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1. Association between lower extremity physical function and physical activity after ischemic stroke: Longitudinal findings from the MOBITEC-Stroke project

Author

Christoph Jäger, Michelle Ryan, Nikki Rommers, Janine Schär, Robert Weibel, Reto W Kressig, Arno Schmidt-Trucksäss, Stefan Engelter, Nils Peters, Timo Hinrichs, and Roland Rössler

Subjects
Medicine (General), R5-920
Abstract

Background: Stroke often results in physical impairments. Physical activity is crucial for rehabilitation, enhancing mobility, strength, and overall health. This study examines the association between Timed Up-and-Go (TUG) test performance and changes in physical activity to improve lower extremity physical function. Methods: The MOBITEC-Stroke Cohort Study (“Recovery of mobility function and life-space mobility after ischemic stroke”) included patients with a first incidence of stroke. Data assessed 3 and 12 months after stroke were used for analysis. Linear regression model adjusted for age, sex, instrumental activities of daily living, Falls Efficacy Scale-International, modified Ranking Scale, and National Institutes of Health Stroke Scale-score was used to examine the relationship between lower extremity physical function (i.e., TUG) and change in physical activity (i.e., minutes of physical activity measured with a wrist-worn accelerometer over 1 week). Results: Longitudinal data of 49 patients (65% male, mean age 71.2 (SD: 10.4) years) were analyzed. Mean daily physical activity was 291.6 (SD: 96.2) min at 3 months and 298.9 (SD: 94.4) min at 12 months, with a change from 3 to 12 months of 7.3 min (95% CI: −9.4 to 24.0; p = 0.394) post-stroke. We observed significant relationships between the baseline TUG performance and the change in total physical activity over 9 months ( p = 0.011) and between the change of TUG performance over time and the change in total physical activity ( p = 0.022). Conclusion: Our findings indicate that better initial lower extremity physical function and higher improvements in function over time are associated with a greater increase in physical activity levels after stroke. This suggests that interventions aimed at maintaining and improving lower extremity physical function may positively affect physical activity levels.

Published
2024
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2. Corrigendum: Tandem occlusions involving the internal carotid and anterior cerebral arteries—A rare form of stroke: results from the multicenter EVATRISP collaboration study

Author

Andrei Filioglo, Naaem Simaan, Asaf Honig, Mirjam Heldner, Alessandro Pezzini, Nicolas Martinez-Majander, Visnja Padjen, Philipp Baumgartner, Panagiotis Papanagiotou, Alexander Salerno, Christian Nolte, Annika Nordanstig, Stefan Engelter, Andrea Zini, Marialuisa Zedde, João Pedro Marto, Marcel Arnold, Mauro Magoni, Henrik Gensicke, Jose Cohen, and Ronen Leker

Subjects
cerebrovascular disease, endovascular, stroke, thrombectomy, anterior cerebral artery, Neurology. Diseases of the nervous system, RC346-429
Published
2024
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3. Interrater reliability of the Fugl-Meyer Motor assessment in stroke patients: a quality management project within the ESTREL study

Author

Karin Wiesner, Anne Schwarz, Louisa Meya, Josefin Emelie Kaufmann, Christopher Traenka, Andreas Rüdiger Luft, Jeremia Philipp Oskar Held, and Stefan Engelter

Subjects
Fugl-Meyer assessment, stroke, motor disorders, recovery, rehabilitation, reliability, Neurology. Diseases of the nervous system, RC346-429
Abstract

IntroductionThe Fugl-Meyer Motor Assessment (FMMA) is recommended for evaluating stroke motor recovery in clinical practice and research. However, its widespread use requires refined reliability data, particularly across different health professions. We therefore investigated the interrater reliability of the FMMA scored by a physical therapist and a physician using video recordings of stroke patients.MethodsThe FMMA videos of 50 individuals 3 months post stroke (28 females, mean age 71.64 years, median National Institutes of Health Stroke Scale score 3.00) participating in the ESTREL trial (Enhancement of Stroke Rehabilitation with Levodopa: a randomized placebo-controlled trial) were independently scored by two experienced assessors (i.e., a physical therapist and a physician) with specific training to ensure consistency. As primary endpoint, the interrater reliability was calculated for the total scores of the entire FMMA and the total scores of the FMMA for the upper and lower extremities using intraclass correlation coefficients (ICC). In addition, Spearman’s rank order correlation coefficients (Spearman’s rho) were calculated for the total score and subscale levels. Secondary endpoints included the FMMA item scores using percentage agreement, weighted Cohen’s kappa coefficients, and Gwet’s AC1/AC2 coefficients.ResultsICCs were 0.98 (95% confidence intervals (CI) 0.96–0.99) for the total scores of the entire FMMA, 0.98 (95% CI 0.96–0.99) for the total scores of the FMMA for the upper extremity, and 0.85 (95% CI 0.70–0.92) for the total scores of the FMMA for the lower extremity. Spearman’s rho ranged from 0.61 to 0.94 for total and subscale scores. The interrater reliability at the item level of the FMMA showed (i) percentage agreement values with a median of 77% (range 44–100%), (ii) weighted Cohen’s kappa coefficients with a median of 0.69 (range 0.00–0.98) and (iii) Gwet’s AC1/AC2 coefficients with a median of 0.84 (range 0.42–0.98).Discussion and conclusionThe FMMA appears to be a highly reliable measuring instrument at the overall score level for assessors from different health professions. The FMMA total scores seem to be suitable for the quantitative measurement of stroke recovery in both clinical practice and research, although there is potential for improvement at the item level.

Published
2024
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4. Real-time video analysis allows the identification of large vessel occlusion in patients with suspected stroke: feasibility trial of a 'telestroke' pathway in Northwestern Switzerland

Author

Sebastian Thilemann, Christoph Kenan Traenka, Fabian Schaub, Lukas Nussbaum, Leo Bonati, Nils Peters, Joachim Fladt, Christian Nickel, Patrick Hunziker, Marc Luethy, Sabine Schädelin, Axel Ernst, Stefan Engelter, Gian Marco De Marchis, and Philippe Lyrer

Subjects
telestroke, telemedicine, LVO, stroke, pre-hospital, triage, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and aimLoss of time is a major obstacle to efficient stroke treatment. Our telestroke path intends to optimize prehospital triage using a video link connecting ambulance personnel and a stroke physician. The objectives were as follows: (1) To identify patients suffering a stroke and (2) in particular large vessel occlusion (LVO) strokes as candidates for endovascular treatment. We have chosen the Rapid Arterial Occlusion Evaluation (RACE) scale for this purpose.MethodsThis analysis aimed to verify the feasibility of prehospital stroke identification by video assessment. In this prospective telestroke cohort study, we included 97 subjects, in which the RACE score (items: facial palsy, arm and leg motor function, head and gaze deviation, and aphasia or agnosia) was applied, and the assessment videotaped by a trained member of the Emergency Medical Services (EMS) in the field using a mobile device. Each recorded patient video was independently assessed by three experienced stroke physicians from a certified stroke center and compared to the neuroimaging gold standard. Within this feasibility study, the stroke code was not altered by the outcome of the RACE assessment, and all patients underwent the standard procedures within the emergency unit.ResultsWe analyzed 97 patients (median age 78 years, 53% women), of whom 51 (52.6%) suffered an acute stroke, 12 (23.5%) of which were due to an LVO and 46 patients had symptoms mimicking a stroke. The sensitivity of stroke identification was 77.8%, and specificity was 53.6%. In regard to the identification of an LVO, sensitivity was 69.4% and specificity was 84.3%. The inter-rater agreement in the RACE-score assessment was ICC = 0.82 (intraclass-correlation coefficient).ConclusionThese results confirm our hypothesis that the local telestroke concept is feasible. It allows correct (i) stroke and (ii) LVO identification in the majority of the cases and thus has the potential to assist in efficient prehospital triage.

Published
2023
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5. Hyperbaric Oxygen in Post-Stroke Patients: A Feasibility Study

Author

Jörg Schmutz, Stefan Engelter, Nils Peters, Patrick Schmucki, and Marco Gelsomino

Subjects
post-stroke, hyperbaric oxygen therapy, feasibility, outpatient, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Background: Hyperbaric oxygen therapy (HBOT) has been shown to improve the outcomes of certain stroke patients. Our objective was to assess the feasibility of employing HBOT in daily practice in unselected stroke patients with mild-to-moderate residual post-stroke symptoms, considering their ability to commute our center. Methods: This was an exploratory, interventional, prospective monocentric study on post-stroke patients who have completed their in-hospital stroke rehabilitation. We aimed to include 10 participants who were able to complete 40 daily HBOT sessions (2.0 ATA). Effectiveness was assessed using the National Institutes of Health Stroke Score (NIHSS) pre- and post-HBOT. Results: We recruited 13 patients (12 males) with a mean age of 61 years. Three patients dropped out (two never started HBOT and one withdrew after five sessions because of traveling distance). Post-stroke time was 4–251 months. Among the 10 patients completing the HBOT program, 8 improved their NIHSS by a mean of 1,3 (1–4), while 2 patients’ NIHSS remained unchanged. There were no serious adverse events and no side effects. Conclusions: HBOT was shown to be feasible for mobile post-stroke patients who have completed standard rehabilitation. In the absence of major safety concerns, HBOT seems to be an interesting option post-stroke, with the potential to further improve residual stroke severity.

Published
2023
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6. Tandem occlusions involving the internal carotid and anterior cerebral arteries—A rare form of stroke: Results from the multicenter EVATRISP collaboration study

Author

Andrei Filioglo, Naaem Simaan, Asaf Honig, Mirjam Heldner, Alessandro Pezzini, Nicolas Martinez-Majander, Visnja Padjen, Philipp Baumgartner, Panagiotis Papanagiotou, Alexander Salerno, Christian Nolte, Annika Nordanstig, Stefan Engelter, Andrea Zini, Marialuisa Zedde, João Pedro Marto, Marcel Arnold, Mauro Magoni, Henrik Gensicke, Jose Cohen, and Ronen Leker

Subjects
cerebrovascular disease, endovascular, stroke, thrombectomy, anterior cerebral artery, Neurology. Diseases of the nervous system, RC346-429
Abstract

BackgroundPatients with stroke secondary to isolated anterior cerebral artery (ACA) occlusions have poor outcomes. Whether tandem occlusions (TO) of the extracranial internal carotid (ICA) and the ACA carry even worse outcomes that remain unknown.MethodsPatients with TO involving ICA and ACA occlusions were identified from 14 participating centers from the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) project which is a multicenter, observational, cohort study with prospective accrual of data followed by retrospective data analysis. Patients with isolated ACA stroke served as controls.ResultsIncluded were 92 patients with isolated ACA and 16 patients with ICA-ACA TO stroke. On univariate analyses, patients with TO had more severe strokes on admission [median NIHSS (IQR) 13.5 (9–21) vs. 8 (5–12), p = 0.003] and were more often treated with thrombectomy (81 vs. 40%, p = 0.002). Mortality rates were higher among TO patients (31 vs. 11%, p = 0.03). Rates of favorable functional outcomes were numerically lower among TO patients (38 vs. 60%) but the difference was not statistically significant (p = 0.09). On multivariate analyses, the presence of TO did not modify the chances for favorable outcomes.ConclusionTO stroke with ICA and isolated ACA involvement is rare and results in more severe initial neurological deficits and higher mortality compared to those seen in patients with isolated ACA stroke.

Published
2022
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7. EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry

Author

Charles B L M Majoie, Martin Bendszus, Patrik Michel, Marcel Arnold, Jan Gralla, Urs Fischer, Jan F Scheitz, Didier Leys, Peter Arthur Ringleb, Daniel Strbian, David J Seiffge, Panagiotis Papanagiotou, George Ntaios, Andreas Kastrup, Ronen R Leker, José E Cohen, Nicolas Bricout, Alex Brehm, Hilde Henon, Zsolt Kulcsar, Turgut Tatlisumak, Alexandros Rentzos, Katarina Jood, Nicolas Martinez-Majander, Alessandro Pezzini, Ashraf Eskandari, Jan Liman, Katharina Feil, Lars Kellert, Markus Möhlenbruch, Georg Bohner, Marios Psychogios, Mauro Magoni, Annika Nordanstig, Andrea Zini, Henrik Gensicke, Sanne M Zinkstok, Sami Curtze, Christian Hametner, Visnja Padjen, Susanne Wegener, Georg Kägi, Christian H Nolte, Jan-Erik Karlsson, Camilla Karlsson, Christopher Traenka, Hebun Erdur, Johannes Weber, Stefan Engelter, Gerli Sibolt, Philippe Lyrer, Merih I Baharoglu, Hakan Sarikaya, Dejana R Jovanovic, Andreas Luft, Kimmo Lappalainen, John Gomori, Ivan Vukasinovic, Vladimir Cvetic, Eftychia Kapsalaki, and Paul J J Nederkoorn

Subjects
Medicine
Abstract

Purpose The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.

Published
2021
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8. Corrigendum: Consensus-Based Core Set of Outcome Measures for Clinical Motor Rehabilitation After Stroke—A Delphi Study

Author

Johannes Pohl, Jeremia Philipp Oskar Held, Geert Verheyden, Margit Alt Murphy, Stefan Engelter, Agnes Flöel, Thierry Keller, Gert Kwakkel, Tobias Nef, Nick Ward, Andreas Rüdiger Luft, and Janne Marieke Veerbeek

Subjects
stroke, motor rehabilitation, clinical, outcome measures, Delphi study, Neurology. Diseases of the nervous system, RC346-429
Published
2021
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9. Acute revascularization in ischemic stroke: Updated Swiss guidelines

Author

Patrik Michel, Michael Diepers, Pasquale Mordasini, Tilman Schubert, David Bervini, Jean-Daniel Rouvé, Yvan Gasche, Guido Schwegler, Christophe Bonvin, Krassen Nedeltchev, Emmanuel Carrera, Georg Kägi, Carlo Cereda, Thomas Nyffeler, Stephan Wetzel, Susanne Wegener, Henrik Gensicke, Stefan Engelter, and Marcel Arnold

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

In acute ischemic stroke, intravenous thrombolysis (IVT) and acute endovascular therapy (EVT) have been shown to reduce long-term disability in randomized trials. International guidelines are partially not up to date and may not address situations for which there is limited scientific evidence. The goals of the present guidelines are to summarize the current scientific data for acute revascularization treatments to make sure that all Swiss Centers apply a similar, evidence, or consensus-based treatment standard. A multidisciplinary working group of the Swiss Stroke Society (SSS) searched and reviewed the literature on new randomized controlled trials (RCTs), large case series, meta-analyses, and other guidelines since the previous recommendations in 2009 to elaborate the consensus guidelines. The new RCTs have confirmed the effectiveness of IVT in various populations up to 4.5 h and proven the benefit of acute EVT up to approximately 8 h. For patients with unknown onset (including wake-up stroke), IVT and EVT can be effective up to 24 h after last proof of good health if patients are selected with advanced neuroimaging. Multiple case series and meta-analyses allow narrowing down the indications and relative and absolute contraindications to optimize the benefit–risk ratio of acute revascularization.

Published
2021
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10. Swiss guidelines for the prehospital phase in suspected acute stroke

Author

Georg Kägi, David Schurter, Julien Niederhäuser, Gian Marco De Marchis, Stefan Engelter, Patrick Arni, Olivier Nyenhuis, Paul Imboden, Christophe Bonvin, Andreas Luft, Susanne Renaud, Krassen Nedeltchev, Emmanuel Carrera, Carlo Cereda, Urs Fischer, Marcel Arnold, and Patrik Michel

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Acute stroke treatment has advanced substantially over the last years. Important milestones constitute intravenous thrombolysis, endovascular therapy (EVT), and treatment of stroke patients in dedicated units (stroke units). At present in Switzerland there are 13 certified stroke units and 10 certified EVT-capable stroke centers. Emerging challenges for the prehospital pathways are that (i) acute stroke treatment remains very time sensitive, (ii) the time window for acute stroke treatment has opened up to 24 h in selected cases, and (iii) EVT is only available in stroke centers. The goal of the current guideline is to standardize the prehospital phase of patients with acute stroke for them to receive the optimal treatment without unnecessary delays. Different prehospital models exist. For patients with large vessel occlusion (LVO), the Drip and Ship model is the most commonly used in Switzerland. This model is challenged by the Mothership model where stroke patients with suspected LVO are directly transferred to the stroke center. This latter model is only effective if there is an accurate triage by paramedics, hence the patient may benefit from the right treatment in the right place, without loss of time. Although the Cincinnati Prehospital Stroke Scale is a well-established scale to detect acute stroke in the prehospital setting, it neglects nonmotor symptoms like visual impairment or severe vertigo. Therefore we suggest “acute occurrence of a focal neurological deficit” as the trigger to enter the acute stroke pathway. For the triage whether a patient has a LVO (yes/no), there are a number of scores published. Accuracy of these scores is borderline. Nevertheless, applying the Rapid Arterial Occlusion Evaluation score or a comparable score to recognize patients with LVO may help to speed up and triage prehospital pathways. Ultimately, the decision of which model to use in which stroke network will depend on local (e.g. geographical) characteristics.

Published
2021
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11. Consensus-Based Core Set of Outcome Measures for Clinical Motor Rehabilitation After Stroke—A Delphi Study

Author

Johannes Pohl, Jeremia Philipp Oskar Held, Geert Verheyden, Margit Alt Murphy, Stefan Engelter, Agnes Flöel, Thierry Keller, Gert Kwakkel, Tobias Nef, Nick Ward, Andreas Rüdiger Luft, and Janne Marieke Veerbeek

Subjects
stroke, motor rehabilitation, clinical, outcome measures, Delphi study, Neurology. Diseases of the nervous system, RC346-429
Abstract

Introduction: Outcome measures are key to tailor rehabilitation goals to the stroke patient's individual needs and to monitor poststroke recovery. The large number of available outcome measures leads to high variability in clinical use. Currently, an internationally agreed core set of motor outcome measures for clinical application is lacking. Therefore, the goal was to develop such a set to serve as a quality standard in clinical motor rehabilitation poststroke.Methods: Outcome measures for the upper and lower extremities, and activities of daily living (ADL)/stroke-specific outcomes were identified and presented to stroke rehabilitation experts in an electronic Delphi study. In round 1, clinical feasibility and relevance of the outcome measures were rated on a 7-point Likert scale. In round 2, those rated at least as “relevant” and “feasible” were ranked within the body functions, activities, and participation domains of the International Classification of Functioning, Disability, and Health (ICF). Furthermore, measurement time points poststroke were indicated. In round 3, answers were reviewed in reference to overall results to reach final consensus.Results: In total, 119 outcome measures were presented to 33 experts from 18 countries. The recommended core set includes the Fugl–Meyer Motor Assessment and Action Research Arm Test for the upper extremity section; the Fugl–Meyer Motor Assessment, 10-m Walk Test, Timed-Up-and-Go, and Berg Balance Scale for the lower extremity section; and the National Institutes of Health Stroke Scale, and Barthel Index or Functional Independence Measure for the ADL/stroke-specific section. The Stroke Impact Scale was recommended spanning all ICF domains. Recommended measurement time points are days 2 ± 1 and 7; weeks 2, 4, and 12; 6 months poststroke and every following 6th month.Discussion and Conclusion: Agreement was found upon a set of nine outcome measures for application in clinical motor rehabilitation poststroke, with seven measurement time points following the stages of poststroke recovery. This core set was specifically developed for clinical practice and distinguishes itself from initiatives for stroke rehabilitation research. The next challenge is to implement this clinical core set across the full stroke care continuum with the aim to improve the transparency, comparability, and quality of stroke rehabilitation at a regional, national, and international level.

Published
2020
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13. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Mark K. Bakker, Jos P. Kanning, Gad Abraham, Amy E. Martinsen, Bendik S. Winsvold, John-Anker Zwart, Romain Bourcier, Tomonobu Sawada, Masaru Koido, Yoichiro Kamatani, Sandrine Morel, Philippe Amouyel, Stéphanie Debette, Philippe Bijlenga, Takiy Berrandou, Santhi K. Ganesh, Nabila Bouatia-Naji, Gregory Jones, Matthew Bown, Gabriel J.E. Rinkel, Jan H. Veldink, Ynte M. Ruigrok, Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex SF Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David CM Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth JF Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda WJH Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna MM Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin NA Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M. Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Lynn Cherkas, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Christian Kubisch, Michel D Ferrari, Andrea C Belin, Maija Wessman, Arn M J M van den Maagdenberg, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Dale R Nyholt, Masato Akiyama, Varinder S. Alg, Joseph P. Broderick, Ben M. Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M. Friedrich, Emília I. Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C. Hostettler, Henry Houlden, Juha E. Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y. Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A. Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W. M. Monique Verschuren, Robin G. Walters, David J. Werring, Cristen J. Willer, Daniel Woo, Bradford B. Worrall, Sirui Zhou, Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Systems Ecology, Sociology and Social Gerontology, Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J. E., Veldink, Jan H., Ruigrok, Ynte M., Girotto, G., All-In Stroke, Hunt, Group, Cadisp, Consortium for Blood Pressure, International, Headache Genetics Consortium, International, Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, International, Utrecht University [Utrecht], Baker Heart and Diabetes Institute (AUSTRALIA), University of Melbourne, University of Oslo (UiO), Norwegian University of Science and Technology (NTNU), Oslo University Hospital [Oslo], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The University of Tokyo (UTokyo), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Université de Genève = University of Geneva (UNIGE), Excellence Laboratory LabEx DISTALZ, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Otago [Dunedin, Nouvelle-Zélande], University of Leicester, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, HUNT All-In Stroke, CADISP group, International Consortium for Blood Pressure, International Headache Genetics Consortium, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group: Anne Hege Aamodt, Anne Heidi Skogholt, Ben M Brumpton, Cristen J Willer, Else C Sandset, Espen S Kristoffersen, Hanne Ellekjær, Ingrid Heuch, Jonas B Nielsen, Knut Hagen, Kristian Hveem, Lars G Fritsche, Laurent F Thomas, Linda M Pedersen, Maiken E Gabrielsen, Oddgeir L Holmen, Sigrid Børte, Wei Zhou, Shérine Abboud, Massimo Pandolfo, Vincent Thijs, Didier Leys, Marie Bodenant, Fabien Louillet, Emmanuel Touzé, Jean-Louis Mas, Yves Samson, Sara Leder, Anne Léger, Sandrine Deltour, Sophie Crozier, Isabelle Méresse, Sandrine Canaple, Olivier Godefroy, Maurice Giroud, Yannick Béjot, Pierre Decavel, Elizabeth Medeiros, Paola Montiel, Thierry Moulin, Fabrice Vuillier, Jean Dallongeville, Antti J Metso, Tiina Metso, Turgut Tatlisumak, Caspar Grond-Ginsbach, Christoph Lichy, Manja Kloss, Inge Werner, Marie-Luise Arnold, Michael Dos Santos, Armin Grau, Martin Dichgans, Constanze Thomas-Feles, Ralf Weber, Tobias Brandt, Alessandro Pezzini, Valeria De Giuli, Filomena Caria, Loris Poli, Alessandro Padovani, Anna Bersano, Silvia Lanfranconi, Simone Beretta, Carlo Ferrarese, Giacomo Giacolone, Stefano Paolucci, Philippe Lyrer, Stefan Engelter, Felix Fluri, Florian Hatz, Dominique Gisler, Leo Bonati, Henrik Gensicke, Margareth Amort, Hugh Markus, Jennifer Majersik, Bradford Worrall, Andrew Southerland, John Cole, Steven Kittner, Evangelos Evangelou, Helen R Warren, He Gao, Georgios Ntritsos, Niki Dimou, Tonu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Jun Ding, Franco Giulianini, Elizabeth G Holliday, Anne U Jackson, Ruifang Li-Gao, Wei-Yu Lin, Jian'an Luan, Massimo Mangino, Christopher Oldmeadow, Bram Peter Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M Willems, Jing-Hua Zhao, John Connell, Renée de Mutsert, Alex Sf Doney, Martin Farrall, Cristina Menni, Andrew D Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E Arking, Kristin L Ayers, Caterina M Barbieri, Chiara Batini, Joshua C Bis, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I Boomsma, Erwin P Bottinger, Peter S Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis Collins, Heather J Cordell, Gail Davies, Martin H de Borst, Eco J de Geus, Ian J Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg B Ehret, Roberto Elosua, Stefan Enroth, A Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J Gow, Vilmundur Gudnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Sarah E Harris, Catharina A Hartman, Aki S Havulinna, Andrew A Hicks, Edith Hofer, Albert Hofman, Jouke-Jan Hottenga, Jennifer E Huffman, Shih-Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo-Riitta Jarvelin, Roby Joehanes, Åsa Johansson, Andrew D Johnson, Peter K Joshi, Pekka Jousilahti, J Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard D Keavney, Kay-Tee Khaw, Paul Knekt, Joanne Knight, Ivana Kolcic, Jaspal S Kooner, Seppo Koskinen, Kati Kristiansson, Zoltan Kutalik, Maris Laan, Marty Larson, Lenore J Launer, Benjamin Lehne, Terho Lehtimäki, David Cm Liewald, Li Lin, Lars Lind, Cecilia M Lindgren, YongMei Liu, Ruth Jf Loos, Lorna M Lopez, Yingchang Lu, Leo-Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P Morris, Alanna C Morrison, Peter J Munson, Mike A Nalls, Priyanka Nandakumar, Christopher P Nelson, Teemu Niiranen, Ilja M Nolte, Teresa Nutile, Albertine J Oldehinkel, Ben A Oostra, Paul F O'Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Aarno Palotie, Alison Pattie, Brenda Wjh Penninx, Markus Perola, Annette Peters, Ozren Polasek, Peter P Pramstaller, Quang Tri Nguyen, Olli T Raitakari, Rainer Rettig, Kenneth Rice, Paul M Ridker, Janina S Ried, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M Rose, Jerome I Rotter, Igor Rudan, Daniela Ruggiero, Yasaman Saba, Cinzia F Sala, Veikko Salomaa, Nilesh J Samani, Antti-Pekka Sarin, Reinhold Schmidt, Helena Schmidt, Nick Shrine, David Siscovick, Albert V Smith, Harold Snieder, Siim Sõber, Rossella Sorice, John M Starr, David J Stott, David P Strachan, Rona J Strawbridge, Johan Sundström, Morris A Swertz, Kent D Taylor, Alexander Teumer, Martin D Tobin, Maciej Tomaszewski, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G Uitterlinden, Ahmad Vaez, Peter J van der Most, Cornelia M van Duijn, Germaine C Verwoert, Veronique Vitart, Uwe Völker, Peter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H Wild, Gonneke Willemsen, James F Wilson, Alan F Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John R Attia, Adam S Butterworth, Daniel I Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna Mm Howson, Markku Laakso, Edward G Lakatta, Claudia Langenberg, Olle Melander, Dennis O Mook-Kanamori, Colin Na Palmer, Lorenz Risch, Robert A Scott, Rodney J Scott, Peter Sever, Tim D Spector, Pim van der Harst, Nicholas J Wareham, Eleftheria Zeggini, Daniel Levy, Patricia B Munroe, Christopher Newton-Cheh, Morris J Brown, Andres Metspalu, Bruce M Psaty, Louise V Wain, Paul Elliott, Mark J Caulfield, Padhraig Gormley, Verneri Anttila, Priit Palta, Tonu Esko, Tune H Pers, Kai-How Farh, Ester Cuenca-Leon, Mikko Muona, Nicholas A Furlotte, Tobias Kurth, Andres Ingason, George McMahon, Lannie Ligthart, Gisela M Terwindt, Mikko Kallela, Tobias M Freilinger, Caroline Ran, Scott G Gordon, Anine H Stam, Stacy Steinberg, Guntram Borck, Markku Koiranen, Lydia Quaye, Hieab H H Adams, Terho Lehtimäki, Antti-Pekka Sarin, Juho Wedenoja, David A Hinds, Julie E Buring, Markus Schürks, Paul M Ridker, Maria Gudlaug Hrafnsdottir, Hreinn Stefansson, Susan M Ring, Jouke-Jan Hottenga, Brenda W J H Penninx, Markus Färkkilä, Ville Artto, Mari Kaunisto, Salli Vepsäläinen, Rainer Malik, Andrew C Heath, Pamela A F Madden, Nicholas G Martin, Grant W Montgomery, Mitja I Kurki, Mart Kals, Reedik Mägi, Kalle Pärn, Eija Hämäläinen, Hailiang Huang, Andrea E Byrnes, Lude Franke, Jie Huang, Evie Stergiakouli, Phil H Lee, Cynthia Sandor, Caleb Webber, Zameel Cader, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Johan G Eriksson, Veikko Salomaa, Kauko Heikkilä, Elizabeth Loehrer, Andre G Uitterlinden, Albert Hofman, Cornelia M van Duijn, Lynn Cherkas, Linda M Pedersen, Audun Stubhaug, Christopher S Nielsen, Minna Männikkö, Evelin Mihailov, Lili Milani, Hartmut Göbel, Ann-Louise Esserlind, Anne Francke Christensen, Thomas Folkmann Hansen, Thomas Werge, Jaakko Kaprio, Arpo J Aromaa, Olli Raitakari, M Arfan Ikram, Tim Spector, Marjo-Riitta Järvelin, Andres Metspalu, Christian Kubisch, David P Strachan, Michel D Ferrari, Andrea C Belin, Martin Dichgans, Maija Wessman, Arn M J M van den Maagdenberg, Dorret I Boomsma, George Davey Smith, Kari Stefansson, Nicholas Eriksson, Mark J Daly, Benjamin M Neale, Jes Olesen, Daniel I Chasman, Dale R Nyholt, Aarno Palotie, Masato Akiyama, Varinder S Alg, Sigrid Børte, Joseph P Broderick, Ben M Brumpton, Jérôme Dauvillier, Hubert Desal, Christian Dina, Christoph M Friedrich, Emília I Gaál-Paavola, Jean-Christophe Gentric, Sven Hirsch, Isabel C Hostettler, Henry Houlden, Kristian Hveem, Juha E Jääskeläinen, Marianne Bakke Johnsen, Liming Li, Kuang Lin, Antti Lindgren, Olivier Martin, Koichi Matsuda, Iona Y Millwood, Olivier Naggara, Mika Niemelä, Joanna Pera, Richard Redon, Guy A Rouleau, Marie Søfteland Sandvei, Sabine Schilling, Eimad Shotar, Agnieszka Slowik, Chikashi Terao, W M Monique Verschuren, Robin G Walters, David J Werring, Cristen J Willer, Daniel Woo, Bradford B Worrall, Sirui Zhou, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Admin, Oskar

Subjects
Advanced and Specialized Nursing, Incidence, risk assessment, Smoking/epidemiology, intracranial aneurysm, genetic heterogeneity, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Risk Factors, Intracranial Aneurysm/epidemiology, Humans, Subarachnoid Hemorrhage/epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, genetics, Neurology (clinical), aneurysmal subarachnoid hemorrhage, genetic, Cardiology and Cardiovascular Medicine
Abstract

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Published
2023

15. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Author

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

Subjects
Male, medicine.medical_specialty, Time Factors, Time Factor, medicine.medical_treatment, Carotid Stenosi, MEDLINE, Carotid endarterectomy, Rate ratio, Risk Assessment, Asymptomatic, law.invention, Randomized controlled trial, law, Risk Factors, carotid artery stenting (CAS), carotid endarterectomy (CEA), Stent, medicine, Humans, Carotid Stenosis, Stroke, Endarterectomy, Aged, Endarterectomy, Carotid, business.industry, carotid artery, Risk Factor, Articles, General Medicine, trial, medicine.disease, Settore MED/22 - CHIRURGIA VASCOLARE, Surgery, Stenosis, Treatment Outcome, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Female, Stents, Human medicine, medicine.symptom, business, Human
Abstract

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Published
2021

16. [Stroke Unit- / Stroke Center Care]

Author

Joachim, Fladt, Stefan, Engelter, Gian Marco, De Marchis, Marios, Psychogios, Philippe, Lyrer, Leo, Bonati, and Henrik, Gensicke

Subjects
Stroke, Humans, Switzerland
Abstract

Stroke Unit- / Stroke Center Care

Published
2021

17. Genetic Imbalance in Patients with Cervical Artery Dissection

Author

Caspar Grond-Ginsbach, Bowang Chen, Michael Krawczak, Rastislav Pjontek, Philip Ginsbach, Yanxiang Jiang, Sherine Abboud, Marie-Luise Arnold, Anna Bersano, Tobias Brandt, Valeria Caso, Stephanie Debette, Martin Dichgans, Andreas Geschwendtner, Giacomo Giacalone, Juan-Jose Martin, Antti Metso, Tiina Metso, Armin Grau, Manja Kloss, Christoph Lichy, Alessandro Pezzini, Christopher Traenka, Stefan Schreiber, Vincent Thijs, Emmanuel Touze, Elisabetta Zotto, Turgut Tatlisumak, Didier Leys, Philippe Lyrer, Stefan Engelter, and Bentham Science Publisher for the CADISP group

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, Cervical Artery, 030105 genetics & heredity, Cervical artery dissection, Article, 03 medical and health sciences, 0302 clinical medicine, Genetic imbalance, Internal medicine, Genetics, medicine, Copy-number variation, Stroke, Genetics (clinical), Copy number variation, business.industry, Odds ratio, medicine.disease, Confidence interval, 3. Good health, Cardiovascular system development, Rare genetic variation, Dissection, Etiology, business, 030217 neurology & neurosurgery
Abstract

Background: Genetic and environmental risk factors are assumed to contribute to the susceptibility to cervical artery dissection (CeAD). To explore the role of genetic imbalance in the etiology of CeAD, copy number variants (CNVs) were identified in high-density microarrays samples from the multicenter CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study and from control subjects from the CADISP study and the German PopGen biobank. Microarray data from 833 CeAD patients and 2040 control subjects (565 subjects with ischemic stroke due to causes different from CeAD and 1475 disease-free individuals) were analyzed. Rare genic CNVs were equally frequent in CeAD-patients (16.4%; n=137) and in control subjects (17.0%; n=346) but differed with respect to their genetic content. Compared to control subjects, CNVs from CeAD patients were enriched for genes associated with muscle organ development and cell differentiation, which suggests a possible association with arterial development. CNVs affecting cardiovascular system development were more common in CeAD patients than in control subjects (p=0.003; odds ratio (OR) =2.5; 95% confidence interval (95% CI) =1.4-4.5) and more common in patients with a familial history of CeAD than in those with sporadic CeAD (p=0.036; OR=11.2; 95% CI=1.2-107). Conclusion: The findings suggest that rare genetic imbalance affecting cardiovascular system development may contribute to the risk of CeAD. Validation of these findings in independent study populations is warranted.

Published
2017

18. Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke

Author

Marta Bilik, Steve Vucic, Waldemar Brola, Monica Badve, Joseph Kwan, David Werring, Graeme Hankey, David Doig, Christian Lueck, Maurizio BALESTRINO, Richard Lindley, Geoffrey Cloud, Francesco Corea, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Manuel Correia, Joanna Wardlaw, Tomasz Litwin, Bartosz Karaszewski, Robert Simister, Grant Mair, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Marc Randall, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie

Subjects
Male, OCCLUSION, 1702 Cognitive Sciences, 030204 cardiovascular system & hematology, Tissue plasminogen activator, law.invention, Brain Ischemia, Brain ischemia, 0302 clinical medicine, CT hyperdense artery sign, Randomized controlled trial, law, PROGNOSTIC-SIGNIFICANCE, 80 and over, IST-3 Collaborative Group, Tomography, Stroke, Aged, 80 and over, trials, ASSOCIATION, Arteries, RANDOMIZED CONTROLLED-TRIAL, X-Ray Computed, medicine.anatomical_structure, Treatment Outcome, Tissue Plasminogen Activator, outcome, Cardiology, Third International Stroke Trial, Female, INTRAVENOUS THROMBOLYSIS, SENSITIVITY, Life Sciences & Biomedicine, IST-3, Artery, medicine.drug, medicine.medical_specialty, IV alteplase, Clinical Neurology, HAS, ischemic stroke, Article, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, Ophthalmology, medicine, Humans, Thrombus, TISSUE-PLASMINOGEN ACTIVATOR, Aged, Science & Technology, Neurology & Neurosurgery, business.industry, 1103 Clinical Sciences, Odds ratio, medicine.disease, Follow-Up Studies, Tomography, X-Ray Computed, Neurology (clinical), Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery, Fibrinolytic agent, SCAN
Abstract

Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). Methods: All prerandomization and follow-up (24–48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. Classification of evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

Published
2016

19. Dabigatran versus warfarin in patients with atrial fibrillation

Author

Job Harenberg, Paul Matthew Pasco, Mario Talajic, Leopoldo Piegas, Kosta Kostov, Ales Tomek, Konstantin Ramshev, Cetin Erol, David McEneaney, Julián Pérez-Villacastín, Tilemachos Zafeiridis, Salim Yusuf, Espen Fengsrud, David Halon, Graeme Hankey, Ru San Tan, David Tanne, ALVARO AVEZUM, Antonis Manolis, Fabio Turazza, Grethe Andersen, John Eikelboom, Valentin Kokorin, Juan Manuel Escudier Villa, JOSEP BRUGADA, Luis Cunha, Joaquin J Alonso, Stefan Engelter, Pedro Adragao, Geert Vanhooren, Sergey Golitsyn, Andrzej Budaj, Sam Schulman, Connolly, Sj, Ezekowitz, Md, Yusuf, S, Eikelboom, J, Oldgren, J, Parekh, A, Pogue, J, Reilly, Pa, Themeles, E, Varrone, J, Wang, S, Alings, M, Xavier, D, Zhu, J, Diaz, R, Lewis, B, Darius, H, Diener, Hc, Joyner, Cd, Wallentin, L, RE LY Steering, Committee, Investigators, Pizzolato, Gilberto, Other departments, Cardiology, and ACS - Amsterdam Cardiovascular Sciences

Subjects
Male, Stroke Atrial fibrillation anticoagulation, Pyridines, medicine.drug_class, Embolism, Myocardial Infarction, Management of atrial fibrillation, Hemorrhage, Dabigatran, Double-Blind Method, Atrial Fibrillation, medicine, Humans, Prodrugs, Dyspepsia, Stroke, Aged, Proportional Hazards Models, HAS-BLED, Chi-Square Distribution, business.industry, Anticoagulant, Warfarin, Anticoagulants, Idarucizumab, General Medicine, Middle Aged, medicine.disease, Liver, Anesthesia, Benzimidazoles, Female, business, PER977, Follow-Up Studies, medicine.drug
Abstract

Udgivelsesdato: 2009-Sep-17 BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P

Published
2009

20. Effect of X-Ray Attenuation of Arterial Obstructions on Intravenous Thrombolysis and Outcome after Ischemic Stroke

Author

Graeme Hankey, Christian Lueck, Richard Lindley, Andrea Zini, Stefan Engelter, Joanna Wardlaw, and Grant Mair

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, Arterial Occlusive Diseases, 030204 cardiovascular system & hematology, X-Ray Therapy, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Hounsfield scale, Medicine, Humans, Thrombolytic Therapy, Prospective Studies, lcsh:Science, Prospective cohort study, Stroke, Aged, Multidisciplinary, medicine.diagnostic_test, business.industry, lcsh:R, Thrombolysis, medicine.disease, Confidence interval, Treatment Outcome, Case-Control Studies, Angiography, lcsh:Q, Administration, Intravenous, Female, Radiology, business, 030217 neurology & neurosurgery, Research Article
Abstract

ObjectiveTo assess whether the x-ray attenuation of intra-arterial obstruction measured on non-contrast CT in ischemic stroke can predict response to thrombolysis and subsequent functional outcome.MethodsThe Third International Stroke Trial (IST-3) was a multicenter randomized-controlled trial of intravenous thrombolysis (rt-PA) given within six hours of ischemic stroke. Ethical approval and informed consent were obtained. In a subgroup of 109 IST-3 patients (38 men, median age 82 years), a single reader, masked to all clinical and other imaging data, manually measured x-ray attenuation (Hounsfield Units, HU) on non-contrast CT at the location of angiographically-proven intra-arterial obstructions, pre-randomization and at 24–48 hour follow-up. We calculated change in attenuation between scans. We assessed the impact of pre-randomization arterial obstruction attenuation on six-month functional outcome.ResultsMost arterial obstructions (64/109, 59%) were hyperattenuating (mean 51.0 HU). Compared with control, treatment with rt-PA was associated with a greater, but non-significant, reduction in obstruction attenuation at follow-up (-8.0 HU versus -1.4 HU in patients allocated control, p = 0.117). In multivariable ordinal regression analysis controlled for patient age, stroke severity, location and extent of obstruction, time from stroke onset to baseline scan and rt-PA treatment allocation, the attenuation of pre-randomization arterial obstruction was not independently associated with six-month outcome (odds ratio = 0.99, 95% confidence interval = 0.94–1.03, p = 0.516).ConclusionsIn ischemic stroke, the x-ray attenuation of the arterial obstruction may decline more rapidly from baseline to 24–48 hours following treatment with thrombolysis but we found no evidence that baseline arterial obstruction attenuation predicts six-month outcome.

Published
2015

21. Abstract W P16: Comparing Outcome Prediction Scoring Systems in the Interventional Management of Stroke (IMS) III Trial: No Clear Winner

Author

Felipe de los Ríos la Rosa, David J Seiffge, Liqiong Fan, Sharon D Yeatts, Pooja Khatri, and Stefan Engelter

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Several prognostic scores have been developed to predict patient outcome after ischemic stroke. We aimed to compare eight scores in the IMS -III dataset. Hypothesis: Prediction of good and poor outcome using different scores is possible in IMS-III. Methods: We retrospectively calculated area under the curve (AUC), sensitivity, and specificity for poor (mRS 4-6) and good (mRS 0-2) 90-day outcome in all IMS-III participants with complete data. The scoring systems analyzed were: Houston Intra-arterial Therapy 2 (HIAT2), Ischemic Stroke Predictive Risk Score (iScore), Totaled Health Risks in Vascular Events (THRIVE), DRAGON, Hemorrhage after Thrombolysis (HAT), Alberta Stroke Programme Early CT Score (ASPECTS), Stroke-Thrombolytic Predictive Instrument (TPI), and Simple Variables Model (SVM). Those receiving IV rtPA followed by endovascular therapy (treatment) and those receiving IV rtPA only (control) were analyzed separately. Results: Among 656 IMS III subjects, 651 had complete data, including 429 treatment and 222 control subjects. Overall, all scoring systems showed good prediction abilities (AUC range 0.60 to 0.78). AUC comparisons did not clearly favor a single scoring system. Treatment group: For predicting poor outcome, the TPI score outperformed ASPECTS (AUC 0.73 vs 0.61; P Control group: For poor outcome, the TPI score was significantly better than ASPECTS and THRIVE (0.78 vs. 0.62 and 0.71, respectively; P Conclusions: Outcome prediction using different scores in IMS III is possible. HIAT2, iSCORE, DRAGON, HAT, TPI, and SVM all performed comparably. Prognostic performances were comparable in both treatment arms.

Published
2015

22. Abstract 208: Vascular Risk Factors But Not Transesophageal Echocardiography (TEE) Features Are Associated With Stroke Recurrence in Patients With Cryptogenic Stroke (CS) and Patent Foramen Ovale (PFO)

Author

Marie-Luise Mono, Timo Kahles, David E. Thaler, Patrik Michel, Christian Weimar, Joaquin Serena, Vincent Thijs, Stefan Engelter, Markus Krämer, Andreas Luft, Franz Eberli, Achim Mallmann, Andreas Müller-Eichelberg, Lester Collins, Dimitri Hemelsoet, Maria Luisa Zedde, Adinda De Pauw, Carmel Armon, Marcel Arnold, Bernhard Meier, Heinrich P. Mattle, and Krassen Nedeltchev

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.

Published
2015

23. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial

Author

Paul Sidhu, Jan Blankensteijn, Jonas Malmstedt, Martin M Brown, Angel Chamorro, Jeroen Hendriks, Karl-olof Lovblad, David Doig, Barry Beiles, Tim McGahan, Gerard Stansby, Lorenz Hirt, Stefan Engelter, Christophe Bonvin, Sami Curtze, Dick Zeilstra, Juan Miguel Macho Fernandez, Geert Vanhooren, Gary A Ford, Carl Magnus Wahlgren, Leo Bonati, Petra Ijäs, Jonathan Tibballs, Bonvin, Christophe, Kalangos, Afksendiyos, Lövblad, Karl-Olof, Sztajzel, Roman, Halliday, A, ACS - Amsterdam Cardiovascular Sciences, Surgery, Neurology, Radiology and Nuclear Medicine, and ANS - Amsterdam Neuroscience

Subjects
PROTOCOL, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, ddc:616.0757, Modified Rankin Scale, Angioplasty, medicine, media_common.cataloged_instance, Humans, Carotid Stenosis, Functional ability, cardiovascular diseases, European union, ANGIOPLASTY, Stroke/etiology/mortality/prevention & control, Stroke, media_common, Endarterectomy, Aged, Endarterectomy, Carotid, Intention-to-treat analysis, ddc:617, business.industry, ARTERY STENOSIS, Articles, General Medicine, Recovery of Function, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], medicine.disease, equipment and supplies, 3. Good health, Surgery, ddc:616.8, surgical procedures, operative, Treatment Outcome, cardiovascular system, Female, Stents, Carotid stenting, business, STROKE, Carotid Stenosis/complications/mortality/therapy, Follow-Up Studies
Abstract

Background Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. Methods Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. Findings 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0–5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72–1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28–2·30, p Interpretation Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. Funding Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.

Published
2015

24. Abstract T P50: ASTRAL-R score Predicts absence of Recanalization after Intravenous Thrombolysis in Acute Ischemic Stroke

Author

Peter Vanacker, Dimitris Lambrou, Mirjam Heldner, David Seiffge, Hubertus Mueller, Ashraf Eskandari, George Ntaios, Pascal J Mosimann, Roman Sztajzel, Vitor Mendes Pereira, Patrick Cras, Stefan Engelter, Philippe Lyrer, Urs Fischer, Marcel Arnold, and Patrik Michel

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Background: Intravenous thrombolysis (IVT) is the best proven recanalization treatment in acute ischemic stroke (AIS), but may be insufficient or of little value in certain patients. By predicting the probability of absence of recanalization after IVT, the decision for more aggressive revascularization treatment can be individualized with the goal to improve clinical outcome. Aim: To derive and internally validate a predictive scoring system for absence of recanalization with IVT, using readily available variables in the prehospital and emergency room phase. Methods: Data from prospective thrombolysis registries of four academic stroke centers were examined. Patients with arterial occlusion on acute imaging and repeat arterial assessment at 24hours were selected. Based on a logistic regression analysis, an integer-based score for each covariate of the fitted multivariate model was generated. The overall score was calculated as the sum of the weighted scores. In a patient with an ASTRAL-R score > 3, the likelihood of absence of recanalization was > 50%. The area under the receiver-operator curve was 0.65 in the derivation cohort. Results: In 534 thrombolyzed AIS patients, five variables were identified as independent predictors of absence of recanalization: Acute glucose >7mmol/L (A), significant extracranial vessel STenosis (ST), decreased Range of visual fields (R), proximal Arterial occlusion (A) and altered Level of consciousness (L). An altered level of consciousness was weighted 2 and all other variables 1 point based on β-coefficients. In a patient with an ASTRAL-R score > 3, the likelihood of absence of recanalization was >50%. The score was highly predictive (OR 0.65, 95%CI 0.55-0.76) in the derivation cohort. Conclusions: A simple 5-item ASTRAL-R score shows high prediction for absence of recanalization at 24hours in thrombolyzed AIS patients. If confirmed by external validation, planning for more aggressive revascularization strategies may facilitate through this tool.

Published
2014

25. Characteristics and Outcomes of Patients With Multiple Cervical Artery Dissection

Author

Yannick, Béjot, Corine, Aboa-Eboulé, Stéphanie, Debette, Alessandro, Pezzini, Turgut, Tatlisumak, Stefan, Engelter, Caspar, Grond-Ginsbach, Emmanuel, Touzé, Maria, Sessa, Tiina, Metso, Antti, Metso, Manja, Kloss, Valeria, Caso, Jean, Dallongeville, Philippe, Lyrer, Didier, Leys, Maurice, Giroud, Massimo, Pandolfo, Shérine, Abboud, and Leo, Bonati

Subjects
Adult, Male, Manipulation, Spinal, medicine.medical_specialty, Cervical Artery, Vertebral artery dissection, Fibromuscular dysplasia, Carotid Artery, Internal, Dissection, Brain Ischemia, Pseudoaneurysm, Disability Evaluation, Risk Factors, Odds Ratio, Medicine, Humans, Prospective Studies, Registries, Prospective cohort study, Stroke, Aged, Cerebral Hemorrhage, Retrospective Studies, Advanced and Specialized Nursing, Aged, 80 and over, Vertebral Artery Dissection, Neck pain, Neck Pain, business.industry, Age Factors, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Data Interpretation, Statistical, Multivariate Analysis, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, Neck
Abstract

Background and Purpose— Little is known about factors contributing to multiple rather than single cervical artery dissections (CeAD) and their associated prognosis. Methods— We compared the baseline characteristics and short-term outcome of patients with multiple to single CeAD included in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. Results— Among the 983 patients with CeAD, 149 (15.2%) presented with multiple CeAD. Multiple CeADs were more often associated with cervical pain at admission (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.10–2.30), a remote history of head or neck surgery (OR, 1.87; 95% CI, 1.16–3.00), a recent infection (OR, 1.71; 95% CI, 1.12–2.61), and cervical manipulation (OR, 2.23; 95% CI, 1.26–3.95). On imaging, cervical fibromuscular dysplasia (OR, 3.97; 95% CI, 2.04–7.74) and the presence of a pseudoaneurysm (OR, 2.91; 95% CI, 1.86–4.57) were more often seen in patients with multiple CeAD. The presence of multiple rather than single CeAD had no effect on functional 3-month outcome (modified Rankin Scale score, ≥3; 12% in multiple CeAD versus 11.9% in single CeAD; OR, 1.20; 95% CI, 0.60–2.41). Conclusions— In the largest published series of patients with CeAD, we highlighted significant differences between multiple and single artery involvement. Features suggestive of an underlying vasculopathy (fibromuscular dysplasia) and environmental triggers (recent infection, cervical manipulation, and a remote history of head or neck surgery) were preferentially associated with multiple CeAD.

Published
2014

26. Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial

Author

Jan Blankensteijn, Jonas Malmstedt, Kirsten Krohg-Sørensen, Hans Rolf Jäger, Martin M Brown, Jeroen Hendriks, Peter Gillgren, Karl-olof Lovblad, Lorenz Hirt, Stefan Engelter, Christophe Bonvin, Geert Vanhooren, Markku Kaste, Carl Magnus Wahlgren, Leo Bonati, Petra Ijäs, Amsterdam Cardiovascular Sciences, Surgery, Neurology, Radiology and Nuclear Medicine, Amsterdam Neuroscience, Cras, Patrick, Hendriks, Jeroen, van Schil, Paul, and ICSS Investigators

Subjects
Male, Risk, medicine.medical_specialty, medicine.medical_treatment, Clinical Neurology, Cerebral Revascularization, Carotid endarterectomy, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Leukoencephalopathies, Internal medicine, Angioplasty, medicine, media_common.cataloged_instance, Humans, Carotid Stenosis, Single-Blind Method, cardiovascular diseases, European union, Stroke, Endarterectomy, media_common, Cardiovascular diseases [DCN MP - Plasticity and memory NCEBP 14], Aged, Aged, 80 and over, Endarterectomy, Carotid, business.industry, Cardiovascular diseases Tissue engineering and pathology [NCEBP 14], Articles, Middle Aged, medicine.disease, 3. Good health, Surgery, Stenosis, Treatment Outcome, Cardiology, Female, Stents, Human medicine, Neurology (clinical), Carotid stenting, business, Cardiovascular diseases Aetiology, screening and detection [NCEBP 14], 030217 neurology & neurosurgery
Abstract

Item does not contain fulltext BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2.76, 95% CI 1.17-6.51; p=0.021; HR for non-disabling stroke 3.00, 1.10-8.36; p=0.031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1.18, 0.40-3.55; p=0.76; HR for disabling or fatal stroke 1.41, 0.38-5.26; p=0.607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2.98, 1.29-6.93; p=0.011; HR for non-disabling stroke 6.34, 1.45-27.71; p=0.014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthelabo, the European Union Research Framework Programme 5.

Published
2013

27. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial

Author

Steff Lewis, Rustam Al-Shahi Salman, William Strain, Marta Bilik, Steve Vucic, Waldemar Brola, Gordon Murray, Monica Badve, Richard Gray, Joseph Kwan, David Werring, Salim Yusuf, Erik Lundström, Anna Czlonkowska, Paul Bentley, Philip Bath, Graeme Hankey, Philip White, Alastair Buchan, David Doig, Chris Armit, Christian Lueck, Maurizio BALESTRINO, Urszula Fiszer, Richard Lindley, Geoffrey Cloud, Francesco Corea, Karl Matz, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Luana Benedetti, Joanna Wardlaw, Peter Sandercock, Michael Hill, Bartosz Karaszewski, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Mark Wardle, Marc Randall, Pippa Tyrrell, and Antonio Arauz

Subjects
Male, Pediatrics, medicine.medical_treatment, 030204 cardiovascular system & hematology, Severity of Illness Index, law.invention, Brain Ischemia, 0302 clinical medicine, Randomized controlled trial, law, Case fatality rate, Secondary Prevention, intravenous thrombolysis, Thrombolytic Therapy, Young adult, Infusions, Intravenous, Stroke, acute ischaemic stroke, Aged, 80 and over, third international stroke trial, General Medicine, Thrombolysis, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, Tissue Plasminogen Activator, recombinant tissue plasminogen activator, Female, IST-3, Adult, medicine.medical_specialty, Adolescent, early treatment, Drug Administration Schedule, 03 medical and health sciences, Young Adult, Age Distribution, Double-Blind Method, Fibrinolytic Agents, Severity of illness, medicine, Humans, Aged, business.industry, Odds ratio, medicine.disease, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract

BACKGROUND: Thrombolysis is of net benefit in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4·5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefit up to 6 h from stroke onset. METHODS: In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defined by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. FINDINGS: 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1·13, 95% CI 0·95-1·35, p=0·181; a non-significant absolute increase of 14/1000, 95% CI -20 to 48). An ordinal analysis showed a significant shift in OHS scores; common OR 1·27 (95% CI 1·10-1·47, p=0·001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6·94, 95% CI 4·07-11·8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1·60, 95% CI 1·22-2·08, p=0·001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). INTERPRETATION: For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. FUNDING: UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University.

Published
2012

28. Abstract 67: Risk of Symptomatic Intracerebral Hemorrhage in Ischemic Stroke Thrombolysis: the SEDAN Score

Author

Daniel Strbian, Atte Meretoja, Patrik Michel, Stefan Engelter, Lucka Sekoranja Bianchi, Frank J Ahlhelm, Satu Mustanoja, Igor Kuzmanovic, Tiina Sairanen, Nina Forss, Philippe Lyrer, Markku Kaste, and Turgut Tatlisumak

Subjects
Advanced and Specialized Nursing, Neurology (clinical), Cardiology and Cardiovascular Medicine
Abstract

Objectives To develop a score for assessing the risk of symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients treated with iv thrombolysis. Methods The score was derived from a cohort of acute ischemic stroke patients treated with iv thrombolysis (n=972) at the Helsinki University Central Hospital (1995-2008). The predictive value of parameters associated with development of sICH (ECASS-2 criteria) was evaluated, and the score was developed according to the magnitude of logistic regression coefficients. The accuracy of the model was evaluated with 1000 bootstrap replicates. To test the performance of the score, we calculated area under receiver operating characteristic curve (AUC-ROC). We calculated absolute risks and likelihood ratios of sICH per increasing score points. The score was validated externally in merged cohort from 3 Swiss cities (Lausanne, Basel, and Geneva) including 828 ischemic stroke patients treated with iv thrombolysis. Findings The SEDAN score (0 to 6 points) consists of blood S ugar (glucose) at baseline [8.1-12.0 mmol/L (145-216 mg/dL)=1; >12.0 mmol/L (>216 mg/dL)=2], E arly infarct signs (yes=1) and (hyper) D ense cerebral artery sign (yes=1) on admission CT scan, A ge (>75=1), and N IH Stroke Scale on admission (>9=1). Accuracy of the score based on 1000 bootstrap replicates was 93.1% (91.4%-94.5%). AUC-ROC was 0.73 (0.67-0.79; p Conclusions The SEDAN score reliably assesses the risk of sICH in iv thrombolysis treated ischemic stroke patients and can support clinical decision-making in the high-risk patients. External validation of the score in the three Swiss cohorts supports its generalizibility.

Published
2012

29. Predicting outcome after acute basilar artery occlusion based on admission characteristics

Author

Maramelia Miranda Alves, Stefan Engelter, Perttu Lindsberg, Marc Ribo, Diederik Dippel, Patrik Michel, Adriana Conforto, Petra Ijäs, ANS - Amsterdam Neuroscience, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Neurology, and Cardiology

Subjects
Adult, Male, medicine.medical_specialty, Neurology, Arterial Occlusive Diseases, Research Support, Logistic regression, Outcome (game theory), Young Adult, DCN NN - Brain networks and neuronal communication NCEBP 9 - Mental health, Patient Admission, Predictive Value of Tests, Risk Factors, Modified Rankin Scale, medicine.artery, Internal medicine, 80 and over, Journal Article, Basilar artery, Humans, Medicine, Comparative Study, Prospective Studies, Registries, Young adult, Non-U.S. Gov't, Prospective cohort study, Aged, Aged, 80 and over, Receiver operating characteristic, business.industry, Research Support, Non-U.S. Gov't, Basilar artery occlusion, Guideline, Middle Aged, medicine.disease, Myasthenia gravis, Surgery, Logistic Models, Treatment Outcome, Basilar Artery, Predictive value of tests, Cardiology, Treatment strategy, Female, Observational study, Neurology (clinical), business
Abstract

Contains fulltext : 109111.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To develop a simple prognostic model to predict outcome at 1 month after acute basilar artery occlusion (BAO) with readily available predictors. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational, international registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO. We considered predictors available at hospital admission in multivariable logistic regression models to predict poor outcome (modified Rankin Scale [mRS] score 4-5 or death) at 1 month. We used receiver operator characteristic curves to assess the discriminatory performance of the models. RESULTS: Of the 619 patients, 429 (69%) had a poor outcome at 1 month: 74 (12%) had a mRS score of 4, 115 (19%) had a mRS score of 5, and 240 (39%) had died. The main predictors of poor outcome were older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIH Stroke Scale (NIHSS) score, and longer time to treatment. A prognostic model that combined demographic data and stroke risk factors had an area under the receiver operating characteristic curve (AUC) of 0.64. This performance improved by including findings from the neurologic examination (AUC 0.79) and CT imaging (AUC 0.80). A risk chart showed predictions of poor outcome at 1 month varying from 25 to 96%. CONCLUSION: Poor outcome after BAO can be reliably predicted by a simple model that includes older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIHSS score, and longer time to treatment.

Published
2012

30. Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

Author

Marta Bilik, Steve Vucic, Waldemar Brola, Monica Badve, Grzegorz Kozera, Joseph Kwan, David Werring, Erik Lundström, Anna Czlonkowska, Paul Bentley, Graeme Hankey, Alastair Buchan, David Doig, Christian Lueck, Maurizio BALESTRINO, Urszula Fiszer, Richard Lindley, Geoffrey Cloud, Francesco Corea, Karl Matz, Cathie Sudlow, Joana Damásio, Rui Felgueiras, Andrea Zini, William Whiteley, Stefan Engelter, Malcolm Robert Macleod, Luana Benedetti, Joanna Wardlaw, Peter Sandercock, Bartosz Karaszewski, Hedley Emsley, Jan Aaseth, Leo Bonati, Marta Leńska-Mieciek, Mark Wardle, Marc Randall, Antonio Arauz, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie

Subjects
Neurology, medicine.medical_treatment, Medicine (miscellaneous), Research & Experimental Medicine, Tissue plasminogen activator, law.invention, Brain Ischemia, 0302 clinical medicine, Randomized controlled trial, law, Brain Ischemia drug therapy, Data monitoring committee, Pharmacology (medical), Thrombolytic Therapy, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Stroke, 1102 Cardiorespiratory Medicine and Haematology, lcsh:R5-920, Thrombolysis, 3. Good health, Medicine, Research & Experimental, Tissue Plasminogen Activator, Acute Disease, lcsh:Medicine (General), Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Double-Blind Method, Fibrinolytic Agents, Humans, Sample Size, Stroke drug therapy, Update, 03 medical and health sciences, ALTEPLASE, Double-Blind Method, Fibrinolytic Agents, IST-3 collaborative group, General & Internal Medicine, medicine, Science & Technology, business.industry, 1103 Clinical Sciences, medicine.disease, Cardiovascular System & Hematology, Emergency medicine, Physical therapy, business, 030217 neurology & neurosurgery, Fibrinolytic agent
Abstract

Background Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Design International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. Results The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. Conclusion The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. Trial registration ISRCTN25765518

Published
2011

33. Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome

Author

Jm, Provenzale, Jr, Petrella, Lc, Cruz, Jc, Wong, Stefan Engelter, and Dp, Barboriak

Subjects
Adult, Male, Headache, Vision Disorders, Brain, Syndrome, Magnetic Resonance Imaging, Diffusion, body regions, Editorial, Seizures, Edema, Humans, Female, Vascular Diseases, Confusion
Abstract

BACKGROUND AND PURPOSE: Previous studies have shown that lesions in posterior reversible encephalopathy syndrome are often isointense on diffusion-weighted MR images. We hypothesized that 1) apparent diffusion coefficient (ADC) maps using various thresholds would show larger abnormalities in posterior white matter (WM) and 2) isointense appearance of lesions on isotropic diffusion-weighted images results from a balance of T2 prolongation effects and diffusibility effects. METHODS: T2-weighted MR images from 11 patients were reviewed. Hyperintense lesions were located in both anterior and posterior WM in eight patients and solely in posterior WM in three patients. The ADC maps were produced by use of ADC values ≥ 3 SD and ≥ 10 SD above the mean value of normal WM. Lesions on diffusion-weighted images were classified as isointense or hypointense. ADC values within lesions (ADC(L)) were compared with those of normal WM (ADC(N)), and compared for isointense lesions and hypointense lesions. RESULTS: The distribution of lesions with ADC values ≥ 3 SD was essentially identical to that on T2-weighted images. Regions with ADC values ≥ 10 SD were found in both anterior WM and posterior WM in two patients and solely in posterior WM in nine patients. On diffusion-weighted images, lesions appeared isointense in seven patients and hypointense in four patients. Mean ADC(L)/ADC(N) for all lesions was 1.81; for hypointense lesions, 2.30. CONCLUSION: Vasogenic edema was more severe in posterior WM. Isointense lesions result from a balance of T2 effects and increased water diffusibility. Hypointense lesions have higher ADC values, which are not balanced by T2 effects.

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