Publications by authors named "Davide Strambo"

46 Publications

EXPRESS: ASPECTS-based selection for late endovascular treatment: a retrospective two-site cohort study.

Int J Stroke 2021 Mar 31:17474930211009806. Epub 2021 Mar 31.

CHUV Lausanne, Neurology, Bugnon 46, Lausanne, Switzerland.

IntroductionThe DAWN trial demonstrated the effectiveness of late endovascular treatment (EVT) in acute ischemic stroke (AIS) patients selected on the basis of a clinical-core mismatch. We explored in a real-world sample of EVT patients if a clinical-ASPECTS (Alberta Stroke Program Early CT Score) mismatch was associated with an outcome benefit after late EVT. MethodsWe retrospectively analysed all consecutive AIS patients admitted 6-24 hours after last proof of good health in two stroke centres, with initial National Institutes of Health Stroke Scale (NIHSS) â¥10 and an internal carotid artery or M1 occlusion. We defined clinical-ASPECTS mismatch as NIHSSâ¥10 and ASPECTSâ¥7, or NIHSSâ¥20 and ASPECTSâ¥5. We assessed the interaction between clinical-ASPECTS mismatch positive and negative patients and late EVT, using ordinal shift analysis of the 3-month modified Rankin Scale and adjusting for multiple confounders.ResultsThe included 337 patients had a median age of 73 years (IQR=61-82), admission NIHSS of 18 (15-22) and baseline ASPECTS of 7 (5-9). Out of 196 (58.2%) patients showing clinical-ASPECTS mismatch, 146 (74.5%) underwent late EVT. Among 141 (41.8%) mismatch negative patients, late EVT was performed in 72 (51.1%) patients. In the adjusted analysis, late EVT was significantly associated with a better outcome in the presence of clinical-ASPECTS mismatch (adjusted Odd Ratio, aOR=2.83; 95% confidence interval, CI: 1.48-5.58) but not in its absence (aOR=1.32; 95%CI: 0.61-2.84). The p-value for the interaction term between clinical-ASPECTS mismatch and late EVT was 0.073. ConclusionsIn our retrospective two-site analysis, late EVT seemed effective in the presence of a clinical-ASPECTS mismatch, but not in its absence. If confirmed in randomized trials, this finding could support the use of an ASPECTS-based selection for late EVT decisions, obviating the need for advanced imaging.
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http://dx.doi.org/10.1177/17474930211009806DOI Listing
March 2021

Embolic Stroke of Undetermined Source and Patent Foramen Ovale: Risk of Paradoxical Embolism Score Validation and Atrial Fibrillation Prediction.

Stroke 2021 Mar 31:STROKEAHA120032453. Epub 2021 Mar 31.

Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland (D.S., G.S., S.N., P.M.).

Background And Purpose: The Risk of Paradoxical Embolism (RoPE) score stratifies patients with stroke according to the probability of having a patent foramen ovale (PFO), which (through Bayes theorem and simple assumptions) can be used to estimate the probability that a PFO is pathogenic in a given subgroup of patients with specific features (ie, a given RoPE score value): a higher PFO prevalence corresponds to a higher probability that a PFO is pathogenic. Among alternative mechanisms in embolic stroke of undetermined source (ESUS), the actual stroke cause may be covert atrial fibrillation. We aimed to validate the RoPE score in a large ESUS population and investigate the rate of stroke recurrence and new incident atrial fibrillation during follow-up according to PFO status and RoPE score.

Methods: We pooled data of consecutive patients with ESUS from 3 prospective stroke registries. We assessed RoPE score's calibration and discrimination for the presence of PFO (and consequently for the probability that it is pathogenic). Multivariate logistic regression analysis was performed to identify factors associated with PFO.

Results: Among 455 patients with ESUS (median age 59 years), 184 (40%) had PFO. The RoPE score's area under the receiver operating characteristic curve was 0.75. In addition to RoPE score variables, absence of left ventricular hypertrophy, absence of atherosclerosis, and infratentorial lesions were independently associated with PFO. In patients with PFO and RoPE 7 to 10, PFO and RoPE 0 to 6, and without PFO, new incident atrial fibrillation rate was 3.1%, 20.5%, and 31.8%, respectively (log-rank test=6.28, =0.04). Stroke recurrences in patients with likely pathogenic PFO were not statistically different from other patients.

Conclusions: This multicenter study validates the RoPE score to predict the presence/absence of PFO in patients with ESUS, which strongly suggests that RoPE score is helpful in identifying patients with ESUS with pathogenic versus incidental PFOs. Left ventricular hypertrophy, atherosclerosis, and infratentorial stroke may further improve the score. Low RoPE scores were associated with more incidental atrial fibrillation during 10-year follow-up.
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http://dx.doi.org/10.1161/STROKEAHA.120.032453DOI Listing
March 2021

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

Cerebral thrombi of cardioembolic etiology have an increased content of neutrophil extracellular traps.

J Neurol Sci 2021 04 21;423:117355. Epub 2021 Feb 21.

Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Electronic address:

Background: Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT).

Methods: We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO cells) and NET content (citH3 area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus.

Results: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62).

Conclusion: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
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http://dx.doi.org/10.1016/j.jns.2021.117355DOI Listing
April 2021

Fishing an anemone in the brain: embolized cardiac fibroelastoma revealed after stroke thrombectomy.

Eur Heart J 2021 Jan 31. Epub 2021 Jan 31.

Neurology Department, San Raffaele Scientific Institute and Vita-Salute University San Raffaele, Milan, Italy.

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http://dx.doi.org/10.1093/eurheartj/ehab019DOI Listing
January 2021

Procedural Complications During Early Versus Late Endovascular Treatment in Acute Stroke: Frequency and Clinical Impact.

Stroke 2021 Mar 20;52(3):1079-1082. Epub 2021 Jan 20.

Stroke Centre, Neurology Service, Department of Clinical Neurosciences (E.M., S.N., D.S., A.E., P.M.), Lausanne University Hospital and University of Lausanne, Switzerland.

Background And Purpose: Endovascular treatment (EVT) in acute ischemic stroke is effective in the late time window in selected patients. However, the frequency and clinical impact of procedural complications in the early versus late time window has received little attention.

Methods: We retrospectively studied all acute ischemic strokes from 2015 to 2019 receiving EVT in the Acute Stroke Registry and Analysis of Lausanne. We compared the procedural EVT complications in the early (<6 hours) versus late (6-24 hours) window and correlated them with short-term clinical outcome.

Results: Among 695 acute ischemic strokes receiving EVT (of which 202 were in the late window), 113 (16.3%) had at least one procedural complication. The frequency of each single, and for overall procedural complications was similar for early versus late EVT (16.2% versus 16.3%, =0.90). Procedural complications lead to a significantly less favorable short-term outcome, reflected by the absence of National Institutes of Health Stroke Scale improvement in late EVT (delta-National Institutes of Health Stroke Scale-24 hours, -2.5 versus 2, =0.01).

Conclusions: In this retrospective analysis of consecutive EVT, the frequency of procedural complications was similar for early and late EVT patients but very short-term outcome seemed less favorable in late EVT patients with complications.
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http://dx.doi.org/10.1161/STROKEAHA.120.031349DOI Listing
March 2021

Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone.

JAMA Neurol 2021 Mar;78(3):321-328

Neurology Department, GHU Paris psychiatrie et neurosciences, Institut de Psychiatrie et Neurosciences de Paris, INSERM U1266, Université de Paris, FHU Neurovasc, Paris, France.

Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy.

Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO.

Design, Setting, And Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019.

Main Outcomes And Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause.

Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively.

Conclusions And Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.
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http://dx.doi.org/10.1001/jamaneurol.2020.4557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802007PMC
March 2021

Acute ischaemic stroke in the absence of established vascular risk factors: Patient characteristics, stroke mechanism and long-term outcome.

Eur J Neurol 2021 Apr 7;28(4):1275-1283. Epub 2020 Dec 7.

Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background And Purpose: Some acute ischaemic stroke (AIS) patients do not display established vascular risk factors (EVRFs). The aim was to assess their clinical characteristics, stroke subtype etiological classification and long-term outcome.

Methods: All consecutive AIS patients from the Acute Stroke Registry of Lausanne (2003-2018) were retrospectively analyzed with complete assessment of the following EVRFs: hypertension, diabetes, major cardioembolic sources, dyslipidemia, smoking, obesity, alcohol abuse, previous stroke/transient ischaemic attack and depression/psychosis. Patients without EVRFs were compared to patients with one or more EVRFs using appropriate statistical models.

Results: Of 4889 included patients, 103 (2.1%) had no EVRFs. In multiple regression analysis, patients without EVRFs were significantly younger (odds ratio [OR] 0.13; 95% confidence interval [CI] 0.08-0.20) and had more multiterritorial strokes (OR 3.38; 95% CI 1.26-9.05). Strokes were more often related to patent foramen ovale (PFO) (OR 3.02; 95% CI 1.44-6.32) and less to atherosclerosis, cardioembolism or small vessel disease. In patients <55 years old, PFO (OR 2.76; 95% CI 1.50-5.08) and contraceptive use in females (OR 2.75; 95% CI 1.40-5.41) were more frequent, whereas sleep apnea syndrome (OR 0.09; 95% CI 0.01-0.63) was less. In patients ≥55 years, female sex (OR 2.84; 95% CI 1.43-5.65) and active cancer (OR 3.27; 95% CI 1.34-7.94) were more prevalent. At 12 months, patients without EVRFs had worse adjusted functional outcome (Rankin shift OR 0.63; 95% CI 0.42-0.95) and higher rate of recurrence and death (adjusted hazard ratio 2.11; 95% CI 1.19-3.74).

Conclusions: In a consecutive cohort of AIS patients, only 2% showed no EVRFs. PFO and contraceptive use exhibited a strong association with the absence of EVRFs in younger patients and female sex and active cancer in elderly patients. Our findings highlight the importance of searching for previously unknown risk factors and/or unusual stroke mechanisms in patients without EVRFs.
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http://dx.doi.org/10.1111/ene.14667DOI Listing
April 2021

Severe Distal Motor Involvement in a Non-compliant Adult With Biotinidase Deficiency: The Necessity of Life-Long Biotin Therapy.

Front Neurol 2020 26;11:516799. Epub 2020 Oct 26.

Division of Genetic Medicine, Center for Molecular Diseases, Lausanne University Hospital, Lausanne, Switzerland.

Biotinidase deficiency is an autosomal recessive disorder in which affected individuals are unable to recycle biotin. Untreated, children usually exhibit hypotonia, seizures, ataxia, developmental delay, and/or hearing loss. Individuals diagnosed by newborn screening have an excellent prognosis with life-long biotin supplementation. We report a young adult diagnosed with profound biotinidase deficiency by newborn screening who was asymptomatic while on therapy. At 18 years of age, 6 months after voluntarily discontinuation of biotin, he developed a progressive distal muscle weakness. Molecular analysis of the gene showed a pathogenic homozygous duplication c.1372_1373dupT p.(Cys458LeuTer26) (1). Despite 16 months since reintroduction of biotin, muscle strength only partially recovered. Transition to adulthood in chronic metabolic diseases is known to be associated with an increased risk for non-compliance. Neurological findings in this adult are similar to those described in others with adult-onset biotinidase deficiency. Long-term prognosis in non-compliant symptomatic adult with biotinidase deficiency likely depends on the delay and/or severity of intervening symptoms until reintroduction of biotin.
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http://dx.doi.org/10.3389/fneur.2020.516799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649240PMC
October 2020

Carotid Atherosclerosis and Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

J Stroke Cerebrovasc Dis 2021 Jan 1;30(1):105409. Epub 2020 Nov 1.

Stroke Center and Neurology Service, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Background: Carotid atherosclerosis and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear.

Aim: To investigate the relation between carotid atherosclerosis and likely pathogenic PFO in patients with ESUS. We hypothesized that ipsilateral carotid atherosclerotic plaques are less prevalent in ESUS with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO.

Methods: The presence of PFO was assessed with transthoracic echocardiography with microbubble test and, when deemed necessary, through trans-oesophageal echocardiography. The presence of PFO was considered as likely incidental if the RoPE (Risk of Paradoxical Embolism) score was 0-6 and likely pathogenic if 7-10.

Results: Among 374 ESUS patients (median age: 61years, 40.4% women), there were 63 (49.6%) with likely incidental PFO, 64 (50.4%) with likely pathogenic PFO and 165 (44.1%) with ipsilateral carotid atherosclerosis. The prevalence of ipsilateral carotid atherosclerosis was lower in patients with likely pathogenic PFO (7.8%) compared to patients with likely incidental PFO (46.0%) or patients without PFO (53.0%) (p<0.001). After adjustment for multiple confounders, the prevalence of ipsilateral carotid atherosclerosis remained lower in patients with likely pathogenic PFO compared to patients with likely incidental PFO or without PFO (adjusted OR=0.32, 95%CI:0.104-0.994, p=0.049).

Conclusions: The presence of carotid atherosclerosis is inversely related to the presence of likely pathogenic PFO in patients with ESUS.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105409DOI Listing
January 2021

Prior Anticoagulation in Patients with Ischemic Stroke and Atrial Fibrillation.

Ann Neurol 2021 01 17;89(1):42-53. Epub 2020 Oct 17.

Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland.

Objective: The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3-month outcomes.

Methods: This was a cohort study of consecutive patients (2014-2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0-2) at 3 months.

Results: Of 8,179 patients (mean [SD] age, 79.8 [9.6] years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, [interquartile range 2-11]) compared with VKA (6, [2-14]) and controls (7, [3-15], p < 0.001; quantile regression: β -2.1, 95% confidence interval [CI] -2.6 to -1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 [63%]; adjusted odds ratio [aOR] 0.67; 95% CI 0.50-0.90) and particularly in patients on DOACs (69 of 464 [15%]; aOR 0.06; 95% CI 0.05-0.08) compared with controls (1,544 of 2,504 [74%]). sICH after IVT occurred in 3.6% (2.6-4.7%) of controls, 9 of 195 (4.6%; 1.9-9.2%; aOR 0.93; 95% CI 0.46-1.90) patients on VKA and 2 of 65 (3.1%; 0.4-10.8%, aOR 0.56; 95% CI 0.28-1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3-month outcome (aOR 1.24; 1.01-1.51).

Interpretation: Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42-53.
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http://dx.doi.org/10.1002/ana.25917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756294PMC
January 2021

A score to predict one-year risk of recurrence after acute ischemic stroke.

Int J Stroke 2020 Jun 17:1747493020932787. Epub 2020 Jun 17.

Stroke Center, Neurology Service, Lausanne University Hospital, Lausanne, Switzerland.

Background: An acute ischemic stroke carries a substantial risk of further recurrences. We aimed at developing and validating a prognostic tool to predict one-year stroke recurrence after acute ischemic stroke.

Methods: An integer score was derived by Cox regression analysis on a hospital-referred cohort of 3246 acute ischemic stroke patients from Switzerland, and tested for external validity in three similar independent cohorts from Athens ( = 2495), Milan ( = 1279), and Helsinki ( = 714) by means of calibration and discrimination.

Results: In the derivation cohort, the recurrence rate was 7% ( = 228/3246). We developed a nine-point score comprising: previous stroke or transient ischemic attack (1-point), stroke mechanism (small vessel disease and unknown mechanism: 0-points; rare stroke mechanism: 3-points; other mechanisms: 1-point), pre-stroke antiplatelets (1-point), active malignancy (2-points), chronic cerebrovascular lesions on imaging (1-point) and absence of early ischemic changes on first imaging (1-point). In the derivation cohort, the one-year risk of re-stroke was 3.0% (95%CI 1.9-4.1) in 932 (29%) patients with a score 0-1, 7.2% (6.1-8.3) in 2038 (63%) with a score 2-4, and 19.2% (14.6-23.9) in 276 (8%) with a score ≥ 5. The score calibrated well in the Athens (recurrences = 208/2495), but not in the Helsinki (recurrences = 15/714) or Milan (recurrences = 65/1279) cohorts. The AUC was 0.67 in the derivation cohort, and 0.56, 0.70, and 0.63 in the Athens, Helsinki, and Milan cohorts, respectively.

Conclusion: We developed a score to predict one-year stroke recurrence risk in patients with acute ischemic stroke. Since the score was not completely validated when applied to external datasets where it displayed poor to fair calibration and discrimination, additional efforts are required to ameliorate our accuracy for predicting stroke recurrence, by better refining this prognostic tool or developing new ones. Clinical and radiological markers of established cerebrovascular disease and stroke etiology were better predictors than the usual demographic vascular risk factors.
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http://dx.doi.org/10.1177/1747493020932787DOI Listing
June 2020

Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

Thromb Haemost 2021 Mar 2;121(3):361-365. Epub 2020 Sep 2.

Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Background:  Atrial cardiopathy and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear.

Methods:  Atrial cardiopathy was defined as increased left atrial diameter index (> 23 mm/m) or left atrial volume index (> 34 mL/m), or PR prolongation (≥ 200 ms), or presence of supraventricular extrasystoles in the electrocardiograms performed during hospitalization for the index stoke. The presence of PFO was assessed by transthoracic echocardiography with microbubble test or by transesophageal echocardiography. The presence of PFO was considered as likely pathogenic if the Risk of Paradoxical Embolism score was 7 to 10.

Results:  Among 367 ESUS patients with available information about the presence of PFO and the presence of atrial cardiopathy (median age: 61 years, 40.6% women), likely pathogenic PFO was diagnosed in 62 (16.9%) and atrial cardiopathy in 122 (33.2%). Only 4 patients (1.1%) had both likely pathogenic PFO and atrial cardiopathy. The prevalence of atrial cardiopathy was lower in patients with likely pathogenic PFO (6.5%) compared with patients with likely incidental PFO (31.2%) or without PFO (40.6%) (Pearson's chi-square test: 26.08,  < 0.001; adjusted odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.09-0.86). The prevalence of likely pathogenic PFO was lower in patients with atrial cardiopathy compared with patients without atrial cardiopathy (3.3% vs. 23.7%, respectively [Pearson's chi-square test: 24.13,  < 0.001; adjusted OR: 0.2, 95% CI: 0.02-0.6]).

Conclusion:  The presence of atrial cardiopathy is inversely related to the presence of likely pathogenic PFO in patients with ESUS.
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http://dx.doi.org/10.1055/s-0040-1715831DOI Listing
March 2021

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Stroke 2020 09 9;51(9):e254-e258. Epub 2020 Jul 9.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom (G.Y.H.L.).

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), =0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], <0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.
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http://dx.doi.org/10.1161/STROKEAHA.120.031208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359900PMC
September 2020

Clinical Reasoning: A 69-year-old man with rare complex visual symptoms.

Neurology 2020 08 30;95(7):316-320. Epub 2020 Jul 30.

From the Department of Clinical Neurosciences, Neurology Service, Lausanne University Hospital and University of Lausanne, Switzerland.

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http://dx.doi.org/10.1212/WNL.0000000000010218DOI Listing
August 2020

Transverse myelitis related to COVID-19 infection.

J Neurol 2020 Dec 29;267(12):3459-3461. Epub 2020 Jun 29.

Neurology Unit, Riviera-Chablais Hospital, Rennaz, Switzerland.

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http://dx.doi.org/10.1007/s00415-020-09997-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322383PMC
December 2020

Identification of patients with embolic stroke of undetermined source and low risk of new incident atrial fibrillation: The AF-ESUS score.

Int J Stroke 2021 Jan 19;16(1):29-38. Epub 2020 May 19.

Stroke Center, Neurology Service, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Background And Aims: Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF.

Methods: We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system.

Results: Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; -1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; -3 points for left ventricular ejection fraction <35%; 1 point for the presence of any supraventricular extrasystole recorded during all available 12-lead standard electrocardiograms performed during hospitalization for the ESUS; -2 points for subcortical infarct; -3 points for the presence of non-stenotic carotid plaques. The rate of new incident AF during follow-up was 1.97% among the 42.3% of the cohort who had a score of ≤0, compared to 26.9% in patients with > 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively.

Conclusions: The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ Unique identifier: NCT02766205.
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http://dx.doi.org/10.1177/1747493020925281DOI Listing
January 2021

Leukocyte Counts and Ratios Are Predictive of Stroke Outcome and Hemorrhagic Complications Independently of Infections.

Front Neurol 2020 3;11:201. Epub 2020 Apr 3.

Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Hospital, Milan, Italy.

Ischemic stroke patients show alterations in peripheral leukocyte counts that may result from the sterile inflammation response as well as the occurrence of early infections. We here aimed to determine whether alterations of circulating leukocytes in acute ischemic stroke are associated with long-term functional outcome and hemorrhagic complications, independently of the occurrence of infections. Blood laboratory values of patients with acute ischemic stroke, presenting within 4.5 h from symptom onset, were collected. Leukocyte subsets were analyzed in relation to 3-month functional outcome, mortality, and parenchymal hemorrhagic transformation (PH). A multivariable logistic regression analysis, considering the occurrence of early post-stroke infections, was performed for each outcome measure. Five-hundred-ten patients were included in the study. Independently of infections, good functional outcome was associated with a lower neutrophil to lymphocyte ratio (NL-R, OR 0.906 [95% CI 0.822-0.998]), a higher lymphocyte count (OR 1.547 [95% CI 1.051-2.277]), a higher eosinophil count (OR 1.027 [95% CI 1.007-1.048]), and a higher eosinophil to leukocyte ratio (EoLeu-R, OR 1.240 [95% CI 1.071-1.436]) at admission. Death within 3 months was associated with higher NL-R (OR 1.103 [95% CI 1.032-1.179]) as well as with lower eosinophil counts (OR 0.909 [95% CI 0.827-0.999]). Patients developing parenchymal hemorrhagic transformation had higher neutrophil counts (OR 1.420 [95% CI 1.197-1.684]) as well as a higher NL-R (OR 1.192 [95% IC 1.088-1.305]). Leukocyte subtype profiles in the acute phase of ischemic stroke represent a predictor of outcome independently of infections. Stroke-evoked sterile inflammation is a pathophysiological relevant mechanism that deserves further investigation.
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http://dx.doi.org/10.3389/fneur.2020.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145963PMC
April 2020

Response by Strambo and Michel to Letter Regarding Article, "Thrombectomy and Thrombolysis of Isolated Posterior Cerebral Artery Occlusion: Cognitive, Visual, and Disability Outcomes".

Stroke 2020 04 4;51(4):e69. Epub 2020 Mar 4.

Stroke Center, Neurology Service Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland.

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http://dx.doi.org/10.1161/STROKEAHA.120.028939DOI Listing
April 2020

Characteristics and outcomes of Embolic Stroke of Undetermined Source according to stroke severity.

Int J Stroke 2020 Oct 2;15(8):866-871. Epub 2020 Mar 2.

Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Background And Aims: Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS.

Methods: In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan-Meier product limit method.

Results: In 772 patients (median NIHSS: 6 (interquartile range: 3-12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27-2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73-1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44-1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05-2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2-48.6) vs. 36.6% (27.8-47.0), log-rank test: 0.01,  = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5-50.0) vs. 34.0% (26.0-43.6) respectively; log-rank test: 4.54,  = 0.033).

Conclusions: Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.
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http://dx.doi.org/10.1177/1747493020909546DOI Listing
October 2020

Supraventricular Extrasystoles on Standard 12-lead Electrocardiogram Predict New Incident Atrial Fibrillation after Embolic Stroke of Undetermined Source: The AF-ESUS Study.

J Stroke Cerebrovasc Dis 2020 Apr 15;29(4):104626. Epub 2020 Jan 15.

Department of Clinical Therapeutics, Medical School of Athens, Alexandra Hospital, Athens, Greece.

Background: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS).

Aims: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up.

Methods: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan-Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE.

Results: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death.

Conclusions: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104626DOI Listing
April 2020

Left atrial diameter thresholds and new incident atrial fibrillation in embolic stroke of undetermined source.

Eur J Intern Med 2020 05 15;75:30-34. Epub 2020 Jan 15.

Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece. Electronic address:

Background And Purpose: We analyzed consecutive patients with embolic stroke of undetermined source (ESUS) from three prospective stroke registries to compare the prognostic performance of different LAD thresholds for the prediction of new incident AF.

Methods: We calculated the sensitivity, specificity, positive prognostic value (PPV), negative prognostic value (NPV) and Youden's J-statistic of different LAD thresholds to predict new incident AF. We performed multivariate stepwise regression with forward selection of covariates to assess the association between the LAD threshold with the highest Youden's J-statistic and AF detection.

Results: Among 675 patients followed for 2437 patient-years, the mean LAD was 38.5 ± 6.8 mm. New incident AF was diagnosed in 115 (17.0%) patients. The LAD threshold of 40mm yielded the highest Youden's J-statistic of 0.35 with sensitivity 0.69, specificity 0.66, PPV 0.27 and NPV 0.92. The likelihood of new incident AF was nearly twice in patients with LAD > 40 mm compared to LAD ≤ 40 mm (HR:1.92, 95%CI:1.24-2.97, p = 0.004). The 10-year cumulative probability of new incident AF was higher in patients with LAD>40 mm compared to LAD ≤ 40 mm (53.5% and 22.4% respectively, log-rank-test: 28.2, p < 0.001). The annualized rate of stroke recurrence of 4.0% in the overall population did not differ significantly in patient above vs. below this LAD threshold (HR:0.96, 95%CI:0.62-1.48, p = 0.85).

Conclusions: The LAD threshold of 40 mm has the best prognostic performance among other LAD values to predict new incident AF after ESUS. The diagnostic yield of prolonged cardiac rhythm monitoring in patients with LAD ≤ 40 mm seems low; therefore, such patients may have lower priority for prolonged cardiac monitoring.
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http://dx.doi.org/10.1016/j.ejim.2020.01.002DOI Listing
May 2020

External Performance of the HAVOC Score for the Prediction of New Incident Atrial Fibrillation.

Stroke 2020 02 12;51(2):457-461. Epub 2019 Dec 12.

Stroke Center and Neurology Service, Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland (G.S., D.S., A.E., P.M.).

Background and Purpose- The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0-4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods- In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results- In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0-4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37-3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%-73.3%). Conclusions- The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.
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http://dx.doi.org/10.1161/STROKEAHA.119.027990DOI Listing
February 2020

Eligibility for late endovascular treatment using DAWN, DEFUSE-3, and more liberal selection criteria in a stroke center.

J Neurointerv Surg 2020 Sep 26;12(9):842-847. Epub 2019 Nov 26.

Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background And Purpose: The real-life application of DAWN and DEFUSE-3 trials has been poorly investigated. We aimed to identify the proportion of patients with acute ischemic stroke (AIS) eligible for late endovascular treatment (EVT) in our stroke center based on trial and more liberal selection criteria.

Methods: All consecutive patients in our stroke registry (2003-2017) admitted within 5-23 hours of last proof of good health were selected if they had complete clinical and radiological datasets. We calculated the proportion of patients eligible for late EVT according to trial (DAWN and/or DEFUSE-3) and more liberal clinical/imaging mismatch criteria (including lower admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score for core estimation).

Results: Of 1705 patients with AIS admitted to our comprehensive stroke center in the late time window, we identified 925 patients with complete clinical and radiological data. Among them, the proportions of late EVT eligibility were 2.5% (n=23) with DAWN, 5.1% (n=47) with DEFUSE-3, and 11.1% (n=103) with more liberal criteria. Considering late-arriving patients with large vessel occlusion (n=221), the percentages of eligible patients were 10.4%, 21.3%, and 46.6%, respectively. A favorable outcome was observed at comparable rates in treated patients selected by trial or liberal criteria (67% vs 58%, p=0.49).

Conclusions: In a long-term stroke registry, the proportion of late EVT eligibility varied greatly according to selection criteria and referral pattern. Among late-arriving patients referred to our comprehensive stroke center, we found 5.6% eligible according to trial (DAWN/DEFUSE-3) and 11.1% according to liberal criteria. These data indicate that late EVT could be offered to a larger population of patients if more liberal criteria are applied.
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http://dx.doi.org/10.1136/neurintsurg-2019-015382DOI Listing
September 2020

Thrombectomy and Thrombolysis of Isolated Posterior Cerebral Artery Occlusion: Cognitive, Visual, and Disability Outcomes.

Stroke 2020 01 13;51(1):254-261. Epub 2019 Nov 13.

From the Stroke Center, Neurology Service, Department of Clinical Neurosciences (D.S., J.P.M., G. Sirimarco, S.N., P.M.), Lausanne University Hospital and University of Lausanne, Switzerland.

Background and Purpose- We investigated efficacy and safety of acute revascularization with intravenous thrombolysis (IVT) and endovascular treatment (EVT) in ischemic stroke from isolated posterior cerebral artery occlusion, by assessing recanalization, disability, visual, cognitive outcomes, and hemorrhagic complications. Methods- For this retrospective single-center cohort study, we selected all consecutive patients with stroke with isolated posterior cerebral artery occlusion from the Acute Stroke Registry and Analysis of Lausanne registry between January 2003 and July 2018, and compared (1) IVT with conservative treatment (CTr) and (2) EVT to best medical therapy (BMT, ie, CTr or IVT) in terms of 3-month disability and visual field defect, and cognitive domains impaired after stroke. Unadjusted analysis, multivariable logistic regression, and propensity score matched analyses were performed. Results- Among 106 patients with isolated posterior cerebral artery occlusion, 21 received EVT (13 bridging), 34 IVT alone, and 51 CTr. Median age was 76 years, 47% were female and median National Institutes of Health Stroke Scale score was 7. Complete 24-hour recanalization was more frequent with IVT than CTr (51% versus 9%; OR [95% CI]=10.62 [2.13-52.92]) and with EVT compared with BMT (68% versus 34%; OR [95% CI]=4.11 [1.35-12.53]). Higher proportions of good disability, visual and cognitive outcomes were observed in IVT versus CTr, ORs (95% CI)=1.65 (0.60-4.52), 2.01 (0.58-7.01), 2.94 (0.35-24.4), respectively, and in EVT versus BMT, ORs (95% CI)=1.44 (0.51-4.10), 4.28 (1.00-18.29), 4.37 (0.72-26.53), respectively. Hemorrhagic complications and mortality did not increase with IVT or EVT. Conclusion s-We show increased odds of recanalization following IVT and even higher after EVT. We observed a trend for a positive effect on disability, visual, and cognitive outcomes with IVT over CTr and with EVT over BMT.
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http://dx.doi.org/10.1161/STROKEAHA.119.026907DOI Listing
January 2020

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk.

Neurology 2019 12 29;93(23):e2094-e2104. Epub 2019 Oct 29.

From the Department of Internal Medicine (G.N., K.P., E. Karagkiozi, V.P., K.M.), Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Clinical Therapeutics (G.G., A.V., E. Koroboki, E.M., K.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Center and Neurology Service (G.S., D.S., A.E., S.N., P.M.), Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Department of Neurology (E.K.), National and Kapodistrian University of Athens, Greece; Division of Brain Sciences (E.K.), Department of Stroke Medicine, Imperial College, London, UK; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.R.P., S.S.-V.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S., M.A.H.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK; and Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy.

Objective: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence.

Methods: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration.

Results: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ: 12.1 [ = 0.357] and χ: 21.7 [ = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively.

Conclusions: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.
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http://dx.doi.org/10.1212/WNL.0000000000008571DOI Listing
December 2019

Twenty-Four-Hour Reocclusion After Successful Mechanical Thrombectomy: Associated Factors and Long-Term Prognosis.

Stroke 2019 10 6;50(10):2960-2963. Epub 2019 Aug 6.

Neuroradiology Unit, Diagnostic and Interventional Radiology Service, Department of Radiology (S.D.H., B.B., F.P., P.M., G.S.), Lausanne University Hospital, Switzerland.

Background and Purpose- Early arterial recanalization is a strong determinant of prognosis in acute ischemic stroke. Nevertheless, reocclusion can occur after initial recanalization. We assessed associated factors and long-term prognosis of reocclusion after successful mechanical thrombectomy (MT). Methods- From the prospectively constructed Acute Stroke Registry and Analysis of Lausanne cohort, we included consecutive patients with anterior and posterior circulation strokes treated by successful MT (modified treatment in cerebral infarction 2b-3) and with 24-hour vascular imaging available. Reocclusion at this time-point was defined as new intracranial occlusion within an arterial segment recanalized at the end of MT. Through multivariate logistic regression, we investigated associated factors and 3-months outcome. In a 4:1 matched-cohort, we also assessed the role of residual thrombus or stenosis on post-recanalization angiographic images as potential predictor of reocclusion. Results- Among 473 patients with successful recanalization, 423 (89%) were included. Of these, 28 (6.6%) had 24-hour reocclusion. Preadmission statin therapy (aOR [adjusted odds ratio], 0.27; 95% CI, 0.08-0.94), intracranial internal carotid artery occlusion (aOR, 3.53; 95% CI, 1.50-8.32), number of passes (aOR, 1.31; 95% CI, 1.06-1.62), transient reocclusion during MT (aOR, 8.55; 95% CI, 2.14-34.09), and atherosclerotic cause (aOR, 3.14; 95% CI, 1.34-7.37) were independently associated with reocclusion. In the matched-cohort analysis, residual thrombus or stenosis was associated with reocclusion (aOR, 15.6; 95% CI, 4.6-52.8). Patients experiencing reocclusion had worse outcome (aOR, 5.0; 95% CI, 1.2-20.0). Conclusions- Reocclusion within 24-hours of successful MT was independently associated with statin pretreatment, occlusion site, more complex procedures, atherosclerotic cause, and residual thrombus or stenosis after recanalization. Reocclusion impact on long-term outcome highlights the need to monitor and prevent this early complication.
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http://dx.doi.org/10.1161/STROKEAHA.119.026228DOI Listing
October 2019

Letter by Semerano et al Regarding Article, "Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source".

Stroke 2019 10 13;50(10):e297. Epub 2019 Sep 13.

Neurology and Neuroimmunology Unit, Institute of Experimental Neurology, IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milano, Italy.

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http://dx.doi.org/10.1161/STROKEAHA.119.026662DOI Listing
October 2019

Associated Factors and Long-Term Prognosis of 24-Hour Worsening of Arterial Patency After Ischemic Stroke.

Stroke 2019 10 15;50(10):2752-2760. Epub 2019 Aug 15.

From the Stroke Centre, Neurology Service, Department of Clinical Neurosciences (J.P.M., D.L., A.E., S.N., D.S., G. Sirimarco, P. Michel), Lausanne University Hospital, Switzerland.

Background and Purpose- Early arterial recanalization in acute ischemic stroke is strongly associated with better outcomes. However, early worsening of arterial patency was seldom studied. We investigated potential predictors and long-term prognosis of worsening of arterial patency at 24 hours after stroke onset. Methods- Patients from the Acute Stroke Registry and Analysis of Lausanne registry including admission and 24-hour vascular imaging (computed tomography or magnetic resonance angiography) were included. Worsening of arterial patency was defined as a new occlusion and significant stenosis in any extracranial or intracranial artery, comparing 24 hours with admission imaging. Variables associated with worsening of arterial patency were assessed by stepwise multiple logistic regression. The impact of arterial worsening on 3-month outcome was investigated with an adjusted modified Rankin Scale shift analysis. Results- Among 2152 included patients, 1387 (64.5%) received intravenous thrombolysis and endovascular treatment, and 65 (3.0%) experienced 24-hour worsening of arterial patency. In multivariable analysis, history of hypertension seemed protective (adjusted odds ratio [aOR], 0.45; 95% CI, 0.27-0.75) while higher admission National Institutes of Health Stroke Scale (aOR, 1.06; 95% CI, 1.02-1.10), intracranial (aOR, 4.78; 95% CI, 2.03-11.25) and extracranial stenosis (aOR, 3.67; 95% CI, 1.95-6.93), and good collaterals (aOR, 3.71; 95% CI, 1.54-8.95) were independent predictors of worsening of arterial patency. Its occurrence was associated with a major unfavorable shift in the distribution of the modified Rankin Scale at 3 months (aOR, 5.97; 95% CI, 3.64-9.79). Conclusions- Stroke severity and admission vascular imaging findings may help to identify patients at a higher risk of developing worsening of arterial patency at 24 hours. The impact of worsening of arterial patency on long-term outcome warrants better methods to detect and prevent this early complication.
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http://dx.doi.org/10.1161/STROKEAHA.119.025787DOI Listing
October 2019