal lobe specimen from 2 CADASIL patients and 5 non neurologically diseased controls in order to identify dysregulated pathways potentially involved in the development of tissue damage in CADASIL. Methods: Transcriptional microarray analysis of material extracted from frontal grey and white matter (WM) identified subsets of up- or down-regulated genes enriched into biological pathways mostly in WM areas. Proteomic analysis of these regions also highlighted cellular processes identified by dysregulated proteins. Results: Discrepancies between proteomic and transcriptomic data were observed, but a number of pathways were commonly associated with genes and corresponding proteins, such as: “ribosome” identified by upregulated genes and proteins in frontal cortex or “spliceosome” associated with down-regulated genes and proteins in frontal WM. Conclusion: This latter finding suggests that defective expression of spliceosomal components may alter widespread splicing profile, potentially inducing expression abnormalities that could contribute to cerebral WM damage in CADASIL.
Published: 2019
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27. Development and Validation of a Prognostic Model of Swallowing Recovery and Enteral Tube Feeding After Ischemic Stroke

Author: Galovic, Marian, Stauber, Anne Julia, Leisi, Natascha, Krammer, Werner, Brugger, Florian, Vehoff, Jochen, Balcerak, Philipp, Müller, Anna, Müller, Marlise, Rosenfeld, Jochen, Polymeris, Alexandros, Thilemann, Sebastian, De Marchis, Gian Marco, Niemann, Thorsten, Leifke, Maren, Lyrer, Philippe, Saladin, Petra, Kahles, Timo, Nedeltchev, Krassen, Sarikaya, Hakan, Jung, Simon, Fischer, Urs, Manno, Concetta, Cereda, Carlo W., Sander, Josemir W., Tettenborn, Barbara, Weder, Bruno J., Stoeckli, Sandro J., Arnold, Marcel, and Kägi, Georg
Abstract: IMPORTANCE: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. OBJECTIVE: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. DESIGN, SETTING, AND PARTICIPANTS: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. EXPOSURES: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). MAIN OUTCOMES AND MEASURES: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. RESULTS: In total, 279 participants (131 women [47.0%]; median age, 77 years [interquartile range, 67-84 years]) were enrolled (153 [54.8%] in the derivation study; 126 [45.2%] in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. CONCLUSIONS AND RELEVANCE: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.
Published: 2019
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28. Carotid Artery Stenting Versus Endarterectomy for Treatment of Carotid Artery Stenosis

Author: Müller, Mandy D., Lyrer, Philippe A., Brown, Martin M., and Bonati, Leo H.
Published: 2021
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29. European Stroke Organisation certification of stroke units and stroke centres

Author: Waje-Andreassen, Ulrike, Nabavi, Darius G, Engelter, Stefan T, Dippel, Diederik WJ, Jenkinson, Damian, Skoda, Ondrej, Zini, Andrea, Orken, Dilek N, Staikov, Ivan, and Lyrer, Philippe
Abstract: To improve quality and to overcome the wide discrepancies in stroke care both within- and between European countries, the European Stroke Organisation Executive Committee initiated in 2007 activities to establish certification processes for stroke units and stroke centres. The rapidly expanding evidence base in stroke care provided the mandate for the European Stroke Organisation Stroke Unit-Committee to develop certification procedures for stroke units and stroke centres with the goals of setting standards for stroke treatment in Europe, improving quality and minimising variation. The purpose of this article is to present the certification criteria and the auditing process for stroke units and stroke centres that aim to standardise and harmonise care for stroke patients, and hence become members of the European Stroke Organisation Stroke Unit and Stroke Centre network. Standardised application forms and guidelines for national and international auditors have been developed and updated by members of the European Stroke Organisation Stroke Unit-Committee. Key features are availability of trained personnel, diagnostic equipment, acute treatment and collaboration with other stroke-caregivers. After submission, the application is reviewed by one national and two international auditors. Based on their reports, the Stroke Unit-Committee will make a final decision. Validating on-site visits for a subset of stroke units and stroke centres are planned. We herein describe a novel, European Stroke Organisation-based online certification process of stroke units and stroke centres. This is a major step forward towards high-quality stroke care across Europe. The additional value by connecting high-quality European Stroke Organisation Stroke Unit and Stroke Centre is facilitation of future collaboration and research activities, enabling building and maintenance of a high-quality stroke care network in Europe.
Published: 2018
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30. Impact of Smoking on Clinical Outcome and Recanalization After Intravenous Thrombolysis for Stroke

Author: Kurmann, Rebekka, Engelter, Stefan T., Michel, Patrik, Luft, Andreas R., Wegener, Susanne, Branscheidt, Meret, Eskioglou, Elissavet, Sirimarco, Gaia, Lyrer, Philippe A., Gensicke, Henrik, Horvath, Thomas, Fischer, Urs, Arnold, Marcel, and Sarikaya, Hakan
Abstract: Supplemental Digital Content is available in the text.
Published: 2018
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31. Endovascular therapy versus intravenous thrombolysis in cervical artery dissection ischemic stroke – Results from the SWISS registry

Author: Traenka, Christopher, Jung, Simon, Gralla, Jan, Kurmann, Rebekka, Stippich, Christoph, Simonetti, Barbara Goeggel, Gensicke, Henrik, Mueller, Hubertus, Lovblad, Karl, Eskandari, Ashraf, Puccinelli, Francesco, Vehoff, Jochen, Weber, Johannes, Wegener, Susanne, Steiner, Levke, Kägi, Georg, Luft, Andreas, Sztajzel, Roman, Fischer, Urs, Bonati, Leo H, Peters, Nils, Michel, Patrik, Lyrer, Philippe A, Arnold, Marcel, and Engelter, Stefan T
Abstract: Introduction In patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications.Materials and methods In a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6 h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0–1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel–Haenszel model.Results Among 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9–11.38]). Sensitivity analyses in a subgroup treated within 4.5 h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00–14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n = 212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38–2.44]) among endovascular therapy patients and intravenous thrombolysis patients.Discussion and Conclusion In this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which – given the limitation of our sample size – does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.
Published: 2018
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32. Predictors of Acute and Persisting Ischemic Brain Lesions in Patients Randomized to Carotid Stenting or Endarterectomy

Author: Rostamzadeh, Ayda, Zumbrunn, Thomas, Jongen, Lisa M., Nederkoorn, Paul J., Macdonald, Sumaira, Lyrer, Philippe A., Kappelle, L. Jaap, Mali, Willem P. Th. M., Brown, Martin M., Worp, H. Bart van der, Engelter, Stefan T., Bonati, Leo H., de Borst, G.J., de Kort, G.A.P., Jongen, L.M., Kappelle, L.J., Lo, T.H., Mali, W.P.Th.M., Moll, F.L., van der Worp, H.B., Bonati, L.H., Engelter, S.T., Fluri, F., Haller, S., Jacob, A.L., Kirsch, E., Lyrer, P.A., Radue, E.-W., Stierli, P., Wasner, M., Wetzel, S.G., Flach, H.Z., Hendriks, J.M., Koudstaal, P.J., Pattynama, P.M.T., van Dijk, L.C., van Sambeek, M.R.H.M., van der Lugt, A., van Urk, H., Verhagen, H.J.M., Clarke, M., Davis, M., Dixit, A.K., Dorman, P., Dyker, A., Ford, G., Golkar, A., Jackson, R., Jayakrishnan, V., Lambert, D., Lees, T., Louw, S., Macdonald, S., Mendelow, D., Rodgers, H., Rose, J., Stansby, G., Wyatt, M., Koelemaij, M.J.W., Majoie, C.B.L.M., Nederkoorn, P.J., Reekers, J.A.A., Roos, Y.B.W.E.M., Adiseshiah, M., Bishop, C., Brew, S., Brookes, J., Brown, M.M., Jäger, H.R., Kitchen, N., Beard, J., Cleveland, T., Dodd, D., Gaines, P.A., Lonsdale, R., Nair, R., Nassef, A., Nawaz, S., and Venables, G.
Abstract: We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study.
Published: 2014
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33. Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes)

Author: Easton, J. Donald, Aunes, Maria, Albers, Gregory W., Amarenco, Pierre, Bokelund-Singh, Sara, Denison, Hans, Evans, Scott R., Held, Peter, Jahreskog, Marianne, Jonasson, Jenny, Minematsu, Kazuo, Molina, Carlos A., Wang, Yongjun, Wong, K.S. Lawrence, Johnston, S. Claiborne, Ameriso, Sebastiá F., Donnan, Geoffrey, Lemmens, Robin, Massaro, Ayrton, Titianova, Ekaterina, Hill, Michael D., Lavados, Pablo, Skoloudik, David, Röther, Joachim, Norbert, Szegedi, Agnelli, Giancarlo, Bornstein, Natan, Tanahashi, Norio, Góngora, Angel Arauz, Pretell, Edwin, San Jose, Maria Cristina Z., Czlonkowska, Anna, Bajenaru, Ovidiu, Stakhovskaya, Ludmila, Brozman, Miroslav, Kim, Jong-Sung, Wahlgren, Nils, Michel, Patrik, Lee, Tsong Hai, Suwanwela, Nijasri Charnnarong, Kutluk, Kursad, Moskovko, Sergii, Kasner, Scott, Laskowitz, Daniel, Clark, Wayne, Nguyen, Huy Thang, Ameriso, Sebastian, Lepera, Sandra, Romano, Marina, Paulon, David, Ioli, Pablo, Zurru, Cristina, Bruera, Guadalupe, Jure, Lorena, Klein, Francisco, Povedano, Guillermo, Levi, Christopher, Phan, Thanh, Markus, Romesh, Anderson, Craig, Sabet, Arman, Davis, Stephen, Lee, Andrew, Kleinig, Timothy, Wong, Andrew, Krause, Martin, Jannes, Jim, Wijeratne, Tissa, Lemmens, Robin, Hemelsoet, Dimitri, Peeters, André, Tack, Philippe, Vanacker, Peter, Laloux, Patrice, Van Landegem, William, Vanhooren, Geert, Desfontaines, Philippe, Van Orshoven, Marc, Oliveira, Fabio, Friedrich, Mauricio, Brondani, Rosane, Gagliardi, Rubens, Fabio, Soraia, Dracoulakis, Marianna, Bazan, Rodrigo, Marrone, Luiz, Pontes Neto, Octavio, Silva, Gisele, Kowacs, Pedro, Titianova, Ekaterina, Stamenova, Paraskeva, Daskalov, Marin, Staikov, Ivan, Baldaranov, Dimo, Maslarov, Dimitar, Lilovski, Hristo, Petkov, Plamen, Petrova, Neli, Mavrov, Radoslav, Markova, Veska, Petrova, Valeria, Beleva, Tanya, Kralev, Borislav, Sotirov, Nikolay, Lekova, Veska, Hristov, Dimcho, Ermenkova, Vera, Mateev, Lyudmil, Mitkova, Rumeliya, Haralanov, Liybomir, Ikonomov, Rosen, Mihailova, Margarita, Georgiev, Ivan, Shuaib, Ashfaq, Hachinski, Vladimir, Boulanger, Jean-Martin, Mann, Sharan, Hassan, Ayman, Mackey, Ariane, Menon, Bijoy, Minuk, Jeffrey, Siddiqui, Muzaffar, Eustace, Marsha, Vieira, Lucia, Selchen, Daniel, Beaudry, Michel, Stotts, Grant, Lavados, Pablo, Castro, Angel, Gasic, Kristo, Rivas, Rodrigo, Sanchez, Pablo, Roldan, Andres, Grossmann, Ingrid, Figueroa, Christian, Li, Jimei, Xu, Xiaolin, Chen, Huisheng, Li, Xiaohong, Yang, Yi, Zhang, Chunsheng, Wang, Baojun, Li, Guanglai, Wang, Dong, Lin, Hong, Tang, Yamei, Xu, Anding, Wang, Yanjiang, Hong, Wenke, Song, Zhi, Zhang, Xu, Jin, Xiaoping, Xu, Yun, Yan, Fuling, Zheng, Weihong, Wang, Xiaoping, Dong, Qiang, Zhao, Zhongxin, Zhang, Baorong, Zhong, Wangtao, Wen, Guoqiang, Xu, Jun, Li, Guozhong, Dong, Xueshuang, Tian, Xiangyang, Zhang, Zhaohui, Xu, En, Liu, Kaixiang, Chen, Jun, Skoda, Ondrej, Skoloudik, David, Ehler, Edvard, Vaclavik, Daniel, Sanak, Daniel, Klimosova, Sylva, Vitkova, Eva, Fiksa, Jan, Mikulik, Robert, Neumann, Jiri, Plny, Richard, Leys, Didier, Sibon, Igor, Mas, Jean-Louis, Alamowitch, Sonia, Pico, Fernando, Hosseini, Hassan, Mahagne, Marie-Hélène, Touze, Emmanuel, Vadot, Wilfried, Vannier, Stéphane, Nighoghossian, Norbert, Samson, Yves, Garnier, Pierre, Ellie, Emmanuel, Guillon, Benoît, Timsit, Serge, Giroud, Maurice, Philippeau, Frédéric, Bagan-Triquenot, Aude, Wolff, Valérie, Raposo, Nicolas, Obadia, Michel, Debiais, Severine, Grimaud, Jérôme, Illouz, Stéphane, Smadja, Didier, Urbanczyk, Cédric, Röther, Joachim, Berrouschot, Jörg, Weimar, Christian, Gahn, Georg, Soda, Hassan, Klimpe, Sven, Nabavi, Darius, Glahn, Jörg, Köhrmann, Martin, Krause, Lars, Terborg, Christoph, Urban, Peter, Steiner, Thorsten, Ferbert, Andreas, Dziewas, Rainer, Seidel, Günter, Thomalla, Götz, Li, Richard, Fong, Wing Chi, Cheung, Raymond, Szegedi, Norbert, Pozsegovits, Krisztián, Valikovics, Attila, Pánczél, Gyula, Rózsa, Csilla, Németh, László, Diószeghy, Péter, Óváry, Csaba, Csányi, Attila, Kerényi, Levente, Nagy, Valéria, Komoly, Sámuel, Bereczki, Dániel, Molnár, Sándor, Kondákor, István, Tanne, David, Raphaeli, Guy, Telman, Gregory, Bornstein, Natan, Leker, Ronen, Lampl, Yair, Agnelli, Giancarlo, Corea, Francesco, Ricci, Stefano, Guidetti, Donata, Malferrari, Giovanni, Marcheselli, Simona, Micieli, Giuseppe, Zini, Andrea, Di Lazzaro, Vincenzo, Gandolfo, Carlo, Salmaggi, Andrea, Tassi, Rossana, Rasura, Maurizia, Orlandi, Giovanni, Comi, Giancarlo, Ricci, Stefano, Mancuso, Michelangelo, Delodovici, Marialuisa, Bovi, Paolo, Consoli, Domenico, Utsugisawa, Kimiaki, Fujita, Tsuneo, Kurihara, Hideyuki, Maruki, Chikashi, Hayashi, Takeshi, Ogiichi, Tsuneaki, Kumagai, Morio, Takenaka, Katsunobu, Toyoda, Kazunori, Takamatsu, Kazuhiro, Ogami, Ryo, Kin, Shigenari, Aoki, Takeshi, Takizawa, Katsumi, Omori, Shigehiro, Umezawa, Takehiko, Toba, Yasuyuki, Nonoyama, Yutaka, Nakagawa, Hidemitsu, Naka, Takashi, Morimoto, Masanori, Matsumoto, Shuichi, Hitotsumatsu, Tsutomu, Shingaki, Tatsuya, Okuda, Satoshi, Ota, Mamoru, Sakai, Nobuyuki, Yamada, Takeshi, Niwa, Jun, Fujita, Hitoshi, Moriki, Akihito, Yoshino, Kimihiro, Fukushima, Yoshihisa, Mori, Takahisa, Sato, Atsushi, Kusano, Yoshikazu, Kubo, Michiya, Yamazaki, Masashi, Ooasa, Takao, Nishizaki, Takafumi, Kitagawa, Naoki, Yasaka, Masahiro, Manabe, Yasuhiro, Yoshioka, Akira, Ishihara, Masayuki, Kagawa, Takato, Ichihashi, Toshikazu, Matsuoka, Hideki, Ito, Yasuhiro, Yamasaki, Masahiro, Takaba, Hitonori, Saito, Hisatoshi, Sato, Masahiro, Fukuda, Kazumasa, Endo, Sumio, Kidooka, Minoru, Umemura, Toshitaka, Kikkawa, Yuriko, Toru, Shuta, Yamada, Kentaro, Sakai, Hideki, Asari, Jun, Ezura, Masayuki, Nitta, Hisashi, Nagano, Keiko, Ochiai, Jun, Sakai, Keiichi, Kobayashi, Yasutaka, Yoshii, Yasuhiro, Miake, Hirotomo, Takita, Tomohiro, Taniguchi, Hidekazu, Kuroki, Kazuhiko, Mizota, Takamitsu, Yamamoto, Kenichi, Nakane, Hiroshi, Iwanaga, Takeshi, Chiba, Kei, Yoshimoto, Tetsuyuki, Torii, Tsuyoshi, Kitagawa, Takeo, Takashima, Hiroshi, Shirasaki, Naoki, Dehara, Makoto, Wada, Naomichi, Hamada, Kensuke, Kato, Noriyuki, Go, Yoshinori, Izumi, Ichiro, Ninomiya, Hirotomo, Kumai, Junichiro, Nakajima, Yoshikazu, Kaku, Yasuhiko, Isayama, Yukihiro, Kawanishi, Masahiro, Noda, Shinya, Yamamoto, Kazuhide, Hazama, Takanori, Takahashi, Hiroshi, Tanaka, Yohei, Hata, Takashi, Kazekawa, Kiyoshi, Furui, Eisuke, Hondo, Hideki, Sato, Nobuyuki, Kusunoki, Katsusuke, Nanri, Kazunori, Abe, Satoshi, Sasaoka, Noboru, Kuroyanagi, Takayuki, Suzuki, Hisahiko, Fukuyama, Kouzou, Nakahara, Kimihiro, Gongora, Fernando, Góngora, Angel Arauz, Cantú Brito, Carlos, Villarreal Careaga, Jorge, Vazquez Alfaro, Rosalia, Aguayo Leytte, Geronimo, Berrospi, Percy, Chavez, Carlos, Pretell, Edwin, Rodriguez, Liliana, Custodio, Nilton, Castañeda, Cesar, Perez, Julio, San Jose, Maria Cristina, Baroque, Alejandro, Collantes, Epifania, Aquino, Abdias, Díaz, Alejandro, Roxas, Artemio, Lokin, Johnny, Advincula, Joel, Calderon, Emerito, Navarro, Jose, Hiyadan, John, Surdilla, Arturo, Czlonkowska, Anna, Ryglewicz, Danuta, Krychowiak, Grzegorz, Fryze, Waldemar, Sobolewski, Piotr, Nowak, Ryszard, Fiszer, Urszula, Papierowska, Beata, Zielińska-Turek, Justyna, Lasek-Bal, Anetta, Kołodziejska, Ewa, Kamińska, Anna, Adamkiewicz, Bożena, Tutaj, Andrzej, Szkopek, Dorota, Musiatowicz, Krzysztof, Bąk, Zbigniew, Brzozowski, Sławomir, Brola, Waldemar, Ferens, Antoni, Zalisz, Marek, Rejdak, Konrad, Rudzińska, Monika, Bajenaru, Ovidiu, Panea, Cristina, Simu, Mihaela, Balasa, Rodica, Cuciureanu, Iulian, Popescu, Bogdan, Sabau, Monica, Roman-Filip, Corina, Pimenov, Leonid, Gekht, Alla, Milto, Anna, Shchukin, Ivan, Parfenov, Vladimir, Stakhovskaya, Liudmila, Arkhipov, Mikhail, Sokolova, Nadezhda, Bogdanov, Enver, Esin, Radiy, Khasanova, Dina, Golikov, Konstantin, Melnikova, Elena, Zaslavskiy, Leonid, Voznyuk, Igor, Nazarov, Alexander, Akhmadeeva, Leila, Iakupova, Aida, Shamalov, Nikolay, Belskaya, Galina, Chuprina, Svetlana, Denisova, Olga, Drozdova, Ekaterina, Karakulova, Yuliya, Sholomov, Ilya, Spirin, Nikolay, Vostrikova, Elena, Mordvintseva, Elena, Grigoryeva, Vera, Zateyshchikov, Dmitry, Gorbachev, Vladimir, Chefranova, Zhanna, Dudarev, Mikhail, Nilk, Rostislav, Rozhdestvenskiy, Alexey, Gurcik, Ladislav, Dvorak, Miloslav, Krastev, Georgi, Kurca, Egon, Vyletelka, Juraj, Brozman, Miroslav, Kim, Jong Sung, Bae, Hee-Joon, Kim, Yong-Won, Kim, Joon-Tae, Cha, Jae-Kwan, Nam, Hyo Suk, Chang, Dae-Il, Lee, Yong-Seok, Oh, Kyungmi, Yu, Sung-Wook, Sohn, Sung-Il, Lee, Jun, Cho, Han Jin, Kim, Eung-Gyu, Rha, Joung-Ho, Kim, Seo Hyun, Molina Cateriano, Carlos, Serena Leal, Joaquín, Vivancos Mora, José, Rodríguez Yañez, Manuel, Roquer González, Jaume, Purroy García, Francisco, Gomis Cortina, Meritxell, Masjuan Vallejo, Jaime, Arenillas Lara, Juan, Segura Martín, Tomás, Herrero, José Antonio Egido, Tembl Ferrairó, Jose Ignacio, Gállego Culleré, Jaime, Moniche Álvarez, Francisco, Steinberg, Anna, Callander, Margarita, Laska, Ann Charlotte, Bokemark, Lena, Mooe, Thomas, Käll, Tor-Björn, Welin, Lennart, Sjöblom, Lars, Hambraeus, Joakim, Teichert, Jörg, Wannberg, Hans, Sanner, Johan, Ramströmer, Bo, Ziedén, Bo, Hau, Stefan Olsson, Gustafsson, Claes, Michel, Patrik, Kahles, Timo, Lyrer, Philippe, Arnold, Marcel, Liesch, Martin, Medlin, Friedrich, Cereda, Carlo, Kägi, Georg, Luft, Andreas, Carrera, Emmanuel, Lee, Tsong-Hai, Po, Helen L., Chern, Chang-Ming, Lien, Li-Ming, Chan, Lung, Liu, Chung-Hsiang, Wu, Shey-Lin, Lee, Jiann-Der, Chen, Chih-Hung, Lin, Huey-Juan, Lin, Ruey-Tay, Chen, Wei-Hsi, Sun, Yu, Suwanwela, Nijasri Charnnarong, Tantirittisak, Tasanee, Muengtaweepongsa, Sombat, Nilanont, Yongchai, Tiamkao, Somsak, Udommongkol, Chesda, Watcharasaksilp, Kanokwan, Jantararotai, Witoon, Kutluk, Kursad, Sirin, Hadiye, Ince, Birsen, Asil, Talip, Arsava, Murat, Incesu, Tulay Kurt, Tireli, Hulya, Kucukoglu, Hayriye, Ak, Fikri, Unal, Ali, Ozturk, Serefnur, Uzuner, Nevzat, Chmyr, Galyna, Lebedynets, Volodymyr, Nikonov, Vadym, Shulga, Lyudmyla, Smolanka, Volodymyr, Moskovko, Sergii, Khavunka, Marta, Yavorska, Valentyna, Tomakh, Nataliya, Kozyolkin, Olexandr, Litovaltseva, Galyna, Lansberg, Maarten, Bernstein, Richard, Brown, David, Clark, Wayne, Dissin, Jonathan, Graffagnino, Carmelo, Harris, Jonathan, Hicks, William, Kasner, Scott, Katzan, Irene, Kramer, Jeffrey, Willey, Joshua, Silliman, Scott, Starkman, Sidney, Thaler, David, Tremwel, Margaret, Concha, Mauricio, Rajamani, Kumar, Dandapani, Bhuvaneswari, Silver, Brian, Deal, Nathan, Chang, Ira, Hassan, Ameer, Rudolph, Steven, Fischer, Kenneth, Kirshner, Howard, Logan, William, Mallenbaum, Sidney, Hefzy, Hebah, Latorre, Julius, Levine, Steven, Ciabarra, Anthony, Dafer, Rima, Anyanwu, Benjamin, Cherian, Laurel, Panezai, Spozhmy, Khanna, Anna, Dodds, Jodi, Torbey, Michel, Gebel, James, Woo, Henry, Chiu, David, Androulakis, Xiao, Burgin, William, Pineda, Maria, Yilmaz, Engin, Altafullah, Irfan, Boutwell, Christine, Cruz-Flores, Salvador, Sapkota, Biggya, Fayad, Pierre, Jacoby, Michael, Rafiq, Shahid, Salgado, Efrain, Lafranchise, Eugene, Felton, Warren, Madhavan, Ramesh, Zaidat, Osama, Pieper, Connie, Riviello, Ralph, Burnett, Aaron, Fischer, Michelle, Gentile, Nina, Calder, Christopher, Dietrich, Dennis, Cross, Jonathan, Blankenship, Larry, Dafer, Rima, Montoya, Liliana, Grogan, Wendell, Young, Mark, Khan, Farrukh, Campbell, Duane, Daboul, Nizar, Espinoza, Andrey, Cullis, Paul, Concepcion, Gilberto, Wulff, John, Afzal, Haider, Jaffrani, Naseem, Reiter, William, Arshad, Tamjeed, Lukovits, Timothy, Welker, James, Chang, Fen Lei, Badruddin, Aamir, Babikian, Viken, Menon, Ravi, Sander, James, Springer, Mellanie, Nanda, Ashish, Mas, Luis, Rajan, Raj, Silverman, Bruce, Hefzy, Hebah, Huang, David, Carpenter, David, Clark, Joni, Ching, Marilou, Santhakumar, Sunitha, Gould, Jeffrey, Bansal, Vibhav, Vidal, Gabriel, Mikesell, Timothy, Brick, John, French, William, Shah, Qaisar, Holmstedt, Christine, Ishag-Osman, Nadir, Kostis, John, Shehadeh, Abbas, Sethi, Pramodkumak, Imam, Asher, Mccomas, Carl, Tran, Duc, Gebreyohanns, Mehari, Wiseman, Brian, Malik, Maheen, Schwarcz, Aron, Altschul, Dorothea, Castaldo, John, Alshekhlee, Amer, Gancher, Stephen, Krish, Nagesh, Nguyen-Huynh, Mai, Tremwell, Margaret, Sharma, Jitendra, Lee, Lance, Neil, William, Siddiqui, Fazeel, Malek, Ali, Romero, Charles, Huy, Thang Nguyen, Hoang, Hoa, Nguyen, Thang, Nguyen, Anh, and Nguyen, Hung
Abstract: Supplemental Digital Content is available in the text.
Published: 2017
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34. Next generation sequencing analysis of patients with familial cervical artery dissection

Author: Grond-Ginsbach, Caspar, Brandt, Tobias, Kloss, Manja, Aksay, Suna Su, Lyrer, Philipp, Traenka, Christopher, Erhart, Philipp, Martin, Juan Jose, Altintas, Ayse, Siva, Aksel, de Freitas, Gabriel R, Thie, Andreas, Machetanz, Jochen, Baumgartner, Ralf W, Dichgans, Martin, and Engelter, Stefan T
Abstract: Background The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection.Patients and methods Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as “benign” or “likely benign” in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database (n= 33,370).Results Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p= 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8–52.9).Conclusion Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.
Published: 2017
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35. Vascular Anatomy Predicts the Risk of Cerebral Ischemia in Patients Randomized to Carotid Stenting Versus Endarterectomy

Author: Müller, Mandy D., Ahlhelm, Frank J., von Hessling, Alexander, Doig, David, Nederkoorn, Paul J., Macdonald, Sumaira, Lyrer, Philippe A., van der Lugt, Aad, Hendrikse, Jeroen, Stippich, Christoph, van der Worp, H. Bart, Richards, Toby, Brown, Martin M., Engelter, Stefan T., and Bonati, Leo H.
Abstract: Supplemental Digital Content is available in the text.
Published: 2017
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36. Cervical artery dissection in patients ≥60 years

Author: Traenka, Christopher, Dougoud, Daphne, Simonetti, Barbara Goeggel, Metso, Tiina M., Debette, Stéphanie, Pezzini, Alessandro, Kloss, Manja, Grond-Ginsbach, Caspar, Majersik, Jennifer J., Worrall, Bradford B., Leys, Didier, Baumgartner, Ralf, Caso, Valeria, Béjot, Yannick, Compter, Annette, Reiner, Peggy, Thijs, Vincent, Southerland, Andrew M., Bersano, Anna, Brandt, Tobias, Gensicke, Henrik, Touzé, Emmanuel, Martin, Juan J., Chabriat, Hugues, Tatlisumak, Turgut, Lyrer, Philippe, Arnold, Marcel, and Engelter, Stefan T.
Published: 2017
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37. Early start of DOAC after ischemic stroke

Author: Seiffge, David J., Traenka, Christopher, Polymeris, Alexandros, Hert, Lisa, Peters, Nils, Lyrer, Philippe, Engelter, Stefan T., Bonati, Leo H., and De Marchis, Gian Marco
Published: 2016
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38. Lipid profiles and outcome in patients treated by intravenous thrombolysis for cerebral ischemia

Author: Nardi, Katiuscia, Engelter, Stefan, Strbian, Daniel, Sarikaya, Hakan, Arnold, Marcel, Casoni, Federica, Ford, Gary A., Cordonnier, Charlotte, Lyrer, Philippe, Bordet, Régis, Soinne, Lauri, Gensicke, Henrik, Duriez, Patrick, Baumgartner, Ralf W., Tatlisumak, Turgut, Leys, Didier, Strbian, D, Soinne, L, Tatlisumak, T, Bordet, AM, Bodenant, M., Bordet, R, Cordonnier, C, Debette, S, Dumont, F, Duriez, P., Gautier, S, Lefebvre, C, Leys, D, Nardi, K, Achnichts, L, Amort, M, Bonati, L, Burow, A, Engelter, ST, Fluri, F, Gensick, H, Hatz, F, Lyrer, PA, Thalmann, R, Baumgartner, RW, Georgiadis, D, Sarikaya, H, Arnold, M, Mattle, HP, Meier, N, Casoni, F, Cavazzuti, M, Zini, A, and Ford, GA
Abstract: To determine whether low low-density lipoprotein cholesterol (LDL-C) but not high-density lipoprotein cholesterol (HDL-C) and triglyceride concentrations are associated with worse outcome in a large cohort of ischemic stroke patients treated with IV thrombolysis.
Published: 2012
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39. Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation

Author: Polymeris, Alexandros A, Zietz, Annaelle, Schaub, Fabian, Meya, Louisa, Traenka, Christopher, Thilemann, Sebastian, Wagner, Benjamin, Hert, Lisa, Altersberger, Valerian L, Seiffge, David J, Lyrer, Flurina, Dittrich, Tolga, Piot, Ines, Kaufmann, Josefin, Barone, Lea, Dahlheim, Ludvig, Flammer, Sophie, Avramiotis, Nikolaos S, Peters, Nils, De Marchis, Gian Marco, Bonati, Leo H, Gensicke, Henrik, Engelter, Stefan T, and Lyrer, Philippe A
Abstract: Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce.Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome – the composite of recurrent ischemic stroke, major bleeding, and all-cause death – among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders.Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC.Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.
Published: 2022
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40. Identification of Inflammatory, Metabolic, and Cell Survival Pathways Contributing to Cerebral Small Vessel Disease by Postmortem Gene Expression Microarray

Author: Ritz, Marie-Françoise, Grond-Ginsbach, Caspar, Kloss, Manja, Tolnay, Markus, Fluri, Felix, H. Bonati, Leo, Traenka, Christopher, Zeis, Thomas, Schaeren-Wiemers, Nicole, Peters, Nils, Thomas Engelter, Stefan, and Alexandre Lyrer, Philippe
Abstract: Cerebral small-vessel disease (SVD) is characterized by periventricular white matter (WM) changes and general brain atrophy. SVD is prevalent in elderly individuals and is frequently associated with the development of vascular dementia (VaD). Studies of the molecular basis of SVD are sparse. We have to gain further insight into the pathogenic mechanisms of SVD. Therefore, we compared gene expression patterns in the brains of SVD and control patients, in order to identify cellular pathways changed in diseased brains. We compared the expression of mRNA transcripts in postmortem, macroscopically normal-appearing human brain tissues isolated from frontal, temporal and occipital cortical and subcortical regions in 5 SVD and 5 non-SVD control patients. Significant expression changes were determined by fold change F>1.2 in either direction, and p<0.05. We identified 228 genes differentially expressed in cortex (89 up-, 139 down-regulated) and 555 genes in WM (223 up-, 332 down-regulated) in SVD patients. Pathway analyses revealed that upregulated genes were associated with inflammation and apoptosis in WM, suggesting active cell death. Downregulated genes were associated with coagulation and fatty and amino acids metabolisms. In the cortex, down-regulated genes were principally associated with neuronal functions. Our data revealed widespread changes in the transcriptome profiles in the cortex and WM of human SVD brains, with a predominance of changes in WM. We provide for the first time a comprehensive view of the molecular alterations in human SVD brains that seem to contribute to the neuropathogenesis of SVD.
Published: 2016

41. Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke

Author: Gensicke, Henrik, Strbian, Daniel, Zinkstok, Sanne M., Scheitz, Jan F., Bill, Olivier, Hametner, Christian, Moulin, Solène, Zini, Andrea, Kägi, Georg, Pezzini, Alessandro, Padjen, Visnja, Béjot, Yannick, Corbiere, Sydney, Zonneveld, Thomas P., Seiffge, David J., Roos, Yvo B., Traenka, Christopher, Putaala, Jukka, Peters, Nils, Bonati, Leo H., Curtze, Sami, Erdur, Hebun, Sibolt, Gerli, Koch, Peter, Vandelli, Laura, Ringleb, Peter, Leys, Didier, Cordonnier, Charlotte, Michel, Patrik, Nolte, Christian H., Lyrer, Philippe A., Tatlisumak, Turgut, Nederkoorn, Paul J., and Engelter, Stefan T.
Abstract: Supplemental Digital Content is available in the text.
Published: 2016
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42. Recanalization Therapies in Acute Ischemic Stroke Patients

Author: Seiffge, David J., Hooff, Robbert-JanVan, Nolte, Christian H., Béjot, Yannick, Turc, Guillaume, Ikenberg, Benno, Berge, Eivind, Persike, Malte, Dequatre-Ponchelle, Nelly, Strbian, Daniel, Pfeilschifter, Waltraud, Zini, Andrea, Tveiten, Arnstein, Næss, Halvor, Michel, Patrik, Sztajzel, Roman, Luft, Andreas, Gensicke, Henrik, Traenka, Christopher, Hert, Lisa, Scheitz, Jan F., De Marchis, Gian Marco, Bonati, Leo H., Peters, Nils, Charidimou, Andreas, Werring, David J., Palm, Frederick, Reinhard, Matthias, Niesen, Wolf-Dirk, Nagao, Takehiko, Pezzini, Alessandro, Caso, Valeria, Nederkoorn, Paul J., Kägi, Georg, von Hessling, Alexander, Padjen, Visnja, Cordonnier, Charlotte, Erdur, Hebun, Lyrer, Philippe A., Brouns, Raf, Steiner, Thorsten, Tatlisumak, Turgut, and Engelter, Stefan T.
Abstract: Supplemental Digital Content is available in the text.
Published: 2015
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43. ASTRAL-R score predicts non-recanalisation after intravenous thrombolysis in acute ischaemic stroke

Author: Vanacker, Peter, Heldner, Mirjam R., Seiffge, David, Mueller, Hubertus, Eskandari, Ashraf, Traenka, Christopher, Ntaios, George, Mosimann, Pascal J., Sztajzel, Roman, Pereira, Vitor Mendes, Cras, Patrick, Engelter, Stefan, Lyrer, Philippe, Fischer, Urs, Lambrou, Dimitris, Arnold, Marcel, and Michel, Patrik
Published: 2015
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44. Diagnosis and Treatment of Cervical Artery Dissection

Author: Engelter, Stefan T., Traenka, Christopher, Von Hessling, Alexander, and Lyrer, Philippe A.
Abstract: Cervical artery dissection (CAD) is a major cause of stroke in the young. A mural hematoma is detected in most CAD patients. The intramural blood accumulation should not be considered a reason to withhold intravenous thrombolysis in patients with CAD-related stroke. Because intravenous-thrombolyzed CAD patients might not recover as well as other stroke patients, acute endovascular treatment is an alternative. Regarding the choice of antithrombotic agents, this article discusses the findings of 4 meta-analyses across observational data, the current status of 3 randomized controlled trials, and arguments and counterarguments favoring anticoagulants over antiplatelets. Furthermore, the role of stenting and surgery is addressed.
Published: 2015
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45. Alteplase for Acute Ischemic Stroke

Author: Lindley, Richard I., Wardlaw, Joanna M., Whiteley, William N., Cohen, Geoff, Blackwell, Lisa, Murray, Gordon D., Sandercock, Peter A.G., Baigent, Colin, Chadwick, David, Tyrrell, Pippa, Lowe, Gordon, Dennis, Martin, Innes, Karen, Goodare, Heather, Farrall, Andrew, von Kummer, Rüdiger, Cala, Lesley, von Heijne, Anders, Morris, Zoe, Adami, Alessandro, Peeters, Andre, Potter, Gillian, Brady, Nick, Collins, Rory, Bath, Philip, van Gijn, Jan, Gray, Richard, Hart, Robert, Yusuf, Salim, Muir, Keith, Hankey, Graeme J., Matz, Karl, Brainin, Michael, Peters, Andre, Gubitz, Gord, Phillips, Stephen, Ricci, Stefano, Arauz, Antonio, Berge, Eivind, Bruins Slot, Karsten, Czlonkowska, Anna, Kobayashi, Adam, Correia, Manuel, Lyrer, Phillippe, Engelter, Stefan, Murray, Veronica, Norrving, Bo, Terént, Andreas, Wester, Per, Venables, Graham, Innes, Karen, Clark, Alison, Perry, David, Soosay, Vera, Buchanan, David, Grant, Sheila, Sakka, Eleni, Drever, Jonathan, Walker, Pauli, Herath, Indee, Brown, Ann Leigh, Chmielnik, Paul, Armit, Christopher, Walton, Andrea, Hautvast, Mischa, Lewis, Steff, Heron, Graeme, Odusanya, Sylvia, Linksted, Pam, Kane, Ingrid, Sellar, Robin, White, Philip, Keston, Peter, Farrell, Andrew, Morris, Zoe, Miranda, Hector, Celani, Maria Grazia, Righetti, Enrico, Cenciarelli, Silvia, Mazzoli, Tatiana, Cantisani, Teresa Anna, Bembenek, Jan, and Isaakson, Eva
Abstract: Our aim was to identify whether particular subgroups of patients had an unacceptably high risk of symptomatic intracranial hemorrhage or low chance of benefit when treated with alteplase (recombinant tissue-type plasminogen activator).
Published: 2015
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46. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

Author: Bonati, Leo H, Dobson, Joanna, Featherstone, Roland L, Ederle, Jörg, van der Worp, H Bart, de Borst, Gert J, Mali, Willem P Th M, Beard, Jonathan D, Cleveland, Trevor, Engelter, Stefan T, Lyrer, Philippe A, Ford, Gary A, Dorman, Paul J, and Brown, Martin M
Abstract: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments.
Published: 2015
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47. Familial occurrence and heritable connective tissue disorders in cervical artery dissection

Author: Debette, Stéphanie, Goeggel Simonetti, Barbara, Schilling, Sabrina, Martin, Juan José, Kloss, Manja, Sarikaya, Hakan, Hausser, Ingrid, Engelter, Stefan, Metso, Tiina M., Pezzini, Alessandro, Thijs, Vincent, Touzé, Emmanuel, Paolucci, Stefano, Costa, Paolo, Sessa, Maria, Samson, Yves, Béjot, Yannick, Altintas, Ayse, Metso, Antti J., Hervé, Dominique, Lichy, Christoph, Jung, Simon, Fischer, Urs, Lamy, Chantal, Grau, Armin, Chabriat, Hugues, Caso, Valeria, Lyrer, Philippe A., Stapf, Christian, Tatlisumak, Turgut, Brandt, Tobias, Tournier-Lasserve, Elisabeth, Germain, Dominique P., Frank, Michael, Baumgartner, Ralf W., Grond-Ginsbach, Caspar, Bousser, Marie-Germaine, Leys, Didier, Dallongeville, Jean, Bersano, Anna, Arnold, Marcel, Abboud, Shérine, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Amouyel, Philippe, Wiest, Tina, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Del Zotto, Elisabetta, Giossi, Alessia, Volonghi, Irene, Padovani, Alessandro, Poli, Loris, Morotti, Andrea, Lanfranconi, Silvia, Baron, Pierluigi, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Worrall, Bradford B, Southerland, Andrew M, Majersik, Jennifer J, Meschia, James F, Cole, John, Kittner, Steven, Buffon, Fréderique, Mawet, Jérôme, Heldner, Mirjam R, Mattle, Heinrich P, and Gralla, Jan
Abstract: In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders.
Published: 2014
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48. Transcranial Laser Therapy in Acute Stroke Treatment

Author: Hacke, Werner, Schellinger, Peter D., Albers, Gregory W., Bornstein, Natan M., Dahlof, Bjorn L., Fulton, Rachael, Kasner, Scott E., Shuaib, Ashfaq, Richieri, Steven P., Dilly, Stephen G., Zivin, Justin, Lees, Kennedy R., Broderick, Joseph, Ivanova, Anastasia, Johnston, Karen, Norrving, Bo, Alexandrov, Andrei, Brown, David, Capone, Patrick, Chiu, David, Clark, Wayne, Cochran, Jack, Deredyn, Colin, Devlin, Thomas, Hickling, William, Howell, George, Huang, David, Hussain, Shazam, Mallenbaum, Sidney, Moonis, Majaz, Nash, Marshall, Rymer, Marilyn, Taylor, Reid, Tremwel, Margaret, Buck, Brian, Perez, Julio, Gerloff, Christian, Greiwing, Bernd, Grond, Martin, Hamman, Gerhard, Haarmeiter, Thomas, Jander, Sebastian, Köhrmann, Martin, Ritter, Martin, Schneider, Dietmar, Sobesky, Jan, Steiner, Thorsten, Steinmetz, Helmuth, Veltkamp, Roland, Weimar, Christian, Gruber, Franz, Andersson, Bjorn, Welin, Lennart, Leys, Didier, Tatlisumak, Turgut, Luft, Andreas, Lyrer, Philippe, Michel, Patrik, Molina, Carlos, and Segura, Tomas
Abstract: On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke.
Published: 2014
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49. Clinical import of Horner syndrome in internal carotid and vertebral artery dissection

Author: Lyrer, Philippe A., Brandt, Tobias, Metso, Tiina M., Metso, Antti J., Kloss, Manja, Debette, Stephanie, Leys, Didier, Caso, Valeria, Pezzini, Alessandro, Bonati, Leo H., Thijs, Vincent, Bersano, Anna, Touzé, Emmanuel, Gensicke, Henrik, Martin, Juan J., Lichy, Christoph, Tatlisumak, Turgut, Engelter, Stefan T., and Grond-Ginsbach, Caspar
Abstract: To study the prognostic importance of Horner syndrome (HS) in patients with internal carotid artery dissection (ICAD) or vertebral artery dissection (VAD).
Published: 2014
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50. Dose-Related Effects of Statins on Symptomatic Intracerebral Hemorrhage and Outcome After Thrombolysis for Ischemic Stroke

Author: Scheitz, Jan F., Seiffge, David J., Tütüncü, Serdar, Gensicke, Henrik, Audebert, Heinrich J., Bonati, Leo H., Fiebach, Jochen B., Tränka, Christopher, Lyrer, Philippe A., Endres, Matthias, Engelter, Stefan T., and Nolte, Christian H.
Abstract: The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.
Published: 2014
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