Publications by authors named "Claus Z Simonsen"

65 Publications

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.

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

Neurology 2021 Mar 25. Epub 2021 Mar 25.

Radiation Oncology, Boston Medical Center.

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
March 2021

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

Eur J Neurol 2021 Mar 3. Epub 2021 Mar 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background And Purpose: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD.

Methods: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale.

Results: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS.

Conclusions: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.
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http://dx.doi.org/10.1111/ene.14797DOI Listing
March 2021

Safety and efficacy of intravenous thrombolysis in stroke patients on prior antiplatelet therapy in the WAKE-UP trial.

Neurol Res Pract 2020 20;2:40. Epub 2020 Nov 20.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: One quarter to one third of patients eligible for systemic thrombolysis are on antiplatelet therapy at presentation. In this study, we aimed to assess the safety and efficacy of intravenous thrombolysis in stroke patients on prescribed antiplatelet therapy in the WAKE-UP trial.

Methods: WAKE-UP was a multicenter, randomized, double-blind, placebo-controlled clinical trial to study the efficacy and safety of MRI-guided intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time. The medication history of all patients randomized in the WAKE-UP trial was documented. The primary safety outcome was any sign of hemorrhagic transformation on follow-up MRI. The primary efficacy outcome was favorable functional outcome defined by a score of 0-1 on the modified Rankin scale at 90 days after stroke, adjusted for age and baseline stroke severity. Logistic regression models were fitted to study the association of prior antiplatelet treatment with outcome and treatment effect of intravenous alteplase.

Results: Of 503 randomized patients, 164 (32.6%) were on antiplatelet treatment. Patients on antiplatelet treatment were older (70.3 vs. 62.8 years,  <  0.001), and more frequently had a history of hypertension, atrial fibrillation, diabetes, hypercholesterolemia, and previous stroke or transient ischaemic attack. Rates of symptomatic intracranial hemorrhage and hemorrhagic transformation on follow-up imaging did not differ between patients with and without antiplatelet treatment. Patients on prior antiplatelet treatment were less likely to achieve a favorable outcome (37.3% vs. 52.6%,  = 0.014), but there was no interaction of prior antiplatelet treatment with intravenous alteplase concerning favorable outcome ( = 0.355). Intravenous alteplase was associated with higher rates of favorable outcome in patients on prior antiplatelet treatment with an adjusted odds ratio of 2.106 (95% CI 1.047-4.236).

Conclusions: Treatment benefit of intravenous alteplase and rates of post-treatment hemorrhagic transformation were not modified by prior antiplatelet intake among MRI-selected patients with unknown onset stroke. Worse functional outcome in patients on antiplatelets may result from a higher load of cardiovascular co-morbidities in these patients.
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http://dx.doi.org/10.1186/s42466-020-00087-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678217PMC
November 2020

Symptoms and probabilistic anatomical mapping of lacunar infarcts.

Neurol Res Pract 2020 3;2:21. Epub 2020 Aug 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background: The anatomical distribution of acute lacunar infarcts has mainly been studied for supratentorial lesions. In addition, little is known about the association with distinct stroke symptoms, not summarized as classical lacunar syndromes. We aimed to describe the spatial lesion distribution of acute supra- and infratentorial lacunar infarcts and their association with stroke symptoms in patients eligible for thrombolysis.

Methods: All patients enrolled in the WAKE-UP trial (efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in wake-up stroke) were screened for lacunar infarcts on diffusion-weighted imaging (DWI). The relationship between the anatomical distribution of supra- and infratentorial lacunar infarcts, their demographic characteristics and acute stroke symptoms, defined by the National Institutes of Health Stroke Scale (NIHSS) score, were correlated and compared.

Results: Maps of lesion distribution from 224 lacunar infarct patients (76 [33.9%] females, mean age [standard deviation] of 63.4 [11.5] years) were generated using computational image mapping methods. Median infarct volume was 0.73 ml (interquartile range [IQR] 0.37-1.15 ml). Median NIHSS sum score on hospital arrival was 4 (IQR 3-6). 165 (73.7%) patients had lacunar infarcts in the supratentorial deep white or grey matter, while 59 (26.3%) patients had infratentorial lacunar infarcts. Patients with supratentorial lacunar infarcts presented with a significantly lower occurrence of deficits in the NIHSS items gaze ( < 0.001) and dysarthria ( = 0.008), but had more often a paresis of the left arm ( = 0.009) and left leg ( = 0.068) compared to patients with infratentorial infarcts.

Conclusions: The anatomical lesion distribution of lacunar infarcts reveals a distinct pattern and supports an association of localization with different stroke symptoms.

Trial Registration: NCT01525290.
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http://dx.doi.org/10.1186/s42466-020-00068-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650076PMC
August 2020

Which Imaging Approach Should Be Used for Stroke of Unknown Time of Onset?

Stroke 2021 01 11;52(1):373-380. Epub 2020 Dec 11.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (G.T.).

Reperfusion therapy with intravenous thrombolysis or mechanical thrombectomy is effective in improving outcome for ischemic stroke but remains underused. Patients presenting with stroke of unknown onset are a common clinical scenario and a common reason for not offering reperfusion therapy. Recent studies have demonstrated the efficacy of reperfusion therapy in stroke of unknown time of onset, when guided by advanced brain imaging. However, translation into clinical practice is challenged by variability in the available data. Comparison between studies is difficult because of use of different imaging modalities (magnetic resonance imaging or computed tomography), different imaging paradigms (imaging biomarkers of lesion age versus imaging biomarkers of tissue viability), and different populations studied (ie, both patients with large vessel occlusion or those with less severe strokes). Physicians involved in acute stroke care are faced with the key question of which imaging approach they should use to guide reperfusion treatment for stroke with unknown time of onset. In this review, we provide an overview of the available evidence for selecting and treating patients with strokes of unknown onset, based on the underlying imaging concepts. The perspective provided is from the viewpoint of the clinician seeing these patients acutely, to provide pragmatic recommendations for clinical practice.
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http://dx.doi.org/10.1161/STROKEAHA.120.032020DOI Listing
January 2021

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Blood Pressure Thresholds During Endovascular Therapy in Ischemic Stroke-Reply.

JAMA Neurol 2020 12;77(12):1579-1580

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1001/jamaneurol.2020.3819DOI Listing
December 2020

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Front Neurol 2020 28;11:957. Epub 2020 Aug 28.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. We performed a analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
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http://dx.doi.org/10.3389/fneur.2020.00957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483750PMC
August 2020

Endovascular Treatment of Intracerebral Giant Cell Arteritis.

Front Neurol 2020 16;11:287. Epub 2020 Apr 16.

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis predominantly affecting large and medium sized vessels. In rare cases, the vasculitis can affect the vessels of the brain. We describe four cases of GCA with involvement of the cerebral vessels causing stroke. These cases were unresponsive to aggressive immunosuppression and we opted to treat with endovascular balloon dilatation of the stenotic areas. The procedure was safe. The four patients were treated in nine sessions and a total of 16 vessels were treated. We observed two dissections with no clinical influence on the patients. In patients with stroke due to progressive GCA that is non-responsive to immunosuppression, endovascular therapy is feasible.
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http://dx.doi.org/10.3389/fneur.2020.00287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177021PMC
April 2020

Different Mismatch Concepts for Magnetic Resonance Imaging-Guided Thrombolysis in Unknown Onset Stroke.

Ann Neurol 2020 06 20;87(6):931-938. Epub 2020 Apr 20.

Department of Neurology, University Hospitals Leuven, Leuven, Belgium.

Objective: To explore the prevalence of the perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch and response to intravenous thrombolysis in the WAKE-UP trial.

Methods: We performed a prespecified post hoc analysis of ischemic stroke patients screened for DWI-fluid-attenuated inversion recovery (FLAIR) mismatch in WAKE-UP who underwent PWI. We defined PWI-DWI mismatch as ischemic core volume < 70ml, mismatch volume > 10ml, and mismatch ratio > 1.2. Primary efficacy end point was a modified Rankin Scale score of 0-1 at 90 days, adjusted for age and symptom severity.

Results: Of 1,362 magnetic resonance imaging-screened patients, 431 underwent PWI. Of these, 57 (13%) had a double mismatch, 151 (35%) only a DWI-FLAIR mismatch, and 54 (13%) only a PWI-DWI mismatch. DWI-FLAIR mismatch was more prevalent than PWI-DWI mismatch (48%, 95% confidence interval [CI] = 43-53% vs 26%, 95% CI = 22-30%; p < 0.0001). Screening for either one of the mismatch profiles resulted in a yield of 61% (95% CI = 56-65%). Prevalence of PWI-DWI mismatch was similar in patients with (27%) or without (24%) DWI-FLAIR mismatch (p = 0.52). In an exploratory analysis in the small subgroup of 208 randomized patients with PWI, PWI-DWI mismatch status did not modify the treatment response (p for interaction = 0.73).

Interpretation: Evaluating both the DWI-FLAIR and PWI-DWI mismatch patterns in patients with unknown time of stroke onset will result in the highest yield of thrombolysis treatment. The treatment benefit of alteplase in patients with a DWI-FLAIR mismatch seems to be driven not merely by the presence of a PWI-DWI mismatch, although this analysis was underpowered. ANN NEUROL 2020;87:931-938.
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http://dx.doi.org/10.1002/ana.25730DOI Listing
June 2020

Blood Pressure Thresholds and Neurologic Outcomes After Endovascular Therapy for Acute Ischemic Stroke: An Analysis of Individual Patient Data From 3 Randomized Clinical Trials.

JAMA Neurol 2020 05;77(5):622-631

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Importance: The optimal blood pressure targets during endovascular therapy (EVT) for acute ischemic stroke (AIS) are unknown.

Objective: To study whether procedural blood pressure parameters, including specific blood pressure thresholds, are associated with neurologic outcomes after EVT.

Design, Setting, And Participants: This retrospective cohort study included adults with anterior-circulation AIS who were enrolled in randomized clinical trials assessing anesthetic strategy for EVT between February 2014 and February 2017. The trials had comparable blood pressure protocols, and patients were followed up for 90 days. A total of 3630 patients were initially approached, and 3265 patients were excluded.

Exposure: Endovascular therapy.

Main Outcomes And Measures: The primary efficacy variable was functional outcome as defined by the modified Rankin Scale (mRS) score at 90 days. Associations of blood pressure parameters and time less than and greater than mean arterial blood pressure (MABP) thresholds with outcome were analyzed.

Results: Of the 365 patients included in the analysis, the mean (SD) age was 71.4 (13.0) years, 163 were women (44.6%), and the median National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 14-21). For the entire cohort, 182 (49.9%) received general anesthesia and 183 (50.1%) received procedural sedation. A cumulated period of minimum 10 minutes with less than 70 mm Hg MABP (adjusted OR, 1.51; 95% CI, 1.02-2.22) and a continuous episode of minimum 20 minutes with less than 70 mm Hg MABP (adjusted OR, 2.30; 95% CI, 1.11-4.75) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 4, respectively. A cumulated period of minimum 45 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.49; 95% CI, 1.11-2.02) and a continuous episode of minimum 115 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.89; 95% CI, 1.01-3.54) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 6, respectively.

Conclusions And Relevance: Critical MABP thresholds and durations for poor outcome were found to be MABP less than 70 mm Hg for more than 10 minutes and MABP greater than 90 mm Hg for more than 45 minutes, both durations with a number needed to harm of 10 patients. Mean arterial blood pressure may be a modifiable therapeutic target to prevent or reduce poor functional outcome after EVT.
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http://dx.doi.org/10.1001/jamaneurol.2019.4838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990929PMC
May 2020

Experiences and needs of patients on the endovascular therapy pathway after acute ischaemic stroke: Being helpless and next to yourself.

Nurs Open 2020 01 24;7(1):299-306. Epub 2019 Oct 24.

Department of Neurology Aarhus University Hospital Aarhus N Denmark.

Aims: To explore the experiences and needs of patients on the endovascular therapy pathway.

Design: A qualitative design using a phenomenological-hermeneutic approach.

Methods: Semi-structured interviews and participant observations were carried out. Data were collected from April 2016-January 2017. Data were analysed using Ricoeur's theory of interpretation, capturing meaning and ensuring comprehensive understanding. The Consolidated Criteria for Reporting Qualitative Research checklist was used as a guideline.

Results: The findings of this study show that the impact of stroke goes far beyond physical disability. During the structural analysis, four themes were identified: (1) Acute admission to a stroke unit - an overwhelming and blurred experience. (2) Being helpless and next to yourself. (3) The important care when you worry about dying. (4) Poststroke feelings of loneliness and uncertainty.
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http://dx.doi.org/10.1002/nop2.391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917975PMC
January 2020

Current Smoking Does Not Modify the Treatment Effect of Intravenous Thrombolysis in Acute Ischemic Stroke Patients-A Analysis of the WAKE-UP Trial.

Front Neurol 2019 22;10:1239. Epub 2019 Nov 22.

Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.

The "smoking paradox" indicates that patients with acute ischemic stroke (AIS) who smoke at the time of their stroke may have a better prognosis after intravenous thrombolysis than non-smokers. However, findings are inconsistent and data analyzing the effect of smoking on treatment efficacy of intravenous thrombolysis are scarce. We performed a pre-specified subgroup analysis of the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial that randomized AIS patients with unknown time of symptom onset who had diffusion-weighted imaging-fluid attenuation inversion recovery (DWI-FLAIR) mismatch to either alteplase or placebo. Patients were categorized as current smokers or non-smokers (including former smokers and never-smokers). Baseline demographic and clinical characteristics, as well as clinical and imaging follow-up data were analyzed according to smoking status. Four hundred and eighty six patients were included in the analysis. Current smokers (133, 27.4%) were younger (60.1 ± 13.0 vs. 67.2 ± 10.3 years; < 0.001) and less often had arterial hypertension (45.0% vs. 56.8%; = 0.02) or atrial fibrillation (3.8% vs. 15.3%; < 0.001). The acute stroke presentation was more often due to large vessel occlusion among current smokers (27.1 vs. 16.2%; = 0.01), and smokers had a trend towards more severe strokes (National Institutes of Health Stroke Scale score>10 in 27.1% vs. 19.5%; = 0.08). The treatment effect of alteplase, quantified as odds ratio for a favorable outcome (modified Rankin Scale [mRS] score at 90 days of 0 or 1), did not differ between current smokers and non-smokers (-value for interaction: 0.59). After adjustment for age and stroke severity, neither the proportion of patients with favorable outcome, nor the median mRS score at 90 days differed between current smokers and non-smokers. When additional potential confounders were included in the model, the median mRS score was higher in current smokers than in non-smokers (cOR of better outcome for current smokers vs. non-smokers: 0.664 [0.451-0.978], = 0.04). In patients with mild to moderate MRI-proven AIS and unknown time of symptom onset with DWI-FLAIR mismatch, current smokers had worse functional outcome as compared to non-smokers. Current smoking did not modify the treatment effect of alteplase. Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012.
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http://dx.doi.org/10.3389/fneur.2019.01239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883001PMC
November 2019

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial.

Stroke 2020 01 30;51(1):209-215. Epub 2019 Oct 30.

From the Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum (B.C., A.N., C.G., G.T.), University Medical Center Hamburg-Eppendorf, Germany.

Background and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (=0.169) and shift analysis (=0.086) but reached significance for mRS score of 0 to 2 (=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
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http://dx.doi.org/10.1161/STROKEAHA.119.027390DOI Listing
January 2020

Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis.

JAMA 2019 Oct;322(13):1283-1293

Department of Neurology, Klinikum Kassel, Kassel, Germany.

Importance: General anesthesia during thrombectomy for acute ischemic stroke has been associated with poor neurological outcome in nonrandomized studies. Three single-center randomized trials reported no significantly different or improved outcomes for patients who received general anesthesia compared with procedural sedation.

Objective: To detect differences in functional outcome at 3 months between patients who received general anesthesia vs procedural sedation during thrombectomy for anterior circulation acute ischemic stroke.

Data Source: MEDLINE search for English-language articles published from January 1, 1980, to July 31, 2019.

Study Selection: Randomized clinical trials of adults with a National Institutes of Health Stroke Scale score of at least 10 and anterior circulation acute ischemic stroke assigned to receive general anesthesia or procedural sedation during thrombectomy.

Data Extraction And Synthesis: Individual patient data were obtained from 3 single-center, randomized, parallel-group, open-label treatment trials with blinded end point evaluation that met inclusion criteria and were analyzed using fixed-effects meta-analysis.

Main Outcomes And Measures: Degree of disability, measured via the modified Rankin Scale (mRS) score (range 0-6; lower scores indicate less disability), analyzed with the common odds ratio (cOR) to detect the ordinal shift in the distribution of disability over the range of mRS scores.

Results: A total of 368 patients (mean [SD] age, 71.5 [12.9] years; 163 [44.3%] women; median [interquartile range] National Institutes of Health Stroke Scale score, 17 [14-21]) were included in the analysis, including 183 (49.7%) who received general anesthesia and 185 (50.3%) who received procedural sedation. The mean 3-month mRS score was 2.8 (95% CI, 2.5-3.1) in the general anesthesia group vs 3.2 (95% CI, 3.0-3.5) in the procedural sedation group (difference, 0.43 [95% CI, 0.03-0.83]; cOR, 1.58 [95% CI, 1.09-2.29]; P = .02). Among prespecified adverse events, only hypotension (decline in systolic blood pressure of more than 20% from baseline) (80.8% vs 53.1%; OR, 4.26 [95% CI, 2.55-7.09]; P < .001) and blood pressure variability (systolic blood pressure >180 mm Hg or <120 mm Hg) (79.7 vs 62.3%; OR, 2.42 [95% CI, 1.49-3.93]; P < .001) were significantly more common in the general anesthesia group.

Conclusions And Relevance: Among patients with acute ischemic stroke involving the anterior circulation undergoing thrombectomy, the use of protocol-based general anesthesia, compared with procedural sedation, was significantly associated with less disability at 3 months. These findings should be interpreted tentatively, given that the individual trials examined were single-center trials and disability was the primary outcome in only 1 trial.
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http://dx.doi.org/10.1001/jama.2019.11455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777267PMC
October 2019

Analysis of Outcome of Intravenous Thrombolysis in Infarcts of Infratentorial Localization in the WAKE-UP Trial.

Front Neurol 2019 11;10:983. Epub 2019 Sep 11.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

In WAKE-UP (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke), patients with an acute stroke of unknown onset time were randomized to treatment with intravenous alteplase or placebo, guided by MRI. In this exploratory secondary analysis we compared clinical and imaging data, as well as treatment effects and safety of intravenous thrombolysis between patients with infra- vs. supratentorial stroke. Forty-eight out of 503 randomized patients (9.5%) presented with a stroke involving the cerebellum or brainstem. Patients with infratentorial stroke were younger compared to patients with supratentorial stroke (mean age 60 vs. 66 years), more frequently male (85 vs. 62%), and less severely affected (median NIHSS 4.5 vs. 6.0). There was no heterogeneity for treatment effect between supratentorial (OR 1.67 95% CI 1.11-2.51) and infratentorial (OR 1.31 95% CI 0.41-4.22) sub-groups (test for interaction = 0.70). In patients with infratentorial stroke, favorable outcome [a score of 0-1 on the modified Rankin scale (mRS) at 90 days] was observed in 12/22 patients (54.5%) in the alteplase group and in 13/25 patients (52.0%) in the placebo group ( = 0.59). The primary safety endpoint (death or mRS 4-6 at day 90) occurred in three patients of the alteplase group (13.6%) and three patients in the placebo group (12.0%); = 0.74. WAKE-UP was underpowered for demonstrating treatment effect in subgroup analyses however, based on our current results, there is no evidence to recommend withholding MRI-guided thrombolysis in patients with unknown onset stroke of infratentorial localization.
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http://dx.doi.org/10.3389/fneur.2019.00983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749039PMC
September 2019

TRIAGE-STROKE: Treatment strategy In Acute larGE vessel occlusion: Prioritize IV or endovascular treatment-A randomized trial.

Int J Stroke 2020 01 25;15(1):103-108. Epub 2019 Aug 25.

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Rationale: For patients with acute ischemic stroke and large vessel occlusions, intravenous thrombolysis and endovascular therapy are standard of care, but the effect of endovascular therapy is superior to intravenous thrombolysis. If a severe stroke with symptoms indicating large vessel occlusions occurs in the catchment area of a primary stroke center, there is equipoise regarding optimal transport strategy.

Aim: For patients presenting with suspected large vessel occlusions (PASS ≥ 2) and a final diagnosis of acute ischemic stroke, we hypothesize that bypassing the primary stroke center will result in an improved 90-day functional outcome.

Sample Size: We aim to randomize 600 patients, 1:1.

Design: A national investigator-driven, multi-center, randomized assessor-blinded clinical trial. The Prehospital Acute Stroke Severity Scale has been developed. It identifies most patients with large vessel occlusions in the pre-hospital setting. Patients without a contraindication for intravenous thrombolysis are randomized to either transport directly to a comprehensive stroke centers for intravenous thrombolysis and of endovascular therapy or to a primary stroke center for intravenous thrombolysis and subsequent transport to a comprehensive stroke centers for of endovascular therapy, if needed.

Outcomes: The primary outcome will be the 90-day modified Rankin Scale score (mRS) for all patients with acute ischemic stroke. Secondary outcomes include 90-day mRS for all randomized patients, all patients with ischemic stroke but without large vessel occlusions, and patients with hemorrhagic stroke. The safety outcomes include severe dependency or death and time to intravenous thrombolysis for ischemic stroke patients.

Discussion: Study results will influence decision making regarding transport strategy for patients with suspected large vessel occlusions.
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http://dx.doi.org/10.1177/1747493019869830DOI Listing
January 2020

Physiologic predictors of collateral circulation and infarct growth during anesthesia - Detailed analyses of the GOLIATH trial.

J Cereb Blood Flow Metab 2020 06 1;40(6):1203-1212. Epub 2019 Aug 1.

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Collateral circulation plays a pivotal role in acute ischemic stroke due to large vessel occlusion (LVO) and may be affected by multiple variables during sedation for endovascular therapy (EVT). We conducted detailed analyses of the GOLIATH trial to identify predictors of collateral circulation grade and infarct growth. We also modified the ASITN collateral grading scale and sought to determine its impact on clinical outcome and infarct growth. Multivariable analysis was used to identify predictors of collaterals and infarct growth. Ordinal analysis demonstrated nominal, but non-significant association between modified ASITN scale and infarct growth. Among all analyzed baseline clinical and procedural variables, the most significant predictors of infarct growth at 24 h were phenylephrine dose (estimate 6.78;  = 0.014) and baseline infarct volume (estimate 0.93;  = 0.03). The most significant predictors of worse collateral grade were mean arterial pressure (MAP) <70 mmHg (OR 0.35;  = 0.048) and baseline infarct volume (OR 0.96;  = 0.003). Hypotension during sedation for EVT for LVO negatively impacts collateral circulation, while higher pressor dose is a strong predictor of infarct growth. Avoidance of anesthesia-induced hypotension and consequent need for pressor therapy may prevent collateral failure and minimize infarct growth.
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http://dx.doi.org/10.1177/0271678X19865219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238375PMC
June 2020

Ischemic lesions in all territories as a marker of malignant hypercoagulability.

Clin Case Rep 2019 Jul 22;7(7):1312-1315. Epub 2019 May 22.

Department of Neurosurgery and Neurology Massachusetts General Hospital Boston Massachusetts.

Hypercoagulability due to cancer is an overlooked cause of stroke and presents with a typical MRI pattern, that is small embolic strokes in several vascular territories.
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http://dx.doi.org/10.1002/ccr3.2211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637358PMC
July 2019

Clinical Characteristics and Outcome of Patients with Lacunar Infarcts and Concurrent Embolic Ischemic Lesions.

Clin Neuroradiol 2020 Sep 3;30(3):511-516. Epub 2019 Jun 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Purpose: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI).

Methods: All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions.

Results: Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years; p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4; p = 0.046), and-among those randomized-had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1; p = 0.011).

Conclusion: Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts.
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http://dx.doi.org/10.1007/s00062-019-00800-5DOI Listing
September 2020

Anesthesia practice for endovascular therapy of acute ischemic stroke in Europe.

Curr Opin Anaesthesiol 2019 Aug;32(4):523-530

Section of Neuroanesthesia, Department of Anesthesia.

Purpose Of Review: Anesthetic assistance is often required during endovascular therapy (EVT) of large vessel occlusion in patients with acute ischemic stroke. It is currently debated whether EVT should be performed under general anesthesia or conscious sedation. This review will summarize the recent literature with emphasis on the influence of anesthesia method on neurological outcome.

Recent Findings: Recent randomized trials have reported no difference in outcome after EVT performed under either conscious sedation or general anesthesia. This is in contrast to a substantial number of retrospective studies, which found that EVT performed under general anesthesia was associated with a worse neurologic outcome compared with conscious sedation. Anesthetic drugs affect vessel tone and the level of blood pressure may influence outcome. The most favorable choice of anesthetic agents and ventilatory strategy is still debated.

Summary: The optimal anesthetic practice for EVT remains to be identified. Currently, conscious sedation is often an easy first-line strategy, but general anesthesia can be considered an equal and safe alternative to conscious sedation when there is a carefully administered anesthetic that maintains strict hemodynamic control. Attention to ventilation is advocated. The presence of a specialized neuroanesthesiologist or otherwise dedicated anesthesia personnel is highly recommended.
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http://dx.doi.org/10.1097/ACO.0000000000000746DOI Listing
August 2019

Safety and quality of endovascular therapy under general anesthesia and conscious sedation are comparable: results from the GOLIATH trial.

J Neurointerv Surg 2019 Nov 29;11(11):1070-1072. Epub 2019 Mar 29.

Neurology, Aarhus University Hospital, Aarhus, Denmark.

Background: The "General or Local Anesthesia in Intra-Arterial Therapy" (GOLIATH) trial compared infarct growth and outcome in patients undergoing endovascular therapy (EVT) under either general anesthesia (GA) or conscious sedation (CS). The results were the same for the primary outcome (infarct growth) but successful reperfusion was higher in the GA arm.

Objective: To further examine differences in the quality and safety of EVT with the two anesthetic regimens in a post hoc analysis of GOLIATH.

Methods: In GOLIATH, 128 subjects with anterior circulation large vessel occlusion stroke within 6 hours of onset were randomized to either GA or CS (1:1 allocation). We compared the quality of reperfusion, treatment delay, use of catheters, and contrast and radiation dosage between the trial arms.

Results: Sixty-five subjects were randomized to GA. Baseline demographic and clinical variables were similar between the treatment arms. We found no difference in procedure time, contrast dose, or radiation dose between the two arms. Tandem occlusions were associated with a longer procedure time, but there was no difference between the two arms. There was no difference in reperfusion rates between the direct aspiration technique and a stent retriever (86% vs 79%, respectively, p=0.54), but aspiration was associated with a shorter procedure time (28 min vs 42 min for a stent retriever), p=0.03.

Conclusion: Safety and quality of EVT under either GA and CS are comparable.

Trial Registration: Unique identifier: NCT02317237;Post-results.
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http://dx.doi.org/10.1136/neurintsurg-2019-014712DOI Listing
November 2019

Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial.

JAMA Neurol 2019 06;76(6):641-649

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment.

Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts.

Design, Setting, And Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information.

Main Outcomes And Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms.

Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93).

Conclusions And Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.
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http://dx.doi.org/10.1001/jamaneurol.2019.0351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563546PMC
June 2019

Endovascular therapy after acute ischaemic stroke-Experiences and needs of relatives.

J Clin Nurs 2019 Mar 19;28(5-6):792-800. Epub 2018 Sep 19.

Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.

Aims And Objectives: To explore the experiences and needs of relatives being part of the endovascular therapy (EVT) pathway.

Background: Ischaemic stroke is the third leading cause of death and the most common cause of acquired disability among adults in the Western world. The most recently approved treatment for major stroke is EVT. Removing the arterial occlusion has proven to be the best predictor of outcome. While patients are treated, relatives are left waiting. Facing the massive shock of their loved ones having a stroke may cause emotional turmoil and leave relatives with various needs. No previous studies have explored experiences and needs of relatives who are part of an EVT pathway.

Design: A qualitative design using a phenomenological-hermeneutic approach.

Methods: Semi-structured interviews and participant observations were carried out. Data were collected from April 2016-January 2017. Data were analysed using Ricoeur's theory of interpretation, capturing meaning and ensuring comprehensive understanding.

Results: Four themes emerged are as follows: (a) The first phase-shock, chaos and feeling paralysed; (b) the all-important information-sharing is pivotal; (c) professional loving care-being seen and heard by caring health professionals; and (d) adjusting to new roles. One essential finding that emerged across all themes was relatives' constant need for care, for support and for health professionals to "be there."

Conclusion: Relatives need support and care during the entire EVT pathway. They tend to be modest and ignore their own needs. Relatives who experience chaos, fear and worry need to be met by professionals with real presence.

Relevance To Clinical Practice: These findings will be used as a foundation for development of local structures and policies that should provide knowledge and ensure a consistent and proactive approach to meet the needs of the relatives in a timely and efficient manner.
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http://dx.doi.org/10.1111/jocn.14664DOI Listing
March 2019

A randomized controlled trial to test efficacy and safety of thrombectomy in stroke with extended lesion and extended time window.

Int J Stroke 2019 01 29;14(1):87-93. Epub 2018 Aug 29.

13 Department of Neurology, University of Hamburg, Germany.

Rationale: The benefit of thrombectomy in patients with intracranial large vessel occlusion of the anterior circulation has been shown in selected patients in previous randomized controlled trials, but patients with extended ischemic lesions were excluded in the majority of these trials. TENSION aims to demonstrate efficacy and safety of thrombectomy in patients with extended lesions in an extended time window (up to 12 h from onset or from last seen well).

Design: TENSION is an investigator-initiated, randomized controlled, open label, blinded endpoint, European, two-arm, postmarket study to compare the safety and effectiveness of thrombectomy as compared to best medical care alone in stroke patients with extended stroke lesions defined by an Alberta Stroke Program Early Computed Tomography Scan score of 3-5 and in an extended time window. In an adaptive design study, up to 665 patients will be randomized.

Outcomes: Primary efficacy endpoint will be clinical outcome defined by the modified Rankin Scale at 90-day poststroke. The main safety endpoint will be death and dependency (modified Rankin Scale 4-6) at 90 days. Additional effect measures include adverse events, health-related quality of life, poststroke depression, and costs utility assessment.

Discussion: TENSION may make effective treatment available for patients with severe stroke in an extended time window, thereby improving functional outcome and quality of life of thousands of stroke patients and reducing the individual, societal, and economic burden of death and disability resulting from severe stroke. TENSION is registered at ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT03094715).
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http://dx.doi.org/10.1177/1747493018798558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604397PMC
January 2019

Additional Factors Regarding Clinical Outcomes of General Anesthesia and Conscious Sedation for Acute Ischemic Stroke-Reply.

JAMA Neurol 2018 09;75(9):1152-1153

Department of Anesthesiology and Intensive Care-North, Section of Neuroanesthesia, Aarhus University Hospital, Aarhus, Denmark.

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http://dx.doi.org/10.1001/jamaneurol.2018.1850DOI Listing
September 2018

Effects of centralizing acute stroke services: A prospective cohort study.

Neurology 2018 07 15;91(3):e236-e248. Epub 2018 Jun 15.

From the Departments of Neurology (S.H., T.T., P.v.W.-M., C.Z.S., N.H., A.T.M., T.H., M.S.P., N.R.d.M.A., D.D., G.A.) and Clinical Epidemiology (S.H., S.P.J., H.H.H.), Aarhus University Hospital; Department of Clinical Medicine, Aarhus University (S.H., C.Z.S., N.H., G.A); and Danish National Registers (H.H.H.), a National Quality Improvement Program (RKKP), Aarhus, Denmark.

Objective: To investigate the effects of centralizing the acute stroke services in the Central Denmark Region (CDR).

Methods: The CDR (1.3 million inhabitants) centralized acute stroke care from 6 to 2 designated acute stroke units with 7-day outpatient clinics. We performed a prospective "before-and-after" cohort study comparing all strokes from the CDR with strokes in the rest of Denmark to discover underlying general trends, adopting a difference-in-differences approach. The population comprised 22,141 stroke cases hospitalized from May 2011 to April 2012 and May 2013 to April 2014.

Results: Centralization was associated with a significant reduction in length of acute hospital stay from a median of 5 to 2 days with a length-of-stay ratio of 0.53 (95% confidence interval 0.38-0.75, data adjusted) with no corresponding change seen in the rest of Denmark. Similarly, centralization led to a significant increase in strokes with same-day admission (mainly outpatients), whereas this remained unchanged in the rest of Denmark. We observed a significant improvement in quality of care captured in 11 process performance measures in both the CDR and the rest of Denmark. Centralization was associated with a nonsignificant increase in thrombolysis rate. We observed a slight increase in readmissions at day 30, but this was not significantly different from the general trend. Mortality at days 30 and 365 remained unchanged, as in the rest of Denmark.

Conclusions: Centralizing acute stroke care in the CDR significantly reduced the length of acute hospital stay without compromising quality. Readmissions and mortality stayed comparable to the rest of Denmark.
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http://dx.doi.org/10.1212/WNL.0000000000005822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059031PMC
July 2018

MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset.

N Engl J Med 2018 08 16;379(7):611-622. Epub 2018 May 16.

From Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf (G.T., B. Cheng, S.G., A.G., C.G.), the Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf (J.F.), and ZytoService Deutschland (E.S.), Hamburg, Universitätsklinik für Neurologie, Medizinische Universität Graz, Graz (F.F.), Centrum für Schlaganfallforschung Berlin (I.G., K.G.H., K.V., M. Ebinger, M. Endres, J.B.F.) and Klinik und Hochschulambulanz für Neurologie (K.G.H., L.N., M. Endres), Charité-Universitätsmedizin Berlin, and Neurologie der Rehaklinik Medical Park Humboldtmühle (M. Ebinger), Berlin, Mediri (J. Gregori, M.G.), the Department of Neurology, Medical Faculty Mannheim, University of Heidelberg (M.H.), and Neurologische Klinik, Universitätsklinikum Heidelberg (P. Ringleb), Heidelberg, Fraunhofer MEVIS and University of Bremen, Bremen (M.G.), and Institut für Neuroradiologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck (A.K.) - all in Germany; the Department of Neurology, Aarhus University Hospital, Aarhus (C.Z.S., G.A.), the Department of Neurology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen (J.M.), and Department of Neurology, Stroke Unit, Aalborg University Hospital, Aalborg (B.M.) - all in Denmark; Hospices Civils de Lyon, Service de Biostatistique (F.B., P. Roy), the Neuroradiology Department, Neurological Hospital, University Lyon (Y.B.), and the Department of Stroke Medicine, Université Claude Bernard Lyon 1, and Hospices Civils de Lyon (T.-H.C., N.N.), Lyon, and Université Lyon 1 and Centre National de la Recherche Scientifique, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne (F.B., P. Roy) - all in France; the Institute of Neuroscience and Psychology (B. Cheripelli, K.W.M.) and the Robertson Centre for Biostatistics (I.F.), University of Glasgow, Glasgow, United Kingdom (I.F.); Fundació Salut Empordà Hospital, Figueres (J. Guibernau), Stroke Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona (N.P.O.), and the Department of Radiology (J.P., S.P.) and the Stroke Unit (J.S.), Hospital Universitari Doctor Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona - all in Spain; the Department of Neurology, St. Antonius Hospital, Nieuwegein, and University Medical Center Utrecht, Utrecht (W.S.) - both in the Netherlands; the Department of Imaging and Pathology, University of Leuven (S.S.), the Department of Neurology, University Hospitals Leuven (A.W., R.L.), KU Leuven-University of Leuven, Department of Neurosciences, Experimental Neurology (A.W., R.L.), and the VIB-KU Leuven Center for Brain and Disease Research, Laboratory of Neurobiology (A.W., R.L.), Leuven, Belgium; and Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC, Australia (V.T.).

Background: Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.

Methods: In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).

Results: The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).

Conclusions: In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .).
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http://dx.doi.org/10.1056/NEJMoa1804355DOI Listing
August 2018

Magnetic Resonance Imaging Selection for Endovascular Stroke Therapy: Workflow in the GOLIATH Trial.

Stroke 2018 06 8;49(6):1402-1406. Epub 2018 May 8.

Neuroradiology (L.H.S.), Aarhus University Hospital, Denmark.

Background And Purpose: The GOLIATH trial (General or Local Anesthesia in Intra-Arterial Therapy) compared infarct growth and outcome in patients undergoing endovascular therapy under either general anesthesia or conscious sedation. Magnetic resonance imaging was performed before and after the procedure to study infarct growth. In this post hoc analysis of GOLIATH, we aimed to characterize the workflow of patients undergoing magnetic resonance imaging selection before endovascular therapy.

Methods: We randomized 128 patients with anterior circulation large vessel occlusion stroke within 6 hours of onset to either general anesthesia or conscious sedation (1:1 allocation). We studied workflow time intervals to examine whether magnetic resonance imaging conferred a time delay in treatment when compared with computed tomography-based studies that emphasized rapid workflow.

Results: Of 128 patients enrolled between March 2015 and February 2017, 65 were randomized to general anesthesia. Baseline demographic and clinical variables were balanced between the treatment arms. The median interval from scan to groin puncture was 56.5 minutes (interquartile range, 44.5-73.5) for all patients. The median interval from admission to groin puncture was 68 minutes (interquartile range, 54.5-87 minutes). Comparable intervals in recent randomized data were 51 minutes (interquartile range, 39-68) for scan to groin puncture in the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) and 90 minutes (interquartile range, 69-120 minutes) for door to groin puncture in the SWIFT-PRIME study (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment).

Conclusions: Workflow in GOLIATH demonstrates that magnetic resonance imaging selection for endovascular therapy can be accomplished rapidly and within a similar time frame as computed tomography-based selection.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02317237.
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http://dx.doi.org/10.1161/STROKEAHA.118.021038DOI Listing
June 2018