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Background Acute stroke patients with comorbid cancer (CC) are more preferably addressed with endovascular treatment (EVT) than thrombolytic therapy, due to the presumed potential risk of hemorrhagic transformation and systemic bleeding. This study aims to evaluate clinical and procedural outcomes of acute stroke patients with CC receiving EVT. Methods Using the Italian Registry of Endovascular Treatment in Acute Stroke, we reviewed prospectively collected data of CC patients treated with EVT from 2011 to 2017. Outcome measures were modified Thrombolysis in Cerebral Infarction score, symptomatic intracranial hemorrhage rate, and 3‐month modified Rankin scale. We also compared CC patients with a control group without cancer (non‐comorbid cancer) receiving EVT and matched the 2 populations with a 1:1 propensity score. Results Out of 4598 stroke patients treated with EVT, 165 (3.6%) had a CC. Modified Thrombolysis in Cerebral Infarction 2b‐3 was obtained in 73.8% of CC and 74.5% of non‐comorbid cancer patients ( P =0.84), whereas the rate of symptomatic intracranial hemorrhage rate was 8.2% and 6.9%, respectively. Three‐month all‐cause mortality was 33.3% in CC patients and 18.6% non‐comorbid cancer patients ( P P =0.012). In CC patients, the presence of metastasis and a more recent diagnosis of cancer were significantly associated with a higher 3‐month mortality ( P =0.018 and 0.021, respectively). Breast cancer showed a significant correlation with mild or no disability (odds ratio, 3.32; CI, 1.28–8.67; P =0.014) and less death cases at 3‐months (odds ratio, 0.44; CI, 0.16–1.21; P =0.114) compared to the other most represented malignancies. Conclusion Although 3‐month all‐cause mortality was significantly higher in CC patients, successful recanalization and hemorrhagic transformation rate were comparable in both groups. In cancer patients, a metastatic and active disease seem to be associated with a poorer functional outcome, whereas a diagnosis of breast cancer appears to be more frequent in patients with a mild or no disability at long term.

Supplemental material, sj-docx-1-eso-10.1177_23969873221131635 for Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis by Michele Romoli, Eleonora Matteo, Ludovica Migliaccio, Mauro Gentile, Maria Giulia Mosconi, Giuseppe Maria Scura, Marcello Naccarato, Enrico Colangeli, Paolo Candelaresi, Vincenzo Andreone, Fabrizio Giammello, Rosa Fortunata Musolino, Cristina Dell’Aera, Federica Nicoletta Sepe, Edoardo Pronello, Leonardo Barbarini, Marcella Caggiula, Federica Rizzo, Marco Petruzzellis, Elisa Giorli, Maria Luisa Zedde, Sabrina Anticoli, Marilena Mangiardi, Mario Muto, Francesco Diana, Maria Vittoria De Angelis, Anna Digiovanni, Letizia Concari, Sara La Gioia, Maria Sessa, Sara Biguzzi, Francesco Cordici, Marco Longoni, Maria Ruggiero, Silvia Cenciarelli, Paolo Eusebi, Simona Sacco, Valeria Caso, Maurizio Paciaroni, Stefano Ricci, Andrea Zini, Danilo Toni and David Giannandrea in European Stroke Journal

The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT.We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage.Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3 months' mortality and successful recanalization, respectively.Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months' mortality.

Supplemental material, sj-doc-1-ine-10.1177_15910199221086429 for Benefit from successful recanalization in an Italian cohort of stroke patients receiving endovascular treatments according to the DIRECT-MT trial criteria by Manuel Cappellari, Valentina Saia, Giovanni Pracucci, Fabrizio Sallustio, Andrea Zini, Mauro Bergui, Cecilia Zivelonghi, Salvatore Mangiafico and Danilo Toni in Interventional Neuroradiology

Importance Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. Objective To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. Design, Setting, and Participants This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. Main Outcomes and Measures Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). Results The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22). Conclusions and Relevance In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Additional file 1. Supplementary Table. Demographics and other clinical characteristics of the study patients. Supplementary Figure. Representative images of serial sections of the clot from the COVID-19 patient with acute myocardial infarction, stained for spike protein (SP) and CD61 for platelets identification.

Supplemental material, sj-docx-1-eso-10.1177_23969873221100897 for Endovascular treatment in patients with acute ischemic stroke and cancer: Systematic review and meta-analysis by Danilo Caimano, Federica Letteri, Francesco Capasso, Nicola Limbucci, Patrizia Nencini, Cristina Sarti, Fana Alemseged, Guido Bigliardi, Andrea Morotti, Danilo Toni, Andrea Zini and Francesco Arba in European Stroke Journal

Supplemental material, sj-docx-2-eso-10.1177_23969873221131635 for Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis by Michele Romoli, Eleonora Matteo, Ludovica Migliaccio, Mauro Gentile, Maria Giulia Mosconi, Giuseppe Maria Scura, Marcello Naccarato, Enrico Colangeli, Paolo Candelaresi, Vincenzo Andreone, Fabrizio Giammello, Rosa Fortunata Musolino, Cristina Dell’Aera, Federica Nicoletta Sepe, Edoardo Pronello, Leonardo Barbarini, Marcella Caggiula, Federica Rizzo, Marco Petruzzellis, Elisa Giorli, Maria Luisa Zedde, Sabrina Anticoli, Marilena Mangiardi, Mario Muto, Francesco Diana, Maria Vittoria De Angelis, Anna Digiovanni, Letizia Concari, Sara La Gioia, Maria Sessa, Sara Biguzzi, Francesco Cordici, Marco Longoni, Maria Ruggiero, Silvia Cenciarelli, Paolo Eusebi, Simona Sacco, Valeria Caso, Maurizio Paciaroni, Stefano Ricci, Andrea Zini, Danilo Toni and David Giannandrea in European Stroke Journal

Supplemental material, sj-docx-1-wso-10.1177_17474930221095965 for Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study by Irene Escudero-Martínez, Marius Matusevicius, Ana Pavia-Nunes, Petr Sevcik, Miroslava Nevsimalova, Viiu-Marika Rand, Janika Kõrv, Manuel Cappellari, Robert Mikulik, Danilo Toni and Niaz Ahmed in International Journal of Stroke

Supplemental material, sj-docx-2-eso-10.1177_23969873221131635 for Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis by Michele Romoli, Eleonora Matteo, Ludovica Migliaccio, Mauro Gentile, Maria Giulia Mosconi, Giuseppe Maria Scura, Marcello Naccarato, Enrico Colangeli, Paolo Candelaresi, Vincenzo Andreone, Fabrizio Giammello, Rosa Fortunata Musolino, Cristina Dell’Aera, Federica Nicoletta Sepe, Edoardo Pronello, Leonardo Barbarini, Marcella Caggiula, Federica Rizzo, Marco Petruzzellis, Elisa Giorli, Maria Luisa Zedde, Sabrina Anticoli, Marilena Mangiardi, Mario Muto, Francesco Diana, Maria Vittoria De Angelis, Anna Digiovanni, Letizia Concari, Sara La Gioia, Maria Sessa, Sara Biguzzi, Francesco Cordici, Marco Longoni, Maria Ruggiero, Silvia Cenciarelli, Paolo Eusebi, Simona Sacco, Valeria Caso, Maurizio Paciaroni, Stefano Ricci, Andrea Zini, Danilo Toni and David Giannandrea in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873221131635 for Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis by Michele Romoli, Eleonora Matteo, Ludovica Migliaccio, Mauro Gentile, Maria Giulia Mosconi, Giuseppe Maria Scura, Marcello Naccarato, Enrico Colangeli, Paolo Candelaresi, Vincenzo Andreone, Fabrizio Giammello, Rosa Fortunata Musolino, Cristina Dell’Aera, Federica Nicoletta Sepe, Edoardo Pronello, Leonardo Barbarini, Marcella Caggiula, Federica Rizzo, Marco Petruzzellis, Elisa Giorli, Maria Luisa Zedde, Sabrina Anticoli, Marilena Mangiardi, Mario Muto, Francesco Diana, Maria Vittoria De Angelis, Anna Digiovanni, Letizia Concari, Sara La Gioia, Maria Sessa, Sara Biguzzi, Francesco Cordici, Marco Longoni, Maria Ruggiero, Silvia Cenciarelli, Paolo Eusebi, Simona Sacco, Valeria Caso, Maurizio Paciaroni, Stefano Ricci, Andrea Zini, Danilo Toni and David Giannandrea in European Stroke Journal

Supplemental material, sj-docx-1-wso-10.1177_17474930221095965 for Association of statin pre-treatment with baseline stroke severity and outcome in patients with acute ischemic stroke and received reperfusion treatment: An observational study by Irene Escudero-Martínez, Marius Matusevicius, Ana Pavia-Nunes, Petr Sevcik, Miroslava Nevsimalova, Viiu-Marika Rand, Janika Kõrv, Manuel Cappellari, Robert Mikulik, Danilo Toni and Niaz Ahmed in International Journal of Stroke

Supplemental material, sj-docx-1-eso-10.1177_23969873221148229 for Association of cholesterol levels with hemorrhagic transformation and cerebral edema after reperfusion therapies by Irene Escudero-Martínez, Magnus Thorén, Marius Matusevicius, Charith Cooray, Andrea Zini, Christine Roffe, Danilo Toni, Georgios Tsivgoulis, Peter Ringleb, Nils Wahlgren and Niaz Ahmed in European Stroke Journal

Supplemental Material, sj-pdf-1-eso-10.1177_23969873221076968 for European Stroke Organisation ��� European Society for Minimally Invasive Neurological Therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion by Guillaume Turc, Georgios Tsivgoulis, Heinrich J. Audebert, Hieronymus Boogaarts, Pervinder Bhogal, Gian Marco De Marchis, Ana Catarina Fonseca, Pooja Khatri, Mika��l Mazighi, Natalia P��rez de la Ossa, Peter D. Schellinger, Daniel Strbian, Danilo Toni, Philip White, William Whiteley, Andrea Zini, Wim van Zwam, and Jens Fiehler in European Stroke Journal

Supplemental material, sj-docx-1-eso-10.1177_23969873221100897 for Endovascular treatment in patients with acute ischemic stroke and cancer: Systematic review and meta-analysis by Danilo Caimano, Federica Letteri, Francesco Capasso, Nicola Limbucci, Patrizia Nencini, Cristina Sarti, Fana Alemseged, Guido Bigliardi, Andrea Morotti, Danilo Toni, Andrea Zini and Francesco Arba in European Stroke Journal

Supplemental material, sj-pdf-1-wso-10.1177_17474930211058012 for Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy by Mukul Sharma, Eric E Smith, Lesly A Pearce, Kanjana S Perera, Scott E Kasner, Byung-Woo Yoon, Sebastian F Ameriso, Josep Puig, Dorte Damgaard, Jochen B Fiebach, Keith W Muir, Roland C Veltkamp, Roland C Veltkamp, Danilo S Toni, Nikolay Shamalov, Rubens J Gagliardi, Robert Mikulik, Stefan T Engelter, Daniel Bereczki, Martin J O���Donnell, Feryal Saad, Ashkan Shoamanesh, Scott D Berkowitz, Hardi Mundl, Robert G Hart and On behalf of the NAVIGATE ESUS MRI Substudy Investigators in International Journal of Stroke

Supplemental material, sj-pdf-1-wso-10.1177_17474930211058012 for Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy by Mukul Sharma, Eric E Smith, Lesly A Pearce, Kanjana S Perera, Scott E Kasner, Byung-Woo Yoon, Sebastian F Ameriso, Josep Puig, Dorte Damgaard, Jochen B Fiebach, Keith W Muir, Roland C Veltkamp, Roland C Veltkamp, Danilo S Toni, Nikolay Shamalov, Rubens J Gagliardi, Robert Mikulik, Stefan T Engelter, Daniel Bereczki, Martin J O���Donnell, Feryal Saad, Ashkan Shoamanesh, Scott D Berkowitz, Hardi Mundl, Robert G Hart and On behalf of the NAVIGATE ESUS MRI Substudy Investigators in International Journal of Stroke

[Background and objective] The optimal timing for initiation of dabigatran after acute ischaemic stroke (AIS) is not established. We aimed to evaluate initiation timing and clinical outcomes of dabigatran in AIS patients with non-valvular atrial fibrillation (NVAF)., [Design] Retrospective study based on prospectively collected data in SITS (Safe Implementation of Treatment in Stroke) Thrombolysis and Thrombectomy Registry from July 2014 to July 2018., [Participants] European NVAF patients (≥18 years) hospitalised after first-ever ischaemic stroke., [Setting] A multinational, observational monitoring register., [Intervention] Dabigatran initiation within 3 months after the ischaemic stroke., [Primary and secondary outcomes] The primary outcome was time from first-ever ischaemic stroke (index event) to dabigatran initiation. Additional outcomes included physicians’ reasons for delaying dabigatran initiation beyond acute hospital discharge and outcomes within 3 months of index event., [Methods] We identified patients with NVAF who received dabigatran within 3 months of the index event. We performed descriptive statistics for baseline and demographic data and clinical outcomes after dabigatran initiation., [Results] In total, 1489 patients with NVAF received dabigatran after AIS treated with thrombolysis and/or thrombectomy. Of these, 1240 had available initiation time. At baseline, median age was 75 years; 53% of patients were women, 15% were receiving an oral anticoagulant, 29% acetylsalicylic acid and 4% clopidogrel. Most patients (82%) initiated dabigatran within 14 days after the index event. Patients initiating earlier had lower stroke severity from median NIHSS 8 (IQR 6–13) if initiated within 7 days to NIHSS 15 (9–19) if initiated between 28 days and 3 months. Most common reasons for delaying initiation were haemorrhagic transformation or intracranial haemorrhage, stroke severity and infarct size. Few thrombotic/haemorrhagic events occurred within 3 months after the index event (20 of 926 patients, 2.2% with the available data)., [Conclusions] Our findings, together with previous observational studies, indicate that dabigatran initiated within the first days after an AIS is safe in patients treated with intravenous thrombolysis, endovascular thrombectomy or both., [Trial registration number] SITS Thrombolysis and Thrombectomy Registry (NCT03258645)., This study is sponsored by Boehringer-Ingelheim. In addition, the SITS registry is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, the Swedish Order of St. John, Friends of Karolinska Institutet, private donors as well as from an unrestricted sponsorship from Boehringer-Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority and Ferrer International, EVER Pharma. SITS is currently conducting studies supported by Boehringer-Ingelheim as well as in collaboration with Karolinska Institutet supported by Stryker, Covidien and Phenox. IE-M has received a grant from 'Fundación Progreso y Salud, Junta de Andalucía' (grant EF-0437-2018).

Supplemental material, sj-pdf-1-eso-10.1177_2396987320920114 for The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial – A post hoc analysis by Johannes AR Pfaff, Martin Bendszus, Geoffrey Donnan, Carlos Molina, Didier Leys, Peter D Schellinger, Stefan Schwab, Danilo Toni, Nils Wahlgren, Werner Hacke and Peter Arthur Ringleb in European Stroke Journal

Supplemental material, sj-pdf-1-eso-10.1177_2396987320945840 for A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke by Manuel Cappellari, David J Seiffge, Masatoshi Koga, Maurizio Paciaroni, Stefano Forlivesi, Gianni Turcato, Paolo Bovi, Sohei Yoshimura, Kanta Tanaka, Masayuki Shiozawa, Takeshi Yoshimoto, Kaori Miwa, Masahito Takagi, Manabu Inoue, Hiroshi Yamagami, Valeria Caso, Georgios Tsivgoulis, Michele Venti, Monica Acciarresi, Andrea Alberti, Danilo Toni, Alexandros Polymeris, Bruno Bonetti, Giancarlo Agnelli, Kazunori Toyoda, Stefan T Engelter, Gian Marco De Marchis and on behalf of the SAMURAI-NVAF, RAF-NOAC, NOACISP LONG-TERM, and Verona Study Groups: on behalf of the DYDA 2 investigators in European Stroke Journal

Supplemental material, sj-pdf-1-eso-10.1177_2396987320945840 for A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke by Manuel Cappellari, David J Seiffge, Masatoshi Koga, Maurizio Paciaroni, Stefano Forlivesi, Gianni Turcato, Paolo Bovi, Sohei Yoshimura, Kanta Tanaka, Masayuki Shiozawa, Takeshi Yoshimoto, Kaori Miwa, Masahito Takagi, Manabu Inoue, Hiroshi Yamagami, Valeria Caso, Georgios Tsivgoulis, Michele Venti, Monica Acciarresi, Andrea Alberti, Danilo Toni, Alexandros Polymeris, Bruno Bonetti, Giancarlo Agnelli, Kazunori Toyoda, Stefan T Engelter, Gian Marco De Marchis and on behalf of the SAMURAI-NVAF, RAF-NOAC, NOACISP LONG-TERM, and Verona Study Groups: on behalf of the DYDA 2 investigators in European Stroke Journal

Supplemental material, sj-pdf-1-wso-10.1177_1747493020976681 for Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke by Giancarlo Salsano, Giovanni Pracucci, Nicola Mavilio, Valentina Saia, Monica B di Poggio, Laura Malfatto, Fabrizio Sallustio, Andrea Wlderk, Nicola Limbucci, Patrizia Nencini, Stefano Vallone, Andrea Zini, Guido Bigliardi, Mariano Velo, Isabella Francalanza, Paola Gennari, Rossana Tassi, Mauro Bergui, Paolo Cerrato, Giuseppe Carità, Cristiano Azzini, Roberto Gasparotti, Mauro Magoni, Salvatore Isceri, Christian Commodaro, Francesco Cordici, Roberto Menozzi, Lilia Latte, Mirco Cosottini, Michelangelo Mancuso, Alessio Comai, Enrica Franchini, Andrea Alexandre, Giacomo Della Marca, Edoardo Puglielli, Alfonsina Casalena, Francesco Causin, Claudio Baracchini, Luca Di Maggio, Andrea Naldi, Andrea Grazioli, Stefano Forlivesi, Luigi Chiumarulo, Marco Petruzzellis, Giuseppina Sanfilippo, Gianpaolo Toscano, Nicola Cavasin, Critelli Adriana, Maria Porzia Ganimede, Maria Pia Prontera, Giorgianni Andrea, Marco Mauri, William Auteri, Alfredo Petrone, Carlo Cirelli, Anne Falcou, Simona Corraine, Valeria Piras, Giuseppe Ganci, Tiziana Tassinari, Nunzio Paolo Nuzzi, Manuel Corato, Simona Sacco, Guido Squassina, Paolo Invernizzi, Ivan Gallesio, Delfina Ferrandi, Giovanni Dui, Gianluca Deiana, Pietro Amistà, Monia Russo, Francesco Pintus, Antonio Baule, Giuseppe Craparo, Marina Mannino, Lucio Castellan, Danilo Toni and Salvatore Mangiafico in International Journal of Stroke

Supplemental material, ESO863606 Supplemental Material for Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11–13 November 2018 by Niaz Ahmed, Heinrich Audebert, Guillaume Turc, Charlotte Cordonnier, Hanne Christensen, Simona Sacco, Else Charlotte Sandset, George Ntaios, Andreas Charidimou, Danilo Toni, Christian Pristipino, Martin Köhrmann, Joji B Kuramatsu, Götz Thomalla, Robert Mikulik, Gary A Ford, Joan Martí-Fàbregas, Urs Fischer, Magnus Thoren, Erik Lundström, Gabriel JE Rinkel, H Bart van der Worp, Marius Matusevicius, Georgios Tsivgoulis, Haralampos Milionis, Marta Rubiera, Robert Hart, Tiago Moreira, Maria Lantz, Christina Sjöstrand, Grethe Andersen, Peter Schellinger, Konstantinos Kostulas, Katharina Stibrant Sunnerhagen, Boris Keselman, Eleni Korompoki, Jan Purrucker, Pooja Khatri, William Whiteley, Eivind Berge, Michael Mazya, Diederik WJ Dippel, Satu Mustanoja, Mads Rasmussen, Åsa Kuntze Söderqvist, Irene Escudero-Martínez and Thorsten Steiner in European Stroke Journal

Supplemental Material for European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE) by Guillaume Turc, Pervinder Bhogal, Urs Fischer, Pooja Khatri, Kyriakos Lobotesis, Mikaël Mazighi, Peter D. Schellinger, Danilo Toni, Joost de Vries, Philip White and Jens Fiehler in European Stroke Journal

Supplemental Material for IER-START nomogram for prediction of three-month unfavorable outcome after thrombectomy for stroke by Manuel Cappellari, Salvatore Mangiafico, Valentina Saia, Giovanni Pracucci, Sergio Nappini, Patrizia Nencini, Daniel Konda, Fabrizio Sallustio, Stefano Vallone, Andrea Zini, Sandra Bracco, Rossana Tassi, Mauro Bergui, Paolo Cerrato, Antonio Pitrone, Francesco Grillo, Andrea Saletti, Alessandro De Vito, Roberto Gasparotti, Mauro Magoni, Edoardo Puglielli, Alfonsina Casalena, Francesco Causin, Claudio Baracchini, Lucio Castellan, Laura Malfatto, Roberto Menozzi, Umberto Scoditti, Chiara Comelli, Enrica Duc, Alessio Comai, Enrica Franchini, Mirco Cosottini, Michelangelo Mancuso, Simone Peschillo, Manuela De Michele, Andrea Giorgianni, Maria Luisa Delodovici, Elvis Lafe, Maria F Denaro, Nicola Burdi, Saverio Internò, Nicola Cavasin, Adriana Critelli, Luigi Chiumarulo, Marco Petruzzellis, Marco Doddi, Antonio Carolei, William Auteri, Alfredo Petrone, Riccardo Padolecchia, Tiziana Tassinari, Marco Pavia, Paolo Invernizzi, Gianni Turcato, Stefano Forlivesi, Elisa Francesca Maria Ciceri, Bruno Bonetti, Domenico Inzitari and Danilo Toni in International Journal of Stroke

Supplemental material, WSO884525 Supplemetal Material for Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials by Svetlana Lorenzano, Annarita Vestri, Paolo Bovi, Manuel Cappellari, Paolo Stanzione, Domenico Samà, Maddalena Bruscoli, Milena Cavazzuti, Andrea Zini, Maurizia Rasura, Mario Beccia, Giancarlo Comi, Maria Sessa, Carlo Gandolfo, Maurizio Balestrino, Giancarlo Agnelli, Valeria Caso, Piercarlo Gerbino Promis, Claudio Pozzessere, Sabrina Anticoli, Francesco Perini, Michela Marcon, Annalisa Vinattieri, Alba Caruso, Mauro Magoni, Mauro Furlan, Giovanni Orlandi, Vincenzo Di Lazzaro, Mariarosaria Valente, Patrizia Nencini and Danilo Toni on behalf of the TESPI trial Investigators in International Journal of Stroke

Supplemental Material for Outcome after intravenous thrombolysis in patients with acute lacunar stroke: An observational study based on SITS international registry and a meta-analysis by Marius Matusevicius, Maurizio Paciaroni, Valeria Caso, Matteo Bottai, Dheeraj Khurana, Mario de Bastos, Sheila CO Martins, Yakup Krespi, Charith Cooray, Danilo Toni and Niaz Ahmed in International Journal of Stroke

Supplemental material, Supplemental Material2 for European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage by Hanne Christensen, Charlotte Cordonnier, Janika Kõrv, Avtar Lal, Christian Ovesen, Jan C Purrucker, Danillo Toni and Thorsten Steiner: on behalf of the VISTA-ICH Collaborators in European Stroke Journal

Supplemental material, ESO ESMINT Guideline for European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE) by Guillaume Turc, Pervinder Bhogal, Urs Fischer, Pooja Khatri, Kyriakos Lobotesis, Mikaël Mazighi, Peter D. Schellinger, Danilo Toni, Joost de Vries, Philip White and Jens Fiehler in European Stroke Journal

Supplemental material, WSO884525 Supplemetal Material for Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials by Svetlana Lorenzano, Annarita Vestri, Paolo Bovi, Manuel Cappellari, Paolo Stanzione, Domenico Samà, Maddalena Bruscoli, Milena Cavazzuti, Andrea Zini, Maurizia Rasura, Mario Beccia, Giancarlo Comi, Maria Sessa, Carlo Gandolfo, Maurizio Balestrino, Giancarlo Agnelli, Valeria Caso, Piercarlo Gerbino Promis, Claudio Pozzessere, Sabrina Anticoli, Francesco Perini, Michela Marcon, Annalisa Vinattieri, Alba Caruso, Mauro Magoni, Mauro Furlan, Giovanni Orlandi, Vincenzo Di Lazzaro, Mariarosaria Valente, Patrizia Nencini and Danilo Toni on behalf of the TESPI trial Investigators in International Journal of Stroke

Supplemental Material for Extending the time window for intravenous thrombolysis in acute ischemic stroke using magnetic resonance imaging-based patient selection by Peter Ringleb, Martin Bendszus, Erich Bluhmki, Geoffrey Donnan, Christoph Eschenfelder, Marc Fatar, Christof Kessler, Carlos Molina, Didier Leys, Girish Muddegowda, Sven Poli, Peter Schellinger, Stefan Schwab, Joaquin Serena, Danilo Toni, Nils Wahlgren, Werner Hacke and for the ECASS-4 study group in International Journal of Stroke

Supplemental material, WSO884523 Supplemental Material for Regional, sex, and age differences in diagnostic testing among participants in the NAVIGATE-ESUS trial by Antonio Arauz, Fabiola Serrano, Lesly A Pearce, Scott E Kasner, Sebastian F Ameriso, Danilo Toni, Daniel Bereczki, James Siegler, Angélica Ruiz-Franco, Carlos Cantú-Brito, Anna Czlonkowska, Wilfried Lang, Scott D Berkowitz, Hardi Mundl and Robert G Hart in International Journal of Stroke

Supplemental material, Supplemental Material1 for European Stroke Organisation Guideline on Reversal of Oral Anticoagulants in Acute Intracerebral Haemorrhage by Hanne Christensen, Charlotte Cordonnier, Janika Kõrv, Avtar Lal, Christian Ovesen, Jan C Purrucker, Danillo Toni and Thorsten Steiner: on behalf of the VISTA-ICH Collaborators in European Stroke Journal

Supplemental Material for Combined intravenous and endovascular treatment versus primary mechanical thrombectomy. The Italian Registry of Endovascular Treatment in Acute Stroke by Ilaria Casetta, Giovanni Pracucci, Andrea Saletti, Valentina Saia, Marina Padroni, Alessandro De Vito, Domenico Inzitari, Andrea Zini, Stefano Vallone, Mauro Bergui, Paolo Cerrato, Sandra Bracco, Rossana Tassi, Roberto Gandini, Fabrizio Sallustio, Mariangela Piano, Cristina Motto, Paolino La Spina, Sergio L Vinci, Francesco Causin, Claudio Baracchini, Roberto Gasparotti, Mauro Magoni, Lucio Castellan, Carlo Serrati, Salvatore Mangiafico, Danilo Toni and on behalf of the The Italian Registry of Endovascular Treatment in Acute Stroke in International Journal of Stroke

Supplemental material for The START nomogram for individualized prediction of the probability of unfavorable outcome after intravenous thrombolysis for stroke by Manuel Cappellari, Gianni Turcato, Stefano Forlivesi, Fabio Bagante, Gianfranco Cervellin, Giuseppe Lippi, Bruno Bonetti, Paolo Bovi and Danilo Toni in International Journal of Stroke

Supplemental material for Small vessel disease and biomarkers of endothelial dysfunction after ischaemic stroke by Francesco Arba, Alessio Giannini, Benedetta Piccardi, Silvia Biagini, Vanessa Palumbo, Betti Giusti, Patrizia Nencini, Anna Maria Gori, Mascia Nesi, Giovanni Pracucci, Giorgio Bono, Paolo Bovi, Enrico Fainardi, Domenico Consoli, Antonia Nucera, Francesca Massaro, Giovanni Orlandi, Francesco Perini, Rossana Tassi, Maria Sessa, Danilo Toni, Rosanna Abbate and Domenico Inzitari in European Stroke Journal

Background and Aims Epidemiological studies show that vascular risk factors are the same across the world but their effect vary between different race-ethnic groups. However, few studies have evaluated differences in recurrent stroke rates in various race-ethnicities. In >20 000 patients spanning 35 countries encompassing most race-ethnicities, we evaluated the incidence of ischemic and hemorrhagic strokes and myocardial infarction in patients within the context of the largest secondary stroke prevention trial (Prevention Regimen for Effectively Avoiding Secondary Strokes) to identify any significant differences. Methods There were 20 332 patients with a recent ischemic stroke randomized in a factorial design to receive the antiplatelet agent clopidogrel vs. aspirin plus extended-release dipyridamole, and 80 mg of the anthypertensive telmisartan vs. placebo. The primary outcome for the trial was the time to any recurrent stroke. Statistical analysis was used to detect race-ethnic differences in recurrent vascular events. Results Mean patient age was 66 (±8·6) years and 36% were women. The study included 58% European/Caucasian, 33% Asians, 5% Latin/Hispanic, and 4% Black African. There were 74% of patients that were hypertensive, and average systolic and diastolic blood pressure was 144·1/83·8 mmHg. There was at least one significant difference in the overall test of all race-ethnic groups in myocardial infarction and symptomatic intracerebral hemorrhage occurrence. In the Kaplan–Meier hemorrhage and stroke-free survival curves, Asians showed a significantly higher recurrence of ischemic stroke risk in the 135–150 mmHg and greater than 150 mm Hg blood pressure groups, and a greater risk of hemorrhage recurrence in the greater than 150 mmHg blood pressure group. Conclusions We found a significant difference in myocardial infarction and symptomatic intracerebral hemorrhage recurrence among different race-ethnic groups. The risk of recurrent ischemic and hemorrhagic stroke was greater in Asians with high blood pressure.

Background and purpose The lack of a wide implementation of stroke units (SU)s in Italy appears to accompany the underuse of the operating units. Community awareness of acute stroke care options may affect stroke resource use. Our aim was to determine the level of knowledge about SUs and tissue-plasminogen activator (t-PA) treatment amongst Italian adults and investigate its relationship to local stroke services implementation. Methods A nation-based telephone survey was carried out in a sample of 1000 residents aged >18 years in May–June 2010. The questionnaire included close-ended questions regarding knowledge of SUs and t-PA treatment. Number and location of both SUs and t-PA treatments were provided by a concurrent national hospital-based survey. The prevalence and distribution of acute stroke care awareness in the community was examined and multivariate analyses were generated. Results Amongst the 1000 participants (474 men, mean age 48.8 ± 17.2), only 26.2% reported knowing about the availability of t-PA treatment and only 15% were aware of the existence of SUs. Awareness of both SUs and t-PA was significantly associated only with education. These associations remained significant in the multivariate analyses. The degree of stroke services implementation (in terms of SUs/inhabitant rates and number of t-PA treatments) was not associated with SU and t-PA awareness. Conclusions This is the first European study that explored public knowledge about t-PA treatment and SUs. Italian adults proved insufficiently educated about SUs and t-PA; there is no higher awareness in areas with a greater supply of stroke services. This might partially explain the underuse of Italian SUs.

Background and Purpose Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. Methods We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5–6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran–Mantel–Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5–6 h, testing for net benefit by Cochran–Mantel–Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0–1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale. Results In the training dataset, limits of 56–95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5–6 h dataset, score limits of 56–95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87–1·47, Cochran–Mantel–Haenszel P = 0·89. More patients achieved modified Rankin score 0–1 (odds ratio 1·44, 1·02–2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01–2·40, P = 0·04; odds ratio 15·6, 3·7–65·8, P = 0·0002, respectively. Conclusion Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial; International audience; BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS: A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS: The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Background and Purpose— National Institutes of Health Stroke Scale (NIHSS) item profiles that were recently proposed and validated may prove useful for clinical prognostication and research studies. We aimed to validate the NIHSS item profiles in hyper-acute stroke patients who received thrombolysis treatment (tissue-type plasminogen activator). Methods— We applied the latent class analysis probabilities of the profile membership generated from the derivation study onto NIHSS data from the Safe Implementation of Thrombolysis in Stroke–Monitoring Study (SITS-MOST). We separately considered NIHSS data collected within 3 hours and at ≈24 hours after stroke onset to obtain 2 sets of symptom groupings. The discrimination and calibration of both sets of symptom profiles were assessed from their association with outcomes. The outcome measures included modified Rankin Scale (mRS; using full distribution and dichotomized, mRS 0–1 or back to baseline) at day 90 and mortality by 90 days. Results— We obtained data for 6843 patients. Ordinal analysis of mRS showed odds of better outcome across the profiles, for each set of symptom profiles, adjusted for age, sex, and prestroke mRS. Dichotomized outcomes mirrored the ordinal findings. There were significant differences in prognostic discrimination ability for the dichotomized outcome measures between the 2 sets of symptom profiles, with the latter set (ie, 24-hour symptom profiles) performing better. Conclusions— The NIHSS item profiles are individually associated with functional outcome and mortality in acute stroke patients treated with tissue-type plasminogen activator. Considering profiles of NIHSS subscores rather than only the total score is informative for prognostication, particularly for assessments collected 24 hours after stroke onset.

In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for the development of the Guideline Documents of the European Stroke Organisation.

Background and purpose Recognizing stroke symptoms and acting quickly can reduce death and disability, but public awareness of stroke risk factors, symptoms and what to do about them is still limited. Stroke educational campaigns are used worldwide but there are few published evaluations of such campaigns. Methods The literature from 1999 to 2012 on the effectiveness of stroke educational campaigns was reviewed and summarized with narrative synthesis. Web-based campaigns were also described. Three databases and one search engine were explored with two keywords (stroke campaign and stroke promotion). The reference lists of all included articles were also examined. Results Twenty-two intervention studies and five web-based campaigns were included in the review. Most interventions proved partially effective, in terms of gender preference (women) or type of information retained or media preferred. Only one intervention proved ineffective. Mass media campaigns can be effective but require sustained funding, and their ability to target high-risk subgroups, whether aging, linguistic or socioeconomic, is unclear. Three community-based participatory stroke promotion interventions proved partially effective, but the small sample sizes might have underpowered the results. Web-based campaigns are efficient in reaching a large number of people but tend to attract a selected and self-selected population. Conclusions Stroke educational campaigns have the potential to improve knowledge and awareness and change the behavior of a large number of people. Health promoters and investigators must adopt flexibility and participatory mentality to develop cost-effective interventions. Both community-based campaigns and E-tools should be integrated within a comprehensive multifaceted stroke promotion strategy to expand their reach.

The Stroke Units (SUs) have been demonstrated to be efficient and cost effective for acute stroke care. Nevertheless, the level of stroke unit implementation in Italy does not correspond to expectations yet. This study is a survey, which aims at assessing the current status of in-hospital stroke care in the Italian regions and at updating SUs. The survey was conducted by means of a semi-structured questionnaire, based on 18 stroke care “quality indicators”, submitted to all the Italian centres that had taken part in the SITS-MOST study, and to other centres advised by the coordinator of SITS studies and by regional opinion leaders of stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated teams that had been formally authorised to administer rt-PA. A statistical analysis was performed by a descriptive statistics and logistic regression model. The study was carried out from November 2009 to September 2010. A total of 168 forms were sent out and 153 replies received. Seven centres, which had not performed any thrombolytic treatment, and 16 which did not fulfil the criteria for the definition of SU were excluded from the study. Most of the centres reported more than 100 stroke patient admissions per year, i.e., 122 (84 %) from 100 to 500, 18 (12 %) more than 500. The 19 % of the centres admitted more than 30 % of patients within 3 h from the symptom onset and only 30 % admitted more than 30 % of patients within 4.5 h. The mean number of thrombolyses performed in the last 6 months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for centres with a doctor on call 24 h a day. The territorial distribution of the SUs is remarkably heterogeneous: 87 SUs (67 %) are located in the North of Italy, 28 (22 %) in the central part of Italy and only 15 (11 %) in the South. The last few years have witnessed a rise in both the diffusion of SUs and access to thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly in the south, where the requirements of healthcare legislation are not met, and access to a dedicated SU and thrombolytic treatment is still limited and poor.

Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P

(1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0-3 vs. 3-6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS).Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints.Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial.In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS.Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.