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251. An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

Author

Paraskevas, Kosmas I., Mikhailidis, Dimitri P., Ringleb, Peter Arthur, Brown, Martin M., Dardik, Alan, Poredos, Pavel, Gray, William A., Nicolaides, Andrew N., Lal, Brajesh K., Mansilha, Armando, Antignani, Pier Luigi, de Borst, Gert J., Cambria, Richard P., Loftus, Ian M., Lavie, Carl J., Blinc, Ales, Lyden, Sean P., Matsumura, Jon S., Jezovnik, Mateja K., and Bacharach, J. Michael

Abstract

Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research. [ABSTRACT FROM AUTHOR]

Published
2024
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252. Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Author

Nogueira, Raul G., Qureshi, Muhammad M., Abdalkader, Mohamad, Martins, Sheila Ouriques, Yamagami, Hiroshi, Qiu, Zhongming, Mansour, Ossama Yassin, Sathya, Anvitha, Czlonkowska, Anna, Tsivgoulis, Georgios, Aguiar de Sousa, Diana, Demeestere, Jelle, Mikulik, Robert, Vanacker, Peter, Siegler, James E., Kõrv, Janika, Biller, Jose, Liang, Conrad W., Sangha, Navdeep S., Zha, Alicia M., Czap, Alexandra L., Holmstedt, Christine Anne, Turan, Tanya N., Ntaios, George, Malhotra, Konark, Tayal, Ashis, Loochtan, Aaron, Ranta, Annamarei, Mistry, Eva A., Alexandrov, Anne W., Huang, David Y., Yaghi, Shadi, Raz, Eytan, Sheth, Sunil A., Mohammaden, Mahmoud H., Frankel, Michael, Bila Lamou, Eric Guemekane, Aref, Hany M., Elbassiouny, Ahmed, Hassan, Farouk, Menecie, Tarek, Mustafa, Wessam, Shokri, Hossam M., Roushdy, Tamer, Sarfo, Fred S., Alabi, Tolulope Oyetunde, Arabambi, Babawale, Nwazor, Ernest O., Sunmonu, Taofiki Ajao, Wahab, Kolawole, Yaria, Joseph, Mohammed, Haytham Hussein, Adebayo, Philip B., Riahi, Anis D., Sassi, Samia Ben, Gwaunza, Lenon, Ngwende, Gift Wilson, Sahakyan, David, Rahman, Aminur, Ai, Zhibing, Bai, Fanghui, Duan, Zhenhui, Hao, Yonggang, Huang, Wenguo, Li, Guangwen, Li, Wei, Liu, Ganzhe, Luo, Jun, Shang, Xianjin, Sui, Yi, Tian, Ling, Wen, Hongbin, Wu, Bo, Yan, Yuying, Yuan, Zhengzhou, Zhang, Hao, Zhang, Jun, Zhao, Wenlong, Zi, Wenjie, Leung, Thomas W., Chugh, Chandril, Huded, Vikram, Menon, Bindu, Pandian, Jeyaraj Durai, Sylaja, PN, Usman, Fritz Sumantri, Farhoudi, Mehdi, Hokmabadi, Elyar Sadeghi, Horev, Anat, Reznik, Anna, Sivan Hoffmann, Rotem, Ohara, Nobuyuki, Sakai, Nobuyuki, Watanabe, Daisuke, Yamamoto, Ryoo, Doijiri, Ryosuke, Tokuda, Naoki, Yamada, Takehiro, Terasaki, Tadashi, Yazawa, Yukako, Uwatoko, Takeshi, Dembo, Tomohisa, Shimizu, Hisao, Sugiura, Yuri, Miyashita, Fumio, Fukuda, Hiroki, Miyake, Kosuke, Shimbo, Junsuke, Sugimura, Yusuke, Yagita, Yoshiki, Takenobu, Yohei, Matsumaru, Yuji, Yamada, Satoshi, Kono, Ryuhei, Kanamaru, Takuya, Yamazaki, Hidekazu, Sakaguchi, Manabu, Todo, Kenichi, Yamamoto, Nobuaki, Sonoda, Kazutaka, Yoshida, Tomoko, Hashimoto, Hiroyuki, Nakahara, Ichiro, Kondybayeva, Aida, Faizullina, Kamila, Kamenova, Saltanat, Zhanuzakov, Murat, Baek, Jang-Hyun, Hwang, Yangha, Lee, Jin Soo, Lee, Si Baek, Moon, Jusun, Park, Hyungjong, Seo, Jung Hwa, Seo, Kwon-Duk, Sohn, Sung Il, Young, Chang Jun, Ahdab, Rechdi, Wan Zaidi, Wan Asyraf, Aziz, Zariah Abdul, Basri, Hamidon bin, Chung, Law Wan, Ibrahim, Aznita Binti, Ibrahim, Khairul Azmi, Looi, Irene, Tan, Wee Yong, Yahya, Nafisah Wan, Groppa, Stanislav, Leahu, Pavel, Al Hashmi, Amal M., Imam, Yahia Zakaria, Akhtar, Naveed, Pineda-Franks, Maria Carissa, Co, Christian Oliver, Kandyba, Dmitriy, Alhazzani, Adel, Al-Jehani, Hosam, Tham, Carol Huilian, Mamauag, Marlie Jane, Venketasubramanian, Narayanaswamy, Chen, Chih-Hao, Tang, Sung-Chun, Churojana, Anchalee, Akil, Esref, aykaç, özlem, Ozdemir, Atilla Ozcan, Giray, Semih, Hussain, Syed Irteza, John, Seby, Le Vu, Huynh, Tran, Anh Duc, Nguyen, Huy Hoang, Nhu Pham, Thong, Nguyen, Thang Huy, Nguyen, Trung Quoc, Gattringer, Thomas, Enzinger, Christian, Killer-Oberpfalzer, Monika, Bellante, Flavio, De Blauwe, Sofie, Vanhooren, Geert, De Raedt, Sylvie, Dusart, Anne, Lemmens, Robin, Ligot, Noemie, Pierre Rutgers, Matthieu, Yperzeele, Laetitia, Alexiev, Filip, Sakelarova, Teodora, Bedeković, Marina Roje, Budincevic, Hrvoje, Cindric, Igor, Hucika, Zlatko, Ozretic, David, Saric, Majda Seferovic, Pfeifer, František, Karpowic, Igor, Cernik, David, Sramek, Martin, Skoda, Miroslav, Hlavacova, Helena, Klecka, Lukas, Koutny, Martin, Vaclavik, Daniel, Skoda, Ondrej, Fiksa, Jan, Hanelova, Katerina, Nevsimalova, Miroslava, Rezek, Robert, Prochazka, Petr, Krejstova, Gabriela, Neumann, Jiri, Vachova, Marta, Brzezanski, Henryk, Hlinovsky, David, Tenora, Dusan, Jura, Rene, Jurák, Lubomír, Novak, Jan, Novak, Ales, Topinka, Zdenek, Fibrich, Petr, Sobolova, Helena, Volny, Ondrej, Krarup Christensen, Hanne, Drenck, Nicolas, Klingenberg Iversen, Helle, Simonsen, Claus Z., Truelsen, Thomas Clement, Wienecke, Troels, Vibo, Riina, Gross-Paju, Katrin, Toomsoo, Toomas, Antsov, Katrin, Caparros, Francois, Cordonnier, Charlotte, Dan, Maria, Faucheux, Jean-Marc, Mechtouff, Laura, Eker, Omer, Lesaine, Emilie, Ondze, Basile, Peres, Roxane, Pico, Fernando, Piotin, Michel, Pop, Raoul, Rouanet, Francois, Gubeladze, Tatuli, Khinikadze, Mirza, Lobjanidze, Nino, Tsiskaridze, Alexander, Nagel, Simon, Ringleb, Peter Arthur, Rosenkranz, Michael, Schmidt, Holger, Sedghi, Annahita, Siepmann, Timo, Szabo, Kristina, Thomalla, Götz, Palaiodimou, Lina, Sagris, Dimitrios, Kargiotis, Odysseas, Klivenyi, Peter, Szapary, Laszlo, Tarkanyi, Gabor, Adami, Alessandro, Bandini, Fabio, Calabresi, Paolo, Frisullo, Giovanni, Renieri, Leonardo, Sangalli, Davide, Pirson, Anne, Uyttenboogaart, Maarten, van den Wijngaard, Ido, Kristoffersen, Espen Saxhaug, Brola, Waldemar, Fudala, Małgorzata, Horoch-Lyszczarek, Ewa, Karlinski, Michal, Kazmierski, Radoslaw, Kram, Pawel, Rogoziewicz, Marcin, Kaczorowski, Rafal, Luchowski, Piotr, Sienkiewicz-Jarosz, Halina, Sobolewski, Piotr, Fryze, Waldemar, Wisniewska, Anna, Wiszniewska, Malgorzata, Ferreira, Patricia, Ferreira, Paulo, Fonseca, Luisa, Marto, João Pedro, Pinho e Melo, Teresa, Nunes, Ana Paiva, Rodrigues, Miguel, Tedim Cruz, Vítor, Falup-Pecurariu, Cristian, Krastev, Georgi, Mako, Miroslav, de Leciñana, María Alonso, Arenillas, Juan F., Ayo-Martin, Oscar, Cruz Culebras, Antonio, Tejedor, Exuperio Diez, Montaner, Joan, Pérez-Sánchez, Soledad, Tola Arribas, Miguel Angel, Rodriguez Vasquez, Alejandro, Mayza, Michael, Bernava, Gianmarco, Brehm, Alex, Machi, Paolo, Fischer, Urs, Gralla, Jan, Michel, Patrik L., Psychogios, Marios-Nikos, Strambo, Davide, Banerjee, Soma, Krishnan, Kailash, Kwan, Joseph, Butt, Asif, Catanese, Luciana, Demchuk, Andrew M., Field, Thalia, Haynes, Jennifer, Hill, Michael D., Khosravani, Houman, Mackey, Ariane, Pikula, Aleksandra, Saposnik, Gustavo, Scott, Courtney Anne, Shoamanesh, Ashkan, Shuaib, Ashfaq, Yip, Samuel, Barboza, Miguel A., Barrientos, Jose Domingo, Portillo Rivera, Ligia Ibeth, Gongora-Rivera, Fernando, Novarro-Escudero, Nelson, Blanco, Anmylene, Abraham, Michael, Alsbrook, Diana, Altschul, Dorothea, Alvarado-Ortiz, Anthony J., Bach, Ivo, Badruddin, Aamir, Barazangi, Nobl, Brereton, Charmaine, Castonguay, Alicia, Chaturvedi, Seemant, Chaudry, Saqib A., Choe, Hana, Choi, Jae H., Dharmadhikari, Sushrut, Desai, Kinjal, Devlin, Thomas G., Doss, Vinodh T., Edgell, Randall, Etherton, Mark, Farooqui, Mudassir, Frei, Don, Gandhi, Dheeraj, Grigoryan, Mikayel, Gupta, Rishi, Hassan, Ameer E., Helenius, Johanna, Kaliaev, Artem, Kaushal, Ritesh, Khandelwal, Priyank, Khawaja, Ayaz M., Khoury, Naim N., Kim, Benny S., Kleindorfer, Dawn O., Koyfman, Feliks, Lee, Vivien H., Leung, Lester Y., Linares, Guillermo, Linfante, Italo, Lutsep, Helmi L., Macdougall, Lisa, Male, Shailesh, Malik, Amer M., Masoud, Hesham, McDermott, Molly, Mehta, Brijesh P., Min, Jiangyong, Mittal, Manoj, Morris, Jane G., Multani, Sumeet S., Nahab, Fadi, Nalleballe, Krishna, Nguyen, Claude B., Novakovic-White, Roberta, Ortega-Gutierrez, Santiago, Rahangdale, Rahul H., Ramakrishnan, Pankajavalli, Romero, Jose Rafael, Rost, Natalia, Rothstein, Aaron, Ruland, Sean, Shah, Ruchir, Sharma, Malveeka, Silver, Brian, Simmons, Marc, Singh, Abhishek, Starosciak, Amy K., Strasser, Sheryl L., Szeder, Viktor, Teleb, Mohamed, Tsai, Jenny P., Voetsch, Barbara, Balaguera, Oscar, Pujol Lereis, Virginia A., Luraschi, Adriana, Almeida, Marcele Schettini, Cardoso, Fabricio Buchdid, Conforto, Adriana, De Deus Silva, Leonardo, Varrone Giacomini, Luidia, Oliveira Lima, Fabricio, Longo, Alexandre L., Magalhães, Pedro S.C., Martins, Rodrigo Targa, Mont'alverne, Francisco, Mora Cuervo, Daissy Liliana, Costa Rebello, Leticia, Valler, Lenise, Zetola, Viviane Flumignan, Lavados, Pablo M., Navia, Victor, Olavarría, Verónica V., Almeida Toro, Juan Manuel, Amaya, Pablo Felipe Ricardo, Bayona, Hernan, Corredor, Angel, Rivera Ordonez, Carlos Eduardo, Mantilla Barbosa, Diana Katherine, Lara, Osvaldo, Patiño, Mauricio R., Diaz Escobar, Luis Fernando, Dejesus Melgarejo Farina, Donoband Edson, Cardozo Villamayor, Analia, Zelaya Zarza, Adolfo Javier, Barrientos Iman, Danny Moises, Rodriguez Kadota, Liliana, Campbell, Bruce, Hankey, Graeme J., Hair, Casey, Kleinig, Timothy, Ma, Alice, Tomazini Martins, Rodrigo, Sahathevan, Ramesh, Thijs, Vincent, Salazar, Daniel, Yuan-Hao Wu, Teddy, Haussen, Diogo C., Liebeskind, David, Yavagal, Dileep R., Jovin, Tudor G., Zaidat, Osama O., and Nguyen, Thanh N.

Published
2021
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253. European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis

Author

Bonati, Leo H, Kakkos, Stavros, Berkefeld, Joachim, de Borst, Gert J, Bulbulia, Richard, Halliday, Alison, van Herzeele, Isabelle, Koncar, Igor, McCabe, Dominick JH, Lal, Avtar, Ricco, Jean-Baptiste, Ringleb, Peter, Taylor-Rowan, Martin, and Eckstein, Hans-Henning

Abstract

Atherosclerotic stenosis of the internal carotid artery is an important cause of stroke. The aim of this guideline is to analyse the evidence pertaining to medical, surgical and endovascular treatment of patients with carotid stenosis. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Based on moderate quality evidence, we recommend carotid endarterectomy (CEA) in patients with ≥60–99% asymptomatic carotid stenosis considered to be at increased risk of stroke on best medical treatment (BMT) alone. We also recommend CEA for patients with ≥70–99% symptomatic stenosis, and we suggest CEA for patients with 50–69% symptomatic stenosis. Based on high quality evidence, we recommend CEA should be performed early, ideally within two weeks of the last retinal or cerebral ischaemic event in patients with ≥50–99% symptomatic stenosis. Based on low quality evidence, carotid artery stenting (CAS) may be considered in patients < 70 years old with symptomatic ≥50–99% carotid stenosis. Several randomised trials supporting these recommendations were started decades ago, and BMT, CEA and CAS have evolved since. The results of another large trial comparing outcomes after CAS versus CEA in patients with asymptomatic stenosis are anticipated in the near future. Further trials are needed to reassess the benefits of carotid revascularisation in combination with modern BMT in subgroups of patients with carotid stenosis.

Published
2021
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254. Embolic strokes of undetermined source: prevalence and patient features in the esus global registry

Author

Perera, K. S., Vanassche, T., Bosch, J., Giruparajah, M., Swaminathan, B., Mattina, K. R., Berkowitz, S. D., Arauz, A., O'Donnell, M. J., Ameriso, S. F., Hankey, G. J., Yoon, B. -W., Lavallee, P., Cunha, L., Shamalov, N., Brouns, R., Gagliardi, R. J., Kasner, S. E., Pieroni, A., Vermehren, P., Kitagawa, K., Wang, Y., Muir, K., Coutinho, J., Vastagh, I., Connolly, S. J., Hart, R. G., Czeto, K., Kahn, M., Gomez Schneider, M., Pujol Lereis, V., Hawkes, M., Pertierra, L., Perera, N., De Smedt, A., Van Dyck, R., Van Hooff, R. J., Yperzeele, L., Baptista Gagliardi, V. D., Cerqueir, L. G., Yang, X., Chen, W., Amarenco, P., Guidoux, C., Ringleb, P. A., Bereczki, D., Canavan, M., Toni, D., Anzini, A., Colosimo, C., De Michele, M., Di Mascio, M. T., Durastanti, L., Falcou, A., Fausti, S., Mancini, A., Mizumo, S., Uchiyama, S., Kim, C. K., Jung, S., Kim, Y., Kim, J. A., J. Y., Jo, Barboza, M., Quiroz-Compean, A., Colin, J., Nederkoorn, P. J., Roxas, A., Perez Marianito, V., Santo, G., Silva, F., Sargento-Freitas, J., Coelho, J., Kustova, M., Meshkova, K., Williams, G., Siegler, J., Zhang, C., Gallatti, N., Kruszewski, M., Clinical sciences, Neuroprotection & Neuromodulation, ANS - Neurovascular Disorders, Neurology, ACS - Amsterdam Cardiovascular Sciences, and ESUS Global Registry Investigators

Subjects
Male, medicine.medical_specialty, Internationality, Cross-sectional study, 030204 cardiovascular system & hematology, stroke-etiology, cerebral embolism, embolism, Atrial fibrillation, Cerebral embolism, Diagnostic evaluation, Embolism, Stroke, Stroke-etiology, Brain Ischemia, 03 medical and health sciences, ischemic-stroke, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Prevalence, Humans, atrial fibrillation, Registries, cardiovascular diseases, Aged, Retrospective Studies, Medicine(all), business.industry, International survey, Retrospective cohort study, Mean age, Middle Aged, diagnostic evaluation, medicine.disease, stroke, atrial-fibrillation, Cross-Sectional Studies, Neurology, stroke—etiology, Ischemic stroke, Cardiology, cryptogenic stroke, Female, Human medicine, business, 030217 neurology & neurosurgery
Abstract

Background Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation ( n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years ( p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions.

Published
2016

255. Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke

Author

Neuberger, Ulf, Vollmuth, Philipp, Nagel, Simon, Scho¨nenberger, Silvia, Weyland, Charlotte Sabine, Gumbinger, Christoph, Ringleb, Peter Arthur, Bendszus, Martin, Pfaff, Johannes Alex Rolf, and Mo¨hlenbruch, Markus Alfred

Abstract

BackgroundDespite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance.MethodsPatients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0–2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms.ResultsOverall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)).ConclusionsAfter complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.

Published
2021
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258. The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial – A post hoc analysis

Author

Pfaff, Johannes AR, Bendszus, Martin, Donnan, Geoffrey, Molina, Carlos, Leys, Didier, Schellinger, Peter D, Schwab, Stefan, Toni, Danilo, Wahlgren, Nils, Hacke, Werner, and Ringleb, Peter Arthur

Abstract

Introduction To investigate the impact of a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) on functional outcome in patients with acute stroke in a prolonged time window or unknown time of symptom onset randomized to intravenous thrombolysis or placebo.Patients and Methods We performed a post-hoc analysis of the European Cooperative Acute Stroke Study-4 (ECASS-4) trial. ECASS-4 was an investigator driven, phase 3, multi-center, double-blind, placebo-controlled study which randomized ischemic stroke patients presenting within 4.5 and 9h of stroke onset or unknown time-window to either rt-PA or placebo after MR-imaging. Two subgroups “no mismatch” (nMM) and “any mismatch” (aMM) were created by applying a DWI-FLAIR-mismatch criterion. We calculated frequency of nMM and aMM and performed a univariate analysis (Fisher's Test) for excellent clinical outcome (mRS 0-1) and mortality (mRS=6).Results MR-Imaging of n=111/119 (93.2%) patients was suitable for this analysis. DWI-FLAIR mismatch was found in 49 patients (44.1%). Proportions of mismatch nMM and aMM were comparable in treatment-groups (aMM: Placebo 46.3%, Alteplase 42.1%; p=0.70). Patients with nMM showed no benefit of rt-PA-treatment (OR (95%CI) mRS 0-1: 0.95 (0.29-3.17)). Patients with aMM showed a point estimate of the odds ratio in favour of a treatment benefit of rt-PA (mRS 0-1: OR (95%CI) 2.62 (0.68-11.1)). Mortality within 90 days was not different in patients treated with rt-PA if nMM (15.2%) or aMM (12.5%) was present.Discussion In this analysis no significant evidence, but subtle indication towards patients treated with rt-PA in a prolonged time window reaching an excellent clinical outcome if a DWI-FLAIR-mismatch is present on initial stroke MR-imaging.Conclusion A DWI-FLAIR mismatch in the region of ischemia as imaging based surrogate parameter for patient selection for i.v. rt-PA should be strongly pursued.

Published
2020
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260. 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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261. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial

Author

Hill, Michael D, Goyal, Mayank, Menon, Bijoy K, Nogueira, Raul G, McTaggart, Ryan A, Demchuk, Andrew M, Poppe, Alexandre Y, Buck, Brian H, Field, Thalia S, Dowlatshahi, Dar, van Adel, Brian A, Swartz, Richard H, Shah, Ruchir A, Sauvageau, Eric, Zerna, Charlotte, Ospel, Johanna M, Joshi, Manish, Almekhlafi, Mohammed A, Ryckborst, Karla J, Lowerison, Mark W, Heard, Kathy, Garman, David, Haussen, Diogo, Cutting, Shawna M, Coutts, Shelagh B, Roy, Daniel, Rempel, Jeremy L, Rohr, Axel CR, Iancu, Daniela, Sahlas, Demetrios J, Yu, Amy Y X, Devlin, Thomas G, Hanel, Ricardo A, Puetz, Volker, Silver, Frank L, Campbell, Bruce C V, Chapot, René, Teitelbaum, Jeanne, Mandzia, Jennifer L, Kleinig, Timothy J, Turkel-Parrella, David, Heck, Donald, Kelly, Michael E, Bharatha, Aditya, Bang, Oh Young, Jadhav, Ashutosh, Gupta, Rishi, Frei, Donald F, Tarpley, Jason W, McDougall, Cameron G, Holmin, Staffan, Rha, Joung-Ho, Puri, Ajit S, Camden, Marie-Christine, Thomalla, Götz, Choe, Hana, Phillips, Stephen J, Schindler, Joseph L, Thornton, John, Nagel, Simon, Heo, Ji Hoe, Sohn, Sung-Il, Psychogios, Marios-Nikos, Budzik, Ronald F, Starkman, Sidney, Martin, Coleman O, Burns, Paul A, Murphy, Seán, Lopez, George A, English, Joey, Tymianski, Michael, Demchuk, Andrew, Barber, Philip, Smith, Eric, Bal, Simerpreet, Subramaniam, Suresh, Peters, Steven, Couillard, Phillippe, Klein, Gary, Stys, Peter, Menon, Bijoy, Coutts, Shelagh, Almekhlafi, Mohammed, Hill, Michael, Goyal, Mayank, Wong, John, Mitha, Alim, Eesa, Muneer, Morrish, William, Alqatani, Saad, Kashani, Nima, Joshi, Manish, Zerna, Charlotte, Ospel, Johanna, Venkatesan, Prasanna, Teleg, Erika, Sitaram, Amith, Graham, Brett, Van Gaal, Stephen, Moussaddy, Aimen, Chakraborty, Debabrata, Maraj, Nicholas, Loockey, Andrew, Chen, Shuo, Singh, Ravinder, Alsultan, Abdulaziz, Asuncion, Ria, Tse, Dominic, Doshi, Darshan, Volny, Ondrej, Ojha, Piyush, Wadhwa, Ankur, Marko, Martha, Singh, Nishita, Wasyliw, Sanchea, Ryckborst, Karla, Kenney, Carol, Save, Supriya, Jambula, Anitha, Newcommon, Nancy, Hull, Gavin, Blackstock, Darcy, Kiszczak, Sharon, Zimmel, Leslie, Wright, Michelle, Jahraus, Cari, Andersen, Linda, Bohn, Shelly, Paul, Joseph, Zhang, Oiao, Doram, Craig, Lowerison, Mark, Hanley, Andrea, Campbell, Lori, Ure, Ashley, Taylor, Francis, Hul, Dominic, Wiebe, Samuel, Saluzzi, Marina, Blenkin, Nicole, Frayne, Richard, Buck, Brian, Butcher, Kenneth, Shuaib, Ashfaq, Jeerakathil, Tom, Jickling, Glen, Emery, Derek, Rempel, Jeremy, Owen, Richard, Ashforth, Robert, Yeo, Tom, Kotylak, Trevor, O'Kelly, Cian, Chow, Michael, Siddiqui, Muzaffer, Saqqur, Maher, D'Souza, Atlantic, Lloret, Mar, Butt, Asif, Nomani, Ali, Kalashyan, Hayrapet, Thirunavukkarasu, Sibi, Jabs, Juline, Fairall, Paige, Piquette, Lori, Phillips, Stephen, Green, A. Laine, Gubitz, Gordon, Heidenreich, Jens, Huynh, Thien, Shankar, Jai, Maloney, William, Vandorpe, Robert, Schmidt, Matthias, Pickett, Gwynedd, Weeks, Adrienne, Jarrett, Judith, MacDonald, Debbie, Arsenault, Joanna, Kinnear, Ruth, Mandzia, Jennifer, Mayich, Michael, Boulton, Melfort, Bullrich, Maria, Fridman, Sebastian, Kiwan, Ruba, Lee, Donald, Lownie, Stephen, Khaw, Alexander, Pandey, Sachin, Sharma, Manas, Sposato, Luciano, Wade, Kevin, Beauchamp, Beth, Lambourn, Lindsay, Amato-Marziali, Belinda, Poppe, Alexandre, Roy, Daniel, Daneault, Nicole, Deschaintre, Yan, Gioia, Laura, Jacquin, Grégory, Odier, Céline, Stapf, Christian, Iancu, Daniela, Raymond, Jean, Weill, Alain, Lapierre, Marlène, Jadil, Nadia, Jolteus, Judlène, Teitelbaum, Jeanne, Angle, Mark, Hannouche, Mathew, Badawy, Mohamed, Letourneau, Justin, Cortes, Maria, Linnell, Grant, Tampieri, Donateela, Vieira, Lucy, Moussaddy, Aimen, Legault, Catherine, Durcan, Liam, Moore, Angela, Cole, Erin, Magnussen, Claire, Salmon, Kristiana, Khalil, Salma, Desloges, Isabelle, Waxman, Lindsay, Abdon, Wynne, Lai, Sonia, Dowlatshahi, Dar, Iancu, Daniela, Shamy, Michel, Stotts, Grant, Blacquiere, Dylan, Lesiuk, Howard, Quateen, Aiman, Drake, Brian, Dewar, Brian, Daham, Zeinab, Kelly, Michael, Hunter, Gary, Peeling, Lissa, Graham, Brett, Whelan, Ruth, Garner, Aaron, Urroz, Lilian, Maley, Sharleen, Silver, Frank, Casaubon, Leanne, Pikula, Aleksandra, Del Campo, Martin, Schaafsma, Joanna, Jaigobin, Cheryl, Krings, Timo, Pereira, Vitor, Agid, Ronit, Farb, Richard, Kalman, Libby, Cayley, Anne, Williams, Janice, Stewart, Tim, Misquitta, Karen, Bharatha, Aditya, Selchen, Daniel, Marotta, Thomas, Sarma, Dipanka, Montanera, Walter, Spears, Juluan, Saposnik, Gustavo, Kostyrko, Pawel, Li, Yangmei, Parra-Farina, Carmen, Bengzon Diestro, Jose Danilo, Camden, Marie-Christine, Verreault, Steve, Mackey, Ariane, Audet, Marie-Eve, Milot, Geneviève, Lavoie, Pascale, Gariépy, Jean-Luc, Collard, Karine, Haché, Annette, Van Adel, Brian, Sahlas, Demetrios, Alshanbari, Ahmed, Baldwin, Josephine, Catanese, Luciana, Chen, Bing, De Sa Boasquevisque, Danielle, Deshmukh, Aviraj, Knapman, Jordan, Lamers, Shana, Larrazabal, Ramiro, MacMillan, Susan, Mai, Lauren, Mattia, Alicia, Nayar, Sumiti, Ng, Kuan, Oczkowski, Wieslaw, Perera, Kanjana, Shawawrah, Mays, Shoamanesh, Ashkan, Sobhi, Gita, Syed, Nabeel, Taher, Noran, Vandervelde, Cheyanne, Wang Pharm, Di, Field, Thalia, Van Gaal, Stephen, Teal, Philip, Benavente, Oscar, Wilson, Laura, Mann, Sharanpal, Yip, Samuel, Murphy, Colleen, Heran, Manraj, Rohr, Axel, Settecase, Fabio, Redekop, Gary, Haw, Charles, Maclean, Genoveva, Murray, Karina, Chiu, Rosalin, Flexman, Alana, Strecha, Eilidh, Gayton, Yolanda, Yip, Judy, Swartz, Richard, Boulos, Mark, Gladstone, David, Yu, Amy, Hopyan, Julia, Khosravani, Houman, Manosalva Alzate, Herbert, Southwell, Alisia, Kamra, Maneesha, Lopes, Kaitlyn, Kapoor, Arunima, da Costa, Leodante, Yang, Victor, Dyer, Erin, Shah, Ruchir, Knowles, Brenda, Nichols, Jennifer, Patterson, Jennifer, Cope, Krista, Dickerson, Lee, Barton, Katrina, Gray, Kimberly, Massengale, Ticey, Miller, Melanie, Simpson, Cindy, Walker, Sabrina, Tennyson-Yemm, Chlin, Devlin, Thomas, Frei, Donald, Bellon, Richard, Atchie, Benjamin, Kaminsky, Ian, Wilson, Duandelyn, Schraeder, Nicolle, Arias, Eric, Kodis, Lisa, Talley, Mark, Edinger, Alex, Talley, Tiffany, Dempsey, Ita, Williams, Laurie, Williams, Scott, Kupniewski, Sonny, Fasbinder, Brad, Snead, Joanna, Choe, Hana, Mackenzie, Larami, Weisman, Davi, Kozak, Osman, Shah, Qaisar, Gzesh, Dan, Kulandaivel, Kandan, Khoury, John, Klein, Brad, Bussinger, Patricia, Griffin, Lisa, dePalmo, Ashley, Oliva, Cynthia, Jadhav, Ashutosh, Jovin, Tudor, Kenmuir, Cynthia, Jankowitz, Brian, Gross, Bradley, Rocha, Marcelo, Starr, Matthew, Brown, Merritt, Hawkes, Christine, Shah, Kavit, Tememe, Danoushka, Walker, Gregory, Patel, Pratit, Klein, Bradley, Ziayee, Habibullah, Limaye, Kaustubh, Baxendell, Lisa, Gilchrist, Vicki, Feineigle, Patricia, Toseki Haibach, Kelsea, Van Every, Cathy, Desai, Shashyat, Zulfiqar, Maryam, Gibson, Linda, Barrett, Sean, Turkel-Parrella, David, Arcot, Karthikeyan, DiCrescento, Steven, Farkas, Jeffrey, Filipowski, Gregory, Frontera, Jennifer, Joset, Danielle, Liff, Jeremy, Scher, Erica, McDougall, Cameron, Kelly, Cheryl, Patel, Akshal, Monteith, Stephen, Starkman, Sidney, Atchaneeyasakul, Kunakorn, Burgos, Adrian, Chua, Janice Anne, Gaines, Nathan, Grunberg, Ileana, Guzy, Judy, Liu, Zuolu, Maluste, Neil, Ramirez, Lucas, Sharma, Latisha, Heck, Donald, Brown, Morry, McDonald, Colin, Calderon, Mateo, Hargis, Mitch, Roels, Christina, Emmady, Prabhu, Alvi, Talat, McTaggart, Ryan, Jayaraman, Mahesh, Cutting, Shawna, Smith, Wendy, Foley, Susan, Paolucci, Gino, Has, Richard, Quinn, Katie, Fuller, Lindsey, Brierley, Rebecca, Watkins, Christina, Demir, Nicole, Lopez, George, Vargas, Alejandro, Osteraas, Nicholas, Holtz, Becky, Sauvageau, Eric, Hanel, Ricardo, Aghaebrahim, Amin, Chmayssani, Mohamad, Naval, Neeraj, Day, Jason, Dellorso, Scott, Ludwig, Benjamin, Schemmel, Derek, Ebreo, Nancy, Bell, Karen, Lewis, Lanai, Delucia, Marjorie, Nogueira, Raul, Haussen, Diogo, Frankel, Michael, Bhatt, Nirav, Bianchi, Nicolas, Anderson, Aaron, Belagaje, Samir, Liberato, Bernardo, Rangaraju, Srikant, Al-Bayati, Alhamza, Grossberg, Jonathan, Craft, Leah, Schindler, Kiva, Schaad, Erin, Schultz, Meagan, Southerly, Lorretta, Doppelheuer, Shannon, Charlton, Jacquelyn, Faggard, Jason, Barbret, Zuzana, DukSoo Han, Ethan, Walters, Robin, Dolia, Jaydevsinh, El-Jamal, Sleiman, Eby, Brendan, Saleem, Yasir, Pearl, Harrison, Patel, Kishan, Rahman, Haseeb, Butt, Reema, English, Stephen, Puri, Ajit, Howk, Mary, Singh, Jasmeet, Massari, Francesco, DeMacedo Rodrigues, Katyucia, Kuhn, Anna, English, Joey, Barazangi, Nobl, Telischak, Nick, Kim, Warren, Ross, Josh, DeVole, Nata, Redford, Jessica, Ferreira, Milena, Ponting, Katie, Shen, Helen, Bedenk, Ann, Patel, Susila, Fernandess, Julia, Ke, Michael, Spokoyny, Ilanit, Gao, Billy, Tong, David, Chen, Charlene, Wong, Christine, Choe, Jessica, Martin, Coleman, Summers, Debbie, Boutwell, Christine, Olds, Karin, Crandall, Suzanne, Eatman, John, Akhtar, Naveed, Holloway, William, Halpin, Jared, Donegan, Brett, Schindler, Joseph, Hwang, David, Gilmore, Emily, Petersen, Nils, Sheth, Kevin, Brown, Stacy, Beekman, Rachel, George, Benjamin, Kaddouh, Firas, Falcone, Guido, Wira, Charles, Matouk, Charles, Loomis, Caitlin, Amin, Hardik, Stretz, Hans Christoph, Narula, Reshma, Jasne, Adam, Sansing, Lauren, Agarwal, Tijil, Jasak, Sara, Fontaine, Briana, King, Zachary, Kuohn, Lindsey, Orgass, Hailey, Leary, Megan, Nye, Joan, Halbert, Kelsey, Nystrom, Karin, Neuschatz, Kaile, Petrucci, Dawn, Coppola, Anna, Tarpley, Jason, Joyce, Treasure, Hou, Sam, Umekubo, Mark, Nakamura, Catrice, Ovando, Renee, Zuniga, Diana, Nien, Yih Lin, Basto, Fernando Mayor, Arch, Allison, Jong, Laura, Conrad, William, Abbott, Tara, Yao, Jay, Caganap, Scott, Jordan, John, Teitelbaum, George, Darflinger, Robert, Gupta, Rishi, Bain, Marianne, Budzik, Ronald, Czerniak, Jennifer, Groezinger, Katherine, Hicks II, William, Kaskar, Omran, Katz, Brian, Loochtan, Aaron, Pema, Peter, Rai, Vivek, Vora, Nirav, Brown, Amanda, Goodman, Diane, Danenbergs, Barb, Gossett, Monica, Bang, Oh Young, Chung, Jong-Won, Jeon, Pyoung, Kim, Keon Ha, Lim, Yun Jeong, Heo, Ji Hoe, Nam, Hyo Suk, Kim, Young Dae, Park, HyungJong, Hwang, In Gun, Ha, Wooseok, Choi, Jin Kyo, Jeong, Kyungsun, Rha, Joung-Ho, Park, Hee-Kwon, Yoon, Cindy, Kim, Bo-Kyung, Sohn, Sung-Il, Kim, Chang-hyun, Yoo, Joonsang, Hong, Jeong-Ho, Park, Hyungjong, Kim, Sohyeon, Choi, Moonkyung, Bae, Hyoeun, Lee, Jun Seok, Lee, Jae-Joon, Jun, Go-Eun, Jeon, Sujeong, Campbell, Bruce, Mitchell, Peter, Yassi, Nawaf, Davis, Stephen, Donnan, Geoffrey, Parsons, Mark, Yan, Bernard, Dowling, Richard, Bush, Steven, Wu, Teddy, Shah, Darshan, Zhao, Henry, Salvaris, Patrick, Alemseged, Fana, Ng, Felix, Williams, Cameron, Balabanski, Anna, Dos Santos, Angela, Ng, Jo-Lyn, McDonald, Amy, Jackson, David, Tsoleridis, Jessica, Pesavento, Lauren, Kleinig, Timothy John, Nurs, Roy Drew, Cranefield, Jennifer, Scroop, Rebecca, Cagi, Lavenia, Harvey, Jackson, Waters, Michael, Thornton, John, Brennan, Robert, O'Hare, Alan, Power, Sarah, Williams, David, Boyle, Karl, Moynihan, Barry, Liddy, Ann-Marie, Large, Margaret, Cullen, Ailbhe, Walsh, Roisin, Martin, Emma, Lynch, Julie, McElroy, Sinéad, Murphy, Seán, Coveney, Sarah, Deegan, Caroline, Horgan, Gillian, Kelly, Peter, Laffan, Aoife, Llamas-Osorio, Yudy, Lynch, Catherine, Mac Mahon, Peter, Marnane, Michael, McCabe, John, Burns, Paul, Tauro, Suzanne, Cuddy, Sarah, Rennie, Ian, Smyth, Graham, Flynn, Peter, Wiggam, Ivan, Kerr, Enda, Gordon, Patricia, Fearon, Patricia, Roberts, Geralt, Patterson, Cathy, Adams, Karen, Wells, Brian, McFarland, Margaret, Holmin, Staffan, Moreira, Tiago, Sjöstrand, Christina, Mazya, Michael, Almqvist, Håkan, Wahlgren, Nils, Steinberg, Anna, Cooray, Charith, Eriksson, Einar, Thorén, Magnus, Keselman, Boris, Ahmed, NIaz, Holmberg, Åke, Axelsson, Maria, Berglund, Annika, Thomalla, Götz, Golsari, Amir, Hoppe, Julia, Deb-Chatterji, Milani, Cheng, Bastian, Barrow, Ewgenia, Schlemm, Eckhard, Lettow, Iris, Jensen, Märit, Otto, Dagmar, Jaramillo, Kirsten, Appelbohm, Hannes, Fiehler, Jens, Bester, Maxim, Schönfeld, Michael, Brekenfeld, Caspar, Holst, Brigitte, Wortmann, Ginette, Koch, Friederike, Puetz, Volker, Gerber, Johannes, Abramyuk, Andrij, Kaiser, Daniel, Winzer, Simon, Prakapenia, Alexandra, Pallesen, Lars-Peder, Siepmann, Timo, Barlinn, Kristian, Haase, Kathrin, Sauer, Angela, Psychogios, Marios-Nikos, Liman, Jan, Brehm, Alex, Maus, Volker, Hollstein, Nicole, Reinke, Annika, Neitz, Gustav, Schnieder, Marlena, Schwarz, Margret, Ibrahim, Allam, Müller, Julia, Meister, Stefanie, Bäumle, Berit, Chapot, René, Pilgram-Pastor, Sara, Wallocha, Marta, Stauder, Michael, Celik, Ekin, Stracke, Paul, Müller, Nicole, Weber, Ralph, Velktamp, Roland, Nagel, Simon, Ringleb, Peter Arthur, Heyse, Miriam, Amiri, Hemasse, Mundiyanapurath, Sibu, Chen, Min, Bevrle, Elisabeth, Beck, Perdita, Möhlenbruch, Markus alfred, Tymianski, Michael, Potvin, Alphonse, Harris, Cameron, Wang, Chong, Adams, Corey, Mayor, Diana, Garman, Dave, Chau, Davis, Wu, Jane, Lunn, Janet, Heard, Kathy, Bermanis, Liat, Teyes, Lucy, Constant, Marc, Galsim, Maria, Helbin, Michael, Leroux, Michelle, Felix, Nicole, Bendre, Nilima, Cuthbert, Sandra, Brokx, Steve, Zhang, Yichuan, Lingham, Trudy, Kohli, Yatika, Salter, Michael, Liebeschuetz, Joseph, Hofmann, Frieder, Constant, John, Soeder, Tom, Snoke, Kara, Bologa, Monica, Stahl, Kimberly, and Graziewicz, Maria

Abstract

Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Published
2020
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262. Tandem occlusions in acute ischemic stroke – impact of antithrombotic medication and complementary heparin on clinical outcome and stent patency

Author

Neuberger, Ulf, Moteva, Konstantina, Vollherbst, Dominik F, Scho¨nenberger, Silvia, Reiff, Tilman, Ringleb, Peter Arthur, Bendszus, Martin, Pfaff, Johannes Alex Rolf, and Mo¨hlenbruch, Markus

Abstract

Background and purposeMechanical thrombectomy (MT) and acute carotid stenting (ACS) of patients with acute ischemic stroke due to tandem occlusions (TO) of the anterior circulation was proven to be safe and effective, but the implications of periprocedural antithrombotic medications are only known to a limited extent.MethodsWe conducted a retrospective analysis of 162 consecutive patients who presented with TO and were treated with MT and ACS in our center. Patients initially either received dual antiplatelet therapy (DAT) or tirofiban periprocedurally. Some patients were also treated with unfractionated heparin. The frequency of intracranial hemorrhages (ICH), as well as the impact on clinical outcome and stent patency of different medical regimes, were evaluated using univariate tests and adjusted multivariate logistic regressions.ResultsPatients who received supportive treatment with heparin had significantly higher occurrences of any (OR, 2.46; 95% CI, 1.15 to 5.28) and symptomatic ICH (OR, 3.71; 95% CI, 1.18 to 14.95). Additionally, these patients were less likely to have a moderate clinical outcome after 90 days (modified Rankin scale 0–3; OR, 0.33; 95% CI, 0.15 to 0.72), but were more likely to have a fatal outcome after 90 days (OR, 2.84; 95% CI 1.10 to 7.31). These findings persisted in patients who received both DAT and heparin, but not for patients who received both tirofiban and heparin.ConclusionSupportive administration of heparin in patients with TO and treatment with MT and ACS should be carefully considered, especially in patients who primarily receive DAT.

Published
2020
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263. Electronic Alberta Stroke Program Early CT score change and functional outcome in a drip-and-ship stroke service

Author

Purrucker, Jan Christoph, Mattern, Nicole, Herweh, Christian, Mo¨hlenbruch, Markus, Ringleb, Peter Arthur, Nagel, Simon, and Gumbinger, Christoph

Abstract

BackgroundDebate continues as to whether patients with acute ischemic stroke with (suspected) large vessel occlusion benefit from direct referral versus secondary transportation.AimsTo analyze the change in early infarct signs, collaterals, and acute ischemia volume and their association with transfer time and functional outcome.MethodsWe retrospectively analyzed consecutive transfers between 2013 and 2016 for patients with anterior circulation stroke transported from referring hospitals to our center as potential candidates for thrombectomy. Alberta Stroke Programme Early CT Scores (ASPECTS) were automatically calculated on external and in-house CT using the Brainomix e-ASPECTS software, and collaterals were assessed using the e-CTA tool. Functional status after stroke using the modified Rankin scale (mRS) was obtained.Results102 patients with CT scans both at the referring hospital and our center were identified. During patient transfer, e-ASPECTS declined by a median of 1 point (0–2). Functional outcome correlated with the change in e-ASPECTS (decline, n=54) (Spearman rs=0.322, 95% CI 0.131 to 0.482, p=0.001). The median image-to-image time was 149 min (IQR 113–190), but did not correlate with change in e-ASPECTS (p=0.754) and mRS score at 3 months (p=0.25). Preserved good collateral status assessed at the comprehensive stroke center was associated with better functional outcome (rs=−0.271, 95% CI −0.485 to −0.037, p=0.02).ConclusionsPatient transfer in a drip-and-ship network was associated with declines in e-ASPECTS associated with worse functional outcome. Image-to-image time did not influence this association, but worsening collateral status did.

Published
2020
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266. Secular Trends in Procedural Stroke or Death Risks of Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis: A Pooled Analysis of Randomized Trials.

Author

Müller, Mandy D., von Felten, Stefanie, Algra, Ale, Becquemin, Jean-Pierre, Bulbulia, Richard, Calvet, David, Eckstein, Hans-Henning, Fraedrich, Gustav, Halliday, Alison, Hendrikse, Jeroen, Howard, George, Gregson, John, Jansen, Olav, Brown, Martin M., Mas, Jean-Louis, Brott, Thomas G., Ringleb, Peter A., and Bonati, Leo H.

Abstract

BACKGROUND: Over the past decades, stroke risk associated with carotid disease has decreased, reflecting improvements in medical therapy and a more rigorous control of vascular risk factors. It is less clear whether the procedural risk of carotid revascularization has declined over time. METHODS: We analyzed temporal changes in procedural risks among 4597 patients with symptomatic carotid stenosis treated with carotid artery stenting (n=2326) or carotid endarterectomy (n=2271) in 4 randomized trials between 2000 and 2008, using generalized linear mixed-effects models with a random intercept for each source trial. Models were additionally adjusted for age and other baseline characteristics predicting treatment risk. The primary outcome event was any procedural stroke or death, occurring during or within 30 days after revascularization. RESULTS: The procedural stroke or death risk decreased significantly over time in all patients (unadjusted odds ratio per year, 0.91; 95% CI, 0.85-0.97; P=0.006). This effect was driven by a decrease in the carotid endarterectomy group (unadjusted odds ratio per year, 0.82; 95% CI, 0.73- 0.92; P=0.003), whereas no significant decrease was found after carotid artery stenting (unadjusted odds ratio, 0.96; 95% CI, 0.88-1.04; P=0.33). Carotid endarterectomy patients had a lower procedural stroke or death risk compared with carotid artery stenting patients, and the difference significantly increased over time (interaction P=0.031). After adjustment for baseline characteristics, the results remained essentially the same. CONCLUSIONS: The risk of stroke or death associated with carotid endarterectomy for symptomatic carotid stenosis decreased over an 8-year period, independent of clinical predictors of procedural risk. No corresponding reduction in procedural risk was seen in patients treated with stenting. [ABSTRACT FROM AUTHOR]

Published
2019
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267. Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Author

Gerner, Stefan T., Kuramatsu, Joji B., Sembill, Jochen A., Sprügel, Maximilian I., Hagen, Manuel, Knappe, Ruben U., Endres, Matthias, Haeusler, Karl Georg, Sobesky, Jan, Schurig, Johannes, Zweynert, Sarah, Bauer, Miriam, Vajkoczy, Peter, Ringleb, Peter A., Purrucker, Jan C., Rizos, Timolaos, Volkmann, Jens, Müllges, Wolfgang, Kraft, Peter, and Schubert, Anna-Lena

Published
2019
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269. Safety of Carotid Revascularization in Patients With a History of Coronary Heart Disease.

Author

Volkers, Eline J., Algra, Ale, Kappelle, L. Jaap, Becquemin, Jean-Pierre, de Borst, Gert J., Brown, Martin M., Bulbulia, Richard, Calvet, David, Eckstein, Hans-Henning, Fraedrich, Gustav, Gregson, John, Halliday, Alison, Hendrikse, Jeroen, Howard, George, Jansen, Olav, Roubin, Gary S., Bonati, Leo H., Brott, Thomas G., Mas, Jean-Louis, and Ringleb, Peter A.

Published
2019
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284. Effect of treatment technique on radiation exposure in mechanical thrombectomy for acute ischaemic stroke: A matched-pair analysis

Author

Weyland, Charlotte S, Neuberger, Ulf, Seker, Fatih, Nagel, Simon, Arthur Ringleb, Peter, Möhlenbruch, Markus A, Bendszus, Martin, and Pfaff, Johannes AR

Abstract

Objective This study aimed to compare radiation exposure (RE) in patients receiving mechanical thrombectomy (MT) for large-vessel occlusions in the anterior circulation using direct thrombo-aspiration (DT) versus stent-retriever thrombectomy under continuous distal aspiration (STA).Methods This was a retrospective single-centre analysis of an Institutional Review Board−approved stroke database of a comprehensive stroke centre focusing on RE per dose area product, procedure time (PT) and fluoroscopy time (FT) in patients receiving MT. Patients who received MT with DT were matched with patients treated using STA according to occlusion location, mode of anaesthesia, manoeuvre count and sex.Results Apart from patient age (DT: M= 74 years (standard deviation (SD)=13 years); STA: M= 79 years (SD= 11 years); p= 0.023), there was no difference in baseline patient characteristics (n= 68 per group). PT (DT: median = 26 minutes (interquartile range (IQR) = 21–38 minutes); STA: median = 49 minutes (IQR 37–77 minutes); p< 0.0001) and FT (DT: median = 12 minutes (IQR 7–18 minutes); STA: median = 26 minutes (IQR 14–43 minutes); p< 0.0001) were shorter in patients who received MT using DT. RE (DT: median = 62.6 Gy·cm2(IQR 41.7–89.4 Gy·cm2); STA: median = 89.8 Gy·cm2(IQR 53.7–131.7 Gy·cm2); p= 0.034) was significantly lower in patients who received MT using DT. This represents a relative increase of RE, FT and PT by 43.6%, 116.6% and 88.5%, respectively, in patients who received MT using STA.Conclusion MT using DT is associated with shorter FT and PT and lower RE compared to matched patients treated with STA.

Published
2024
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285. Efficient Electron Collection by Electrodeposited ZnO in Dye-Sensitized Solar Cells with TEMPO+/0as the Redox Mediator

Author

Ruess, Raffael, Horn, Jonas, Ringleb, Andreas, and Schlettwein, Derck

Abstract

The power conversion efficiency in established dye-sensitized solar cells (DSSCs) suffers from high overpotentials needed because of slow electron transfer kinetics. If redox couples are used that have a low reorganization energy, fast dye regeneration can be achieved, but fast recombination reactions can barely be suppressed. If they become competitive to electron transport to the back electrode, solar cell efficiencies drastically drop. In this work, it is shown that electron transport is facilitated by substituting the commonly used photoanode material, nanoparticulate TiO2, by electrodeposited ZnO, which, albeit more complex surface reactions, provides electron transport by orders of magnitude faster than nanoparticulate TiO2. With TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) as the redox mediator, the dye is efficiently regenerated with overpotentials well below 0.2 V. We demonstrate that the external quantum efficiency with TiO2-based photoanodes is significantly limited by recombination, while it is maintained at high values for electrodeposited ZnO. It is thereby shown that redox couples with fast kinetics can be employed in DSSCs without drawbacks in quantum efficiency if sufficient fast electron transport in the porous semiconductor network is provided.

Published
2024
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287. Medical complications during interhospital transfer for thrombectomy in patients with acute ischemic stroke

Author

Mirkov, Damjan, Jenetzky, Ekkehart, Thieme, Andrea S., Qabalan, Adeeb, Gumbinger, Christoph, Wick, Wolfgang, Ringleb, Peter A., and Rizos, Timolaos

Abstract

Introduction: Patients with acute ischemic stroke (AIS) and large-vessel occlusion are frequently transferred by emergency physicians (EPs) from primary to comprehensive stroke centers (CSC) for thrombectomy, particular when thrombolysed. Data on complications during such transfers are highly limited.Patients and methods: Consecutive AIS patients transferred between 01/2015 and 10/2021 to our CSC were included. Associations of major (MACO) and minor (MICO) complications with clinical and imaging data were assessed.Results: In total, 985 patients were included in the analysis (58.5% thrombolysed). MACO developed in 1.6%, MICO in 14.6%. Compared to patients without complications (NOCO), patients with MACO did not differ in terms of demographics, cerebrovascular risk factors, or site of vessel occlusion. They had more severe strokes (p= 0.026), neurological worsening was more severe (p= 0.008), and transport duration was longer (p= 0.050) but geographical distances did not differ. Thrombolysed patients had any complication more often than patients without thrombolysis (20.3% vs 10.5%; p<0.001); however, this finding was driven by patients with MICO (p<0.001) only (MACO: p= 0.804). No associations were observed between stroke severity and complications in either thrombolysed or nonthrombolysed patients. Neurological deterioration during transfer was observed in 21.2%, but multivariate analysis revealed no association with thrombolysis (OR 0.962; 95%CI 0.670–1.380, p= 0.832). Asymptomatic intracerebral hemorrhage was present in 1.1%, symptomatic in 0.1%.Discussion and conclusion: In this large cohort, no patient-specific factor increasing the risk of complications during interhospital transfer was identified. Specifically, our results do not indicate that thrombolysis increases MACO. Hence, interhospital transfer without EPs appears reasonable in most patients.

Published
2024
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291. Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke

Author

Mujanovic, Adnan, Strbian, Daniel, Demeestere, Jelle, Marto, João Pedro, Puetz, Volker, Nogueira, Raul G, Abdalkader, Mohamad, Nagel, Simon, Raymond, Jean, Ribo, Marc, Michel, Patrik, Yoshimura, Shinichi, Zaidat, Osama O, Winzer, Simon, Ortega-Gutierrez, Santiago, Sheth, Sunil A, Siegler, James E, Dusart, Anne, Haussen, Diogo C, Henon, Hilde, Serrallach, Bettina L, Mohammaden, Mahmoud H, Möhlenbruch, Markus A, Olive-Gadea, Marta, Puri, Ajit S, Sakai, Nobuyuki, Klein, Piers, Tomppo, Liisa, Caparros, Francois, Ramos, João Nuno, Jumaa, Mouhammad, Zaidi, Syed, Dobrocky, Tomas, Martinez-Majander, Nicolas, Nannoni, Stefania, Bellante, Flavio, Rodriguez-Calienes, Aaron, Salazar-Marioni, Sergio, Virtanen, Pekka, Kaiser, Daniel PO, Ventura, Rita, Jesser, Jessica, Castonguay, Alicia C, Qureshi, Muhammad M, Masoud, Hesham E, Galecio-Castillo, Milagros, Requena, Manuel, Lauha, Riikka, Hu, Wei, Lin, Eugene, Miao, Zhongrong, Roy, Daniel, Yamagami, Hiroshi, Seiffge, David J, Strambo, Davide, Ringleb, Peter A, Lemmens, Robin, Fischer, Urs, Nguyen, Thanh N, and Kaesmacher, Johannes

Abstract

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0–5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6–24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed with ordinal and logistic regressions.Results: Among 5098 screened patients, 2451 were included in the analysis (median age 73, 55% women). Of patients with ASPECTS 0–5 (n= 310), receiving EVT (n= 209/310) was associated with lower 3-month mRS when compared to medical management (median 4 IQR 3–6 vs 6 IQR 4–6; aOR 0.4, 95% CI 0.2–0.7). Patients undergoing EVT had higher sICH (11.2% vs 4.0%; aOR 4.1, 95% CI 1.2–18.8) and lower mortality (31.6% vs 58.4%, aOR 0.4; 95% CI 0.2–0.9) compared to medically managed patients. The relative benefit of EVT was comparable between patients with ASPECTS 0 and 5 and 6–10 in the extended time window (interaction aOR 0.9; 95% CI 0.5–1.7).Conclusion: In the extended time window, patients with ASPECTS 0–5 may have preserved relative treatment benefit of EVT compared to patients with ASPECTS 6–10. These findings are in line with recent trials showing benefit of EVT among real-world patients with large ischemic core in the extended time window.Trial registration number: clinicaltrials.gov; Unique identifier: NCT04096248

Published
2024
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292. Initial Formation of Positively Charged Gold on MgO(001) Thin Films: Identification by Experiment and Structural Assignment by Theory

Author

Brown, Matthew A., Ringleb, Franziska, Fujimori, Yuichi, Sterrer, Martin, Freund, Hans-Joachim, Preda, Gloria, and Pacchioni, Gianfranco

Abstract

Infrared spectroscopy experiments using CO as a probe and X-ray photoelectron spectroscopy were used to study the initial nucleation of gold on the surface of MgO(001)/Ag(001) thin films at 90 K. The most intense CO infrared signal observed at low gold coverage was at 2154 cm–1, indicating the formation of positively charged Au species. Both infrared and photoemission data reveal details about the thermally induced sinter behavior of metallic and positively charged gold species on the MgO(001) surface. Density functional theory was used to examine different defect types on the MgO surface for their ability to form positively charged Au species and to assign the observed IR stretch vibration to Aun+–CO species on specific binding sites on the MgO(001) surface.

Published
2024
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293. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial

Author

Viscoli, C. M., Brass, L. M., Carolei, Antonio, Conwit, R., Ford, G. A., Furie, K. L., Gorman, M., Guarino, P. D., Inzucchi, S. E., Lovejoy, A. M., Parsons, M. W., Peduzzi, P. N., Ringleb, P. A., Schwartz, G. G., Spence, J. D., Tanne, D., Young, L. H., Kernan, W. N., and IRIS Trial investigators

Subjects
Adult, Male, medicine.medical_specialty, Acute coronary syndrome, medicine.drug_class, Myocardial Infarction, Risk Assessment, Article, Insulin resistance, Double-Blind Method, Risk Factors, Diabetes mellitus, Internal medicine, medicine, Secondary Prevention, Humans, Hypoglycemic Agents, cardiovascular diseases, Myocardial infarction, Thiazolidinedione, Stroke, Dose-Response Relationship, Drug, Pioglitazone, business.industry, Middle Aged, medicine.disease, Survival Analysis, Surgery, Patient Outcome Assessment, Ischemic Attack, Transient, Female, Thiazolidinediones, Metabolic syndrome, Insulin Resistance, Cardiology and Cardiovascular Medicine, business, Cognition Disorders, medicine.drug
Abstract

Background Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack (TIA). The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events. Specifically, IRIS will test the effectiveness of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, for reducing the risk for stroke and myocardial infarction (MI) among insulin resistant, nondiabetic patients with a recent ischemic stroke or TIA. Design Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment–Insulin Resistance >3.0 without meeting criteria for diabetes. Within 6 months of the index stroke or TIA, patients were randomly assigned to pioglitazone (titrated from 15 to 45 mg/d) or matching placebo and followed for up to 5 years. The primary outcome is time to stroke or MI. Secondary outcomes include time to stroke alone, acute coronary syndrome, diabetes, cognitive decline, and all-cause mortality. Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013. Participant follow-up will continue until July 2015. Summary The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic, insulin-resistant patients with stroke or TIA. Results are expected in early 2016.

Published
2014

294. Endovascular Stroke Treatment of Nonagenarians

Author

Möhlenbruch, M., primary, Pfaff, J., additional, Schönenberger, S., additional, Nagel, S., additional, Bösel, J., additional, Herweh, C., additional, Ringleb, P., additional, Bendszus, M., additional, and Stampfl, S., additional

Published
2016
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300. Immediate and Delayed Procedural Stroke or Death in Stenting Versus Endarterectomy for Symptomatic Carotid Stenosis.

Author

Müller, Mandy D., von Felten, Stefanie, Algra, Ale, Becquemin, Jean-Pierre, Brown, Martin, Bulbulia, Richard, Calvet, David, Eckstein, Hans-Henning, Fraedrich, Gustav, Halliday, Alison, Hendrikse, Jeroen, Gregson, John, Howard, George, Jansen, Olav, Mas, Jean-Louis, Brott, Thomas G., Ringleb, Peter A., Bonati, Leo H., and Carotid Stenosis Trialists’ Collaboration

Published
2018
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