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51. Correction to: Radiological prognostic factors of chronic subdural hematoma recurrence: a systematic review and meta-analysis

Author: Hester F. Lingsma, Frits R. Rosendaal, Korné Jellema, Ruben Dammers, Niels A van der Gaag, Ishita P Miah, Yeliz Tank, Wilco C. Peul, and Heleen M. den Hertog
Subjects: medicine.medical_specialty, Neurology, business.industry, Correction, Prognosis, Risk Assessment, Radiography, Text mining, Chronic subdural hematoma, Recurrence, Hematoma, Subdural, Chronic, Radiological weapon, Meta-analysis, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Radiology, Neurosurgery, Cardiology and Cardiovascular Medicine, business, Aged, Neuroradiology
Abstract: Chronic subdural hematoma (CSDH) is associated with high recurrence rates. Radiographic prognostic factors may identify patients who are prone for recurrence and who might benefit further optimization of therapy. In this meta-analysis, we systematically evaluated pre-operative radiological prognostic factors of recurrence after surgery.Electronic databases were searched until September 2020 for relevant publications. Studies reporting on CSDH recurrence in symptomatic CSDH patients with only surgical treatment were included. Random or fixed effects meta-analysis was used depending on statistical heterogeneity.Twenty-two studies were identified with a total of 5566 patients (mean age 69 years) with recurrence occurring in 801 patients (14.4%). Hyperdense components (hyperdense homogeneous and mixed density) were the strongest prognostic factor of recurrence (pooled RR 2.83, 95% CI 1.69-4.73). Laminar and separated architecture types also revealed higher recurrence rates (RR 1.37, 95% CI 1.04-1.80 and RR 1.76 95% CI 1.38-2.16, respectively). Hematoma thickness and midline shift above predefined cut-off values (10 mm and 20 mm) were associated with an increased recurrence rate (RR 1.79, 95% CI 1.45-2.21 and RR 1.38, 95% CI 1.11-1.73, respectively). Bilateral CSDH was also associated with an increased recurrence risk (RR 1.34, 95% CI 0.98-1.84).Limitations were no adjustments for confounders and variable data heterogeneity. Clinical factors could also be predictive of recurrence but are beyond the scope of this study.Hyperdense hematoma components were the strongest prognostic factor of recurrence after surgery. Awareness of these findings allows for individual risk assessment and might prompt clinicians to tailor treatment measures.
Published: 2020

52. Clot Burden Score on Baseline Computerized Tomographic Angiography and Intra-Arterial Treatment Effect in Acute Ischemic Stroke

Author: Kilian M. Treurniet, Albert J. Yoo, Olvert A. Berkhemer, Hester F. Lingsma, Anna M.M. Boers, Puck S.S. Fransen, Debbie Beumer, Lucie A. van den Berg, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Geert J. Lycklama À Nijeholt, Marianne A.A. van Walderveen, Joseph C.J. Bot, Ludo F.M. Beenen, René van den Berg, Wim H. van Zwam, Aad van der Lugt, Robert J. van Oostenbrugge, Diederik W.J. Dippel, Yvo B.W.E.M. Roos, Henk A. Marquering, Charles B.L.M. Majoie, Wouter J. Schonewille, Jan Albert Vos, Paul J. Nederkoorn, Marieke J.H. Wermer, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Jan S.P. van den Berg, Willem Jan J. van Rooij, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Peter J. Koudstaal, H. Zwenneke Flach, Ewout W Steyerberg, ANS - Neurovascular Disorders, Other departments, Radiology and Nuclear Medicine, Neurology, Biomedical Engineering and Physics, MUMC+: MA AIOS Neurologie (9), RS: CARIM - R3.11 - Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Radiology and nuclear medicine, ICaR - Ischemia and repair, Public Health, and Radiology & Nuclear Medicine
Subjects: inorganic chemicals, Male, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Computed Tomography Angiography, 030218 nuclear medicine & medical imaging, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Internal medicine, Outcome Assessment, Health Care, Intra arterial, Medicine, Humans, Infusions, Intra-Arterial, Treatment effect, Favorable outcome, Acute ischemic stroke, Stroke, Aged, thrombolytic therapy, Advanced and Specialized Nursing, neuroimaging, medicine.diagnostic_test, business.industry, Intracranial Embolism, organic chemicals, Other Research Radboud Institute for Health Sciences [Radboudumc 0], nutritional and metabolic diseases, Thrombosis, Middle Aged, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], stroke, Surgery, Cerebral Angiography, thrombectomy, Angiography, Cardiology, intracranial embolism, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose— A high clot burden score (CBS) is associated with favorable outcome after intravenous treatment for acute ischemic stroke. The added benefit of intra-arterial treatment might be less in these patients. The aim of this exploratory post hoc analysis was to assess the relation of CBS with neurological improvement and endovascular treatment effect. Methods— For 499 of 500 patients in the MR CLEAN study (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the CBS was determined. Ordinal logistic regression models with and without main baseline prognostic variables were used to assess the association between CBS (continuous or dichotomized at CBS of 6) and a shift toward better outcome on the modified Rankin Scale. The model without main baseline prognostic variables only included treatment allocation and CBS. Models with and without a multiplicative interaction term of CBS and treatment were compared using the χ 2 test to assess treatment effect modification by CBS. Results— Higher CBS was associated with a shift toward better outcome on the modified Rankin Scale; adjusted common odds ratio per point CBS was 1.12 (95% confidence interval, 1.04–1.20]. Dichotomized CBS had an adjusted common odds ratio of 1.67 (95% confidence interval, 1.12–2.51). Both effect estimates were slightly attenuated by adding baseline prognostic variables. The addition of the interaction terms did not significantly improve the fit of the models. There was a small and insignificant increase of intra-arterial treatment efficacy in the high CBS group. Conclusions— A higher CBS is associated with improved outcome and may be used as a prognostic marker. We found no evidence that CBS modifies the effect of intra-arterial treatment. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR1804. URL: http://www.controlled-trials.com . Unique identifier: ISRCTN10888758.
Published: 2016

53. Clinical prediction of thrombectomy eligibility: A systematic review and 4-item decision tree

Author: Birgitta K. Velthuis, Ido R. van den Wijngaard, Hannah R. Rowling, Gaia T Koster, Nyika D. Kruyt, Erik W. van Zwet, Bjarty L. Garcia, Marieke J.H. Wermer, Yvo B.W.E.M. Roos, T. Truc My Nguyen, Jan Bosch, Heleen M. den Hertog, Marianne A. A. van Walderveen, Wouter J. Schonewille, Neurology, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Neuroscience - Neurovascular Disorders
Subjects: Male, medicine.medical_specialty, Databases, Factual, Vessel occlusion, Acute ischemic stroke, Decision tree, Clinical scale, intra-arterial thrombectomy, endovascular thrombectomy, 030204 cardiovascular system & hematology, Research Support, Severity of Illness Index, Databases, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Predictive Value of Tests, large vessel occlusion, Journal Article, Medicine, Humans, Prospective Studies, Validation Studies, Non-U.S. Gov't, Factual, Thrombectomy, Aged, clinical scale, business.industry, Research, Patient Selection, Research Support, Non-U.S. Gov't, Decision Trees, Middle Aged, prehospital, Multicenter Study, Multicenter study, Neurology, Female, business, 030217 neurology & neurosurgery, Algorithms, Thrombectomy/standards, Large vessel occlusion
Abstract: Background A clinical large anterior vessel occlusion (LAVO)-prediction scale could reduce treatment delays by allocating intra-arterial thrombectomy (IAT)-eligible patients directly to a comprehensive stroke center. Aim To subtract, validate and compare existing LAVO-prediction scales, and develop a straightforward decision support tool to assess IAT-eligibility. Methods We performed a systematic literature search to identify LAVO-prediction scales. Performance was compared in a prospective, multicenter validation cohort of the Dutch acute Stroke study (DUST) by calculating area under the receiver operating curves (AUROC). With group lasso regression analysis, we constructed a prediction model, incorporating patient characteristics next to National Institutes of Health Stroke Scale (NIHSS) items. Finally, we developed a decision tree algorithm based on dichotomized NIHSS items. Results We identified seven LAVO-prediction scales. From DUST, 1316 patients (35.8% LAVO-rate) from 14 centers were available for validation. FAST-ED and RACE had the highest AUROC (both >0.81, p Conclusion External validation of seven LAVO-prediction scales showed AUROCs between 0.75 and 0.83. Most scales, however, appear too complex for Emergency Medical Services use with prehospital validation generally lacking. GACE is the first LAVO-prediction scale using a simple decision tree as such increasing feasibility, while maintaining high accuracy. Prehospital prospective validation is planned.
Published: 2019

54. Endovascular Treatment The Role of Dominant Caliber M2 Segment Occlusion in Ischemic Stroke

Author: Kars C.J. Compagne, Pieter M. van der Sluijs, Ido R. van den Wijngaard, Bob Roozenbeek, Maxim J.H.L. Mulder, Wim H. van Zwam, Bart J. Emmer, Charles B.L.M. Majoie, Albert J. Yoo, Geert J. Lycklama à Nijeholt, Hester F. Lingsma, Diederik W.J. Dippel, Aad van der Lugt, Adriaan C.G.M. van Es, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Jelis Boiten, Jan Albert Vos, Ivo G.H. Jansen, Robert-Jan B. Goldhoorn, Wouter J. Schonewille, Jonathan M. Coutinho, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, Paul L.M. de Kort, Jo J.P. Peluso, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Joost Bot, Pieter-Jan van Doormaal, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Corina Puppels, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Cathelijn van Rijswijk, Gert Messchendorp, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, M. Wollaert, D. Jeurrissen, Ernas Bos, Yvonne Drabbe, Berber Zweedijk, Mostafa Khalilzada, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Wouter Hinseveld, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon Kappelhof, Manon L. Tolhuijsen, Heitor Alves, Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, ACS - Microcirculation, Neurology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA Niet Med Staf Neurologie (9), Promovendi CD, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: DA BV AIOS Nucleaire Geneeskunde (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: DA BV AIOS Radiologie (9), Radiology & Nuclear Medicine, and Public Health
Subjects: Male, medicine.medical_treatment, Original Contributions, M1, ANGIOGRAPHY, THERAPY, Stroke/mortality, 030218 nuclear medicine & medical imaging, law.invention, 0302 clinical medicine, Randomized controlled trial, Modified Rankin Scale, law, Occlusion, Registries, Middle Cerebral Artery/surgery, Netherlands, OUTCOMES, Cerebral infarction, Endovascular Procedures, Infarction, Middle Cerebral Artery, Thrombolysis, Middle Cerebral Artery/mortality, Middle Aged, stroke, reperfusion, Survival Rate, Infarction, thrombectomy, Middle cerebral artery, Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Clinical Sciences, Netherlands/epidemiology, Disease-Free Survival, 03 medical and health sciences, medicine.artery, Internal medicine, MIDDLE CEREBRAL-ARTERY, SCORE, medicine, Humans, Infarction, Middle Cerebral Artery/mortality, Aged, Advanced and Specialized Nursing, Intracerebral hemorrhage, middle cerebral artery, business.industry, MECHANICAL THROMBECTOMY, Correction, Odds ratio, medicine.disease, treatment outcome, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Supplemental Digital Content is available in the text., Background and Purpose— It is unclear whether endovascular treatment (EVT) is beneficial for patients with acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery. We aimed to compare functional outcomes, technical aspects, and complications of EVT between patients with acute ischemic stroke because of M2 and M1 occlusions in clinical practice. Furthermore, outcome and complications after EVT in dominant and nondominant caliber M2 division occlusions were studied. Methods— Data were obtained from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) which is an ongoing observational study in 16 Dutch centers performing EVT in the Netherlands. Functional outcome was measured with the modified Rankin Scale score at 90 days. Neurological recovery (delta National Institutes of Health Stroke Scale), successful reperfusion rates (extended Thrombolysis in Cerebral Infarction ≥2B), and safety outcomes were also investigated. Associations between occlusion location and outcome were analyzed with ordinal logistic regression models, with adjustment for other prognostic factors. Results— In total, 244 (24%) patients with an M2 and 759 (76%) patients with an M1 occlusion who underwent EVT were analyzed. Functional outcomes were not significantly different between patients with M2 versus M1 occlusions (adjusted common odds ratio, 1.24; 95% CI, 0.87–1.73). Occurrence of symptomatic intracerebral hemorrhage was also similar for M2 and M1 occlusions (6.6% versus 5.9%; P=0.84). Further analysis about dominance of an M2 branch was performed in 175 (72%) patients. Neurological recovery was comparable (mean delta National Institutes of Health Stroke Scale, −2±10 for dominant M2, −5±5 for nondominant M2, and −4±9 [P=0.24] for M1 occlusions). Furthermore, the effect of reperfusion status on functional outcome was comparable between occlusion divisions (common odds ratio, 1.27; 95% CI, 1.06–1.53 for dominant M2; common odds ratio, 1.32; 95% CI, 0.93–1.87 for nondominant M2; and common odds ratio, 1.35; 95% CI, 1.24–1.46 for M1 occlusions). Conclusions— Outcomes and complication rates after EVT were similar in patients with M2 and M1 occlusions. Although based on observational data and a limited sample size, a similar association of reperfusion status with functional outcome for all subgroups provides no evidence that patients with either a dominant or a nondominant M2 occlusion should be routinely excluded from EVT.
Published: 2019

55. Corticosteroid treatment compared with surgery in chronic subdural hematoma: a systematic review and meta-analysis

Author: Heleen M. den Hertog, Kuan Hua Kho, Ruben Dammers, Clemens M F Dirven, Niels A van der Gaag, Korné Jellema, Dana C Holl, Victor Volovici, Hester F. Lingsma, Ishita P Miah, Fop van Kooten, Wilco C. Peul, Neurosurgery, Public Health, and Neurology
Subjects: medicine.medical_specialty, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, Outcome Assessment, Health Care, Medicine, Corticosteroids, Nonsurgical treatment, Humans, Medical management, Neuroradiology, Burr hole, medicine.diagnostic_test, business.industry, Interventional radiology, Chronic subdural hematoma, Confidence interval, Surgery, Meta-analysis, Relative risk, Hematoma, Subdural, Chronic, Drainage, Observational study, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery, Craniotomy
Abstract: There is an ongoing debate on the role of corticosteroids in the treatment of chronic subdural hematoma (CSDH). This study aims to evaluate the effectiveness of corticosteroids for the treatment of CSDH compared to surgery. A systematic search was performed in relevant databases up to January 2019 to identify RCTs or observational studies that compared at least two of three treatment modalities: the use of corticosteroids as a monotherapy (C), corticosteroids as an adjunct to surgery (CS), and surgery alone (S). Outcome measures were good neurological outcome, need for reintervention, mortality, and complications. Effect estimates were pooled and presented as relative risk (RR) with 95% confidence interval (95%CI). Of 796 initially identified studies, 7 were included in the meta-analysis. Risk of bias was generally high. There were no differences in good neurological outcome between treatment modalities. The need for reintervention varied between 4 and 58% in C, 4–12% in CS, and 7–26% in S. The need for reintervention was lower in CS compared with C (RR 3.34 [95% CI 1.53–7.29]; p
Published: 2019

56. Glucose Modifies the Effect of Endovascular Thrombectomy in Patients With Acute Stroke

Author: Ángel, Chamorro, Scott, Brown, Sergio, Amaro, Michael D, Hill, Keith W, Muir, Diederik W J, Dippel, Wim, van Zwam, Ken, Butcher, Gary A, Ford, Heleen M, den Hertog, Peter J, Mitchell, Andrew M, Demchuk, Charles B L M, Majoie, Serge, Bracard, Igor, Sibon, Ashutosh P, Jadhav, Blanca, Lara-Rodriguez, Aad, van der Lugt, Elizabeth, Osei, Arturo, Renú, Sébastien, Richard, David, Rodriguez-Luna, Geoffrey A, Donnan, Anand, Dixit, Mohammed, Almekhlafi, Sandrine, Deltour, Jonathan, Epstein, Benoit, Guillon, Serge, Bakchine, Meritxell, Gomis, Richard, du Mesnil de Rochemont, Demetrius, Lopes, Vivek, Reddy, Gernot, Rudel, Yvo B W E M, Roos, Alain, Bonafe, Hans-Christoph, Diener, Olvert A, Berkhemer, Geoffrey C, Cloud, Stephen M, Davis, Robert, van Oostenbrugge, Francis, Guillemin, Mayank, Goyal, Bruce C V, Campbell, and Bijoy K, Menon
Subjects: Blood Glucose, Stroke, Treatment Outcome, Meta-Analysis as Topic, Risk Factors, Hyperglycemia, Endovascular Procedures, Medizin, Humans, Randomized Controlled Trials as Topic, Thrombectomy
Abstract: Background and Purpose- Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods- Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0-6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results- Median (interquartile range) serum glucose on admission was 120 (104-140) mg/dL (6.6 mmol/L [5.7-7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69-2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucoseor90 mg/dL (5.0 mmol/L; P=0.019 for interaction; acOR, 3.81; 95% CI, 1.73-8.41 for patients90 mg/dL versus 1.83; 95% CI, 1.53-2.19 for patients90 mg/dL), and glucoseor100 mg/dL (5.5 mmol/L; P=0.004 for interaction; acOR, 3.17; 95% CI, 2.04-4.93 versus acOR, 1.72; 95% CI, 1.42-2.08) but not between subgroups above these levels of glucose. Conclusions- EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0-5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.
Published: 2019

57. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

Author: Bruce C V Campbell, Charles B L M Majoie, Gregory W Albers, Bijoy K Menon, Nawaf Yassi, Gagan Sharma, Wim H van Zwam, Robert J van Oostenbrugge, Andrew M Demchuk, Francis Guillemin, Philip White, Antoni Dávalos, Aad van der Lugt, Kenneth S Butcher, Aboubaker Cherifi, Henk A Marquering, Geoffrey Cloud, Juan M Macho Fernández, Jeremy Madigan, Catherine Oppenheim, Geoffrey A Donnan, Yvo B W E M Roos, Jai Shankar, Hester Lingsma, Alain Bonafé, Hélène Raoult, María Hernández-Pérez, Aditya Bharatha, Reza Jahan, Olav Jansen, Sébastien Richard, Elad I Levy, Olvert A Berkhemer, Marc Soudant, Lucia Aja, Stephen M Davis, Timo Krings, Marie Tisserand, Luis San Román, Alejandro Tomasello, Debbie Beumer, Scott Brown, David S Liebeskind, Serge Bracard, Keith W Muir, Diederik W J Dippel, Mayank Goyal, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Lucie A van den Berg, Hester F Lingsma, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Vitor Mendes Pereira, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, Xavier Ducrocq, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Olivier Naggara, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Anand Dixit, Andrew Clifton, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, Clinical Neurophysiology, Weimar, Christian (Beitragende*r), Radiology and nuclear medicine, Rheumatology, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: Carim - B06 Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: MA AIOS Neurologie (9), The Royal Melbourne Hospital, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Stanford University, University of Calgary, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University [Maastricht], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Universitat Autònoma de Barcelona (UAB), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Alberta, Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Monash University [Melbourne], St George’s University Hospitals, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dalhousie University [Halifax], Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [Montpellier], Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], St. Michael's Hospital, University of California [Los Angeles] (UCLA), University of California, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University at Buffalo [SUNY] (SUNY Buffalo), State University of New York (SUNY), Toronto Western Hospital, Hôpital Foch [Suresnes], Vall d'Hebron University Hospital [Barcelona], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Glasgow, Queen Elizabeth University Hospital (Glasgow), David Geffen School of Medicine [Los Angeles], University of California-University of California, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Radiology & Nuclear Medicine, Public Health, Neurology, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Pulmonary hypertension & thrombosis, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, ARD - Amsterdam Reproduction and Development, Biomedical Engineering and Physics, APH - Personalized Medicine, APH - Quality of Care, and AMS - Restoration & Development
Subjects: SELECTION, COMPUTED TOMOGRAPHIC PERFUSION, Medizin, Perfusion scanning, 030204 cardiovascular system & hematology, Brain Ischemia, 0302 clinical medicine, Modified Rankin Scale, REPERFUSION, Stroke, ComputingMilieux_MISCELLANEOUS, Thrombectomy, Aged, 80 and over, medicine.diagnostic_test, Penumbra, Endovascular Procedures, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Cerebral blood flow, Tissue Plasminogen Activator, INFARCT, Cardiology, Female, TRIAL, CT, medicine.medical_specialty, Perfusion Imaging, Neuroimaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Fibrinolytic Agents, ALTEPLASE, Internal medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Aged, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Magnetic resonance imaging, Odds ratio, medicine.disease, Neurology (clinical), business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Fibrinolytic agent, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.Methods In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1,2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mu m(2)/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.Findings We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0.47 [95% CI 0.30-0.72], p=0.0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0.77 [0.69-0.86] per 10 mL, p(interaction)=0.29; diffusion MRI OR 0.87 [0.81-0.94] per 10 mL, p(interaction)=0.94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.Interpretation Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imagingto-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
Published: 2019

58. Determinants of intention to change health-related behavior and actual change in patients with TIA or minor ischemic stroke

Author: Heleen M. den Hertog, Lenneke van Genugten, Peter J. Koudstaal, Dorien Brouwer-Goossensen, Hester F. Lingsma, Diederik W.J. Dippel, Neurology, and Public Health
Subjects: Adult, Male, Health Behavior, Psychological intervention, Intention, Logistic regression, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Adaptation, Psychological, Severity of illness, medicine, Humans, In patient, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Exercise, Stroke, Aged, Self-efficacy, Smoking, Behavior change, Stroke Rehabilitation, Fear, General Medicine, Middle Aged, medicine.disease, Self Efficacy, Logistic Models, Ischemic Attack, Transient, Female, sense organs, Psychology, Attitude to Health, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Objective: To assess determinants of intention to change health-related behavior and actual change in patients with TIA or ischemic stroke. Methods: In this prospective cohort study, 100 patients with TIA or minor ischemic stroke completed questionnaires on behavioral intention and sociocognitive factors including perception of severity, susceptibility, fear, response-efficacy and self-efficacy at baseline. Questionnaires on physical activity, diet and smoking were completed at baseline and at 3 months. Associations between sociocognitive factors and behavioral intention and actual change were studied with multivariable linear and logistic regression. Results: Self-efficacy, response efficacy, and fear were independently associated with behavioral intention, with self-efficacy as the strongest determinant of intention to increase physical activity (aBeta 0.40; 95% CI 0.12-0.71), adapt a healthy diet (aBeta 0.49; 95% CI 0.23-0.75), and quit smoking (aBeta 0.51; 95% CI 0.13-0.88). Intention to change tended to be associated with actual health-related behavior change. Conclusion: Self-efficacy, fear, and response-efficacy were determinants of intention to change health-related behavior after TIA or ischemic stroke. Practice implications: These determinants of intention to change health-related behavior after TIA or ischemic stroke should be taken into account in the development of future interventions promoting health-related behavior change in these group of patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Published: 2016

59. Nonfocal Symptoms in Patients with Transient Ischemic Attack or Ischemic Stroke: Occurrence, Clinical Determinants, and Association with Cardiac History

Author: Heleen M. den Hertog, Diederik W.J. Dippel, P. J. A. M. Brouwers, Heleen A. Booij, Peter J. Koudstaal, Gerben J. J. Plas, Marjolein Brusse-Keizer, and Neurology
Subjects: Brain Infarction, Male, medicine.medical_specialty, Time Factors, Heart Diseases, Amnesia, 030204 cardiovascular system & hematology, Risk Assessment, Positive visual phenomena, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Atrial Fibrillation, Humans, Medicine, Outpatient clinic, In patient, Registries, cardiovascular diseases, Aged, business.industry, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, nervous system diseases, Stenosis, Neurology, Ischemic Attack, Transient, Relative risk, Cardiology, Etiology, Female, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background: Transient ischemic attacks (TIAs) accompanied by nonfocal symptoms are associated with a higher risk of cardiovascular events, in particular cardiac events. Reported frequencies of TIAs accompanied by nonfocal symptoms range from 18 to 53%. We assessed the occurrence of nonfocal symptoms in patients with TIA or minor ischemic stroke in a neurological outpatient clinic in terms of clinical determinants, cardiac history, and atrial fibrillation (AF). Methods: We included 1,265 consecutive patients with TIA or minor stroke who visited the outpatient clinic. During these visits, we systematically asked for nonfocal symptoms. Nonfocal symptoms included decreased consciousness, amnesia, positive visual phenomena, non-rotatory dizziness, and paresthesias. Relative risks for the presence of nonfocal symptoms in relation to clinical determinants, AF, and cardiac history were calculated. Results: In 243 (19%) of 1,265 patients, TIA or minor ischemic stroke was accompanied by one or more nonfocal symptoms. Non-rotatory dizziness, paresthesia, and amnesia were the most common nonfocal symptoms. In patients with an event of the posterior circulation or obesity, the qualifying TIA or minor stroke was more frequently accompanied by nonfocal symptoms, and in patients with significant carotid stenosis, nonfocal symptoms occurred less frequently. AF was related only with amnesia. Conclusion: Nonfocal symptoms are present in one out of 5 patients with TIA or ischemic stroke, in particular when located in the posterior circulation. A cardiac history or AF was not directly related to nonfocal symptoms. A heterogeneous etiology is suggested.
Published: 2016

60. Contents Vol. 42, 2016

Author: Christopher Beynon, Hyeong-Joong Yi, Xia Zhang, Zeljka Calic, Christina Hamisch, Paul J.A.M. Brouwers, Serge Timsit, Martin Griebe, Jijun Shi, Yanlin Zhang, Timolaos Rizos, Ji-Sung Lee, Bernt Harald Helleberg, Jae Min Kim, Gert J. de Borst, Adnan I. Qureshi, Soo Joo Lee, Boris Krischek, Gerben J. J. Plas, Markus A Möhlenbruch, Angela C Webster, Paola Forti, Diogo C Haussen, Michael Kettner, Fayyaz Orfi, Paul J. Nederkoorn, Qiao Han, Chunfeng Liu, Joon-Tae Kim, Joan Montaner, Carlotta Barbara, John A Oostema, Daniela Niemann, Iris Q. Grunwald, Mohammad Rauf Afzal, Shoujiang You, Güliz Acker, Valérie Martin, Huihui Liu, Mark Stroick, Tetsuro Ago, Mathew J. Reeves, Matthijs C. Brouwer, Tai Hwan Park, Thorsten Steiner, Y.B.W.E.M. Roos, Min Uk Jang, Richard I. Lindley, Rainer Kollmar, Helmuth Steinmetz, Jun Lee, Yoshinobu Wakisaka, Tae-Hee Cho, Druckerei Stückle, Hee-Joon Bae, Nauman Jahangir, Yong Ko, Laura Mechtouff, Wei Xuan, Takanari Kitazono, Marco Zoli, Jan-Dirk Vermeij, Roland Veltkamp, Dennis Cordato, Nathan Mewton, Christophe Gaudin, Leticia C. Rebello, Gerrit Brinker, Laurent Suissa, Michael G. Hennerici, Peter Schmiedek, Fabiola Maioli, Peter J. Koudstaal, Matthias Manitz, Beom Joon Kim, Young-Chai Ko, Anne Huibers, Djurre de Waard, Marc Fatar, Klaus Fassbender, Christian Foerch, Umut Yilmaz, Ryu Matsuo, Ekkehart Jenetzky, Philip B. Gorelick, Hanne Ellekjaer, Ahmed A Malik, Kyung Bok Lee, Junya Kuroda, Kyung-Ho Yu, Jiro Kitayama, Dae Hyun Kim, Jong-Moo Park, Oliver C. Singer, Günther Hedtmann, Ki-Hyun Cho, Mario Abruscato, Kyusik Kang, Stefan Helwig, Marcus Czabanka, Eric Greveson, Marjolein Brusse-Keizer, Choong Hyun Kim, Patrick J. Kelly, Peter Sander, Raul G Nogueira, Marco Timmer, Peter A. Ringleb, Andreas Ragoschke-Schumm, Adam Strzelczyk, Sven Thonke, Peter Vajkoczy, Chongke Zhong, M. Fareed K. Suri, Heleen A. Booij, Keun-Sik Hong, Diederik van de Beek, Moon-Ku Han, Pierre Suchon, Jun Hata, Björn Misselwitz, Yves Donazzolo, Juneyoung Lee, Young-Soo Kim, Lenka Schwindling, Stefan H. Kreisel, Seena Dehkharghani, Tobias Neumann-Haefelin, Elodie Ong, Jin Hwan Cheong, Oliver Josef Müller, Jae Kwan Cha, Masahiro Kamouchi, Yong-Jin Cho, Michel Ovize, Sung Il Sohn, Byung-Chul Lee, Willeke F. Westendorp, Safwan Roumia, Mi Sun Oh, Michael Reiner, Vincent Larrue, Trevor Carle, Jihoon Kang, Dana Farahmand, Marie-Hélène Mahagne, Michael Frankel, Silke Walter, Martin Lesmeister, Gaetano Procaccianti, Jan C. Purrucker, Jonathan C. Craig, Anke Reihs, Svenja Schüler, Martin Gallagher, Valeria Nativio, Carina Hohmann, Mikayel Grigoryan, Jae Guk Kim, Benno Ikenberg, M. Laible, Heleen M. den Hertog, Waltraud Pfeilschifter, Jiaping Xu, Mathieu Zuber, Craig S. Anderson, Alison Halliday, Laurent Derex, Bent Indredavik, Jay Chol Choi, Hiromi Ishikawa, Yongjun Cao, Yvo B.W.E.M. Roos, Diederik W.J. Dippel, Jonathan A. Grossberg, Susanne Goerdes, Anastasios Mpotsaris, Philip Masson, Andreas Ferbert, Raf Brouns, Maura Coveri, Jeong-Ho Hong, Igor Sibon, Andrey Lima, Anna Mezzapesa, Alan Cass, Myung Hoon Han, Richard Bulbulia, Luigi Simonetti, Hiroshi Nakane, Pantelis Stavrinou, Zhichao Huang, Noriko Makihara, Mar Castellanos, Giuseppe Di Pasquale, Michele Domenico Spampinato, Roland Goldbrunner, Cecilia Cappelen-Smith, Sradha Kotwal, Wolfgang Reith, Marie-Christine Alessi, Angelika Alonso, Björn Reuter, Sang-Soon Park, Luyao Shi, Nadine Talia, Philippe Grosjean, and Norbert Nighoghossian
Subjects: Neurology, Traditional medicine, business.industry, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published: 2016

61. Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke

Author: Olvert A. Berkhemer, Ivo G.H. Jansen, Debbie Beumer, Puck S.S. Fransen, Lucie A. van den Berg, Albert J. Yoo, Hester F. Lingsma, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Geert J. Lycklama à Nijeholt, Marianne A.A. van Walderveen, René van den Berg, Joseph C.J. Bot, Ludo F.M. Beenen, Anna M.M. Boers, Cornelis H. Slump, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Diederik W.J. Dippel, Aad van der Lugt, Wim H. van Zwam, Henk A. Marquering, Charles B.L.M. Majoie, Wouter J. Schonewille, Jan-Albert Vos, Paul J. Nederkoorn, Marieke J.H. Wermer, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Jan S.P. van den Berg, Boudewijn A.A.M. van Hassel, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Peter J. Koudstaal, H. Zwenneke Flach, Ewout W. Steyerberg, Martin M. Brown, Thomas Liebig, Theo Stijnen, Radiology and nuclear medicine, ICaR - Ischemia and repair, MUMC+: MA AIOS Neurologie (9), RS: CARIM - R3.03 - Cerebral small vessel disease, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: CARIM - R3.11 - Imaging, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, ANS - Neurovascular Disorders, Graduate School, Other Research, Neurology, Biomedical Engineering and Physics, Public Health, and Radiology & Nuclear Medicine
Subjects: Male, endovascular treatment, OCCLUSION, THERAPY, 030218 nuclear medicine & medical imaging, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Modified Rankin Scale, VESSELS, Occlusion, stent-retriever, ACUTE ISCHEMIC-STROKE, collateral circulation, Stroke, INTERVENTIONAL MANAGEMENT, OUTCOMES, medicine.diagnostic_test, Endovascular Procedures, Middle Aged, THROMBECTOMY, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Collateral circulation, stroke, INFARCT, CT-ANGIOGRAPHY, Female, Radiology, Cardiology and Cardiovascular Medicine, cerebrovascular circulation, Cerebral angiography, medicine.medical_specialty, intra-arterial treatment, retrievable stent, 03 medical and health sciences, medicine, Humans, Infusions, Intra-Arterial, Aged, Advanced and Specialized Nursing, III TRIAL, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, medicine.disease, Confidence interval, Cerebral Angiography, treatment outcome, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals ( P =0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com . Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.
Published: 2016

62. A Reduction in Time with Electronic Monitoring In Stroke (ARTEMIS): study TA protocol for a randomised multicentre trial

Author: Heleen M. den Hertog, Yvo B.W.E.M. Roos, Adrien E. Groot, Gaia T Koster, Jan Bosch, Jonathan M. Coutinho, Ale Algra, T. Truc My Nguyen, Marieke J.H. Wermer, Nyika D. Kruyt, Marianne A. A. van Walderveen, Amsterdam Neuroscience - Neurovascular Disorders, Neurology, Graduate School, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Emergency Medical Services, acute ischemic stroke, medicine.medical_specialty, endocrine system, Time Factors, time to treatment, medicine.medical_treatment, intra-arterial thrombectomy, Monitoring, Ambulatory, total system delay, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Fibrinolytic Agents, treatment delay, Protocol, Emergency medical services, medicine, Humans, Multicenter Studies as Topic, intravenous thrombolysis, Prospective Studies, 030212 general & internal medicine, Trial registration, Stroke, Randomized Controlled Trials as Topic, Thrombectomy, Protocol (science), business.industry, Stroke mimics, General Medicine, EMS dispatch, Thrombolysis, medicine.disease, Treatment Outcome, Neurology, Emergency medicine, business, 030217 neurology & neurosurgery
Abstract: IntroductionTime is the most crucial factor limiting efficacy of intravenous thrombolysis (IVT) and intra-arterial thrombectomy (IAT). The delay between alarming the Emergency Medical Services (EMS) dispatch office and IVT/IAT initiation, that is, the‘total system delay’(TSD), depends on logistics and team effort. A promising method to reduce TSD is real-time audio-visual feedback to caregivers involved. With ‘A Reduction in Time with Electronic Monitoring in Stroke’ (ARTEMIS), we aim to investigate the effect of real-time audio-visual feedback on actual TSD to IVT/IAT to caregivers.Methods and analysisARTEMIS is a multiregional, multicentre, randomised open end-point trial including patients ≥18 years considered IVT/IAT-eligible by the EMS dispatch office or on-site EMS personnel. Patients are electronically tracked and randomised for real-time audio-visual feedback on TSD to caregivers via premounted handhelds and tablets throughout the TSD trajectory. Primary outcome is TSD to IVT/IAT. Secondary outcomes comprise proportion of IVT/IAT-treated patients, symptomatic intracerebral haemorrhage, IVT/IAT-treated stroke mimics, clinical outcome after three months and cost-effectiveness. Separate analyses for IAT-patients with or without prior IVT, within or out of office hours and EMS region will be performed. With 75 IAT-patients and 225 IVT-patients in each arm, we will be able to demonstrate a 20 min difference in TSD to IAT and a 10 min difference in TSD to IVT (p=0.05 and power=0.8).Ethics and disseminationStudy findings will be disseminated through peer-reviewed journals and (inter)national conference presentations.Trial registration numberNCT02808806
Published: 2018

63. Development and validation of the Dutch Stroke Score for predicting disability and functional outcome after ischemic stroke: A tool to support efficient discharge planning

Author: Inger R. de Ridder, Diederik W.J. Dippel, Heleen M. den Hertog, Maaike Scheele, Ewout W. Steyerberg, Gerard M. Ribbers, Willeke F. Westendorp, Simone A. Dijkland, Maaike Dirks, Paul J. Nederkoorn, Diederik van de Beek, Hester F. Lingsma, Neurology, Public Health, Rehabilitation Medicine, Graduate School, ACS - Atherosclerosis & ischemic syndromes, and ANS - Neuroinfection & -inflammation
Subjects: medicine.medical_specialty, medicine.medical_treatment, Outcome (game theory), Prognostic score, rehabilitation, 03 medical and health sciences, 0302 clinical medicine, discharge planning, Original Research Articles, clinical prediction model, medicine, In patient, 030212 general & internal medicine, Stroke, Acute ischemic stroke, Rehabilitation, business.industry, medicine.disease, hospital discharge, Discharge planning, Ischemic stroke, Emergency medicine, Neurology (clinical), prognosis, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Introduction We aimed to develop and validate a prognostic score for disability at discharge and functional outcome at three months in patients with acute ischemic stroke based on clinical information available on admission. Patients and methods The Dutch Stroke Score (DSS) was developed in 1227 patients with ischemic stroke included in the Paracetamol (Acetaminophen) In Stroke study. Predictors for Barthel Index (BI) at discharge (‘DSS-discharge’) and modified Rankin Scale (mRS) at three months (‘DSS-3 months’) were identified in multivariable ordinal regression. The models were internally validated with bootstrapping techniques. The DSS-3 months was externally validated in the PRomoting ACute Thrombolysis in Ischemic StrokE study (1589 patients) and the Preventive Antibiotics in Stroke Study (2107 patients). Model performance was assessed in terms of discrimination, expressed by the area under the receiver operating characteristic curve (AUC), and calibration. Results At model development, the strongest predictors of Barthel Index at discharge were age per decade over 60 (odds ratio = 1.55, 95% confidence interval (CI) 1.41–1.68), National Institutes of Health Stroke Scale (odds ratio = 1.24 per point, 95% CI 1.22–1.26) and diabetes (odds ratio = 1.62, 95% CI 1.32–1.91). The internally validated AUC was 0.76 (95% CI 0.75–0.79). The DSS-3 months, additionally consisting of previous stroke and atrial fibrillation, performed similarly at internal (AUC 0.75, 95% CI 0.74–0.77) and external validation (AUC 0.74 in PRomoting ACute Thrombolysis in Ischemic StrokE (95% CI 0.72–0.76) and 0.69 in Preventive Antibiotics in Stroke Study (95% CI 0.69–0.72)). Observed outcome was slightly better than predicted. Discussion: The DSS had satisfactory performance in predicting BI at discharge and mRS at three months in ischemic stroke patients. Conclusion If further validated, the DSS may contribute to efficient stroke unit discharge planning alongside patients' contextual factors and therapeutic needs.
Published: 2018

64. Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Author: Bruce C V Campbell, Wim H van Zwam, Mayank Goyal, Bijoy K Menon, Diederik W J Dippel, Andrew M Demchuk, Serge Bracard, Philip White, Antoni Dávalos, Charles B L M Majoie, Aad van der Lugt, Gary A Ford, Natalia Pérez de la Ossa, Michael Kelly, Romain Bourcier, Geoffrey A Donnan, Yvo B W E M Roos, Oh Young Bang, Raul G Nogueira, Thomas G Devlin, Lucie A van den Berg, Frédéric Clarençon, Paul Burns, Jeffrey Carpenter, Olvert A Berkhemer, Dileep R Yavagal, Vitor Mendes Pereira, Xavier Ducrocq, Anand Dixit, Helena Quesada, Jonathan Epstein, Stephen M Davis, Olav Jansen, Marta Rubiera, Xabier Urra, Emilien Micard, Hester F Lingsma, Olivier Naggara, Scott Brown, Francis Guillemin, Keith W Muir, Robert J van Oostenbrugge, Jeffrey L Saver, Tudor G Jovin, Michael D Hill, Peter J Mitchell, Puck SS Fransen, Debbie Beumer, Albert J Yoo, Wouter J Schonewille, Jan Albert Vos, Paul J Nederkoorn, Marieke JH Wermer, Marianne AA van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Jaap Kappelle, Rob H Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Willem Jan J. van Rooij, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Ewout W. Steyerberg, Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, René van den Berg, Peter J. Koudstaal, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Emilie Santos, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, MD Hill, M Goyal, AM Demchuk, BK Menon, M Eesa, KJ Ryckborst, MR Wright, NR Kamal, L Andersen, PA Randhawa, T Stewart, S Patil, P Minhas, M Almekhlafi, S Mishra, F Clement, T Sajobi, A Shuaib, WJ Montanera, D Roy, FL Silver, TG Jovin, DF Frei, B Sapkota, JL Rempel, J Thornton, D Williams, D Tampieri, AY Poppe, D Dowlatshahi, JH Wong, AP Mitha, S Subramaniam, G Hull, MW Lowerison, M Salluzzi, M Maxwell, S Lacusta, E Drupals, K Armitage, PA Barber, EE Smith, WF Morrish, SB Coutts, C Derdeyn, B Demaerschalk, D Yavagal, R Martin, R Brant, Y Yu, RA Willinsky, A Weill, C Kenney, H Aram, PK Stys, TW Watson, G Klein, D Pearson, P Couillard, A Trivedi, D Singh, E Klourfeld, O Imoukhuede, D Nikneshan, S Blayney, R Reddy, P Choi, M Horton, T Musuka, V Dubuc, TS Field, J Desai, S Adatia, A Alseraya, V Nambiar, R van Dijk, NJ Newcommon, B Schwindt, KS Butcher, T Jeerakathil, B Buck, K Khan, SS Naik, DJ Emery, RJ Owen, TB Kotylak, RA Ashforth, TA Yeo, D McNally, M Siddiqui, M Saqqur, D Hussain, H Kalashyan, A Manosalva, M Kate, L Gioia, S Hasan, A Mohammad, M Muratoglu, A Cullen, P Brennan, A O'Hare, S Looby, D Hyland, S Duff, M McCusker, B Hallinan, S Lee, J McCormack, A Moore, M O'Connor, C Donegan, L Brewer, A Martin, S Murphy, K O'Rourke, S Smyth, P Kelly, T Lynch, T Daly, P O'Brien, A O'Driscoll, M Martin, R Collins, T Coughlan, D McCabe, D O'Neill, M Mulroy, O Lynch, T Walsh, M O'Donnell, T Galvin, J Harbison, P McElwaine, K Mulpeter, C McLoughlin, M Reardon, E Harkin, E Dolan, M Watts, N Cunningham, C Fallon, S Gallagher, P Cotter, M Crowe, R Doyle, I Noone, M Lapierre, VA Coté, S Lanthier, C Odier, A Durocher, J Raymond, N Daneault, Y Deschaintre, B Jankowitz, L Baxendell, L Massaro, C Jackson-Graves, S Decesare, P Porter, K Armbruster, A Adams, J Billigan, J Oakley, A Ducruet, A Jadhav, D-V Giurgiutiu, A Aghaebrahim, V Reddy, M Hammer, M Starr, V Totoraitis, L Wechsler, S Streib, S Rangaraju, D Campbell, M Rocha, D Gulati, T Krings, L Kalman, A Cayley, J Williams, R Wiegner, LK Casaubon, C Jaigobin, JM del Campo, E Elamin, JD Schaafsma, R Agid, R Farb, K ter Brugge, BL Sapkoda, BW Baxter, K Barton, A Knox, A Porter, A Sirelkhatim, T Devlin, C Dellinger, N Pitiyanuvath, J Patterson, J Nichols, S Quarfordt, J Calvert, H Hawk, C Fanale, A Bitner, A Novak, D Huddle, R Bellon, D Loy, J Wagner, I Chang, E Lampe, B Spencer, R Pratt, R Bartt, S Shine, G Dooley, T Nguyen, M Whaley, K McCarthy, J Teitelbaum, W Poon, N Campbell, M Cortes, C Lum, R Shamloul, S Robert, G Stotts, M Shamy, N Steffenhagen, D Blacquiere, M Hogan, M AlHazzaa, G Basir, H Lesiuk, D Iancu, M Santos, H Choe, DC Weisman, K Jonczak, A Blue-Schaller, Q Shah, L MacKenzie, B Klein, K Kulandaivel, O Kozak, DJ Gzesh, LJ Harris, JS Khoury, J Mandzia, D Pelz, S Crann, L Fleming, K Hesser, B Beauchamp, B Amato-Marzialli, M Boulton, P Lopez- Ojeda, M Sharma, S Lownie, R Chan, R Swartz, P Howard, D Golob, D Gladstone, K Boyle, M Boulos, J Hopyan, V Yang, L Da Costa, CA Holmstedt, AS Turk, R Navarro, E Jauch, S Ozark, R Turner, S Phillips, J Shankar, J Jarrett, G Gubitz, W Maloney, R Vandorpe, M Schmidt, J Heidenreich, G Hunter, M Kelly, R Whelan, L Peeling, PA Burns, A Hunter, I Wiggam, E Kerr, M Watt, A Fulton, P Gordon, I Rennie, P Flynn, G Smyth, S O'Leary, N Gentile, G Linares, P McNelis, K Erkmen, P Katz, A Azizi, M Weaver, C Jungreis, S Faro, P Shah, H Reimer, V Kalugdan, G Saposnik, A Bharatha, Y Li, P Kostyrko, T Marotta, W Montanera, D Sarma, D Selchen, J Spears, JH Heo, K Jeong, DJ Kim, BM Kim, YD Kim, D Song, K-J Lee, J Yoo, OY Bang, S Rho, J Lee, P Jeon, KH Kim, J Cha, SJ Kim, S Ryoo, MJ Lee, S-I Sohn, C-H Kim, H-G Ryu, J-H Hong, H-W Chang, C-Y Lee, J Rha, Bruce CV Campbell, Leonid Churilov, Bernard Yan, Richard Dowling, Nawaf Yassi, Thomas J Oxley, Teddy Y Wu, Gabriel Silver, Amy McDonald, Rachael McCoy, Timothy J Kleinig, Rebecca Scroop, Helen M Dewey, Marion Simpson, Mark Brooks, Bronwyn Coulton, Martin Krause, Timothy J Harrington, Brendan Steinfort, Kenneth Faulder, Miriam Priglinger, Susan Day, Thanh Phan, Winston Chong, Michael Holt, Ronil V Chandra, Henry Ma, Dennis Young, Kitty Wong, Tissa Wijeratne, Hans Tu, Elizabeth Mackay, Sherisse Celestino, Christopher F Bladin, Poh Sien Loh, Amanda Gilligan, Zofia Ross, Skye Coote, Tanya Frost, Mark W Parsons, Ferdinand Miteff, Christopher R Levi, Timothy Ang, Neil Spratt, Lara Kaauwai, Monica Badve, Henry Rice, Laetitia de Villiers, P. Alan Barber, Ben McGuinness, Ayton Hope, Maurice Moriarty, Patricia Bennett, Andrew Wong, Alan Coulthard, Andrew Lee, Jim Jannes, Deborah Field, Gagan Sharma, Simon Salinas, Elise Cowley, Barry Snow, John Kolbe, Richard Stark, John King, Richard Macdonnell, John Attia, Cate D'Este, Hans-Christoph Diener, Elad I. Levy, Alain Bonafé, Reza Jahan, Gregory W. Albers, Christophe Cognard, David J. Cohen, Werner Hacke, Tudor G. Jovin, Heinrich P. Mattle, Raul G. Nogueira, Adnan H. Siddiqui, Dileep R. Yavagal, Rüdiger von Kummer, Wade Smith, Francis Turjman, Scott Hamilton, Richard Chiacchierini, Arun Amar, Nerses Sanossian, Yince Loh, B Baxter, VK Reddy, A Horev, M Star, A Siddiqui, LN Hopkins, K Snyder, R Sawyer, S Hall, V Costalat, C Riquelme, P Machi, E Omer, C Arquizan, I Mourand, M Charif, X Ayrignac, N Menjot de Champfleur, N Leboucq, G Gascou, M Moynier, R du Mesnil de Rochemont, O Singer, J Berkefeld, C Foerch, M Lorenz, W Pfeilschifer, E Hattingen, M Wagner, SJ You, S Lescher, H Braun, S Dehkharghani, SR Belagaje, A Anderson, A Lima, M Obideen, D Haussen, R Dharia, M Frankel, V Patel, K Owada, A Saad, L Amerson, C Horn, S Doppelheuer, K Schindler, DK Lopes, M Chen, R Moftakhar, C Anton, M Smreczak, JS Carpenter, S Boo, A Rai, T Roberts, A Tarabishy, L Gutmann, C Brooks, J Brick, J Domico, G Reimann, K Hinrichs, M Becker, E Heiss, C Selle, A Witteler, S Al-Boutros, M-J Danch, A Ranft, S Rohde, K Burg, C Weimar, V Zegarac, C Hartmann, M Schlamann, S Göricke, A Ringlestein, I Wanke, C Mönninghoff, M Dietzold, R Budzik, T Davis, G Eubank, WJ Hicks, P Pema, N Vora, J Mejilla, M Taylor, W Clark, A Rontal, J Fields, B Peterson, G Nesbit, H Lutsep, H Bozorgchami, R Priest, O Ologuntoye, S Barnwell, A Dogan, K Herrick, C Takahasi, N Beadell, B Brown, S Jamieson, MS Hussain, A Russman, F Hui, D Wisco, K Uchino, Z Khawaja, I Katzan, G Toth, E Cheng-Ching, M Bain, S Man, A Farrag, P George, S John, L Shankar, A Drofa, R Dahlgren, A Bauer, A Itreat, A Taqui, R Cerejo, A Richmond, P Ringleb, M Bendszus, M Möhlenbruch, T Reiff, H Amiri, J Purrucker, C Herweh, M Pham, O Menn, I Ludwig, I Acosta, C Villar, W Morgan, C Sombutmai, F Hellinger, E Allen, M Bellew, R Gandhi, E Bonwit, J Aly, RD Ecker, D Seder, J Morris, M Skaletsky, J Belden, C Baker, LS Connolly, P Papanagiotou, C Roth, A Kastrup, M Politi, F Brunner, M Alexandrou, H Merdivan, C Ramsey, C Given II, S Renfrow, V Deshmukh, K Sasadeusz, F Vincent, JT Thiesing, J Putnam, A Bhatt, A Kansara, D Caceves, T Lowenkopf, L Yanase, J Zurasky, S Dancer, B Freeman, T Scheibe-Mirek, J Robison, J Roll, D Clark, M Rodriguez, B-FM Fitzsimmons, O Zaidat, JR Lynch, M Lazzaro, T Larson, L Padmore, E Das, A Farrow-Schmidt, A Hassan, W Tekle, C Cate, O Jansen, C Cnyrim, F Wodarg, C Wiese, A Binder, C Riedel, A Rohr, N Lang, H Laufs, S Krieter, L Remonda, M Diepers, J Añon, K Nedeltchev, T Kahles, S Biethahn, M Lindner, V Chang, C Gächter, C Esperon, M Guglielmetti, JF Arenillas Lara, M Martínez Galdámez, AI Calleja Sanz, E Cortijo Garcia, P Garcia Bermejo, S Perez, P Mulero Carrillo, E Crespo Vallejo, M Ruiz Piñero, L Lopez Mesonero, FJ Reyes Muñoz, C Brekenfeld, J-H Buhk, A Krützelmann, G Thomalla, B Cheng, C Beck, J Hoppe, E Goebell, B Holst, U Grzyska, G Wortmann, S Starkman, G Duckwiler, R Jahan, N Rao, S Sheth, K Ng, A Noorian, V Szeder, M Nour, M McManus, J Huang, J Tarpley, S Tateshima, N Gonzalez, L Ali, D Liebeskind, J Hinman, M Calderon-Arnulphi, C Liang, J Guzy, S Koch, K DeSousa, G Gordon-Perue, M Elhammady, E Peterson, V Pandey, S Dharmadhikari, P Khandelwal, A Malik, R Pafford, P Gonzalez, K Ramdas, G Andersen, D Damgaard, P Von Weitzel-Mudersbach, C Simonsen, N Ruiz de Morales Ayudarte, M Poulsen, L Sørensen, S Karabegovich, M Hjørringgaard, N Hjort, T Harbo, K Sørensen, E Deshaies, D Padalino, A Swarnkar, JG Latorre, E Elnour, Z El-Zammar, M Villwock, H Farid, A Balgude, L Cross, K Hansen, M Holtmannspötter, D Kondziella, J Hoejgaard, S Taudorf, H Soendergaard, A Wagner, M Cronquist, T Stavngaard, M Cortsen, LH Krarup, T Hyldal, H-P Haring, S Guggenberger, M Hamberger, J Trenkler, M Sonnberger, K Nussbaumer, C Dominger, E Bach, BD Jagadeesan, R Taylor, J Kim, K Shea, R Tummala, H Zacharatos, D Sandhu, M Ezzeddine, A Grande, D Hildebrandt, K Miller, J Scherber, A Hendrickson, M Jumaa, S Zaidi, T Hendrickson, V Snyder, M Killer-Oberpfalzer, J Mutzenbach, F Weymayr, E Broussalis, K Stadler, A Jedlitschka, A Malek, N Mueller-Kronast, P Beck, C Martin, D Summers, J Day, I Bettinger, W Holloway, K Olds, S Arkin, N Akhtar, C Boutwell, S Crandall, M Schwartzman, C Weinstein, B Brion, S Prothmann, J Kleine, K Kreiser, T Boeckh-Behrens, H Poppert, S Wunderlich, ML Koch, V Biberacher, A Huberle, G Gora-Stahlberg, B Knier, T Meindl, D Utpadel-Fischler, M Zech, M Kowarik, C Seifert, B Schwaiger, A Puri, S Hou, A Wakhloo, M Moonis, N Henninger, R Goddeau, F Massari, A Minaeian, JD Lozano, M Ramzan, C Stout, A Patel, A Tunguturi, S Onteddu, R Carandang, M Howk, M Ribó, E Sanjuan, M Rubiera, J Pagola, A Flores, M Muchada, P Meler, E Huerga, S Gelabert, P Coscojuela, A Tomasello, D Rodriguez, E Santamarina, O Maisterra, S Boned, L Seró, A Rovira, CA Molina, M Millán, L Muñoz, N Pérez de la Ossa, M Gomis, L Dorado, E López-Cancio, E Palomeras, J Munuera, P García Bermejo, S Remollo, C Castaño, R García-Sort, P Cuadras, P Puyalto, M Hernández-Pérez, M Jiménez, A Martínez-Piñeiro, G Lucente, A Dávalos, A Chamorro, X Urra, V Obach, A Cervera, S Amaro, L Llull, J Codas, M Balasa, J Navarro, H Ariño, A Aceituno, S Rudilosso, A Renu, JM Macho, L San Roman, J Blasco, A López, N Macías, P Cardona, H Quesada, F Rubio, L Cano, B Lara, MA de Miquel, L Aja, J Serena, E Cobo, Gregory W Albers, Kennedy R Lees, J Arenillas, R Roberts, F Al-Ajlan, L Zimmel, S Patel, J Martí-Fàbregas, M Salvat-Plana, S Bracard, René Anxionnat, Pierre-Alexandre Baillot, Charlotte Barbier, Anne-Laure Derelle, Jean-Christophe Lacour, Sébastien Richard, Yves Samson, Nader Sourour, Flore Baronnet-Chauvet, Frédéric Clarencon, Sophie Crozier, Sandrine Deltour, Federico Di Maria, Raphael Le Bouc, Anne Leger, Gurkan Mutlu, Charlotte Rosso, Zoltan Szatmary, Marion Yger, Chiara Zavanone, Serge Bakchine, Laurent Pierot, Nathalie Caucheteux, Laurent Estrade, Krzysztof Kadziolka, Alexandre Leautaud, Céline Renkes, Isabelle Serre, Hubert Desal, Benoît Guillon, Claire Boutoleau-Bretonniere, Benjamin Daumas-Duport, Solène De Gaalon, Pascal Derkinderen, Sarah Evain, Fanny Herisson, David-Axel Laplaud, Thibaud Lebouvier, Alina Lintia-Gaultier, Hélène Pouclet-Courtemanche, Tiphaine Rouaud, Violaine Rouaud Jaffrenou, Aurélia Schunck, Mathieu Sevin-Allouet, Frederique Toulgoat, Sandrine Wiertlewski, Jean-Yves Gauvrit, Thomas Ronziere, Vincent Cahagne, Jean-Christophe Ferre, Jean-François Pinel, Hélène Raoult, Jean-Louis Mas, Jean-François Meder, Amen-Adam Al Najjar-Carpentier, Julia Birchenall, Eric Bodiguel, David Calvet, Valérie Domigo, Sylvie Godon-Hardy, Vincent Guiraud, Catherine Lamy, Loubna Majhadi, Ludovic Morin, Denis Trystram, Guillaume Turc, Jérôme Berge, Igor Sibon, Patrice Menegon, Xavier Barreau, François Rouanet, Sabrina Debruxelles, Annabelle Kazadi, Pauline Renou, Olivier Fleury, Anne Pasco-Papon, Frédéric Dubas, Jildaz Caroff, Sophie Godard Ducceschi, Marie-Aurélie Hamon, Alderic Lecluse, Guillaume Marc, Maurice Giroud, Frédéric Ricolfi, Yannick Bejot, Adrien Chavent, Arnaud Gentil, Apolline Kazemi, Guy-Victor Osseby, Charlotte Voguet, Marie-Hélène Mahagne, Jacques Sedat, Yves Chau, Laurent Suissa, Sylvain Lachaud, Emmanuel Houdart, Christian Stapf, Frédérique Buffon Porcher, Hugues Chabriat, Pierre Guedin, Dominique Herve, Eric Jouvent, Jérôme Mawet, Jean-Pierre Saint-Maurice, Hans-Martin Schneble, Norbert Nighoghossian, Nadia-Nawel Berhoune, Françoise Bouhour, Tae-Hee Cho, Laurent Derex, Sandra Felix, Hélène Gervais-Bernard, Benjamin Gory, Luis Manera, Laura Mechtouff, Thomas Ritzenthaler, Roberto Riva, Fabrizio Salaris Silvio, Caroline Tilikete, Raphael Blanc, Michaël Obadia, Mario Bruno Bartolini, Antoine Gueguen, Michel Piotin, Silvia Pistocchi, Hocine Redjem, Jacques Drouineau, Jean-Philippe Neau, Gaelle Godeneche, Matthias Lamy, Emilia Marsac, Stephane Velasco, Pierre Clavelou, Emmanuel Chabert, Nathalie Bourgois, Catherine Cornut-Chauvinc, Anna Ferrier, Jean Gabrillargues, Betty Jean, Anna-Raquel Marques, Nicolas Vitello, Olivier Detante, Marianne Barbieux, Kamel Boubagra, Isabelle Favre Wiki, Katia Garambois, Florence Tahon, Vasdev Ashok, Oguzhan Coskun, Georges Rodesch, Bertrand Lapergue, Frédéric Bourdain, Serge Evrard, Philippe Graveleau, Jean Pierre Decroix, Adrien Wang, François Sellal, Guido Ahle, Gabriela Carelli, Marie-Hélène Dugay, Claude Gaultier, Ariel Pablo Lebedinsky, Lavinia Lita, Raul Mariano Musacchio, Catherine Renglewicz-Destuynder, Alain Tournade, Françis Vuillemet, Francisco Macian Montoro, Charbel Mounayer, Frederic Faugeras, Laetitia Gimenez, Catherine Labach, Géraldine Lautrette, Christian Denier, Guillaume Saliou, Olivier Chassin, Claire Dussaule, Elsa Melki, Augustin Ozanne, Francesco Puccinelli, Marina Sachet, Mariana Sarov, Jean-François Bonneville, Thierry Moulin, Alessandra Biondi, Elisabeth De Bustos Medeiros, Fabrice Vuillier, Patrick Courtheoux, Fausto Viader, Marion Apoil-Brissard, Mathieu Bataille, Anne-Laure Bonnet, Julien Cogez, Emmanuel Touze, Xavier Leclerc, Didier Leys, Mohamed Aggour, Pierre Aguettaz, Marie Bodenant, Charlotte Cordonnier, Dominique Deplanque, Marie Girot, Hilde Henon, Erwah Kalsoum, Christian Lucas, Jean-Pierre Pruvo, Paolo Zuniga, Caroline Arquizan, Vincent Costalat, Paolo Machi, Isabelle Mourand, Carlos Riquelme, Pierre Bounolleau, Charles Arteaga, Anthony Faivre, Marc Bintner, Patrice Tournebize, Cyril Charlin, Françoise Darcel, Pascale Gauthier-Lasalarie, Marcia Jeremenko, Servane Mouton, Jean-Baptiste Zerlauth, Chantal Lamy, Deramond Hervé, Hosseini Hassan, André Gaston, Francis-Guy Barral, Pierre Garnier, Rémy Beaujeux, Valérie Wolff, Denis Herbreteau, Séverine Debiais, Alicia Murray, Gary Ford, Martin M Brown, Andy Clifton, Janet Freeman, Ian Ford, Hugh Markus, Joanna Wardlaw, Andy Molyneux, Thompson Robinson, Steff Lewis, John Norrie, Fergus Robertson, Richard Perry, Geoffrey Cloud, Andrew Clifton, Jeremy Madigan, Christine Roffe, Sanjeev Nayak, Kyriakos Lobotesis, Craig Smith, Amit Herwadkar, Naga Kandasamy, Tony Goddard, John Bamford, Ganesh Subramanian, Rob Lenthall, Edward Littleton, Sal Lamin, Kelley Storey, Rita Ghatala, Azra Banaras, John Aeron-Thomas, Bath Hazel, Holly Maguire, Emelda Veraque, Louise Harrison, Rekha Keshvara, James Cunningham, University of Melbourne, University of Calgary, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of Amsterdam [Amsterdam] (UvA), Universitat Autònoma de Barcelona (UAB), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Neurology, Graduate School, Other Research, APH - Personalized Medicine, APH - Quality of Care, Biomedical Engineering and Physics, ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, ACS - Pulmonary hypertension & thrombosis, Radiology & Nuclear Medicine, Public Health, Weimar, Christian (Beitragende*r), Molecular cell biology and Immunology, Pathology, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, Rheumatology, Beeldvorming, RS: CARIM - R3.03 - Cerebral small vessel disease, RS: CARIM - R3.11 - Imaging, MUMC+: DA BV Medisch Specialisten Radiologie (9), Klinische Neurowetenschappen, and MUMC+: MA Neurologie (3)
Subjects: Male, medicine.medical_specialty, Sedation, Medizin, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Anesthesia, General, CONTROLLED-TRIAL, THERAPY, law.invention, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Randomized controlled trial, law, Modified Rankin Scale, Journal Article, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Medicine, Humans, General anaesthesia, Stroke, Aged, Randomized Controlled Trials as Topic, Thrombectomy, Aged, 80 and over, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, MR, Middle Aged, Outcome and Process Assessment (Health Care), medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], 3. Good health, Surgery, Outcome and Process Assessment, Health Care, Meta-analysis, Observational study, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Meta-Analysis
Abstract: BACKGROUND: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care.METHODS: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered.FINDINGS: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09-2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75-3·10, pINTERPRETATION: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons.FUNDING: Medtronic.
Published: 2018

65. Paracetamol (Acetaminophen) in stroke 2 (PAIS 2): Protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36.5 degrees C or above

Author: Ritu Saxena, Ale Algra, Heleen M. den Hertog, Frank Jan de Jong, Diederik W.J. Dippel, Hester F. Lingsma, Peter J. Koudstaal, H. Maarten A. van Gemert, A. H C M L Tobien Schreuder, Inger R. de Ridder, Jordie H. van Tuijl, Annemieke Ruitenberg, L. Jaap Kappelle, E. Lisette Maasland, Peter Oomes, H. Bart van der Worp, Neurology, and Public Health
Subjects: Male, Antipyretics, Fever, Placebo, Body Temperature, law.invention, Clinical Protocols, Double-Blind Method, Randomized controlled trial, law, Modified Rankin Scale, medicine, Humans, Multicenter Studies as Topic, Stroke, Acetaminophen, Randomized Controlled Trials as Topic, Intracerebral hemorrhage, Dose-Response Relationship, Drug, business.industry, digestive, oral, and skin physiology, Odds ratio, medicine.disease, Clinical trial, Neurology, Anesthesia, Female, business, medicine.drug
Abstract: Rationale In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37·0°C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1·43; 95% confidence interval: 1·02–1·97). This relation was also found in the patients with a body temperature of 36·5°C or higher (odds ratio 1·31; 95% confidence interval 1·01–1·68). These findings need confirmation. Aim The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36·5°C or above on functional outcome. Design The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0·05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36·5°C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. Study outcomes The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. Discussion If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide.
Published: 2015

66. Safety and feasibiLIty of Metformin in patients with Impaired glucose Tolerance and a recent TIA or minor ischemic stroke (LIMIT) trial - a multicenter, randomized, open-label phase II trial

Author: Peter J. Koudstaal, Ale Algra, Sefanja Achterberg, Sarah E. Vermeer, Diederik W.J. Dippel, Heleen M. den Hertog, L. J. Kappelle, Adrienne A.M. Zandbergen, and Neurology
Subjects: Blood Glucose, Male, medicine.medical_specialty, Neurology, Carbohydrate metabolism, Clinical Trial, Phase II, law.invention, Impaired glucose tolerance, Randomized controlled trial, law, Internal medicine, Antidiabetics, medicine, Journal Article, Humans, Hypoglycemic Agents, Lead (electronics), Secondary stroke prevention, Medicine(all), Ischemic stroke, business.industry, TIA, Middle Aged, medicine.disease, Clinical Trial, Metformin, Phase II, Surgery, Discontinuation, Stroke, Multicenter Study, Ischemic Attack, Transient, Randomized Controlled Trial, Female, business, medicine.drug
Abstract: Background and purpose We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. Methods We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8–11.0 mmol/l) were randomized to metformin, in a daily dose of 2 g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. Results Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3–10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97 mmol/l (95% CI 0·11–1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71 mmol/l; 95% CI −0·36 to 1·78). Conclusions Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.
Published: 2015

67. Critical illness-induced dysglycemia and the brain

Author: Heleen M. den Hertog, Tarek Sharshar, Djillali Annane, Fabrice Chrétien, Greet Van den Berghe, Ilse Vanhorebeek, Romain Sonneville, and Neurology
Subjects: Blood Glucose, medicine.medical_specialty, endocrine system diseases, Critical Illness, medicine.medical_treatment, Hypoglycemia, Critical Care and Intensive Care Medicine, Neuroprotection, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Intensive care, Internal medicine, Anesthesiology, Humans, Hypoglycemic Agents, Medicine, Intensive care medicine, Glucose Metabolism Disorders, 030304 developmental biology, Intracranial pressure, Brain Diseases, 0303 health sciences, Rehabilitation, business.industry, nutritional and metabolic diseases, Brain, Isolated brain, medicine.disease, 3. Good health, Endocrinology, business, 030217 neurology & neurosurgery
Abstract: Dysglycemia is a characteristic feature of critical illness associated with adverse outcome. Whether dysglycemia contributes to brain dysfunction during critical illness and long-term neurological complications is unclear. We give an overview of glucose metabolism in the brain and review the literature on critical illness-induced dysglycemia and the brain. Medline database search using relevant search terms on dysglycemia, critical illness, acute brain injury/dysfunction, and randomized controlled trial. Hyperglycemia has been associated with deleterious effects on the nervous system. Underlying mechanisms in critical illness remain largely speculative and are often extrapolated from knowledge in diabetes mellitus. Increased hyperglycemia-induced blood–brain barrier permeability, oxidative stress, and microglia activation may play a role and compromise neuronal and glial cell integrity. Hypoglycemia is feared as critically ill patients cannot recognize or communicate hypoglycemic symptoms, which furthermore are masked by sedation and analgesia. However, observational data on the impact of brief hypoglycemia on the brain in critical illness are controversial. Secondary analysis of two large randomized studies suggested neuroprotection by strict glycemic control with insulin during intensive care, with lowered intracranial pressure, reduction of seizures, and better long-term rehabilitation in patients with isolated brain injury, and reduced incidence of critical illness polyneuromyopathy in the general critically ill patient population. Several subsequent studies failed to reproduce neurological benefit, likely explained by methodological issues, which include divergent achieved glucose levels and inaccurate glucose monitoring tools. Preventing hyperglycemia during critical illness holds promise as a neuroprotective strategy to preserve brain cell viability and prevent acute brain dysfunction and long-term cognitive impairment in survivors.
Published: 2015

68. Prediabetes in Patients with Stroke or Transient Ischemic Attack: Prevalence, Risk and Clinical Management

Author: Adrienne A.M. Zandbergen, Heleen M. den Hertog, Peter J. Koudstaal, and Susanne Fonville
Subjects: Risk, medicine.medical_specialty, business.industry, medicine.disease, Impaired fasting glucose, Prediabetic State, Stroke, Impaired glucose tolerance, Clinical trial, Endocrinology, Insulin resistance, Neurology, Ischemic Attack, Transient, Diabetes mellitus, Internal medicine, Prevalence, Secondary Prevention, medicine, Humans, Neurology (clinical), Prediabetes, Risk factor, Cardiology and Cardiovascular Medicine, business
Abstract: Background: The prevalence of diabetes is emerging worldwide and is an important modifiable risk factor for stroke. People with prediabetes, an intermediate metabolic state between normal glucose metabolism and diabetes, have a tenfold increased risk of developing diabetes compared to those with a normal glucose metabolism. Prediabetes is comprised of impaired fasting glucose and/or impaired glucose tolerance and/or disturbed glycosylated hemoglobin levels. Prediabetes is highly prevalent in nondiabetic patients with transient ischemic attack (TIA) or ischemic stroke and nearly doubles their risk of stroke. This offers new options for secondary stroke prevention. Summary: Several detection methods exist for identifying (pre)diabetes, including fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels. The concordance between these tests is not 100%, and they seem to be complementary. Screening for (pre)diabetes after stroke with fasting plasma glucose levels alone is insufficient, and 2-hour postload glucose and/or glycosylated hemoglobin levels should be determined as well. The prevalence of prediabetes in previously nondiabetic patients with a recent TIA or stroke ranges from 23 to 53%. This high prevalence in the acute phase after stroke can be transient or persistent, representing undiagnosed abnormal glucose metabolism. Impaired fasting glucose and impaired glucose tolerance have different pathophysiological mechanisms, including hepatic insulin resistance and muscle insulin resistance, respectively. Prediabetes seems to be a modest predictor for stroke, but doubles the risk for recurrent stroke. The relation between prediabetes after stroke and functional outcome is still unknown. However, it is most likely that prediabetes is a risk factor for a poor clinical outcome after stroke. There is a growing recognition that patients with prediabetes should be treated more aggressively. Both lifestyle and pharmacological interventions are possible treatment strategies. They are at least equally effective in preventing progression to diabetes. Lifestyle changes are difficult to maintain over a long period. The evidence of pharmacological interventions on stroke or other cardiovascular diseases is limited though and is still subject of several clinical trials. Conclusions: As the prevalence of prediabetes is growing rapidly, prediabetes might become one of the most important modifiable therapeutic targets in both primary and secondary prevention.
Published: 2014

69. Contents Vol. 37, 2014

Author: Charles DeCarli, Pierre Etienne Leblanc, Yan Borné, Yukako Yazawa, Yasuhiro Ishibashi, Ying Kuen Cheung, Mitsuhiro Yoshita, Clinton B. Wright, Denis Ducreux, Joshua Z. Willey, Guillaume Saliou, Yeseon P. Moon, Druckerei Stückle, Yasushi Okada, Kozo Tanno, Christian Marescaux, Michael J. Lynn, Zoran Rumboldt, Peter J. Koudstaal, Fredrik Björklund, Anna Graipe, Heleen M. den Hertog, Akira Ogawa, Hisatomi Arima, Bernard Geny, Kenta Kawata, Eisuke Furui, Jean-Paul Armspach, Rémy Beaujeux, Catherine Ract, Valérie Lauer, Gunnar Engström, Kiyomi Sakata, Yuki Yoshida, John Berntsson, Shyam Prabhakaran, Kuniaki Ogasawara, Nobuyuki Yasui, Yasuhiro Hasegawa, Alejandro M. Brunser, Ryo Itabashi, Maria Matheus, Stina Jakobsson, Kazuyuki Nagatsuka, Hannah Gardener, Elisabet Zia, Motoyuki Nakamura, Olle Melander, Toshiyuki Uehara, Etsuro Mori, Thomas Mooe, Verónica V. Olavarría, Pablo M. Lavados, Marc I. Chimowitz, Kazuyoshi Itai, Stephane Heritier, Masaki Ohsawa, Kazuo Minematsu, Toshiyuki Onoda, Elena López-Cancio, Olivier Rouyer, Shoichiro Sato, Shinichi Omama, Mitchell S.V. Elkind, Satz Mengensatzproduktion, Daniel Huber, Bo Hedblad, Cécile Cauquil, Susanne Fonville, Valérie Wolff, Ralph L. Sacco, David S Liebeskind, Nicolas Meyer, Adrienne A.M. Zandbergen, Craig S. Anderson, Jose G. Romano, Tanya N. Turan, George Cotsonis, Paula Muñoz-Venturelli, Monica Manisor, and Marie Théaudin
Subjects: Neurology, Traditional medicine, business.industry, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published: 2014

70. Common variants associated with plasma triglycerides and risk for coronary artery disease

Author: Richard S. Cooper, Angela Döring, Cisca Wijmenga, Jerome I. Rotter, Linda S. Adair, Tõnu Esko, Jennifer L. Bragg-Gresham, Danish Saleheen, Narisu Narisu, Xiaohui Li, Kathleen Stirrups, Ulf de Faire, Nicholas G. Martin, Dmitry Shungin, Peter Vollenweider, Yii-Der Ida Chen, Dharambir K. Sanghera, George Dedoussis, Toshiko Tanaka, Manjinder S. Sandhu, Anne U. Jackson, Nancy L. Pedersen, Maria Dimitriou, Shih-Yi Lin, David P. Strachan, Isleifur Olafsson, Ruth J. F. Loos, Kay-Tee Khaw, Antero Kesäniemi, Rainer Rauramaa, Wendy L. McArdle, Gonneke Willemsen, Dena G. Hernandez, May E. Montasser, Amy J. Swift, Colin A. McKenzie, Aaron Isaacs, Latonya F. Been, Leif Groop, Massimo Mangino, Martina Müller-Nurasyid, Karen L. Mohlke, Ci Song, Sailaja Vedantam, Anna-Liisa Hartikainen, Lori L. Bonnycastle, Ilja M. Nolte, Jaakko Kaprio, Anneli Pouta, Unnur Thorsteinsdottir, Paul Elliott, Muredach P. Reilly, Jean Ferrières, Daniel J. Rader, Elizabeth H. Young, Jaspal S. Kooner, Leena Moilanen, Markku Laakso, Albert Hofman, Kelly A. Volcik, Sekar Kathiresan, Tamara B. Harris, Eric Kim, Aimo Ruokonen, Andrea Ganna, Serena Sanna, John J.P. Kastelein, Martha L. Gravito, Ronald M. Krauss, Ken K. Ong, Paul M. Ridker, Kristian Hveem, Ayse Demirkan, Alena Stančáková, Pierre Meneton, Thomas Quertermous, John Danesh, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Christopher J. Groves, Jaakko Tuomilehto, Michael Boehnke, Jose M. Ordovas, Alan B. Feranil, Chao A. Hsiung, Wayne Huey-Herng Sheu, Igor Rudan, Christa Meisinger, Rebecca N. Nsubuga, Bruna Gigante, Inger Njølstad, Göran Hallmans, Aroon D. Hingorani, Jouko Saramies, Deepti Gurdasani, Fernando Rivadeneira, Andres Metspalu, Stephen E. Epstein, Gonçalo R. Abecasis, Braxton D. Mitchell, Devin Absher, Marcus E. Kleber, Sonia Shah, Pierre Fontanillas, Jeffrey R. O'Connell, Louise A. Donnelly, Jing Hua Zhao, Martin L. Buchkovich, Francis S. Collins, Gabrielle Müller, Matti Uusitupa, Evelin Mihailov, Nicholas J. Wareham, Andrew A. Hicks, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Jaana Lindström, Mark I. McCarthy, Evita G. Van Den Herik, Kirsten Ohm Kyvik, Vilmundur Gudnason, Jackie F. Price, Joel N. Hirschhorn, Winfried März, Aravinda Chakravarti, Pontiano Kaleebu, James F. Wilson, Lindsay L. Waite, Leo-Pekka Lyytikäinen, Sebanti Sengupta, Mika Kivimäki, David Altshuler, Hilma Holm, Rona J. Strawbridge, Harald Grallert, Ramaiah Nagaraja, Laurence Tiret, G. Kees Hovingh, Meena Kumari, Nilesh J. Samani, Daniel F. Freitag, Nelson B. Freimer, Thomas Illig, Panos Deloukas, Bernhard O. Boehm, Nicholas W.J. Wainwright, Mark J. Daly, Mika Kähönen, Michel Burnier, Norman Klopp, L. Adrienne Cupples, Aarno Palotie, Markus Perola, Bamidele O. Tayo, Timo A. Lakka, Matthew Jones, Sarah H. Wild, Patricia B. Munroe, Antti Jula, François Mach, Peter J. Koudstaal, Pirjo Komulainen, Eric Boerwinkle, L. Joost van Pelt, Veikko Salomaa, Ann-Kristin Petersen, Ida Surakka, Andrew Wong, Caroline Hayward, Chi Gao, Cristen J. Willer, Stephen S. Rich, Yi Jen Hung, Peter P. Pramstaller, Diana Kuh, Ron Do, Dominique Arveiler, Mark O. Goodarzi, Ross M. Fraser, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Mary Susan Burnett, Patrik K. E. Magnusson, John C. Chambers, Benjamin M. Neale, Peter Schwarz, Jennifer L. Bolton, Murielle Bochud, Heleen M. den Hertog, Christian Gieger, Cristina Pomilla, Teresa Ferreira, Lars Wallentin, Richa Saxena, André G. Uitterlinden, Kaisa Silander, Ying Wu, Bruce M. Psaty, Jian'an Luan, Hsing-Yi Chang, Jin Chen, Daniel I. Chasman, Ulf Gyllensten, Kari Stefansson, Kauko Heikkilä, Tom Wilsgaard, Alan R. Shuldiner, Carlos Iribarren, Stavroula Kanoni, John Whitfield, Gershim Asiki, Marika Kaakinen, Georg Ehret, Elina Hyppönen, Claudia Langenberg, Gina M. Peloso, Cecilia M. Lindgren, Carlo Sidore, Gudmundur I. Eyjolfsson, Cameron D. Palmer, Jacques S. Beckmann, Hubert Scharnagl, Tanya M. Teslovich, Mary F. Feitosa, Terho Lehtimäki, Steve E. Humphries, Chris Power, Benjamin F. Voight, Stefania Bandinelli, Andrew D. Morris, Gudmar Thorleifsson, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Themistocles L. Assimes, Pascal Bovet, Luigi Ferrucci, Johannes Kettunen, Inês Barroso, Franklyn I. Bennett, Stefan Gustafsson, Paolo Brambilla, Theodore Papamarkou, Elena Tremoli, Janet Seeley, Alex S. F. Doney, Johanna Kuusisto, Giancarlo Cesana, Bruce H. R. Wolffenbuttel, Lars Lind, Stefan R. Bornstein, Åsa Johansson, Anders Hamsten, Marjo-Riitta Järvelin, Krista Fischer, Agneta Siegbahn, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, Do, Ron, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Hyppönen, Elina, Kathiresan, Sekar, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Do, R, Willer, C, Schmidt, E, Sengupta, S, Gao, C, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stančáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Altshuler, D, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Mohlke, K, Ingelsson, E, Abecasis, G, Daly, M, Neale, B, and Kathiresan, S
Subjects: Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Heart disease, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, ISCHEMIC-HEART-DISEASE, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Polymorphism (computer science), Risk Factors, High-density-lipoprotein, Genetic epidemiology, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Cholesterol, HDL/blood, Cholesterol levels, Loci, Contribute, Single Nucleotide, LDL/blood, Triglycerides/blood, Cholesterol, Cholesterol, LDL/blood, HDL/blood, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, Human, medicine.medical_specialty, TYPE-2 DIABETES-MELLITUS, Biology, Polymorphism, Single Nucleotide, Article, HIGH-DENSITY-LIPOPROTEIN ISCHEMIC-HEART-DISEASE TYPE-2 DIABETES-MELLITUS MENDELIAN RANDOMIZATION CARDIOVASCULAR-DISEASE GENETIC EPIDEMIOLOGY CHOLESTEROL LEVELS LOCI CONTRIBUTE THERAPY, 03 medical and health sciences, Coronary Artery Disease/blood, SDG 3 - Good Health and Well-being, Cardiovascular-disease, Internal medicine, Mendelian randomization, Genetics, medicine, Humans, Polymorphism, plasma, Triglycerides, 030304 developmental biology, Science & Technology, Risk Factor, Cholesterol, HDL, Biological Transport, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, Heart-disease, lipoproteins, Endocrinology, chemistry, Therapy, Developmental Biology
Abstract: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10 -8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. © 2013 Nature America, Inc. All rights reserved.
Published: 2013

71. Discovery and refinement of loci associated with lipid levels

Author: Benjamin F. Voight, Stefania Bandinelli, Pascal Bovet, Latonya F. Been, Ci Song, Luigi Ferrucci, Johannes Kettunen, Andrew D. Morris, Mary Susan Burnett, Ronald M. Krauss, Igor Rudan, Heleen M. den Hertog, Stavroula Kanoni, G. Kees Hovingh, Elina Hyppönen, Kauko Heikkilä, Richard S. Cooper, Daniel I. Chasman, Bruna Gigante, Stefan Gustafsson, Jian'an Luan, Sarah H. Wild, Patricia B. Munroe, Göran Hallmans, Jeffrey R. O'Connell, Danish Saleheen, Aarno Palotie, Leena Moilanen, Jerome I. Rotter, Caroline Hayward, Jennifer L. Bragg-Gresham, Nicholas G. Martin, Claudia Langenberg, George Dedoussis, Carlo Sidore, Ulf Gyllensten, Marika Kaakinen, Jing Hua Zhao, Aimo Ruokonen, Diana Kuh, Maria Dimitriou, Shih-Yi Lin, Gina M. Peloso, Marcus E. Kleber, Christopher J. Groves, Alena Stančáková, Michel Burnier, Patrik K. E. Magnusson, John C. Chambers, Giancarlo Cesana, Francis S. Collins, Gabrielle Müller, Angela Döring, Colin A. McKenzie, Paul Elliott, Lars Lind, Vilmundur Gudnason, Dharambir K. Sanghera, Jean Ferrières, Toshiko Tanaka, Stefan R. Bornstein, Gershim Asiki, Jacques S. Beckmann, Anneli Pouta, Timo A. Lakka, Daniel J. Rader, Elizabeth H. Young, Kelly A. Volcik, Dena G. Hernandez, Ann-Kristin Petersen, Kristian Hveem, Amy J. Swift, Murielle Bochud, Pierre Meneton, Paul M. Ridker, Kathleen Stirrups, Stephen S. Rich, Isleifur Olafsson, Ruth J. F. Loos, Serena Sanna, Markus Perola, Meena Kumari, Cameron D. Palmer, Carlos Iribarren, Nancy L. Pedersen, Mark O. Goodarzi, Panos Deloukas, Norman Klopp, Cristina Pomilla, Stephen E. Epstein, Antti Jula, Themistocles L. Assimes, Martina Müller-Nurasyid, Marjo-Riitta Järvelin, Chao A. Hsiung, Sonia Shah, Christian Gieger, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Nicholas J. Wareham, Krista Fischer, Wendy L. McArdle, Linda S. Adair, Kay-Tee Khaw, Bruce M. Psaty, André G. Uitterlinden, Aaron Isaacs, Tõnu Esko, Jennifer L. Bolton, Rebecca N. Nsubuga, Eric Boerwinkle, L. Joost van Pelt, Jouko Saramies, François Mach, Pierre Fontanillas, Teresa Ferreira, Lars Wallentin, Michael Boehnke, Christa Meisinger, Wayne Huey-Herng Sheu, Gonçalo R. Abecasis, Inês Barroso, Franklyn I. Bennett, Dmitry Shungin, Jaakko Kaprio, Kirsten Ohm Kyvik, Deepti Gurdasani, Anne U. Jackson, Paolo Brambilla, Georg Ehret, Cecilia M. Lindgren, Fernando Rivadeneira, Theodore Papamarkou, Jaakko Tuomilehto, Cristen J. Willer, Martin L. Buchkovich, Antero Kesäniemi, Hubert Scharnagl, Xiaohui Li, Elena Tremoli, Nelson B. Freimer, Mika Kähönen, Ron Do, Karen L. Mohlke, Thomas Illig, Gudmar Thorleifsson, Peter J. Koudstaal, Andres Metspalu, Ulf de Faire, Dominique Arveiler, Harald Grallert, Jaana Lindström, Laurence Tiret, Jaspal S. Kooner, Braxton D. Mitchell, Sebanti Sengupta, Gonneke Willemsen, Anna-Liisa Hartikainen, Terho Lehtimäki, Steve E. Humphries, Peter Schwarz, Dorret I. Boomsma, Harry Campbell, Ellen M. Schmidt, Tom Wilsgaard, Janet Seeley, Alex S. F. Doney, Alan R. Shuldiner, John Whitfield, Markku Laakso, Peter Vollenweider, Gudmundur I. Eyjolfsson, Winfried März, Mika Kivimäki, Ying Wu, Johanna Kuusisto, Andrew A. Hicks, Bruce H. R. Wolffenbuttel, May E. Montasser, Bamidele O. Tayo, Unnur Thorsteinsdottir, Muredach P. Reilly, Leo-Pekka Lyytikäinen, Eric Kim, John Danesh, Ida Surakka, Åsa Johansson, Anders Hamsten, Thomas Quertermous, Hsing-Yi Chang, Jin Chen, Agneta Siegbahn, Narisu Narisu, Samia Mora, Erik Ingelsson, Colin N. A. Palmer, Sekar Kathiresan, Manjinder S. Sandhu, Leif Groop, Jose M. Ordovas, Alan B. Feranil, Evelin Mihailov, Hilma Holm, Pontiano Kaleebu, Lindsay L. Waite, Ramaiah Nagaraja, Andrew Wong, Rona J. Strawbridge, David P. Strachan, Yii-Der Ida Chen, Tamara B. Harris, Jackie F. Price, Aravinda Chakravarti, Veikko Salomaa, Sailaja Vedantam, Albert Hofman, Devin Absher, Ross M. Fraser, Kaisa Silander, Pirjo Komulainen, Yi Jen Hung, Peter P. Pramstaller, Kari Stefansson, Aroon D. Hingorani, Tanya M. Teslovich, Matti Uusitupa, L. Adrienne Cupples, Cisca Wijmenga, Lori L. Bonnycastle, Ilja M. Nolte, Andrea Ganna, Ken K. Ong, Inger Njølstad, Bernhard O. Boehm, Nicholas W.J. Wainwright, Richa Saxena, Rainer Rauramaa, Louise A. Donnelly, James F. Wilson, Matthew Jones, Ingrid B. Borecki, Steven C. Hunt, Weihua Zhang, Massimo Mangino, John J.P. Kastelein, Martha L. Gravito, Mark I. McCarthy, Evita G. Van Den Herik, Joel N. Hirschhorn, Nilesh J. Samani, Daniel F. Freitag, Ayse Demirkan, Mary F. Feitosa, Tuomo Nieminen, Tim D. Spector, Paul W. Franks, Chris Power, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Willer, C, Schmidt, E, Sengupta, S, Peloso, G, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, M, Mora, S, Beckmann, J, Bragg Gresham, J, Chang, H, Demirkan, A, Den Hertog, H, Do, R, Donnelly, L, Ehret, G, Esko, T, Feitosa, M, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, R, Freitag, D, Gurdasani, D, Heikkilä, K, Hyppönen, E, Isaacs, A, Jackson, A, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, M, Li, X, Luan, J, Lyytikäinen, L, Magnusson, P, Mangino, M, Mihailov, E, Montasser, M, Müller Nurasyid, M, Nolte, I, O'Connell, J, Palmer, C, Perola, M, Petersen, A, Sanna, S, Saxena, R, Service, S, Shah, S, Shungin, D, Sidore, C, Song, C, Strawbridge, R, Surakka, I, Tanaka, T, Teslovich, T, Thorleifsson, G, Van den Herik, E, Voight, B, Volcik, K, Waite, L, Wong, A, Wu, Y, Zhang, W, Absher, D, Asiki, G, Barroso, I, Been, L, Bolton, J, Bonnycastle, L, Brambilla, P, Burnett, M, Cesana, G, Dimitriou, M, Doney, A, Döring, A, Elliott, P, Epstein, S, Eyjolfsson, G, Gigante, B, Goodarzi, M, Grallert, H, Gravito, M, Groves, C, Hallmans, G, Hartikainen, A, Hayward, C, Hernandez, D, Hicks, A, Holm, H, Hung, Y, Illig, T, Jones, M, Kaleebu, P, Kastelein, J, Khaw, K, Kim, E, Klopp, N, Komulainen, P, Kumari, M, Langenberg, C, Lehtimäki, T, Lin, S, Lindström, J, Loos, R, Mach, F, Mcardle, W, Meisinger, C, Mitchell, B, Müller, G, Nagaraja, R, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Ong, K, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Rader, D, Reilly, M, Ridker, P, Rivadeneira, F, Rudan, I, Ruokonen, A, Samani, N, Scharnagl, H, Seeley, J, Silander, K, Stancáková, A, Stirrups, K, Swift, A, Tiret, L, Uitterlinden, A, van Pelt, L, Vedantam, S, Wainwright, N, Wijmenga, C, Wild, S, Willemsen, G, Wilsgaard, T, Wilson, J, Young, E, Zhao, J, Adair, L, Arveiler, D, Assimes, T, Bandinelli, S, Bennett, F, Bochud, M, Boehm, B, Boomsma, D, Borecki, I, Bornstein, S, Bovet, P, Burnier, M, Campbell, H, Chakravarti, A, Chambers, J, Chen, Y, Collins, F, Cooper, R, Danesh, J, Dedoussis, G, de Faire, U, Feranil, A, Ferrières, J, Ferrucci, L, Freimer, N, Gieger, C, Groop, L, Gudnason, V, Gyllensten, U, Hamsten, A, Harris, T, Hingorani, A, Hirschhorn, J, Hofman, A, Hovingh, G, Hsiung, C, Humphries, S, Hunt, S, Hveem, K, Iribarren, C, Järvelin, M, Jula, A, Kähönen, M, Kaprio, J, Kesäniemi, A, Kivimaki, M, Kooner, J, Koudstaal, P, Krauss, R, Kuh, D, Kuusisto, J, Kyvik, K, Laakso, M, Lakka, T, Lind, L, Lindgren, C, Martin, N, März, W, Mccarthy, M, Mckenzie, C, Meneton, P, Metspalu, A, Moilanen, L, Morris, A, Munroe, P, Njølstad, I, Pedersen, N, Power, C, Pramstaller, P, Price, J, Psaty, B, Quertermous, T, Rauramaa, R, Saleheen, D, Salomaa, V, Sanghera, D, Saramies, J, Schwarz, P, Sheu, W, Shuldiner, A, Siegbahn, A, Spector, T, Stefansson, K, Strachan, D, Tayo, B, Tremoli, E, Tuomilehto, J, Uusitupa, M, van Duijn, C, Vollenweider, P, Wallentin, L, Wareham, N, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Boerwinkle, E, Thorsteinsdottir, U, Chasman, D, Rotter, J, Franks, P, Ripatti, S, Cupples, L, Sandhu, M, Rich, S, Boehnke, M, Deloukas, P, Kathiresan, S, Mohlke, K, Ingelsson, E, Abecasis, G, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Ehret, Georg Benedikt, Mach, François, Epidemiology, Surgery, Public Health, Ophthalmology, Neurology, Medical Microbiology & Infectious Diseases, Obstetrics & Gynecology, Internal Medicine, National Institute for Health Research, Global Lipids Genetics Consortium, Willer, Cristen, Sengupta, Sebanti, Peloso, Gina, Hypponen, Elina Tuulikki, and Abecasis, Gonçalo R
Subjects: Netherlands Twin Register (NTR), HOMEOSTASIS, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Blood lipids, Genome-wide association study, Type 2 diabetes, Coronary Artery Disease, 030204 cardiovascular system & hematology, Triglyceride, Coronary artery disease, chemistry.chemical_compound, 0302 clinical medicine, European Continental Ancestry Group/genetics, triglycerides, IDENTIFIES 13, 11 Medical and Health Sciences, African Continental Ancestry Group, 2. Zero hunger, Genetics, Genetics & Heredity, ddc:616, RISK, 0303 health sciences, Cholesterol, HDL/blood, PLASMA, Global Lipids Genetics Consortium, Cholesterol, HDL/blood/genetics, Lipid, Lipids, 3. Good health, LDL/blood, Triglycerides/blood, Lipids/blood/genetics, Cholesterol, Cholesterol, LDL/blood, DENSITY-LIPOPROTEIN CHOLESTEROL, CARDIOVASCULAR-DISEASE, HDL/blood, CORONARY-ARTERY-DISEASE, lipids (amino acids, peptides, and proteins), Life Sciences & Biomedicine, coronary artery disease, TRAITS, Human, Coronary Artery Disease/blood/genetics, Asian Continental Ancestry Group, Genotype, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Black People, HEART-DISEASE, Biology, Article, White People, lipids, 03 medical and health sciences, Coronary Artery Disease/blood, CORONARY-ARTERY-DISEASE DENSITY-LIPOPROTEIN CHOLESTEROL GENOME-WIDE ASSOCIATION HEART-DISEASE CARDIOVASCULAR-DISEASE SUSCEPTIBILITY LOCI IDENTIFIES 13 RISK GENE METAANALYSIS, Triglycerides/blood/genetics, Asian People, SDG 3 - Good Health and Well-being, Mendelian randomization, medicine, Humans, Asian Continental Ancestry Group/genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Genotyping, Triglycerides, METAANALYSIS, 030304 developmental biology, Science & Technology, Lipids/blood, Cholesterol, HDL, cholesterol, African Continental Ancestry Group/genetics, Cholesterol, LDL, 06 Biological Sciences, medicine.disease, GENE, chemistry, Cholesterol, LDL/blood/genetics, Lipoprotein, Developmental Biology, Genome-Wide Association Study
Abstract: Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research. © 2013 Nature America, Inc. All rights reserved.
Published: 2013
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72. Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke

Author: Emilie M.M. Santos, Henk A. Marquering, Mark D. den Blanken, Olvert A. Berkhemer, Anna M.M. Boers, Albert J. Yoo, Ludo F. Beenen, Kilian M. Treurniet, Carrie Wismans, Kim van Noort, Hester F. Lingsma, Diederik W.J. Dippel, Aad van der Lugt, Wim H. van Zwam, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wiro J. Niessen, Charles B. Majoie, Puck S.S. Fransen, Debbie Beumer, Lucie A. van den Berg, Wouter J. Schonewille, Jan Albert Vos, Paul J. Nederkoorn, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jacques A. van Oostayen, Geert J. Lycklama à Nijeholt, Jelis Boiten, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, Ewoud J. van Dijk, Joost de Vries, Paul L.M. de Kort, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Marieke C. Visser, Joseph C.J. Bot, Patrick C. Vroomen, Omid Eshghi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Alexander V. Tielbeek, Heleen M. den Hertog, Dick G. Gerrits, Renske M. van den Berg-Vos, Giorgos B. Karas, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Peter J. Koudstaal, H. Zwenneke Flach, Ewout W. Steyerberg, Martin M. Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich P. Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Annemieke Lindl-Velema, Corina Puppels, Wilma Pellikaan, Kirsten Janssen, Nicole Aaldering, Marjan Elfrink, Joke de Meris, Annet Geerlings, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Willy Struijk, Tiny Simons, Gert Messchendorp, Friedus van der Minne, Hester Bongenaar, Karin Bodde, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie-Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets, Merel Boers, Jordi Borst, Ivo Jansen, Manon Kappelhof, Marit Lucas, Ralph Geuskens, Renan Sales Barros, Roeland Dobbe, Marloes Csizmadia, Other departments, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, Biomedical Engineering and Physics, Graduate School, Other Research, Neurology, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.11 - Imaging, RS: CARIM - R3.03 - Cerebral small vessel disease, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), Medical Informatics, Radiology & Nuclear Medicine, and Public Health
Subjects: Male, Brain Ischemia, 030218 nuclear medicine & medical imaging, Brain ischemia, arteries, 0302 clinical medicine, Stroke, Netherlands, Endovascular Procedures, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Thrombosis, stroke, reperfusion, Treatment Outcome, medicine.anatomical_structure, cardiovascular system, Female, TRIAL, Radiology, INTRAVENOUS THROMBOLYSIS, Cardiology and Cardiovascular Medicine, BURDEN, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Artery, medicine.medical_specialty, Capillary Permeability, 03 medical and health sciences, medicine, Humans, cardiovascular diseases, Thrombus, VESSEL OCCLUSIONS, thrombosis, Aged, Advanced and Specialized Nursing, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Blood flow, medicine.disease, CT ANGIOGRAPHY, Confidence interval, Radiography, Intracranial Thrombosis, SIZE, Neurology (clinical), permeability, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose— Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. Methods— Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. Results— Patients with Δ≥10.9 HU (n=81 [44%]) and ε≥6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7–6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3–4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, −0.39 for Δ and −0.40 for ε). Conclusions— This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.
Published: 2016

73. Impact of Hyperglycemia on Neuropathological Alterations during Critical Illness

Author: Ilse Vanhorebeek, Romain Sonneville, Djillali Annane, Heleen M. den Hertog, Jean-Philippe Brouland, Inge Derese, Françoise Gray, Philippe Charlier, Andrea Polito, Jan Gunst, Greet Van den Berghe, Fabrice Chrétien, Pieter Wouters, Fabian Güiza, and Tarek Sharshar
Subjects: Adult, Blood Glucose, Male, endocrine system diseases, Critical Illness, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Context (language use), Hippocampus, Biochemistry, Neuroprotection, law.invention, Endocrinology, Risk Factors, law, Animals, Humans, Hypoglycemic Agents, Insulin, Medicine, Aged, Out of hospital, Brain Diseases, business.industry, Critically ill, Biochemistry (medical), nutritional and metabolic diseases, Middle Aged, Intensive care unit, Frontal Lobe, Disease Models, Animal, Hyperglycemia, Anesthesia, Critical illness, Female, Microglia, Rabbits, business, Hyperglycemic agent
Abstract: Although preventing excessive hyperglycemia during critical illness may provide clinical neuroprotection, it remains debated whether normoglycemia is without risk for the brain.To address this question, we compared the neuropathological alterations in microglia, astrocytes, and neurons, with uncontrolled hyperglycemia, moderately controlled hyperglycemia, and normoglycemia during human critical illness. We further investigated the time course in an animal model.We analyzed brain specimens from patients who died in the intensive care unit and from critically ill rabbits randomized to hyper- or normoglycemia. PATIENTS/OTHER PARTICIPANTS: We compared 10 critically ill patients randomized to normoglycemia (104 ±9 mg/dl) or moderate hyperglycemia (173 ±32 mg/dl), and five patients with uncontrolled hyperglycemia (254 ±83 mg/dl) with 16 controls (out of hospital sudden deaths). Critically ill rabbits were randomized to hyperglycemia (315 ±32 mg/dl) or normoglycemia (85 ±13 mg/dl) and studied after 3 and 7 d.Insulin was infused to control blood glucose.Patients with uncontrolled hyperglycemia showed 3.7-6-fold increased microglial activation, 54-95% reduced number and activation of astrocytes, more than 9-fold increased neuronal and glial apoptosis, and a 1.5-2-fold increase in damaged neurons in hippocampus and frontal cortex (all P ≤ 0.05). Most of these abnormalities were attenuated with moderate hyperglycemia and virtually absent with normoglycemia. Frontal cortex of hyperglycemic rabbits that had been critically ill for 3 d only revealed microglial activation, followed after 7 d by astrocyte and neuronal abnormalities similar to those observed in patients, all prevented by normoglycemia.Preventing hyperglycemia with insulin during critical illness reduced neuropathological abnormalities, with microglial activation being the earliest preventable event. Whether these pathological findings associate with neurological outcome remains unknown.
Published: 2012

74. Health Education in Patients with a Recent Stroke or Transient Ischaemic Attack: A Comprehensive Review

Author: Diederik W.J. Dippel, Dorien Brouwer-Goossensen, Lisette Maasland, Peter J. Koudstaal, Heleen M. den Hertog, and Neurology
Subjects: Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Health Behavior, Population, MEDLINE, Disease, Coronary artery disease, Patient Education as Topic, SDG 3 - Good Health and Well-being, Risk Factors, Case fatality rate, medicine, Humans, In patient, Intensive care medicine, education, Health Education, Stroke, education.field_of_study, business.industry, medicine.disease, Treatment Outcome, Neurology, Ischemic Attack, Transient, Physical therapy, Health education, Clinical Competence, business
Abstract: Health education aims at the acquisition of skills and attitudes to modify behaviour that influences health, leads to a modification of risk factors and ultimately to a decrease in disability and case fatality from stroke. Health education is an underdeveloped but important aspect of stroke care. Health education could promote compliance and healthy behaviour, improve patients' understanding of their health status and treatment options and facilitate communication. We reviewed the effect of health education in stroke and transient ischaemic attack patients, aiming at feasibility, effectiveness at the level of knowledge, attitude and skills, health behaviour changes and stroke outcome. We also describe the current status of health education for patients with recent coronary artery disease and public health education in stroke. Basic knowledge of stroke and transient ischaemic attack patients of their disease and associated risk factors is not sufficient. This is also observed in patients with coronary artery disease and in the general population. A beneficial effect of health education in stroke and transient ischaemic attack patients on health behaviour, risk reduction or stroke outcome has not been proven. Trials in patients with coronary artery disease, however, have shown that health education could result in a change of lifestyle. No specific method is superior, although the individualised, repetitive and active methods appear more successful. More intervention studies of health education in stroke and transient ischaemic attack patients are needed. Future trials should be large, have a long follow-up, should use an intensive and repetitive approach and involve patients' relatives to induce and maintain a healthy lifestyle.
Published: 2011

75. gamma '/total fibrinogen ratio is associated with short-term outcome in ischaemic stroke

Author: Frank W.G. Leebeek, Lonneke M. L. de Lau, Elim Y. L. Cheung, Diederik W.J. Dippel, Peter J. Koudstaal, Heleen M. den Hertog, Moniek P.M. de Maat, Evita G. Van Den Herik, Neurology, Epidemiology, and Hematology
Subjects: Male, medicine.medical_specialty, Logistic regression, Fibrinogen, Brain ischemia, Ischemia, Risk Factors, Modified Rankin Scale, Internal medicine, Odds Ratio, medicine, Humans, Prospective Studies, Prospective cohort study, Stroke, Aged, business.industry, Fibrinogens, Abnormal, Hematology, Odds ratio, Middle Aged, Prognosis, medicine.disease, Confidence interval, Surgery, Treatment Outcome, Cardiology, Regression Analysis, Female, business, medicine.drug
Abstract: SummaryFibrinogen γ’ (γ’) is a natural isoform of fibrinogen, and alters the rate of formation and the properties of clots. It could therefore affect outcome after ischaemic stroke. The prognostic significance of γ’ fibrinogen levels is, however, still unclear. It was the objective of this study to assess levels of γ’ in ischaemic stroke, and its association with short-term outcome. We included 200 ischaemic stroke patients and 156 control persons. Total fibrinogen and γ’ levels were measured; outcome at discharge was assessed by means of the modified Rankin Scale score (defined as unfavourable when >2). We compared levels between patients and controls using multiple linear regression analysis, and logistic regression analysis was used to assess the relationship between levels and outcome. All analyses were adjusted for age and sex. Mean γ’ levels were significantly higher in patients with ischaemic stroke than in controls (0.37 vs. 0.32 g/l, p
Published: 2011

76. Cooling therapy for acute stroke

Author: Heleen M. den Hertog, Diederik W.J. Dippel, H. Bart van der Worp, Mei-Chiun Tseng, and Neurology
Subjects: medicine.medical_specialty, MEDLINE, Dipyrone, Ibuprofen, law.invention, Randomized controlled trial, law, Modified Rankin Scale, Hypothermia, Induced, medicine, Humans, Pharmacology (medical), In patient, Adverse effect, Stroke, Acute stroke, Acetaminophen, Randomized Controlled Trials as Topic, business.industry, Cooling therapy, Anti-Inflammatory Agents, Non-Steroidal, Odds ratio, Hypothermia, medicine.disease, Clinical trial, Meta-analysis, Emergency medicine, Closed head injury, Acute Disease, Physical therapy, medicine.symptom, business
Abstract: Background Increased body temperatures are common in patients with acute stroke and are associated with poor outcome. In animal models of focal cerebral ischaemia, temperature-lowering therapy reduces infarct volume. In patients with acute stroke, lowering temperature may therefore improve outcome. This is an update of a Cochrane review first published in 1999. Objectives To assess the effects of pharmacological and physical strategies to reduce body or brain temperature in patients with acute stroke. Search strategy We searched the Cochrane Stroke Group trials register (last searched December 2007). In addition, we searched MEDLINE and EMBASE (January 1998 to December 2007). We scanned references and contacted authors of included trials. For the previous version of this review, the authors contacted pharmaceutical companies and manufactures of cooling equipment in this field. Selection criteria We considered all completed randomised or non-randomised controlled clinical trials, published or unpublished, where pharmacological or physical strategies or both to reduce temperature were applied in patients with acute ischaemic stroke or intracerebral haemorrhage. Outcome measures were death or dependency (modified Rankin Scale score >/= 3) at the end of follow up, and adverse effects. Data collection and analysis Two review authors independently applied the inclusion criteria, assessed trial quality, and extracted and cross-checked the data. Main results We included five pharmacological temperature reduction trials and three physical cooling trials involving a total of 423 participants. We found no statistically significant effect of pharmacological or physical temperature-lowering therapy in reducing the risk of death or dependency (odds ratio (OR) 0.9, 95% confidence interval (CI) 0.6 to 1.4) or death (OR 0.9, 95% CI 0.5 to 1.5). Both interventions were associated with a non-significant increase in the occurrence of infections. Authors' conclusions There is currently no evidence from randomised trials to support routine use of physical or pharmacological strategies to reduce temperature in patients with acute stroke. Large randomised clinical trials are needed to study the effect of such strategies.
Published: 2009

77. Therapeutic hypothermia in acute ischemic stroke

Author: Diederik W.J. Dippel, Maarten van Gemert, Heleen M. den Hertog, Bart van der Worp, and Neurology
Subjects: Ischemia, Phases of clinical research, law.invention, Body Temperature, Brain Ischemia, Randomized controlled trial, law, Hypothermia, Induced, medicine, Animals, Humans, Pharmacology (medical), cardiovascular diseases, Antipyretic, Stroke, business.industry, General Neuroscience, Hypothermia, medicine.disease, Acetaminophen, Heart Arrest, Anesthesia, Brain Injuries, Neurology (clinical), Animal studies, medicine.symptom, business, medicine.drug
Abstract: Increased body temperatures are common in the acute phase of stroke. Experimental and clinical studies have suggested that increased body temperatures are related to poor outcome. In animal studies of focal cerebral ischemia, early hypothermia consistently reduced infarct volume. Based on these findings, several Phase II clinical trials have been performed to study physical methods to reduce body temperature in patients with acute stroke. The feasibility and safety of these methods have not yet been established with sufficient certainty. Pharmacological lowering of body temperature may be an attractive alternative approach. In guidelines for the treatment of acute stroke, antipyretics are generally recommended to reduce fever, although their effect on functional outcome is unknown. There is currently no evidence from randomized trials to support routine use of physical or pharmacological cooling in acute stroke. Large randomized clinical trials are needed to study the effect of both physical and medical cooling on functional outcome after stroke.
Published: 2007

78. Clinical Practice Variation Needs to be Considered in Cost-Effectiveness Analyses: A Case Study of Patients with a Recent Transient Ischemic Attack or Minor Ischemic Stroke

Author: Leander R. Buisman, Heleen M. den Hertog, Aad van der Lugt, William K. Redekop, Adriana J. Rijnsburger, Health Economics (HE), Radiology & Nuclear Medicine, and Health Technology Assessment (HTA)
Subjects: Economics and Econometrics, medicine.medical_specialty, Pediatrics, Cost effectiveness, Cost-Benefit Analysis, MEDLINE, Psychological intervention, Minor (academic), Health administration, Interviews as Topic, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Medicine, Humans, Carotid Stenosis, 030212 general & internal medicine, Original Research Article, Practice Patterns, Physicians', Intensive care medicine, Stroke, Health economics, business.industry, 030503 health policy & services, Health Policy, General Medicine, Health Care Costs, medicine.disease, Variation (linguistics), Ischemic Attack, Transient, Guideline Adherence, 0305 other medical science, business
Abstract: Background and Objective The cost-effectiveness of clinical interventions is often assessed using current care as the comparator, with national guidelines as a proxy. However, this comparison is inadequate when clinical practice differs from guidelines, or when clinical practice differs between hospitals. We examined the degree of variation in the way patients with a recent transient ischemic attack (TIA) or minor ischemic stroke are assessed and used the results to illustrate the importance of investigating possible clinical practice variation, and the need to perform hospital-level cost-effectiveness analyses (CEAs) when variation exists. Methods Semi-structured interviews were conducted with 16 vascular neurologists in hospitals throughout the Netherlands. Questions were asked about the use of initial and confirmatory diagnostic imaging tests to assess carotid stenosis in patients with a recent TIA or minor ischemic stroke, criteria to perform confirmatory tests, and criteria for treatment. We also performed hospital-level CEAs to illustrate the consequences of the observed diagnostic strategies in which the diagnostic test costs, sensitivity and specified were varied according to the local hospital conditions. Results 56 % (9/16) of the emergency units and 63 % (10/16) of the outpatient clinics use the initial and confirmatory diagnostic tests to assess carotid stenosis in accordance with the national guidelines. Of the hospitals studied, only one uses the recommended criteria for use of a confirmatory test, 38 % (6/16) follow the guidelines for treatment. The most cost-effective diagnostic test strategy differs between hospitals. Conclusions If important practice variation exists, hospital-level CEAs should be performed. These CEAs should include an assessment of the feasibility and costs of switching to a different strategy. Electronic supplementary material The online version of this article (doi:10.1007/s40258-015-0167-4) contains supplementary material, which is available to authorized users.
Published: 2015

79. Newly-Diagnosed Disturbed Glucose Metabolism is Associated with Atherosclerosis in Patients with Transient Ischemic Attack or Ischemic Stroke

Author: Heleen M. den Hertog, Evita G. Van Den Herik, Aad van der Lugt, Peter J. Koudstaal, Taihra Zadi, Anouk van Dijk, Hester F. Lingsma, and Susanne Fonville
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Odds ratio, Carbohydrate metabolism, medicine.disease, Stenosis, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Cardiology, Glucose test, Hemoglobin, business, Stroke, Calcification
Abstract: Objective: Newly-diagnosed disturbed glucose metabolism is highly prevalent in non-diabetic patients with transient ischemic attack (TIA) or ischemic stroke, and increases the risk of recurrent stroke. Diabetes mellitus is associated with atherosclerosis. We aimed to assess whether newly-diagnosed disturbed glucose metabolism is associated with atherosclerosis as well. Research design and methods: Patients with a recent TIA or ischemic stroke were classified in three groups based on glucose levels and use of antidiabetic drugs. Pre-existent diabetes mellitus was defined as the use of antidiabetic drugs prior to the event. Newly-diagnosed disturbed glucose metabolism was defined as two or more disturbed glucose tests: fasting plasma glucose level ≥ 5.6 mmol/L, 2-hour post-load glucose level ≥ 7.8 mmol/L, and/or glycosylated hemoglobin level ≥ 39 mmol/mol. We used CT-angiography to assess stenosis in the carotid artery bifurcations and calcification volume in the aortic arch, carotid bifurcations and intracranial carotid arteries. The relation between glucose groups and measures of atherosclerosis was expressed as odds ratios and beta coefficients with corresponding 95% CI, adjusted for potential confounders. Results: Of the 1217 patients, 384 (32%) had newly-diagnosed disturbed glucose metabolism, and 210 (17%) had pre-existent diabetes mellitus. Newly-diagnosed disturbed glucose metabolism was independently associated with stenosis ≥ 50% (aOR (95%CI) 1.15 (1.04-2.20)). Pre-existent diabetes mellitus was associated with stenosis ≥ 50% and with calcification volume in all regions, especially in patients without the use of cholesterol-lowering drugs prior to the event. Conclusions: Our study shows that newly-diagnosed disturbed glucose metabolism in patients with a recent TIA or ischemic stroke is associated with more severe extra- and intracranial atherosclerosis, similar to pre-existent diabetes mellitus.
Published: 2015

80. Diagnostic yield of external loop recording in patients with acute ischemic stroke or TIA

Author: Jorieke Bos, Marcoen F. Scholten, Bob Oude Velthuis, Heleen M. den Hertog, P. J. A. M. Brouwers, and Gerben J. J. Plas
Subjects: Male, medicine.medical_specialty, Neurology, Brain Ischemia, Risk Factors, Internal medicine, medicine, Humans, In patient, cardiovascular diseases, Prospective Studies, Risk factor, Prospective cohort study, Stroke, Neuroradiology, Aged, Aged, 80 and over, business.industry, Atrial fibrillation, Middle Aged, medicine.disease, Ischemic Attack, Transient, Cardiology, Female, Neurology (clinical), business, Atrial flutter
Abstract: Atrial fibrillation (AF) is a strong risk factor for first-ever stroke and stroke recurrence. The detection rate is low and detection is often costly and time-consuming. We evaluated the diagnostic yield of an external loop recorder (ELR) in patients with acute ischemic stroke or TIA, and assessed factors that are associated with AF detection. We prospectively studied patients admitted to the stroke unit with ischemic stroke or TIA, without a history of AF, and no AF on routine-ECG and 24-h telemetry. Patients received an ELR for another 24-h registration. Rhythm registration with an ELR was performed in 94 patients. AF was identified in 5 patients (5 %). AF was associated with cryptogenic stroke and cortical or subcortical involvement. If ELR was limited to patients with cryptogenic stroke in combination with cortical or subcortical involvement, the detection rate increased to 17 %. Automated recording with ELR was easy to use in the acute setting of ischemic stroke or TIA and seems promising to detect AF or atrial flutter, in particular in patients with cryptogenic stroke in combination with cortical or subcortical symptoms.
Published: 2014

81. [Glossopharyngeal neuralgia and syncope]

Author: Linda M M, Stijnman, Marieke J, Hazewinkel, Jasper J, Hoorweg, Marijke E, van Bolhuis, and Heleen M, den Hertog
Subjects: Diagnosis, Differential, Male, Nerve Compression Syndromes, Carcinoma, Humans, Middle Aged, Dizziness, Glossopharyngeal Nerve, Glossopharyngeal Nerve Diseases, Syncope, Parotid Neoplasms
Abstract: The causes of neuralgia are usually not known, but the condition can be caused by an underlying condition.A 58-year-old man presented at the accident and emergency department with a 6-week history of continuous nagging pain in the region of his right ear, extending to the lower jaw and the right side of his neck; this worsened in progressive attacks, which were sometimes followed by non-rotatory dizziness and loss of consciousness. This clinical picture lead us to suspect glossopharyngeal neuralgia (GPN) because of the distribution of the pain and the secondary syncope, but the continuous nature of the pain was atypical and a reason for further investigation. This revealed metastatic parotid gland carcinoma with compression of the right glossopharyngeal nerve. Following palliative radiotherapy, the pain improved and there were no further episodes of loss of consciousness.When GPN is suspected and there is continuous pain, or neurological investigations reveal abnormalities, an underlying condition should be considered and additional investigations should be carried out.
Published: 2014

82. The Johann Jacob Wepfer Award 2013

Author: Heleen M. den Hertog, Yee Kai Tee, Bruce C.V. Campbell, Kwang Soo Lee, Kook-Jin Ahn, Masatoshi Koga, J.-C. Baron, Adrienne A.M. Zandbergen, Kazuo Minematsu, Stephen M. Davis, Melanie Jones, Stephen J. Payne, Naoaki Yamada, Fumio Miyashita, Haruko Yamamoto, So Lyung Jung, I.M. Macrae, Shoji Arihiro, Gregory Y.H. Lip, Junji Takasugi, Yong Sam Shin, Kazunori Toyoda, Sarah E. Vermeer, Atte Meretoja, Paolo Eusebi, Satz Mengensatzproduktion, Diederik W.J. Dippel, George Harston, Werner Hacke, James Kennedy, Kennedy R. Lees, Hyun Seok Choi, Druckerei Stückle, Walter N. Kernan, Kazuyuki Nagatsuka, Peter J. Koudstaal, Hans T.H. Tu, Stefano Ricci, Jaseong Koo, Tomoyuki Kawada, Hiroshi Yamagami, Takuya Okata, Leonid Churilov, Hans-Christoph Diener, Xinfeng Liu, Fintan Sheerin, Susanne Fonville, Geoffrey A. Donnan, Bum-Soo Kim, G Pope, U. Dirnagl, Tae-Won Kim, Wen Sun, and H.P. Adams
Subjects: Stroke, Neurology, business.industry, Awards and Prizes, Art history, Medicine, Humans, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published: 2013

83. Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

Author: Susanne Fonville, Heleen M. den Hertog, Peter J. Koudstaal, Hester F. Lingsma, Adrienne A.M. Zandbergen, Neurology, Internal Medicine, and Public Health
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Disease, Carbohydrate metabolism, Brain Ischemia, Impaired glucose tolerance, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, Glucose Intolerance, medicine, Humans, cardiovascular diseases, Stroke, Aged, Receiver operating characteristic, Triglyceride, business.industry, Rehabilitation, Glucose Tolerance Test, Middle Aged, medicine.disease, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Ischemic Attack, Transient, Cardiology, Disease Progression, Surgery, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: Background Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. Methods Patients admitted to the stroke unit or TIA clinic of the Erasmus Medical Center with ischemic stroke or TIA and impaired glucose tolerance (2-hour postload glucose level of 7.8-11.0 mmol/L) were consecutively enrolled between July 2009 and June 2012. The oral glucose tolerance test was repeated after 3 months and patients were classified as having transient impaired glucose tolerance or persistent impaired glucose tolerance. We developed a prediction model by means of a multivariable logistic regression model. We calculated the area under the receiver operating characteristic curve (AUC) to quantify the performance of the model and the internal validity by bootstrapping. Results Of the 101 patients included, 53 (52%) had persistent impaired glucose tolerance or progression to diabetes. These patients were older and more often had hypertension and used statins. A prediction model including age, current smoking, statin use, triglyceride, hypertension, previous ischemic cardiovascular disease, body mass index, and fasting plasma glucose accurately predicted persistent impaired glucose tolerance (bootstrapped AUC, .777), with statin use, triglyceride, and fasting plasma glucose as the most important predictors. Conclusions Half of the patients with impaired glucose tolerance after a TIA or ischemic stroke have persistent impaired glucose tolerance. We provide a prediction model to identify patients at risk of persistent impaired glucose tolerance, with statin use, triglyceride, and fasting plasma glucose as the most important predictors, which after external validation might be used to optimize secondary prevention.
Published: 2013

84. Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits

Author: Greet Van den Berghe, Romain Sonneville, Sarah Derde, Fabian Güiza, Ilse Vanhorebeek, Heleen M. den Hertog, and Inge Derese
Subjects: Blood Glucose, Male, Parenteral Nutrition, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Critical Care and Intensive Care Medicine, medicine.disease_cause, Internal medicine, medicine, Animals, Insulin, Neurons, Nutrition and Dietetics, Glial fibrillary acidic protein, biology, Microglia, business.industry, Disease Models, Animal, Glucose, medicine.anatomical_structure, Parenteral nutrition, Endocrinology, Hyperglycemia, biology.protein, Neuroglia, Administration, Intravenous, Rabbits, Neuron, business, Oxidative stress, Astrocyte
Abstract: BACKGROUND & AIMS: Preventing severe hyperglycemia with insulin reduced the neuropathological alterations in frontal cortex during critical illness. We investigated the impact of increasing glucose load under normoglycemia on neurons and glial cells. METHODS: Hyperinflammatory critically ill rabbits were randomized to fasting or combined parenteral nutrition containing progressively increasing amounts of glucose (low, intermediate, high) within the physiological range but with a similar amount of amino acids and lipids. In all groups, normoglycemia was maintained with insulin. On day 7, we studied the neuropathological alterations in frontal cortex neurons, astrocytes and microglia, and MnSOD as marker of oxidative stress. RESULTS: The percentage of damaged neurons was comparable among all critically ill and healthy rabbits. Critical illness induced an overall 1.8-fold increase in astrocyte density and activation status, largely irrespective of the nutritional intake. The percentage of microglia activation in critically ill rabbits was comparable with that in healthy rabbits, irrespective of glucose load. Likewise, MnSOD expression was comparable in critically ill and healthy rabbits without any clear impact of the nutritional interventions. CONCLUSIONS: During prolonged critical illness, increasing intravenous glucose infusion while strictly maintaining normoglycemia appeared safe for neuronal integrity and did not substantially affect glial cells in frontal cortex. publisher: Elsevier articletitle: Increasing glucose load while maintaining normoglycemia does not evoke neuronal damage in prolonged critically ill rabbits journaltitle: Clinical Nutrition articlelink: http://dx.doi.org/10.1016/j.clnu.2013.01.003 content_type: article copyright: Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. ispartof: Clinical Nutrition vol:32 issue:6 pages:1077-1080 ispartof: location:England status: published
Published: 2013

85. Increased Benefit of Alteplase in Patients with Ischemic Stroke and a High Body Temperature

Author: Heleen M. den Hertog, Maarten van Gemert, Inger R. de Ridder, Bart van der Worp, Diederik W.J. Dippel, and Neurology
Subjects: Male, medicine.medical_specialty, Randomization, Antipyretics, Time Factors, medicine.medical_treatment, law.invention, Body Temperature, Brain Ischemia, Brain ischemia, Randomized controlled trial, Double-Blind Method, Fibrinolytic Agents, Modified Rankin Scale, law, Internal medicine, medicine, Odds Ratio, Humans, Thrombolytic Therapy, Stroke, Acetaminophen, Aged, Aged, 80 and over, business.industry, Thrombolysis, Odds ratio, Middle Aged, medicine.disease, Surgery, Clinical trial, Logistic Models, Treatment Outcome, Neurology, Tissue Plasminogen Activator, Cardiology, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract: Background: In observational studies, a high body temperature has been associated with unfavorable outcome. In in vitro studies, the fibrinolytic activity of alteplase decreased 5% per degree Celsius reduction in temperature. The modifying effect of body temperature on treatment with alteplase in patients with acute ischemic stroke is unclear. We assessed the influence of baseline body temperature on the effect of alteplase on functional outcome in patients with acute ischemic stroke, included in the Paracetamol (Acetaminophen) in Stroke (PAIS) trial. Methods: PAIS was a randomized, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke. For this study, we selected all patients with ischemic stroke and randomization within 6 h of symptom onset. We estimated the effect of treatment with alteplase on the modified Rankin Scale score at 3 months with ordinal logistic regression, stratified by baseline body temperature. We made adjustments for confounding factors and expressed associations as adjusted odds ratios (aOR) with 95% confidence intervals (CI). We also tested for interaction between treatment with alteplase and body temperature. Results: We included 647 of the 1,400 patients in PAIS in our study. Treatment with alteplase was associated with improved functional outcome at 3 months (aOR 1.51, 95% CI 1.09–2.08). In the 286 patients (44%) with a baseline body temperature of 37.0°C or higher, alteplase was associated with a larger effect (aOR 2.13, 95% CI 1.28–3.45) than in patients with a temperature below 37.0°C (aOR 1.11, 95% CI 0.71–1.69). A test for interaction between body temperature and alteplase did not reach statistical significance (p = 0.18). Conclusion: Patients with ischemic stroke and a high body temperature may have a larger benefit of treatment with alteplase than patients with lower body temperatures. These findings are in line with those from in vitro studies, in which lowering temperature decreased the fibrinolytic activity of the enzyme alteplase. This interaction should be explored further in randomized clinical trials of thrombolytic therapy or modification of body temperature. Trials of therapeutic hypothermia should be controlled for treatment with thrombolytics, and trials of thrombolytic treatment should consider body temperature as a potential effect modifier.
Published: 2013

86. Preventive Antibiotics in Acute Stroke

Author: Willeke F. Westendorp, Diederik W.J. Dippel, Heleen M. den Hertog, Jan-Dirk Vermeij, Diederik van de Beek, Frederique H Vermeij, Paul J. Nederkoorn, Graduate School, Amsterdam institute for Infection and Immunity, Amsterdam Neuroscience, Neurology, and Amsterdam Cardiovascular Sciences
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, medicine.drug_class, business.industry, Urinary system, Antibiotics, Placebo, law.invention, Randomized controlled trial, law, Relative risk, Internal medicine, Meta-analysis, medicine, Neurology (clinical), Major complication, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, Acute stroke
Abstract: Stroke is a major cause of morbidity and mortality worldwide. One of the major complications in the acute phase of stroke is infection; especially pneumonia and urinary tract infection occur often. Poststroke infections are strongly associated with poor outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce infections and improve functional outcome. ### Study Objective The objective of this study was to assess whether preventive antibiotic therapy in patients with acute stroke reduces infection rate, the risk of dependency, and the risk of death at follow-up.1 ### Selection Criteria Randomized controlled trials of preventive antibiotic therapy vs control (placebo or open control) in patients with acute ischemic or hemorrhagic stroke were used. ### Data Collection and Analysis Two authors independently selected articles and performed data extraction; methodologic quality was assessed by an independent observer. We calculated relative risks for dichotomous …
Published: 2012

87. Antibiotic therapy for preventing infections in patients with acute stroke

Author: Paul J. Nederkoorn, Diederik W.J. Dippel, Jan-Dirk Vermeij, Willeke F. Westendorp, Heleen M. den Hertog, Frederique H Vermeij, Diederik van de Beek, Neurology, ANS - Neuroinfection & -inflammation, AII - Infectious diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, ANS - Neurovascular Disorders, ACS - Amsterdam Cardiovascular Sciences, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Medicine General & Introductory Medical Sciences, medicine.medical_specialty, education, Cochrane Library, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antibiotic therapy, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Antibiotic prophylaxis, Adverse effect, Intensive care medicine, Stroke, Randomized Controlled Trials as Topic, Cause of death, Acute stroke, Advanced and Specialized Nursing, business.industry, Mortality rate, Pneumonia, Bacterial Infections, Antibiotic Prophylaxis, medicine.disease, Anti-Bacterial Agents, Clinical trial, Relative risk, Meta-analysis, Urinary Tract Infections, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract: Background Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. Objectives To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. Search methods We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Selection criteria Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Data collection and analysis Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality. Main results We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay. Authors' conclusions Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.
Published: 2012

88. An early rise in body temperature is related to unfavorable outcome after stroke: data from the PAIS study

Author: Diederik W.J. Dippel, Peter J. Koudstaal, H. Maarten A. van Gemert, Jan van Gijn, H. Bart van der Worp, Ale Algra, Heleen M. den Hertog, L. Jaap Kappelle, Neurology, and Cardiology
Subjects: Male, medicine.medical_specialty, Antipyretics, Neurology, Fever, Clinical Neurology, Central nervous system disease, Modified Rankin Scale, Internal medicine, medicine, Humans, Multicenter Studies as Topic, Body temperature, Risk factor, Stroke, Acetaminophen, Aged, Randomized Controlled Trials as Topic, Original Communication, Clinical outcome, Vascular disease, business.industry, Confounding, Recovery of Function, Odds ratio, medicine.disease, Surgery, Treatment Outcome, Female, Neurology (clinical), business
Abstract: Subfebrile temperature or fever is present in about a third of patients on the first day after stroke onset and is associated with poor outcome. However, the temporal profile of this association is not well established. We aimed to assess the relationship between body temperature on admission as well as the change in body temperature from admission to 24 h thereafter and functional outcome and death. We analyzed data of 1,332 patients admitted within 12 h of stroke onset. The relation between body temperature on admission or the change in body temperature from admission to 24 h thereafter (adjusted for body temperature on admission) on the one hand and unfavorable outcome (death, or a modified Rankin Scale score > 2) at 3 months on the other were expressed as odds ratio per 1.0A degrees C increase in body temperature. Adjustments for potential confounders were made with a multiple logistic regression model. No relation was found between admission body temperature and poor outcome (aOR 1.06; 95% CI 0.85-1.32) and death (aOR 1.23; 95% CI 0.95-1.60). In contrast, increased body temperature in the first 24 h after stroke onset was associated with poor outcome (aOR 1.30; 95% CI 1.05-1.63) and death (aOR 1.51; 95% CI 1.15-1.98). An early rise in body temperature rather than high body temperature on admission is a risk factor for unfavorable outcome in patients with acute stroke.
Published: 2011

89. Antibiotic therapy for preventing infections in patients with acute stroke

Author: Frederique Vermeij, Paul J Nederkoorn, Heleen M Den Hertog, Diederik van de Beek, and Diederik WJ Dippel
Published: 2010

90. No effectiveness of synthetic anti-inflammatory tetrapeptides in a mouse model of ischemic stroke

Author: Dirk J Duncker, Peter J. Koudstaal, Heleen M. den Hertog, Matthias Endres, Karen Gertz, Wim A Dik, Nisar Ahmed Khan, and Robbert Benner
Subjects: Oligopeptide, medicine.drug_class, business.industry, Cognitive Neuroscience, Ischemia, Neuroscience (miscellaneous), Inflammation, Pharmacology, medicine.disease, Intercellular adhesion molecule, Pathophysiology, Anti-inflammatory, Human chorionic gonadotropin, Neurology, Immunology, medicine, Tumor necrosis factor alpha, Neurology (clinical), medicine.symptom, business
Abstract: Background. Inflammation plays an important role in the pathophysiology of ischemic stroke and may contri-bute to secondary damage following ischemic stroke. Recently, it has been shown that synthetic oligopeptides related to human chorionic gonadotropin (hCG) and various other synthetic oligopeptides may have immuno-modulatory effects. We aimed to investigate the effects of two promising synthetic anti-inflammatory tetrapeptides, namely the hCG-related peptide AQGV and the p53-related peptide EPPE on infarct volume and on inflammatory gene expres-sion in a mouse model of focal cerebral ischemia. Methods. In a randomized single-blinded fashion, mice received two intravenous injections of either AQGV (30 mg/kg bodyweight) or EPPE (30mg/kg bodyweight) or phosphate buffered saline. The first dose was adminis-tered directly before 90-minutes middle cerebral artery occlusion, and the second dose was injected directly af-ter reperfusion. Infarct volume and gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), E-selectin and intercellular adhesion molecule-I (ICAM-1) were measured 24 hours after reperfusion. Results. We found no significant effect of either AQGV (108.7 +/- 12.1 mm3 versus PBS 114.9 +/- 23.9 mm3; P=0.7) or EPPE (131.8 +/-12.8 mm3 versus PBS 114.9 +/- 23.9 mm3 Conclusion. AQGV and EPPE did not show any beneficial effects in this mouse model of acute ischemic stroke. Further studies are needed to investigate the nature and dynamics of the immunomodulatory effects of synthetic oligopeptides in acute ischemic stroke. ; P=0.1) on direct lesion volume. All three experimental groups displayed similar mRNA expression levels of TNF-α, IL-6, E-selectin and ICAM-1 at 24 hours after the ischemic insult.
Published: 2010

91. Predicting and preventing stroke after transient ischemic attack

Author: Peter J. Koudstaal, Heleen M. den Hertog, Lonneke M. L. de Lau, Evita G. Van Den Herik, and Neurology
Subjects: Secondary prevention, medicine.medical_specialty, Vascular disease, business.industry, General Neuroscience, Vascular risk, medicine.disease, Clinical trial, Stroke, Lifestyle factors, Increased risk, Ischemic Attack, Transient, Predictive Value of Tests, Risk Factors, Predictive value of tests, Physical therapy, medicine, Humans, Pharmacology (medical), cardiovascular diseases, Neurology (clinical), Intensive care medicine, business, Platelet Aggregation Inhibitors
Abstract: The prognosis of transient ischemic attacks (TIAs) is not as favorable as previously thought. Given a risk of stroke of approximately 10% in the first week following a TIA, urgent evaluation and initiation of treatment are required. Recently developed scores to predict the early risk of subsequent stroke in individual patients may guide treatment decisions in the acute phase. Lately it has become clear that transient attacks with nonfocal symptoms are not benign either, as these were found to be associated with an increased risk of vascular disease. The significance of this finding and its implications for treatment are not yet clear. There is substantial evidence from a number of clinical trials that adequate secondary prevention therapies can reduce the risk of stroke after TIA. In addition to the conventional vascular risk factors, interest has grown in less strong but more prevalent lifestyle factors, but trials evaluating the effect of modifying these factors are as yet lacking.
Published: 2009

92. Temperature-Lowering Therapy for Acute Stroke

Author: Heleen M. den Hertog, Diederik W.J. Dippel, H. Bart van der Worp, Mei-Chiun Tseng, and University of Groningen
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, Ischemia, clinical outcome, temperature-lowering therapy, Hypothermia, medicine.disease, stroke, Surgery, Cardiac surgery, Stroke onset, Internal medicine, Infarct volume, medicine, Cardiology, In patient, cardiovascular diseases, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, business, body temperature, Stroke, Acute stroke
Abstract: Graeme J. Hankey MD, FRCP Section Editor: Body temperatures above 37.5°C have been observed in 4% to 25% of patients within the first 24 to 36 hours after stroke onset and are associated with poor long-term outcome. In the observational Copenhagen Stroke study, a 1°C increase in body temperature measured within 12 hours after stroke onset doubled the odds of poor outcome. In animal models of focal cerebral ischemia, cooling reduces infarct volume. Hypothermia is successfully used in cardiac surgery and has been associated with a more favorable neurological outcome in patients who were resuscitated after cardiac arrest. These observations suggest that reduction of body temperature and prevention …
Published: 2009

93. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial

Author: Diederik W.J. Dippel, Peter J. Koudstaal, H. Bart van der Worp, H. Maarten A. van Gemert, Jan van Gijn, Ate Algra, Heleen M. den Hertog, L. Jaap Kappelle, Neurology, Cardiology, University of Groningen, and ANS - Amsterdam Neuroscience
Subjects: medicine.medical_specialty, Placebo, GUIDELINES, law.invention, CLINICAL-TRIAL, REANALYSIS, Randomized controlled trial, law, Modified Rankin Scale, Internal medicine, medicine, MANAGEMENT, ACUTE ISCHEMIC-STROKE, Adverse effect, Stroke, OUTCOMES, business.industry, MORTALITY, Odds ratio, BODY-TEMPERATURE, CARE, medicine.disease, Acetaminophen, Clinical trial, SEVERITY, Physical therapy, Neurology (clinical), business, medicine.drug
Abstract: BACKGROUND: High body temperature in the first 12-24 h after stroke onset is associated with poor functional outcome. The Paracetamol (Acetaminophen) In Stroke (PAIS) trial aimed to assess whether early treatment with paracetamol improves functional outcome in patients with acute stroke by reducing body temperature and preventing fever. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, patients with ischaemic stroke or intracerebral haemorrhage and body temperature between 36 degrees C and 39 degrees C were randomly assigned treatment with paracetamol (6 g daily) or placebo within 12 h from symptom onset. Treatment allocation was based on a computer-generated list of random numbers with varying block size. The primary outcome was improvement beyond expectation on the modified Rankin scale at 3 months, according to the sliding dichotomy approach. This trial is registered, number ISRCTN74418480. FINDINGS: Between March, 2003, and May, 2008, 1400 patients were randomly allocated treatment. 260 (37%) of 697 patients receiving paracetamol and 232 (33%) of 703 receiving placebo improved beyond expectation (adjusted odds ratio [OR] 1.20, 95% CI 0.96-1.50). In a post-hoc analysis of patients with baseline body temperature 37-39 degrees C, treatment with paracetamol was associated with improved outcome (1.43, 1.02-1.97). There were 55 serious adverse events in the paracetamol group (8%) and 70 in the placebo group (10%). INTERPRETATION: These results do not support routine use of high-dose paracetamol in patients with acute stroke. Paracetamol might have a beneficial effect on functional outcome in patients admitted with a body temperature 37-39 degrees C, but this post-hoc finding needs further study. FUNDING: Netherlands Heart Foundation
Published: 2009

94. Acetaminophen for Temperature Reduction in Acute Stroke: Potential but Unproven Benefits

Author: Diederik W.J. Dippel, H. Bart van der Worp, H. Maarten A. van Gemert, and Heleen M. den Hertog
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, business.industry, Hypothermia, Acetaminophen, Clinical trial, Cooling methods, Ischemic stroke, medicine, Physical therapy, Observational study, Neurology (clinical), medicine.symptom, Cardiology and Cardiovascular Medicine, Intensive care medicine, business, medicine.drug, Acute stroke
Abstract: To the Editor: We read with interest the review by Hemmen and Lyden on induced hypothermia for acute ischemic stroke.1 The review focuses on physical cooling methods in acute stroke. Some points, however, deserve in our opinion a more extensive discussion. The authors state that controlling body temperature below 36.5°C has been proven to correlate with good clinical outcome. They do not cite controlled clinical trials to support their point, but refer to 2 observational studies instead. Indeed, well-designed studies have shown a consistent relationship between increased …
Published: 2007

95. Elevated fibrinogen gamma ' ratio is associated with cardiovascular diseases and acute phase reaction but not with clinical outcome

Author: Heleen M. den Hertog, J. Wouter Jukema, Hans L. Vos, Elim Y. L. Cheung, Moniek P.M. de Maat, Marieke J. H. A. Kruip, Hematology, and Neurology
Subjects: medicine.medical_specialty, business.industry, Immunology, Treatment outcome, Acute-phase protein, Cell Biology, Hematology, Fibrinogen, Biochemistry, Gastroenterology, Surgery, SDG 3 - Good Health and Well-being, Internal medicine, Medicine, business, medicine.drug
Abstract: To the editor: Recently, Nowak-Gottl et al reported on the association between the fibrinogen γ′/total fibrinogen ratio (γ′ ratio) and thromboembolism in children.[1][1] We and others previously reported on this association in adults.[2][2][⇓][3][⇓][4][⇓][5]–[6][6] However, the
Published: 2009

96. Front and Back Matter

Author: Ryu Matsuo, Ekkehart Jenetzky, Adam Strzelczyk, Kyusik Kang, Heleen A. Booij, Helmuth Steinmetz, Yoshinobu Wakisaka, Yanlin Zhang, Jonathan A Grossberg, Vincent Larrue, Willeke F. Westendorp, Xia Zhang, Laura Mechtouff, Wei Xuan, Christina Hamisch, Roland Veltkamp, Peter J. Koudstaal, Zeljka Calic, Mohammad Rauf Afzal, Mathieu Zuber, Young-Soo Kim, Young-Chai Ko, Soo Joo Lee, Gerben J. J. Plas, Markus A Möhlenbruch, Gaetano Procaccianti, Chongke Zhong, Qiao Han, Iris Q. Grunwald, Anna Mezzapesa, Kyung Bok Lee, Stefan Helwig, Peter A. Ringleb, Timolaos Rizos, Fayyaz Orfi, Eric Greveson, Hiromi Ishikawa, Cecilia Cappelen-Smith, Yong Ko, Dennis Cordato, Silke Walter, Jun Hata, Björn Misselwitz, Gert J. de Borst, Serge Timsit, Dae Hyun Kim, Philippe Grosjean, Norbert Nighoghossian, Michael Reiner, Christopher Beynon, Hyeong-Joong Yi, Waltraud Pfeilschifter, Junya Kuroda, Günther Hedtmann, M. Fareed K. Suri, Jiro Kitayama, Mikayel Grigoryan, Tae-Hee Cho, Andreas Ferbert, Mark Stroick, Laurent Derex, Bent Indredavik, Peter Sander, Paola Forti, Diogo C Haussen, Sradha Kotwal, Anne Huibers, Wolfgang Reith, Björn Reuter, Patrick J. Kelly, Heleen M. den Hertog, Jae Min Kim, Jae Guk Kim, Richard I. Lindley, John A Oostema, Diederik van de Beek, Mathew J. Reeves, P. J. A. M. Brouwers, Sang-Soon Park, Umut Yilmaz, Luyao Shi, Oliver C. Singer, Michael Kettner, Chunfeng Liu, Y.B.W.E.M. Roos, Pantelis Stavrinou, Lenka Schwindling, Sung Il Sohn, Jiaping Xu, Joan Montaner, Nadine Talia, Craig S. Anderson, Nathan Mewton, Daniela Niemann, Christophe Gaudin, Diederik W.J. Dippel, Marco Zoli, Alison Halliday, Mario Abruscato, Raul G Nogueira, Peter Vajkoczy, Marie-Hélène Mahagne, Martin Griebe, Mi Sun Oh, Beom Joon Kim, Paul J. Nederkoorn, Fabiola Maioli, Djurre D. de Waard, Juneyoung Lee, Pierre Suchon, Gerrit Brinker, Stefan H. Kreisel, Svenja Schüler, Masahiro Kamouchi, Yong-Jin Cho, Ji-Sung Lee, Bernt Harald Helleberg, Christian Foerch, Jong-Moo Park, Roland Goldbrunner, Marie-Christine Alessi, Takanari Kitazono, Jay Chol Choi, Jijun Shi, Safwan Roumia, Güliz Acker, Marc Fatar, Michael Frankel, Klaus Fassbender, Boris Krischek, Trevor Carle, Valérie Martin, Jihoon Kang, Andreas Ragoschke-Schumm, Carlotta Barbara, Huihui Liu, Matthijs C. Brouwer, Thorsten Steiner, Jan C. Purrucker, Jonathan C. Craig, Anke Reihs, Marcus Czabanka, M. Laible, Benno Ikenberg, Min Uk Jang, Joon-Tae Kim, Angelika Alonso, Yongjun Cao, Hee-Joon Bae, Carina Hohmann, Susanne Goerdes, Angela C Webster, Richard Bulbulia, Adnan I Qureshi, Ki-Hyun Cho, Sven Thonke, Tetsuro Ago, Valeria Nativio, Rainer Kollmar, Shoujiang You, Byung Chul Lee, Philip B. Gorelick, Hanne Ellekjær, Choong Hyun Kim, Laurent Suissa, Michael G. Hennerici, Oliver Josef Müller, Jae Kwan Cha, Tobias Neumann-Haefelin, Tai Hwan Park, Hiroshi Nakane, Raf Brouns, Peter Schmiedek, Moon-Ku Han, Kyung-Ho Yu, Keun-Sik Hong, Jeong-Ho Hong, Dana Farahmand, Elodie Ong, Jin Hwan Cheong, Michel Ovize, Jun Lee, Martin Lesmeister, Jan-Dirk Vermeij, Myung Hoon Han, Alan Cass, Martin Gallagher, Marco Timmer, Luigi Simonetti, Marjolein Brusse-Keizer, Ahmed A Malik, Giuseppe Di Pasquale, Michele Domenico Spampinato, Matthias Manitz, Yves Donazzolo, Yvo B.W.E.M. Roos, Leticia C Rebello, Seena Dehkharghani, Zhichao Huang, Maura Coveri, Igor Sibon, Noriko Makihara, Andrey Lima, Mar Castellanos, Anastasios Mpotsaris, Philip Masson, Druckerei Stückle, and Nauman Jahangir
Subjects: Optics, Neurology, business.industry, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Front (military)
Published: 2013

97. PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial [ISCRTN 74418480]

Author: Peter J. Koudstaal, H. Maarten A. van Gemert, Jan van Gijn, Ale Algra, Diederik W.J. Dippel, H. Bart van der Worp, Heleen M. den Hertog, L. Jaap Kappelle, Bewegingswetenschappen, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, and Neurology
Subjects: lcsh:Diseases of the circulatory (Cardiovascular) system, Fever, Phases of clinical research, Placebo, law.invention, Body Temperature, Study Protocol, Randomized controlled trial, Clinical Protocols, Double-Blind Method, law, medicine, Humans, Multicenter Studies as Topic, Antipyretic, Stroke, Acetaminophen, Randomized Controlled Trials as Topic, business.industry, Correction, Odds ratio, Analgesics, Non-Narcotic, medicine.disease, Clinical trial, lcsh:RC666-701, Ischemic Attack, Transient, Anesthesia, business, Cardiology and Cardiovascular Medicine, medicine.drug
Abstract: Background In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. Methods/design Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. Discussion This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one.
Published: 2005

98. Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial

Author: Susanne Fonville, Laus J.M.M. Mulder, Hester F. Lingsma, Heleen M. den Hertog, P. J. A. M. Brouwers, Elizabeth Osei, Diederik W.J. Dippel, Adrienne A.M. Zandbergen, Peter J. Koudstaal, Neurology, and Public Health
Subjects: Blood Glucose, medicine.medical_specialty, Time Factors, Medicine (miscellaneous), law.invention, Sitagliptin Phosphate, Impaired glucose tolerance, Study Protocol, Clinical Protocols, Randomized controlled trial, SDG 3 - Good Health and Well-being, Predictive Value of Tests, law, Modified Rankin Scale, Internal medicine, Glucose Intolerance, medicine, Humans, Hypoglycemic Agents, Pharmacology (medical), Stroke, Netherlands, Glucose tolerance test, medicine.diagnostic_test, business.industry, Glucose Tolerance Test, medicine.disease, Metformin, Treatment Outcome, Endocrinology, Ischemic Attack, Transient, Research Design, Sitagliptin, Feasibility Studies, Anti-diabetic drugs, business, Biomarkers, medicine.drug
Abstract: Background Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. Methods/Design The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (
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99. Endovascular treatment in anterior circulation stroke beyond 6.5 hours after onset or time last seen well: results from the MR CLEAN Registry

Author: Robert J van Oostenbrugge, Wim H van Zwam, Maarten Uyttenboogaart, Yvo B W E M Roos, Jeannette Hofmeijer, Jasper M Martens, Ivo G H Jansen, Ludo F M Beenen, Hester F Lingsma, Albert J Yoo, Diederik W J Dippel, Charles B L M Majoie, Olvert A Berkhemer, Bart J Emmer, Marianne A A van Walderveen, Sjoerd F M Jenniskens, Wouter J Schonewille, Jan Albert Vos, Julie Staals, Geert J Lycklama à nijeholt, Jelis Boiten, Rob H Lo, Ewoud J Van Dijk, René J Dallinga, Koos Keizer, Heleen M Den Hertog, Katinka R van Kranendonk, Kilian M Treurniet, Esmee Venema, Bob Roozenbeek, Robin Lemmens, Robert-Jan B Goldhoorn, Ido R van den Wijngaard, Jonathan M Coutinho, Stefan D Roosendaal, Joost Bot, Naziha El Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, D Jeurrissen, Erna Bos, Yvonne Drabbe, Berber Zweedijk, Daan Muijres, J Huguet, Marieke A Mens, Manon Kappelhof, Heitor Alves, Manon L Tolhuisen, Alida A Postma, Reinoud P H Bokkers, Maxim J H L Mulder, Kars C J Compagne, Josje Brouwer, Wouter H Hinsenveld, Marieke J H Wermer, J de Vries, Julia van Tuijl, Jo P Peluso, Puck Fransen, Leo A M Aerden, Omid Eschgi, Tobien H C M L Schreuder, Roel J J Heijboer, Lonneke S F Yo, Emiel J C Sturm, Paul J A M Brouwers, Marieke E S Sprengers, René van den Berg, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Dick Gerrits, Wouter Dinkelaar, Auke P A Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, Michelle Simons, Marjolein Vossers, Nynke Nicolaij, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, Michelle Sandiman, Nicoline Aaldering, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Annick J Weterings, Lieve M Schupp, Sabine Collette, Natalie E LeCouffe, Praneeta R Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A Ramos, C Lukas, Luuk Dekker, F Anne V Pirson, Adriaan C G M van Es, Sanne J den Hartog, Sebastiaan F de Bruijnl, H van Dijk, Bart van der Worp, D Boogaarts Hieronymus, Paul L M de Kort, Jan S P van den Berg, Boudewijn A A M van Hasselt, Bas F W van der Kallen, P Marc, G van Proosdij;, Menno Krietemeijer, Roger R M Harmsma, M M Anna Boers, P F C Groot, Eleonora L F Kirkels, Eva J H F Voogd, and Adrien E D Groot
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Background Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice.Methods The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death.Results Of 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, p
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