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1. Additional treatment after primary conservative treatment in patients with chronic subdural hematoma—A retrospective study

Author

Rahman Fakhry, Clemens M. F. Dirven, Walid Moudrous, S. Mirjam Droger, Nabil Asahaad, Christiaan deBrabander, Hester F. Lingsma, Niels A. van derGaag, Heleen M. den Hertog, Bram Jacobs, Korné Jellema, Ruben Dammers, and Dana C. Holl

Subjects
conservative, CSDH, treatment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Objective Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment. Methods Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment. Results In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69). Conclusions Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.

Published
2024
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2. Dual thrombolytic therapy with mutant pro-urokinase and small bolus alteplase for ischemic stroke (DUMAS): study protocol for a multicenter randomized controlled phase II trial

Author

Nadinda A. M. van der Ende, Bob Roozenbeek, Lucas E. M. Smagge, Sven P. R. Luijten, Leo A. M. Aerden, Petra Kraayeveld, Ido R. van den Wijngaard, Geert J. Lycklama à Nijeholt, Heleen M. den Hertog, H. Zwenneke Flach, Alexis C. Wallace, Victor Gurewich, Gregory J. del Zoppo, William J. Meurer, Hester F. Lingsma, Aad van der Lugt, Diederik W. J. Dippel, and on behalf of the DUMAS Investigators

Subjects
Thrombolytic treatment, Mutant pro-urokinase, Alteplase, Ischemic stroke, Randomized controlled trial, Medicine (General), R5-920
Abstract

Abstract Background The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Therefore, this treatment has the potential to be safer and more efficacious than treatment with alteplase alone. The aim of this study is to assess the safety and efficacy of thrombolytic treatment consisting of a small bolus alteplase followed by m-proUK compared with standard thrombolytic treatment with alteplase in patients presenting with ischemic stroke. Methods DUMAS is a multicenter, phase II trial with a prospective randomized open-label blinded end-point (PROBE) design, and an adaptive design for dose optimization. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients are randomly assigned (1:1) to receive a bolus of IV alteplase (5mg) followed by a continuous IV infusion of m-proUK (40 mg/h during 60 min) or usual care with alteplase (0.9 mg/kg). Depending on the results of interim analyses, the dose of m-proUK may be revised to a lower dose (30 mg/h during 60 min) or a higher dose (50 mg/h during 60 min). We aim to include 200 patients with a final diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on neuroimaging at 24 h according to the Heidelberg Bleeding Classification, analyzed with binary logistic regression. Efficacy outcomes include stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5–7 days, score on the modified Rankin scale (mRS) assessed at 30 days, change (pre-treatment vs. post-treatment) in abnormal perfusion volume, and blood biomarkers of thrombolysis at 24 h. Secondary safety endpoints include symptomatic intracranial hemorrhage, death, and major extracranial hemorrhage. This trial will use a deferred consent procedure. Discussion When dual thrombolytic therapy with a small bolus alteplase and m-proUK shows the anticipated effect on the outcome, this will lead to a 13% absolute reduction in the occurrence of ICH in patients with ischemic stroke. Trial registration NL7409 (November 26, 2018)/NCT04256473 (February 5, 2020)

Published
2022
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3. Impact of the lockdown on acute stroke treatments during the first surge of the COVID-19 outbreak in the Netherlands

Author

Faysal Benali, Lotte J. Stolze, Anouk D. Rozeman, Wouter Dinkelaar, Jonathan M. Coutinho, Bart J. Emmer, Rob A. R. Gons, Lonneke F. S. Yo, Julia H. van Tuijl, Issam Boukrab, Dianne H. K. van Dam-Nolen, Ido R. van den Wijngaard, Geert J. Lycklama à Nijeholt, Karlijn F. de Laat, Lukas C. van Dijk, Heleen M. den Hertog, H. Zwenneke Flach, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Paul J. A. M. Brouwers, Tomas Bulut, Sarah E. Vermeer, Marie Louise E. Bernsen, Maarten Uyttenboogaart, Reinoud P. H. Bokkers, Jeroen D. Boogaarts, Frank-Erik de Leeuw, H. Bart van der Worp, Irene C. van der Schaaf, Wouter J. Schonewille, Jan A. Vos, Michel J. M. Remmers, Farshad Imani, Diederik W. J. Dippel, Wim H. van Zwam, Paul J. Nederkoorn, and Robert J. van Oostenbrugge

Subjects
COVID-19, Lockdown, Acute stroke care, Intravenous thrombolytics, Endovascular thrombectomy, NIHSS, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Introduction We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. Methods We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. Results A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of

Published
2022
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4. Detection of Major Cardioembolic Sources in Real-World Patients with Ischemic Stroke or Transient Ischemic Attack of Undetermined Cause

Author

Gerlinde van der Maten, Jorieke M.B. Reimer, Matthijs F.L. Meijs, Clemens von Birgelen, Marjolein G.J. Brusse-Keizer, and Heleen M. den Hertog

Subjects
atrial fibrillation, brain ischemia, echocardiography, embolism, ischemic stroke, transient ischemic attack, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background/Aim: Current guidelines recommend transthoracic echocardiography (TTE) and ambulatory rhythm monitoring following ischemic stroke or transient ischemic attack (TIA) of undetermined cause for identifying cardioembolic sources (CES). Due to ongoing controversies about this routine strategy, we evaluated its yield in a real-world setting. Methods: In a tertiary medical center, we retrospectively evaluated consecutive patients with ischemic stroke or TIA of undetermined cause, who (after standard work-up) underwent TTE, ambulatory rhythm monitoring, or both. CES were classified as major if probably related to ischemic events and warranting a change of therapy. Results: Between January 2014 and December 2017, 674 patients had ischemic stroke or TIA of undetermined cause. Of all 484 patients (71.8%) who underwent TTE, 9 (1.9%) had a major CES. However, 7 of them had already been identified for cardiac evaluation due to new major electrocardiographic abnormalities or cardiac symptoms. Thus, only 2 patients (0.4%) truly benefitted from unselected TTE screening. Ambulatory rhythm monitoring was performed in 411 patients (61.0%) and revealed AF in 10 patients (2.4%). Conclusion: Detecting a major CES is essential because appropriate treatment lowers the risk of recurrent stroke. Nonetheless, in this real-world study that aimed at routine use of TTE and ambulatory rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause, the prevalence of major CES was low. Most patients with major CES on TTE already had an indication for referral to a cardiologist, suggesting that major CES might also have been identified with a much more selective use of TTE.

Published
2021
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5. Multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke. The effect of periprocedural medication: acetylsalicylic acid, unfractionated heparin, both, or neither (MR CLEAN-MED). Rationale and study design

Author

Vicky Chalos, Rob A. van de Graaf, Bob Roozenbeek, Adriaan C. G. M. van Es, Heleen M. den Hertog, Julie Staals, Lukas van Dijk, Sjoerd F.M. Jenniskens, Robert J. van Oostenbrugge, Wim H. van Zwam, Yvo B.W.E.M. Roos, Charles B.L.M. Majoie, Hester F. Lingsma, Aad van der Lugt, Diederik W.J. Dippel, and on behalf of the MR CLEAN-MED investigators

Subjects
Ischemic stroke, Acetylsalicylic acid, Heparin, Cerebrovascular disorders, Randomized controlled trial, Endovascular treatment, Medicine (General), R5-920
Abstract

Abstract Background Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT. Methods MR CLEAN-MED is a multicenter phase III trial with a prospective, 2 × 3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300 mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS ≥ 2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6 h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24 h and at 5–7 days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality. Discussion Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. Trial registration ISRCT, ISRCTN76741621 . Dec 6, 2017.

Published
2020
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6. Association of Ischemic Core Imaging Biomarkers With Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry

Author

Miou S. Koopman, Jan W. Hoving, Manon Kappelhof, Olvert A. Berkhemer, Ludo F. M. Beenen, Wim H. van Zwam, Hugo W. A. M. de Jong, Jan Willem Dankbaar, Diederik W. J. Dippel, Jonathan M. Coutinho, Henk A. Marquering, Bart J. Emmer, Charles B. L. M. Majoie, for the MR CLEAN Registry Investigators, Aad van der Lugt, Yvo B. W. E. M. Roos, Robert J. van Oostenbrugge, Jelis Boiten, Jan Albert Vos, Ivo G. H. Jansen, Maxim J. H. L. Mulder, Robert-Jan B. Goldhoorn, Kars C. J. Compagne, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Bob Roozenbeek, Adriaan C. G. M. van Es, Wouter J. Schonewille, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L. M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S. P. van den Berg, Boudewijn A. A. M. van Hasselt, Leo A. M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H. C. M. L. Schreuder, Roel J. J. Heijboer, Koos Keizer, Lonneke S. F. Yo, Heleen M. den Hertog, Emiel J. C. Sturm, Paul J. A. M. Brouwers, Marieke E. S. Sprengers, Sjoerd F. M. Jenniskens, René van den Berg, Albert J. Yoo, Alida A. Postma, Stefan D. Roosendaal, Bas F. W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Reinoud P. H. Bokkers, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P. A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Hester F. Lingsma, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R. M. Harmsma Daan Muijres, Anouk de Jong, Anna M. M. Boers, J. Huguet, P. F. C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L. F. Kirkels, Lieve M. Schupp, Eva J. H. F. Voogd, Sabine Collette, Adrien E. D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte- Terreros, and Lucas A. Ramos

Subjects
CT perfusion (CTP), ischemic core, thrombectomy, stroke, alberta stroke program early CT score (ASPECTS), collaterals, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice.Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days.Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS.Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS.

Published
2022
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7. Neurosurgical and Perioperative Management of Chronic Subdural Hematoma

Author

Jurre Blaauw, Bram Jacobs, Heleen M. den Hertog, Niels A. van der Gaag, Korné Jellema, Ruben Dammers, Hester F. Lingsma, Joukje van der Naalt, Kuan H. Kho, and Rob J. M. Groen

Subjects
chronic subdural hematoma, neurosurgery, anesthesia, bilateral chronic subdural hematoma, logistic regression, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: Surgery and specifically burr hole craniostomy is the most common first choice treatment of patients with Chronic Subdural Hematoma (CSDH). However, several aspects of neurosurgical and peri-operative management are still a subject of research, such as how to treat bilateral CSDH and the anesthetic approach. We aim to investigate the effect of the surgical approach to bilateral CSDH and the effect of anesthesia modality on outcome of CSDH patients.Methods: We retrospectively included surgically treated CSDH patients between 2005 and 2019 in three hospitals in the Netherlands. The effect of the surgical approach to bilateral CSDH (unilateral vs. bilateral decompression) and anesthesia modality (general vs. local anesthesia) on outcome (complications, recurrence, and length of hospital stay over 4 days) was studied with logistic regression adjusting for potentially confounding radiological and clinical characteristics.Results: Data of 1,029 consecutive patients were analyzed, mean age was 73.5 years (±11) and 75% of patients were male. Bilateral CSDH is independently associated with an increased risk of recurrence within 3 months in logistic regression analysis (aOR 1.7, 95% CI: 1.1–2.5) but recurrence rate did not differ between primary bilateral or unilateral decompression of bilateral CSDH. (15 vs. 17%, p = 0.775). Logistic regression analysis showed that general anesthesia was independently associated with an increased risk of complications (aOR 1.8, 95% CI: 1.0–3.3) and with a length of hospital admission of over 4 days (aOR 8.4, 95% CI: 5.6–12.4).Conclusions: Bilateral CSDH is independently associated with higher recurrence rates. As recurrence rates in bilateral CSDH are similar for different surgical approaches, the optimal choice for primary bilateral decompression of bilateral CSDH could vary per patient. General anesthesia for surgical treatment of CSDH is associated with higher complication rates and longer hospital admission.

Published
2020
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8. Dexamethasone therapy versus surgery for chronic subdural haematoma (DECSA trial): study protocol for a randomised controlled trial

Author

Ishita P. Miah, Dana C. Holl, Wilco C. Peul, Robert Walchenbach, Nyika Kruyt, Karlijn de Laat, Radboud W. Koot, Victor Volovici, Clemens M. F. Dirven, Fop van Kooten, Kuan H. Kho, Heleen M. den Hertog, Joukje van der Naalt, Bram Jacobs, Rob J. M. Groen, Hester F. Lingsma, Ruben Dammers, Korné Jellema, Niels A. van der Gaag, and on behalf of the Dutch Subdural Hematoma Research Group (DSHR)

Subjects
Dexamethasone, DXM, Chronic subdural haematoma, CSDH, Burr-hole craniostomy, BHC, Medicine (General), R5-920
Abstract

Abstract Background Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH. Methods/Design This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow–up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority

Published
2018
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9. Endovascular treatment versus no endovascular treatment after 6-24 h in patients with ischaemic stroke and collateral flow on CT angiography (MR CLEAN-LATE) in the Netherlands

Author

Susanne G H Olthuis, F Anne V Pirson, Florentina M E Pinckaers, Wouter H Hinsenveld, Daan Nieboer, Angelique Ceulemans, Robrecht R M M Knapen, M M Quirien Robbe, Olvert A Berkhemer, Marianne A A van Walderveen, Geert J Lycklama à Nijeholt, Maarten Uyttenboogaart, Wouter J Schonewille, P Matthijs van der Sluijs, Lennard Wolff, Henk van Voorst, Alida A Postma, Stefan D Roosendaal, Anouk van der Hoorn, Bart J Emmer, Menno G M Krietemeijer, Pieter-Jan van Doormaal, Bob Roozenbeek, Robert-Jan B Goldhoorn, Julie Staals, Inger R de Ridder, Christiaan van der Leij, Jonathan M Coutinho, H Bart van der Worp, Rob T H Lo, Reinoud P H Bokkers, Ewoud I van Dijk, Hieronymus D Boogaarts, Marieke J H Wermer, Adriaan C G M van Es, Julia H van Tuijl, Hans G J Kortman, Rob A R Gons, Lonneke S F Yo, Jan-Albert Vos, Karlijn F de Laat, Lukas C van Dijk, Ido R van den Wijngaard, Jeannette Hofmeijer, Jasper M Martens, Paul J A M Brouwers, Tomas Bulut, Michel J M Remmers, Thijs E A M de Jong, Heleen M den Hertog, Boudewijn A A M van Hasselt, Anouk D Rozeman, Otto E H Elgersma, Bas van der Veen, Davy R Sudiono, Hester F Lingsma, Yvo B W E M Roos, Charles B L M Majoie, Aad van der Lugt, Diederik W J Dippel, Wim H van Zwam, Robert J van Oostenbrugge, Pediatrics, Radiology and nuclear medicine, ACS - Atherosclerosis & ischemic syndromes, Neurology, Public Health, Radiology & Nuclear Medicine, Neurosurgery, Erasmus MC other, General Practice, Radiology and Nuclear Medicine, ANS - Cellular & Molecular Mechanisms, Biomedical Engineering and Physics, Graduate School, ANS - Brain Imaging, ANS - Neurovascular Disorders, ACS - Microcirculation, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), MUMC+: MA AIOS Neurologie (9), RS: Carim - B06 Imaging, RS: Carim - B05 Cerebral small vessel disease, MUMC+: MA Niet Med Staf Neurologie (9), Beeldvorming, MUMC+: DA BV Research (9), MUMC+: DA BV AIOS Radiologie (8), MUMC+: DA BV AIOS Nucleaire Geneeskunde (8), MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: MA Neurologie (3), and MUMC+: Hersen en Zenuw Centrum (3)

Subjects
Male, Computed Tomography Angiography, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], General Medicine, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Stroke/therapy, All institutes and research themes of the Radboud University Medical Center, Treatment Outcome, Brain Ischemia/diagnostic imaging, Humans, Female, Ischemic Stroke/complications, Intracranial Hemorrhages/etiology, Netherlands
Abstract

BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

Published
2023

10. External validation of prognostic models predicting outcome after chronic subdural hematoma

Author

Dana C. Holl, Ana Mikolic, Jurre Blaauw, Roger Lodewijkx, Merijn Foppen, Korné Jellema, Niels A. van der Gaag, Heleen M. den Hertog, Bram Jacobs, Joukje van der Naalt, Dagmar Verbaan, K. H. Kho, C. M. F. Dirven, Ruben Dammers, Hester F. Lingsma, David van Klaveren, Molecular Neuroscience and Ageing Research (MOLAR), Graduate School, Neurology, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, Public Health, and Clinical Neurophysiology

Subjects
Prognostic models, Recurrence, Hematoma, Subdural, Chronic, Quality of Life, Humans, Surgery, Neurology (clinical), Chronic subdural hematoma, Mortality, Prognosis, Retrospective Studies, External validation
Abstract

BackgroundSeveral prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH.MethodsWe systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for ResultsWe identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63–0.77]; 0.46 [0.35–0.56]; 0.59 [0.51–0.66], respectively).ConclusionsNone of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted.

Published
2022

11. Validity of Early Outcomes as Indicators for Comparing Hospitals on Quality of Stroke Care

Author

Marzyeh Amini, Frank Eijkenaar, Hester F. Lingsma, Sanne J. den Hartog, Susanne G. H. Olthuis, Jasper Martens, Bart van der Worp, Wim van Zwam, Anouk van der Hoorn, Stefan D. Roosendaal, Bob Roozenbeek, Diederik Dippel, Nikki van Leeuwen, Diederik W. J. Dippel, Aad van der Lugt, Charles B. L. M. Majoie, Yvo B. W. E. M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Jelis Boiten, Jan Albert Vos, Josje Brouwer, Wouter H. Hinsenveld, Manon Kappelhof, Kars C. J. Compagne, Robert‐Jan B. Goldhoorn, Maxim J. H. L. Mulder, Ivo G. H. Jansen, Adriaan C. G. M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L. M. de Kort, Julia van Tuijl, Jo Jo P. Peluso, Puck Fransen, Jan S. P. van den Berg, Boudewijn A. A. M. van Hasselt, Leo A. M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P. H. Bokkers, Tobien H. C. M. L. Schreuder, Roel J. J. Heijboer, Koos Keizer, Lonneke S. F. Yo, Heleen M. den Hertog, Emiel J. C. Sturm, Paul Brouwers, Marieke E. S. Sprengers, Sjoerd F. M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F. M. Beenen, Alida A. Postma, Bas F. W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter‐Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Jo P. Peluso, Rob Lo, Wouter Dinkelaar, Auke P. A. Appelman, Bas Hammer, Sjoert Pegge, Saman Vinke, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Corina Puppels, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Cathelijn van Rijswijk, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Mostafa Khalilzada, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R. M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M. M. Boers, J. Huguet, P. F. C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L. F. Kirkels, Eva J. H. F. Voogd, Lieve M. Schupp, Sabine Collette, Adrien E. D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte‐Terreros, Lucas A. Ramos, Public Health, Health Systems and Insurance (HSI), Neurology, Radiology & Nuclear Medicine, Pediatrics, Radiology and nuclear medicine, Radiology and Nuclear Medicine, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
acute ischemic stroke, expanded thrombolysis in cerebral infarction, THROMBECTOMY, PERFORMANCE, case-mix, National Institutes of Health Stroke Scale, hospitals' patient volume, early outcome, quality of care, IMPUTATION, HEALTH, RATES, Cardiology and Cardiovascular Medicine, hospitals’ patient volume, SCALE
Abstract

Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between‐hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between‐hospital variation in outcomes was assessed using the variance of random hospital effects (tau 2 ). In addition, we estimated the correlation between hospitals' EVT‐patient volume and (case‐mix–adjusted) outcomes. Both early outcomes and case‐mix characteristics varied significantly across hospitals. Between‐hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case‐mix adjustment (tau 2 =0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case‐mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT‐patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores ( r =0.48) and weakly with lower NIHSS score at 24 to 48 hours ( r =0.15). Conclusions Between‐hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case‐mix but not by patient volume. In contrast, between‐hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT‐patient volume but not by case‐mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case‐mix is applied for NIHSS score.

Published
2023

12. Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice

Author

Henk van Voorst, Agnetha A.E. Bruggeman, Jurr Andriessen, Jan W. Hoving, Praneeta R. Konduri, Wenjin Yang, Manon Kappelhof, Nerea Arrarte Terreros, Yvo B.W.E.M. Roos, Wim H. van Zwam, Aad van der Lugt, Anouk van der Hoorn, Jelis Boiten, Stefan Roosendaal, Sjoerd Jenniskens, Matthan W.A. Caan, Henk A. Marquering, Bart J. Emmer, Charles B.L.M. Majoie, Diederik W.J. Dippel, Robert J. van Oostenbrugge, Jan Albert Vos, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Bob Roozenbeek, Adriaan C.G.M. van Es, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Paul J.A.M. Brouwers, Marieke E.S. Sprengers, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Saman Vinke, H. Zwenneke Flach, Hester F. Lingsma, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Haryadi Prasetya, Lucas A. Ramos, Radiology and Nuclear Medicine, Biomedical Engineering and Physics, ANS - Brain Imaging, APH - Methodology, APH - Aging & Later Life, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, ACS - Microcirculation, Pediatrics, Radiology and nuclear medicine, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)

Subjects
IMPACT, RECANALIZATION, GUIDELINES, functional status, All institutes and research themes of the Radboud University Medical Center, Brain Ischemia/diagnostic imaging, LENGTH, ischemic stroke, Humans, Ischemic Stroke/complications, thrombosis, Retrospective Studies, Advanced and Specialized Nursing, Other Research Radboud Institute for Health Sciences [Radboudumc 0], THROMBECTOMY, Endovascular Procedures/methods, Treatment Outcome, Thrombosis/diagnostic imaging, Thrombectomy/methods, stents, HEART, Neurology (clinical), prognosis, Cardiology and Cardiovascular Medicine, STROKE, Stroke/diagnostic imaging
Abstract

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71–0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16–0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24–0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50–0.89]; P =0.005; adjusted cOR, 0.74 [95% CI, 0.55–1.0]; P =0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.

Published
2023

13. Impaired Visual Emotion Recognition After Minor Ischemic Stroke

Author

Wilma Smith–Spijkerboer, Job van der Palen, Lucille D.A. Dorresteijn, Moniek S.E. van Hout, Heleen M. den Hertog, Anneke S. Smeets–Schouten, and Karen Meeske

Subjects
medicine.medical_specialty, Traumatic brain injury, medicine.medical_treatment, Emotions, UT-Hybrid-D, Physical Therapy, Sports Therapy and Rehabilitation, Neuropsychological Tests, Audiology, Modified Rankin Scale, medicine, Prevalence, Humans, Neuropsychological assessment, Facial emotion recognition, Stroke, Ischemic Stroke, Rehabilitation, medicine.diagnostic_test, business.industry, Montreal Cognitive Assessment, Recognition, Psychology, Cognition, medicine.disease, Facial Expression, Mood, business
Abstract

Objective To assess the prevalence of impaired visual emotion recognition in patients who have suffered a minor ischemic stroke in the subacute phase and to determine associated factors of impaired visual emotion recognition. Design A prospective observational study. Setting Stroke-unit of a teaching hospital. Participants 112 patients with minor ischemic stroke. Interventions Not applicable. Main outcome measures Patients with minor stroke underwent a neuropsychological assessment in the sub-acute phase for visual emotion recognition by the Ekman 60 Faces Test and for general cognition. Univariable linear regression analyses were performed to identify associated factors of emotion recognition impairment. Results In 112 minor stroke patients we found a prevalence of 25% of impaired visual emotion recognition. This was significantly correlated with impaired general cognition. Nevertheless 10.9% of patients with normal general cognition still had impaired emotion recognition. Mood was negatively associated. Stroke localization, hemisphere side and gender were not associated. Conclusion Impaired visual emotion recognition is found in about a quarter of patients with minor ischemic stroke.

Published
2022

14. Added Value of a Blinded Outcome Adjudication Committee in an Open-Label Randomized Stroke Trial

Author

Nadinda A.M. van der Ende, Bob Roozenbeek, Olvert A. Berkhemer, Peter J. Koudstaal, Jelis Boiten, Ewoud J. van Dijk, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Wim van Zwam, Hester F. Lingsma, Aad van der Lugt, Diederik W.J. Dippel, Puck S.S. Fransen, Debbie Beumer, Lucie A. van den Berg, Albert J. Yoo, 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 a Nijeholt, Patrick A. Brouwer, Bart J. Emmer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, L. Jaap Kappelle, Rob H. Lo, 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, Rene 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, H. Zwenneke Flach, Henk A. Marquering, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, Ludo F.M. Beenen, Rene van den Berg, Radiology and Nuclear Medicine, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Neurology, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Neurovascular Disorders, ACS - Microcirculation, Radiology & Nuclear Medicine, Public Health, Klinische Neurowetenschappen, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), and RS: Carim - B06 Imaging

Subjects
Male, IMPACT, Original Contributions, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Outcome assessment, Outcome (game theory), Brain Ischemia, odds ratio, Single-Blind Method, Prospective Studies, Stroke, SCALE, Netherlands, MISCLASSIFICATION, clinical trial, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Treatment Outcome, BIAS, AGREEMENT, RELIABILITY, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, telephone, Open label, Cardiology and Cardiovascular Medicine, CLINICAL-TRIALS, medicine.medical_specialty, Advisory Committees, TRAUMATIC BRAIN-INJURY, Clinical and Population Sciences, All institutes and research themes of the Radboud University Medical Center, Added value, medicine, ischemic stroke, Humans, Aged, Advanced and Specialized Nursing, algorithm, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Odds ratio, medicine.disease, ADJUDICATION COMMITTEE, Clinical trial, Physical therapy, Neurology (clinical), MEASUREMENT ERROR, business
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Blinded outcome assessment in trials with prospective randomized open blinded end point design is challenging. Unblinding can result in misclassified outcomes and biased treatment effect estimates. An outcome adjudication committee assures blinded outcome assessment, but the added value for trials with prospective randomized open blinded end point design and subjective outcomes is unknown. We aimed to assess the degree of misclassification of modified Rankin Scale (mRS) scores by a central assessor and its impact on treatment effect estimates in a stroke trial with prospective randomized open blinded end point design. Methods: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). The primary outcome was the mRS at 90 days. Standardized, algorithm-based telephone interviews to assess the mRS were conducted from a central location by an experienced research nurse, unaware but not formally blinded to treatment allocation (central assessor). Masked reports of these interviews were adjudicated by a blinded outcome committee. Misclassification was defined as an incorrect classification of the mRS by the central assessor. The effect of endovascular treatment on the mRS was assessed with multivariable ordinal logistic regression. Results: In MR CLEAN, 53/500 (10.6%) of the mRS scores were misclassified. The degree and direction of misclassification did not differ between treatment arms (P=0.59). Benefit of endovascular treatment was shown on the mRS when scored by the central assessor (adjusted common odds ratio, 1.60 [95% CI, 1.16–2.21]) and the outcome adjudication committee (adjusted common odds ratio, 1.67 [95% CI, 1.21–2.20]). Conclusions: Misclassification by the central assessor was small, randomly distributed over treatment arms, and did not affect treatment effect estimates. This study suggests that the added value of a blinded outcome adjudication committee is limited in a stroke trial with prospective randomized open blinded end point design applying standardized, algorithm-based outcome assessment by a central assessor, who is unaware but not formally blinded to treatment allocation. Registration: URL: https://www.isrctn.com; Unique identifier: ISRCTN10888758.

Published
2022

15. Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19

Author

Wouter M. Sluis, Marijke Linschoten, Julie E. Buijs, J. Matthijs Biesbroek, Heleen M. den Hertog, Tessa Ribbers, Dennis J. Nieuwkamp, Reinier C. van Houwelingen, Andreas Dias, Ingeborg W.M. van Uden, Joost P. Kerklaan, H. Paul Bienfait, Sarah E. Vermeer, Sonja W. de Jong, Mariam Ali, Marieke J.H. Wermer, Marieke T. de Graaf, Paul J.A.M. Brouwers, Folkert W. Asselbergs, L. Jaap Kappelle, H. Bart van der Worp, Annemijn M. Algra, Richard C.J.M. Donders, D. Martijn O. Pruissen, Aaf F.M. Kuijper, Clara E.E. van Ofwegen-Hanekamp, Rik S. Hermanides, Hortence E. Haerkens-Arends, Rutger L. Anthonio, Mireille E. Emans, René A. Tio, Jur M. ten Berg, Björn E. Groenemeijer, Ron Pisters, P. Marc van der Zee, Hans-Marc J. Siebelink, Derk O. Verschure, Matthijs F.L. Meijs, Astrid Schut, Robert G. Tieleman, Wanda Hermans-van Ast, Jeroen Schaap, Lucia S. Jewbali, Peter C. Smits, Pim van der Harst, Maarten van Smeden, Wiek H. van Gilst, Cardiovascular Centre (CVC), Neurology, Cardiology, Neurosurgery, and Intensive Care

Subjects
Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Patient discharge, Netherlands/epidemiology, law.invention, Cohort Studies, law, Ischemic Stroke/epidemiology, Risk Factors, Internal medicine, 80 and over, Medicine, Humans, Cumulative incidence, In patient, Hospital Mortality, Stroke, Ischemic Stroke, Netherlands, Aged, COVID-19/epidemiology, Advanced and Specialized Nursing, Aged, 80 and over, business.industry, SARS-CoV-2, Incidence (epidemiology), Incidence, Pulmonary embolism, Clinical course, Age Factors, COVID-19, Middle Aged, medicine.disease, Prognosis, Intensive care unit, Hospitalization, Intensive Care Units, Functional Status, Ischemic stroke, Female, Pulmonary Embolism/epidemiology, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Background and Purpose: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. Methods: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. Results: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P =0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52–2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13–2.15]) than patients without stroke. Conclusions: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.

Published
2021

16. Mortality after chronic subdural hematoma is associated with frailty

Author

Jurre Blaauw, Bram Jacobs, Heleen M. den Hertog, Niels A. van der Gaag, Korné Jellema, Ruben Dammers, Kuan H. Kho, Rob J. M. Groen, Joukje van der Naalt, Hester F. Lingsma, Public Health, Neurosurgery, Clinical Neurophysiology, TechMed Centre, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Male, Frailty, Survival, Chronic Subdural hematoma, Cohort Studies, SDG 3 - Good Health and Well-being, Hematoma, Subdural, Chronic, Humans, Surgery, Female, Neurology (clinical), Mortality, Aged, Proportional Hazards Models, Retrospective Studies
Abstract

Purpose Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. Methods A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. Results A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD ± 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0–213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2–1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0–1.7), inability to live independently (HR 1.4, 95% CI: 1.1–1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1–1.9), and number of medications used (HR 1.0; 95% CI: 1.0–1.1) were independently associated with mortality. Conclusions CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted.

Published
2022

17. Prediction of Outcome and Endovascular Treatment Benefit Validation and Update of the MR PREDICTS Decision Tool

Author

Esmee Venema, Bob Roozenbeek, Maxim J.H.L. Mulder, Scott Brown, Charles B.L.M. Majoie, Ewout W. Steyerberg, Andrew M. Demchuk, Keith W. Muir, Antoni Dávalos, Peter J. Mitchell, Serge Bracard, Olvert A. Berkhemer, Geert J. Lycklama à Nijeholt, Robert J. van Oostenbrugge, Yvo B.W.E.M. Roos, Wim H. van Zwam, Aad van der Lugt, Michael D. Hill, Philip White, Bruce C.V. Campbell, Francis Guillemin, Jeffrey L. Saver, Tudor G. Jovin, Mayank Goyal, Diederik W.J. Dippel, Hester F. Lingsma, Jelis Boiten, Jan Albert Vos, Ivo G.H. Jansen, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Adriaan C.G.M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, 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, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Tomas Bulut, Paul J.A.M. Brouwers, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte- Terreros, Lucas A. Ramos, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: Hersen en Zenuw Centrum (3), RS: Carim - B05 Cerebral small vessel disease, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, Neurology, Public Health, Radiology & Nuclear Medicine, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ANS - Cellular & Molecular Mechanisms, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, SELECTION, Original Contributions, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Cardiorespiratory Medicine and Haematology, registry, GUIDELINES, THERAPY, ANGIOGRAPHY, Brain Ischemia, law.invention, 0302 clinical medicine, Randomized controlled trial, Interquartile range, Modified Rankin Scale, law, 80 and over, Registries, 030212 general & internal medicine, ACUTE ISCHEMIC-STROKE, uncertainty, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Endovascular Procedures, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Outcome (probability), reperfusion, Treatment Outcome, thrombectomy, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology and Cardiovascular Medicine, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], medicine.medical_specialty, Concordance, Clinical Trials and Supportive Activities, Clinical Sciences, Clinical and Population Sciences, 03 medical and health sciences, Clinical Research, medicine, ischemic stroke, Humans, Endovascular treatment, Aged, Advanced and Specialized Nursing, Neurology & Neurosurgery, business.industry, MECHANICAL THROMBECTOMY, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Neurosciences, medicine.disease, Brain Disorders, HERMES collaborators and MR CLEAN Registry Investigators, Emergency medicine, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Supplemental Digital Content is available in the text., Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (

Published
2021

18. Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment

Author

Wouter van der Steen, P. Matthijs van der Sluijs, Rob A. van de Graaf, Ruisheng Su, Lennard Wolff, Henk van Voorst, Heleen M. den Hertog, Pieter Jan van Doormaal, Adriaan C.G.M. van Es, Julie Staals, Wim van Zwam, Hester F. Lingsma, René van den Berg, Charles B.L.M. Majoie, Aad van der Lugt, Diederik W.J. Dippel, Bob Roozenbeek, Radiology & Nuclear Medicine, Neurology, Public Health, Biomedical Engineering and Physics, Graduate School, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurovascular Disorders, ACS - Microcirculation, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: Carim - B05 Cerebral small vessel disease, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, and Radiology and nuclear medicine

Subjects
Aspirin, Heparin, Rehabilitation, Endovascular Procedures, Ischemic stoke, Microvascular reperfusion, Brain Ischemia, Stroke, Periprocedural medication, Treatment Outcome, Fibrinolytic Agents, Infarction, Reperfusion, Humans, Surgery, Endovascular treatment, Neurology (clinical), Cardiology and Cardiovascular Medicine, Intracranial Hemorrhages, Thrombectomy
Abstract

OBJECTIVES: We aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure.MATERIALS AND METHODS: We performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage.RESULTS: Of 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups.CONCLUSIONS: The overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Published
2022

19. Determinants of Symptomatic Intracranial Hemorrhage After Endovascular Stroke Treatment: A Retrospective Cohort Study

Author

Wouter van der Steen, Nadinda A.M. van der Ende, Katinka R. van Kranendonk, Vicky Chalos, Robert J. van Oostenbrugge, Wim H. van Zwam, Yvo B.W.E.M. Roos, Pieter J. van Doormaal, Adriaan C.G.M. van Es, Hester F. Lingsma, Charles B.L.M. Majoie, Aad van der Lugt, Diederik W.J. Dippel, Bob Roozenbeek, Jelis Boiten, Jan Albert Vos, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Josje Brouwer, Sanne J. den Hartog, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Tomas Bulut, Paul J.A.M. Brouwers, Geert J. Lycklama, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Wouter Dinkelaar, P.A. Auke, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte- Terreros, Lucas A. Ramos, Martin M. Brown, Thomas Liebig, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Annet Geerling, Annemieke Lindl-Velema, Ans de Ridder, Paut Greebe, Jose de Bont- Stikkelbroeck, MC Haaglanden, Kirsten Janssen, Silvan Licher, Nikki Boodt, Adriaan Ros, 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, Marit Lucas, Ralph Renan Geuskens, Roeland Sales Barros, Neurology, Radiology & Nuclear Medicine, Public Health, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: Carim - B05 Cerebral small vessel disease, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, Radiology and nuclear medicine, ACS - Atherosclerosis & ischemic syndromes, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Graduate School, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, and ANS - Neurovascular Disorders

Subjects
OCCLUSION, IMPACT, intracranial hemorrhages, MULTICENTER, THERAPY, Intracranial Hemorrhages/complications, Brain Ischemia/diagnostic imaging, blood glucose, Endovascular Procedures/adverse effects, cardiovascular diseases, ACUTE ISCHEMIC-STROKE, PREDICTORS, humans, Ischemic Stroke, Thrombectomy, Advanced and Specialized Nursing, INTRAVENOUS ALTEPLASE, MECHANICAL THROMBECTOMY, adult, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Endovascular Procedures, RANDOMIZED-TRIAL, TRANSFORMATION, brain ischemia, Stroke, retrospective studies, Treatment Outcome, Thrombectomy/adverse effects, Neurology (clinical), Cardiology and Cardiovascular Medicine, Stroke/diagnostic imaging
Abstract

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06–2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02–1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16–2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/ ; Unique identifier: ISRCTN10888758.

Published
2022

20. Etiology of Large Vessel Occlusion Posterior Circulation Stroke: Results of the MR CLEAN Registry

Author

F.A.V. (Anne) Pirson, Nikki Boodt, Josje Brouwer, Agnetha A.E. Bruggeman, Wouter H. Hinsenveld, Julie Staals, Wim H. van Zwam, Christiaan van der Leij, Rutger J.B. Brans, Charles B.L.M. Majoie, Diederik W.J. Dippel, Aad van der Lugt, Wouter J. Schonewille, Robert J. van Oostenbrugge, Yvo B.W.E.M. Roos, Jelis Boiten, Jan Albert Vos, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Sanne J. den Hartog, Bob Roozenbeek, Bart J. Emmer, Jonathan M. Coutinho, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Adriaan C.G.M. van Es, Jeannette Hofmeijer, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Paul J.A.M. Brouwers, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, Sandra Cornelissen, Rutger Brans, H. Zwenneke Flach, Hester F. Lingsma, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A. Ramos, Anne F.A.V. Pirson, Graduate School, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, ANS - Brain Imaging, ANS - Neurovascular Disorders, Neurology, Radiology & Nuclear Medicine, Public Health, Klinische Neurowetenschappen, RS: Carim - B05 Cerebral small vessel disease, MUMC+: MA Niet Med Staf Neurologie (9), MUMC+: MA Med Staf Spec Neurologie (9), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, MUMC+: MA Neurologie (3), MUMC+: Hersen en Zenuw Centrum (3), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Radiology and nuclear medicine

Subjects
DIAGNOSIS, EMBOLIC STROKES, UNDETERMINED SOURCE, embolic stroke, ischemic stroke, Humans, Prospective Studies, Registries, Advanced and Specialized Nursing, OUTCOMES, BASILAR ARTERY-OCCLUSION, CLINICAL-FEATURES, Endovascular Procedures, Other Research Radboud Institute for Health Sciences [Radboudumc 0], reperfusion, Stroke, Treatment Outcome, ISCHEMIC-STROKE, thrombectomy, ENDOVASCULAR TREATMENT, RISK-FACTORS, Neurology (clinical), atherosclerosis, Cardiology and Cardiovascular Medicine, SUBTYPE, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Background: In patients with large vessel occlusion stroke of the anterior circulation, underlying cause is a determinant of outcome. Whether this is the case for posterior circulation large vessel occlusion stroke has yet to be determined. We aimed to report on cause in patients with posterior circulation stroke treated with endovascular thrombectomy and to analyze the association with functional outcome. Methods: We used data of patients with posterior circulation stroke included in the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, a prospective multicenter observational study, between 2014 and 2018. Stroke cause was categorized into large artery atherosclerosis (LAA), cardioembolism, arterial dissection, embolic stroke of undetermined source (ESUS), other determined cause, or undetermined cause. For primary analysis on the association between cause and outcome, we used multivariable ordinal logistic regression analysis to estimate the adjusted common odds ratio for a shift towards a better functional outcome on the modified Rankin Scale at 90 days with LAA as a reference group. Secondary outcomes included favorable functional outcome (modified Rankin Scale score 0–3), National Institutes of Health Stroke Scale score at 24 to 48 hours, reperfusion on digital subtraction angiography, and stroke progression. Results: Of 264 patients with posterior circulation stroke, 84 (32%) had LAA, 48 (18%) cardioembolism, 31 (12%) dissection, and 14 (5%) ESUS. Patients with a dissection were younger (48 [interquartile range, 43–60] years) and had a lower National Institutes of Health Stroke Scale at baseline (12 [interquartile range, 6–31]) than patients with other cause. Functional outcome was better for patients with cardioembolism and ESUS compared to LAA (modified Rankin Scale adjusted common odds ratio, 2.4 [95% CI, 1.1–5.2], respectively adjusted common odds ratio, 3.1 [95% CI, 1.0–9.3]). Patients with a dissection had a lower chance of successful reperfusion compared with LAA (adjusted odds ratio, 0.20 [95% CI, 0.06–0.70]). Conclusions: Unlike the anterior circulation, most frequent cause in our posterior large vessel occlusion stroke cohort is LAA followed by cardioembolism, dissection, and ESUS. Patients with cardioembolism and ESUS have a better prognosis for functional outcome after endovascular thrombectomy than patients with LAA.

Published
2022

21. Surgery After Primary Dexamethasone Treatment for Patients with Chronic Subdural Hematoma-A Retrospective Study

Author

Dana C. Holl, Rahman Fakhry, Clemens M.F. Dirven, Florien A.L. te Braake, Orit K. Begashaw, Walid Moudrous, S. Mirjam Droger, Nabil Asahaad, Christiaan de Brabander, Gerben J.J. Plas, Bram Jacobs, Joukje van der Naalt, Heleen M. den Hertog, Niels A. van der Gaag, Korné Jellema, Ruben Dammers, Hester F. Lingsma, Molecular Neuroscience and Ageing Research (MOLAR), Neurosurgery, and Public Health

Subjects
Treatment, Hematoma, Subdural, Chronic, Medical, Humans, Surgery, Nonsurgical, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, CSDH, Dexamethasone, Retrospective Studies
Abstract

Background: We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics associated with additional surgery. Methods: Data were retrospectively collected from 283 patients with CSDH, primarily treated with dexamethasone, in 3 hospitals from 2008 to 2018. Primary outcome was the need for additional surgery. The association between baseline characteristics and additional surgery was analyzed with univariable and multivariable logistic regression analysis and presented as adjusted odds ratios (aOR). Results: In total, 283 patients with CSDH were included: 146 patients (51.6%) received 1 dexamethasone course (DXM group), 30 patients (10.6%) received 2 dexamethasone courses (DXM-DXM group), and 107 patients (37.8%) received additional surgery (DXM-SURG group). Patients who underwent surgery more often had a Markwalder Grading Scale of 2 (as compared with 1, aOR 2.05; 95% confidence interval [CI] 0.90–4.65), used statins (aOR 2.09; 95% CI 1.01–4.33), had a larger midline shift (aOR 1.10 per mm; 95% CI 1.01–1.21) and had larger hematoma thickness (aOR 1.16 per mm; 95% CI 1.09–1.23), had a bilateral hematoma (aOR 1.85; 95% CI 0.90–3.79), and had a separated hematoma (as compared with homogeneous, aOR 1.77; 95% CI 0.72–4.38). Antithrombotics (aOR 0.45; 95% CI 0.21–0.95) and trabecular hematoma (as compared with homogeneous, aOR 0.31; 95% CI 0.12–0.77) were associated with a lower likelihood of surgery. Conclusions: More than one-third of patients with CSDH primarily treated with dexamethasone received additional surgery. These patients were more severely affected amongst others with larger hematomas.

Published
2022

22. Improvements in endovascular treatment for acute ischemic stroke

Author

Kars C.J. Compagne, Manon Kappelhof, Wouter H. Hinsenveld, Josje Brouwer, Robert-Jan B. Goldhoorn, Maarten Uyttenboogaart, Reinoud P.H. Bokkers, Wouter J. Schonewille, Jasper M. Martens, Jeannette Hofmeijer, H. Bart van der Worp, Rob T.H. Lo, Koos Keizer, Lonneke S.F. Yo, Geert J. Lycklama à Nijeholt, Heleen M. den Hertog, Emiel J.C. Sturm, Paul J.A.M. Brouwers, Marianne A.A. van Walderveen, Marieke J.H. Wermer, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Hieronymus D. Boogaarts, Ewout J. van Dijk, Julia H. van Tuijl, Jo P.P. Peluso, Paul L.M. de Kort, Boudewijn A.A.M. van Hasselt, Puck S. Fransen, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Sjoerd F.M. Jenniskens, Marieke E.S. Sprengers, Elias Ghariq, Ido R. van den Wijngaard, Stefan D. Roosendaal, Anton F.J.A. Meijer, Ludo F.M. Beenen, Alida A. Postma, René van den Berg, Albert J. Yoo, Pieter Jan van Doormaal, Marc P. van Proosdij, Menno G.M. Krietemeijer, Dick G. Gerrits, Sebastiaan Hammer, Jan Albert Vos, Jelis Boiten, Jonathan M. Coutinho, Bart J. Emmer, Ad C.G.M. van Es, Bob Roozenbeek, Yvo B.W.E.M. Roos, Wim H. van Zwam, Robert J. van Oostenbrugge, Charles B.L.M. Majoie, Diederik W.J. Dippel, Aad van der Lugt, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Sanne J. den Hartog, Julie Staals, Rob H. Lo, Ewoud J. van Dijk, J. de Vries, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Leo A.M. Aerden, René J. Dallinga, Omid Eschgi, Tomas Bulut, Bas F.W. van der Kallen, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Rob Lo, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Hester F. Lingsma, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A. Ramos, TechMed Centre, Clinical Neurophysiology, Klinische Neurowetenschappen, RS: Carim - B05 Cerebral small vessel disease, MUMC+: MA AIOS Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: DA BV AIOS Radiologie (9), Beeldvorming, MUMC+: DA BV AIOS Nucleaire Geneeskunde (9), MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, MUMC+: MA Neurologie (3), MUMC+: Hersen en Zenuw Centrum (3), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Radiology & Nuclear Medicine, Neurology, Radiology and Nuclear Medicine, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, ANS - Neurovascular Disorders, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, Graduate School, ACS - Pulmonary hypertension & thrombosis, Pediatrics, and Radiology and nuclear medicine

Subjects
ratio, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], SOCIETY, registry, GUIDELINES, Brain Ischemia, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], MANAGEMENT, IMPUTATION, Humans, Longitudinal Studies, Registries, groin odds, SCALE, Ischemic Stroke, Advanced and Specialized Nursing, OUTCOMES, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Endovascular Procedures, THROMBECTOMY, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], reperfusion, Stroke, Treatment Outcome, RELIABILITY, Neurology (clinical), puncture, Cardiology and Cardiovascular Medicine, SYSTEMATIC EVALUATION, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P P P Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Published
2022

23. Prevalence of cognitive complaints and impairment in patients with Chronic Subdural Hematoma and recovery after treatment

Author

Jurre Blaauw, Wilco C. Peul, Anke G. Boxum, Niels A van der Gaag, Rob J. M. Groen, Joukje van der Naalt, Ruben Dammers, Heleen M. den Hertog, Bram Jacobs, Hester F. Lingsma, Korné Jellema, Public Health, Neurosurgery, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
cognition, 030506 rehabilitation, Pediatrics, medicine.medical_specialty, Disease, PsycINFO, 03 medical and health sciences, 0302 clinical medicine, Chronic subdural hematoma, systematic review, Prevalence, Medicine, Humans, Cognitive deficit, cognitive impairment, Coma, business.industry, Cognition, Recovery of Function, Confidence interval, chronic subdural hematoma, Hematoma, Subdural, Chronic, Neurology (clinical), Headaches, medicine.symptom, 0305 other medical science, business, Cognition Disorders, cognitive complaints, 030217 neurology & neurosurgery
Abstract

Chronic subdural hematoma (CSDH) is a frequently occurring neurological disease associated with older age and use of anticoagulants. Symptoms vary from headaches to coma, but cognitive deficits can also be present. However, exact prevalence and severity of cognitive deficits in CSDH are still unknown. In this systematic review, we aim to assess cognitive status of patients with CSDH, at presentation and after treatment. PubMed, Embase and PsycInfo were searched for articles concerning cognition in CSDH. We divided cognitive changes into subjective cognitive deficit (cognitive complaints [CC]) and objective cognitive deficit (cognitive impairment [CI]). Two reviewers independently selected studies for inclusion and subsequently extracted data. Quality assessment was done by means of the Newcastle-Ottawa Scale. Reported prevalence of CC and CI was pooled with random effects meta-analysis. Out of 799 identified references, 22 met inclusion criteria. Twenty-one articles reported on prevalence of CC/CI and one study reported solely on CSDH patients with cognitive deficit. Estimated pooled prevalence of both CC and CI in CSDH at presentation was 45% (95% confidence interval [CI]: 36-54%). Four studies concerned a prospective evaluation of the effect of surgical treatment on cognition. These proved to be of fair to good quality after quality assessment. The estimated pre-treatment prevalence of objectified cognitive impairment was 61% (95% CI: 51-70%) decreasing to 18% (95% CI: 8-32%) post-surgery. From this review it can be concluded that CC and CI are very common in CSDH, with a tendency to improve after treatment. Therefore, we underline the importance of increased attention to cognitive status of these patients, with proper testing methods and treatment-testing intervals.

Published
2021

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

Author

Ishita P Miah, Hester F. Lingsma, Wilco C. Peul, Korné Jellema, Frits R. Rosendaal, Yeliz Tank, Heleen M. den Hertog, Ruben Dammers, Niels A van der Gaag, Neurosurgery, and Public Health

Subjects
medicine.medical_specialty, Neurology, business.industry, Predictors, Confounding, Review, Chronic subdural hematoma, medicine.disease, CSDH, Study heterogeneity, Hematoma, Midline shift, Recurrence, Meta-analysis, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Radiology, Neurosurgery, Cardiology and Cardiovascular Medicine, business, Neuroradiology, CT
Abstract

Purpose 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. Methods 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. Results 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 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. Conclusions 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

25. Transient neurological deficit in patients with chronic subdural hematoma

Author

Jurre Blaauw, Heleen M. den Hertog, Josje M. van Zundert, Niels A. van der Gaag, Korné Jellema, Ruben Dammers, Kuan H. Kho, Rob J. M. Groen, Hester F. Lingsma, Joukje van der Naalt, Bram Jacobs, Public Health, Neurosurgery, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Epilepsy, Neurology, Seizures, Neurology (clinical), Chronic subdural hematoma, Functional outcome, Anti-seizure medication, Transient neurological deficits
Abstract

RATIONALE: Symptoms of chronic subdural hematoma (CSDH) vary widely, including transient neurological deficit(s) (TND). The precise prevalence and the clinical aspects of TND are yet to be determined. Most TNDs are regarded and treated as symptomatic seizures, but the rationale for this decision is not always clear.METHODS: Patients with temporary symptoms were selected from a retrospective cohort of CSDH patients. We analyzed the association of TND characteristics with patients being classified as having a symptomatic seizure and with functional outcome using logistic regression analysis.RESULTS: Of the included 1307 CSDH patients, 113 (8.6%) had at least one episode of TND. Most common TNDs were aphasia/dysphasia, impaired awareness or clonic movements. Of these 113 patients, 50 (44%) were diagnosed with symptomatic seizure(s) by their treating physician. Impaired awareness, clonic movements and the presence of 'positive symptoms' showed the strongest association with the diagnosis symptomatic seizure (OR 36, 95% CI 7.8-163; OR 24, 95% CI 6.4-85; and OR 3.1, 95% CI 1.3-7.2). Aphasia/dysphasia lowered the chance of TND being classified as symptomatic seizure together with a longer TND duration (OR 0.2, 95% CI 0.1-0.6; and OR 0.91, 95% CI 0.84-0.99). Treatment with anti-epileptic drugs was related to unfavorable functional outcome (aOR 5.4, 95% CI 1.4-20.7).CONCLUSION: TND was not a rare phenomenon in our cohort of CSDH patients. A TND episode of 5 min, aphasia/dysphasia and/or absence of 'positive' symptoms are suggestive of a different TND pathophysiology than symptomatic seizures. Our results further suggest that treatment of TND in CSDH deserves careful consideration as management choices might influence patient outcome.

Published
2022

26. Hospital Variation in Time to Endovascular Treatment for Ischemic Stroke: What Is the Optimal Target for Improvement?

Author

Sanne J. den Hartog, Hester F. Lingsma, Pieter‐Jan van Doormaal, Jeannette Hofmeijer, Lonneke S. F. Yo, Charles B. L. M. Majoie, Diederik W. J. Dippel, Aad van der Lugt, Bob Roozenbeek, Yvo B. W. E. M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Jelis Boiten, Jan Albert Vos, Ivo G. H. Jansen, Maxim J. H. L. Mulder, Robert‐ Jan B. Goldhoorn, Kars C. J. Compagne, Manon Kappelhof, Josje Brouwer, Wouter H. Hinsenveld, Adriaan C. G. M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J. H. Wermer, Marianne A. A. van Walderveen, Julie Staals, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L. M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S. P. van den Berg, Boudewijn A. A. M. van Hasselt, Leo A. M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P. H. Bokkers, Tobien H. C. M. L. Schreuder, Roel J. J. Heijboer, Koos Keizer, Heleen M. den Hertog, Emiel J. C. Sturm, Paul J. A. M. Brouwers, Marieke E. S. Sprengers, Sjoerd F. M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F. M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F. W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Dick Gerrits, Wouter Dinkelaar, Auke P. A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R. M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M. M. Boers, J. Huguet, P. F. C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L. F. Kirkels, Eva J. H. F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E. D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte‐Terreros, Lucas A. Ramos, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, Radiology & Nuclear Medicine, Neurology, Public Health, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
Other Research Radboud Institute for Health Sciences [Radboudumc 0], Endovascular Procedures, Hospitals, Stroke, Brain ischemia, Treatment Outcome, surgical procedures, operative, RC666-701, Reperfusion, Humans, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, Quality improvement, Cardiology and Cardiovascular Medicine, Ischemic Stroke, Thrombectomy
Abstract

Background Time to reperfusion in patients with ischemic stroke is strongly associated with functional outcome and may differ between hospitals and between patients within hospitals. Improvement in time to reperfusion can be guided by between‐hospital and within‐hospital comparisons and requires insight in specific targets for improvement. We aimed to quantify the variation in door‐to‐reperfusion time between and within Dutch intervention hospitals and to assess the contribution of different time intervals to this variation. Methods and Results We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. The door‐to‐reperfusion time was subdivided into time intervals, separately for direct patients (door‐to‐computed tomography, computed tomography‐to‐computed tomography angiography [CTA], CTA‐to‐groin, and groin‐to‐reperfusion times) and for transferred patients (door‐to‐groin and groin‐to‐reperfusion times). We used linear mixed models to distinguish the variation in door‐to‐reperfusion time between hospitals and between patients. The proportional change in variance was used to estimate the amount of variance explained by each time interval. We included 2855 patients of 17 hospitals providing endovascular treatment. Of these patients, 44% arrived directly at an endovascular treatment hospital. The between‐hospital variation in door‐to‐reperfusion time was 9%, and the within‐hospital variation was 91%. The contribution of case‐mix variables on the variation in door‐to‐reperfusion time was marginal (2%–7%). Of the between‐hospital variation, CTA‐to‐groin time explained 83%, whereas groin‐to‐reperfusion time explained 15%. Within‐hospital variation was mostly explained by CTA‐to‐groin time (33%) and groin‐to‐reperfusion time (42%). Similar results were found for transferred patients. Conclusions Door‐to‐reperfusion time varies between, but even more within, hospitals providing endovascular treatment for ischemic stroke. Quality of stroke care improvements should not only be guided by between‐hospital comparisons, but also aim to reduce variation between patients within a hospital, and should specifically focus on CTA‐to‐groin time and groin‐to‐reperfusion time.

Published
2022

27. Presenting symptoms and functional outcome of chronic subdural hematoma patients

Author

Bram Jacobs, Jurre Blaauw, Heleen M. den Hertog, Rob J. M. Groen, Niels A van der Gaag, Ghislaine A Meelis, Hester F. Lingsma, Korné Jellema, Joukje van der Naalt, Kuan Hua Kho, Public Health, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
cognition, Male, medicine.medical_specialty, presenting symptoms, Glasgow Outcome Scale, Signs and symptoms, functional outcome, Chronic subdural hematoma, Internal medicine, INJURY, medicine, Humans, In patient, Glasgow Coma Scale, RECURRENCE, Aged, Retrospective Studies, business.industry, Confounding, Cognition, General Medicine, REVERSIBLE DEMENTIA, MILD, Outcome (probability), Treatment Outcome, Neurology, chronic subdural hematoma, Hematoma, Subdural, Chronic, Neurology (clinical), business
Abstract

Background: Patients with chronic subdural hematoma (CSDH) can present with a variety of signs and symptoms. The relationship of these signs and symptoms with functional outcome is unknown. Knowledge of these associations might aid clinicians in the choice to initiate treatment and may allow them to better inform patients on expected outcomes. Objective: To investigate if presenting signs and symptoms influence functional outcome in patients with CSDH. Methods: We conducted a retrospective analysis of consecutive CSDH patients in three hospitals. Glasgow Outcome Scale Extended (GOS-E) scores were obtained from the first follow-up visit after treatment. An ordinal multivariable regression analysis was performed, to assess the relationship between the different signs and symptoms on the one hand and functional outcome on the other adjusted for potential confounders. Results: We included 1,307 patients, of whom 958 (73%) were male and mean age was 74 (SD ± 11) years. Cognitive complaints were associated with lower GOS-E scores at follow-up (aOR 0.7, 95% CI: 0.5 – 0.8) Headache and higher Glasgow Coma Scale (GCS) scores were associated with higher GOS-E scores. (aOR 1.9, 95% CI: 1.5–2.3 and aOR 1.3, 95% CI: 1.2–1.4). Conclusion: Cognitive complaints are independently associated with worse functional outcome, whereas headache and higher GCS scores are associated with better outcome. The increased probability of unfavorable outcome in patients with CSDH who present with cognitive complaints favors a more prominent place of assessing cognitive status at diagnosis.

Published
2022

28. A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

Author

Rob A R Gons, Diederik W.J. Dippel, Jonathan M Coutinho, Lukas C van Dijk, Manon Kappelhof, Farshad Imani, Pieter-Jan van Doormaal, Henk van Voorst, Aad van der Lugt, Bart J. Emmer, Yves Samson, Jeannette Hofmeijer, Jelis Boiten, Inger R de Ridder, Floris H B M Schreuder, Olvert A. Berkhemer, Paul J A M Brouwers, Michel J M Remmers, Hester F. Lingsma, Leon A. Rinkel, Jasper M Martens, Yvo B.W.E.M. Roos, Kilian M. Treurniet, Robert J van Oostenbrugge, Adriaan C G M van Es, Ido R van den Wijngaard, Frédéric Clarençon, Clean–No Iv Investigators, Reinoud P H Bokkers, Hans Kortman, Hieronymus D Boogaarts, Koos Keizer, Bob Roozenbeek, Charles B. L. M. Majoie, Denis Brisbois, Tomas Bulut, Karlijn F de Laat, Robin Lemmens, Anouk van Norden, H Bart van der Worp, G Menno Krietemeijer, Wouter J Schonewille, Natalie E. LeCouffe, Julia H van Tuijl, Ludo F M Beenen, Manon L Tolhuisen, Lennard Wolff, Agnetha A E Bruggeman, René van den Berg, Philippe Desfontaines, Otto E H Elgersma, Boudewijn A A M van Hasselt, Rob T H Lo, Wim H van Zwam, Heleen M den Hertog, Maarten Uyttenboogaart, Jan-Albert Vos, Anouk van der Hoorn, Jelle Demeestere, Vincent Costalat, Anouk D Rozeman, Geert J Lycklama À Nijeholt, Alida A Postma, Caroline Arquizan, Daan Nieboer, Lonneke S F Yo, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, MUMC+: MA Neurologie (3), RS: Carim - B05 Cerebral small vessel disease, MUMC+: Hersen en Zenuw Centrum (3), Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, MUMC+: MA Med Staf Spec Neurologie (9), Radiology & Nuclear Medicine, Neurology, Public Health, Hematology, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ACS - Microcirculation, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, ANS - Brain Imaging, Biomedical Engineering and Physics, ACS - Pulmonary hypertension & thrombosis, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
Male, Infusions, medicine.medical_specialty, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], MEDLINE, GUIDELINES, Severity of Illness Index, THERAPY, law.invention, Tissue Plasminogen Activator/therapeutic use, All institutes and research themes of the Radboud University Medical Center, Fibrinolytic Agents, Randomized controlled trial, law, 80 and over, medicine, Humans, cardiovascular diseases, ACUTE ISCHEMIC-STROKE, Endovascular treatment, Infusions, Intravenous, Acute ischemic stroke, Stroke, Ischemic Stroke, Aged, Thrombectomy, Aged, 80 and over, THROMBOLYSIS, business.industry, Fibrinolytic Agents/therapeutic use, MECHANICAL THROMBECTOMY, Endovascular Procedures, Other Research Radboud Institute for Health Sciences [Radboudumc 0], General Medicine, Middle Aged, CARE, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Combined Modality Therapy, Europe, Treatment Outcome, Tissue Plasminogen Activator, Emergency medicine, Female, Ischemic Stroke/drug therapy, Intravenous, business
Abstract

Alteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial involving European patients did not show noninferiority or superiority of endovascular treatment alone.Background The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. Methods We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. Results The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). Conclusions In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, .)

Published
2021

29. White matter lesions and outcomes after endovascular treatment for acute ischemic stroke MR CLEAN registry results

Author

Simone M. Uniken Venema, Alida A. Postma, Ido R. van den Wijngaard, Jan Albert Vos, Hester F. Lingsma, Reinoud P.H. Bokkers, Jeannette Hofmeijer, Diederik W.J. Dippel, Charles B. Majoie, H. Bart van der Worp, Aad van der Lugt, Yvo B.W.E.M. Roos, Robert J. van Oostenbrugge, Wim H. van Zwam, Jelis Boiten, Ivo G.H. Jansen, Maxim J.H.L. Mulder, Robert- Jan B. Goldhoorn, Kars C.J. Compagne, Manon Kappelhof, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Bob Roozenbeek, Adriaan C.G.M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Wouter J. Schonewille, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Jasper M. Martens, Geert J. Lycklama à Nijeholt, Sebastiaan F. de Bruijn, Lukas C. van Dijk, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Paul J.A.M. Brouwers, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Stefan D. Roosendaal, Bas F.W. van der Kallen, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Esmee Venema, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine L. Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A. Ramos, Radiology and Nuclear Medicine, ACS - Microcirculation, Amsterdam Neuroscience - Neurovascular Disorders, ACS - Atherosclerosis & ischemic syndromes, TechMed Centre, Clinical Neurophysiology, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Neurology, Public Health, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Beeldvorming, MUMC+: DA BV AIOS Nucleaire Geneeskunde (9), MUMC+: DA BV AIOS Radiologie (9), and MUMC+: DA BV Medisch Specialisten Radiologie (9)

Subjects
medicine.medical_treatment, Original Contributions, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], LEUKOARAIOSIS, Logistic regression, THERAPY, ANGIOGRAPHY, law.invention, Brain Ischemia, HEMORRHAGE, Randomized controlled trial, law, Modified Rankin Scale, odds ratio, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Cerebral infarction, Endovascular Procedures, Thrombolysis, Middle Aged, THROMBECTOMY, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], White Matter, Stroke, COLLATERALS, AGREEMENT, Cardiology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, cerebral small vessel diseases, Cardiology and Cardiovascular Medicine, Intracranial Hemorrhages, radiography, Cohort study, medicine.medical_specialty, acute ischemic stroke, FUTILE RECANALIZATION, SMALL-VESSEL DISEASE, Clinical and Population Sciences, Internal medicine, medicine, Humans, METAANALYSIS, Aged, Advanced and Specialized Nursing, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], registries, Odds ratio, medicine.disease, Hyperintensity, Neurology (clinical), business
Abstract

Supplemental Digital Content is available in the text., Background: Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice. Methods: We analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)—a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category. Results: Of 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0–2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13–1.60] for mild WML and 1.67 [95% CI, 1.39–2.01] for moderate-to-severe WML; Ptrend

Published
2021

30. Glucose modifies the effect of endovascular thrombectomy in patients with acute stroke: A pooled-data meta-analysis

Author

Wim H. van Zwam, David Rodriguez-Luna, Arturo Renú, Peter Mitchell, Yvo B.W.E.M. Roos, Sébastien Richard, Ashutosh P Jadhav, Bruce C.V. Campbell, Aad van der Lugt, Michael D. Hill, Bijoy K Menon, Heleen M. den Hertog, Keith W. Muir, Serge Bracard, Elizabeth Osei, Diederik W.J. Dippel, Anand Dixit, Gary A. Ford, Hans-Christoph Diener, Charles B. L. M. Majoie, Benoit Guillon, Kenneth Butcher, Igor Sibon, Mayank Goyal, Andrew M. Demchuk, Demetrius K. Lopes, Gernot Rudel, Francis Guillemin, Meritxell Gomis, Geoffrey A. Donnan, Sandrine Deltour, Alain Bonafe, Jonathan A. Epstein, Ángel Chamorro, Vivek Y. Reddy, Sergio Amaro, Richard du Mesnil de Rochemont, Blanca Lara-Rodriguez, Scott Brown, Robert J. van Oostenbrugge, Olvert A. Berkhemer, Stephen M. Davis, Serge Bakchine, Geoffrey Cloud, Mohammed A. Almekhlafi, Neurology, Radiology & Nuclear Medicine, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Atherosclerosis & ischemic syndromes, RS: Carim - B06 Imaging, RS: Carim - B05 Cerebral small vessel disease, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: CARIM - R3.03 - Cerebral small vessel disease, RS: CARIM - R3.11 - Imaging, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, and MUMC+: MA Neurologie (3)

Subjects
medicine.medical_specialty, URIC-ACID, 030204 cardiovascular system & hematology, Gastroenterology, patients, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, Modified Rankin Scale, Internal medicine, medicine, oxidative stress, blood glucose, ACUTE ISCHEMIC-STROKE, Stroke, Advanced and Specialized Nursing, therapy, OUTCOMES, business.industry, Standard treatment, MECHANICAL THROMBECTOMY, Odds ratio, trial, medicine.disease, 3. Good health, meta-analysis, chemistry, thrombectomy, Meta-analysis, ADMISSION GLUCOSE, Uric acid, Neurology (clinical), hyperglycemia, poststroke hyperglycemia, Cardiology and Cardiovascular Medicine, business, intraarterial treatment, 030217 neurology & neurosurgery
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 glucose < or >90 mg/dL (5.0 mmol/L; P =0.019 for interaction; acOR, 3.81; 95% CI, 1.73–8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53–2.19 for patients >90 mg/dL), and glucose < or >100 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

31. 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, Adrien E D Groot, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Neurovascular Disorders, ACS - Atherosclerosis & ischemic syndromes, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Neurology, Public Health, Klinische Neurowetenschappen, MUMC+: MA Niet Med Staf Neurologie (9), RS: Carim - B05 Cerebral small vessel disease, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), and RS: Carim - B06 Imaging

Subjects
medicine.medical_treatment, Perfusion scanning, GUIDELINES, lcsh:RC346-429, Brain Ischemia, EARLY MANAGEMENT, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Modified Rankin Scale, Occlusion, Medicine, Prospective Studies, Registries, ACUTE ISCHEMIC-STROKE, 030212 general & internal medicine, Stroke, Original Research, Thrombectomy, OUTCOMES, medicine.diagnostic_test, Endovascular Procedures, Thrombolysis, THROMBECTOMY, Cardiology, INFARCTION, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, medicine.medical_specialty, Clinical Neurology, 03 medical and health sciences, Internal medicine, SCORE, Humans, lcsh:Neurology. Diseases of the nervous system, Ischemic Stroke, HEALTH-CARE PROFESSIONALS, Science & Technology, business.industry, Other Research Radboud Institute for Health Sciences [Radboudumc 0], CT ANGIOGRAPHY, medicine.disease, United States, Angiography, Propensity score matching, Neurosciences & Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

BackgroundRandomised 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.MethodsThe 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.ResultsOf 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, pConclusionsWithout the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window.

Published
2021

32. Detection of major cardioembolic sources in real-world patients with ischemic stroke or transient ischemic attack of undetermined cause

Author

Heleen M. den Hertog, Jorieke M B Reimer, Matthijs F.L. Meijs, Clemens von Birgelen, Gerlinde van der Maten, Marjolein Brusse-Keizer, Health Technology & Services Research, and TechMed Centre

Subjects
Adult, Male, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Heart Diseases, Embolism, 030204 cardiovascular system & hematology, Risk Assessment, Brain ischemia, 03 medical and health sciences, 0302 clinical medicine, Recurrent stroke, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, In patient, cardiovascular diseases, Transient ischemic attack, Aged, Retrospective Studies, Aged, 80 and over, Original Paper, Ischemic stroke, business.industry, Atrial fibrillation, Middle Aged, medicine.disease, Echocardiography, Doppler, body regions, Neurology, lcsh:RC666-701, Ischemic Attack, Transient, Echocardiography, Ambulatory, Cardiology, Electrocardiography, Ambulatory, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery, Cardiac symptoms
Abstract

Background/Aim: Current guidelines recommend transthoracic echocardiography (TTE) and ambulatory rhythm monitoring following ischemic stroke or transient ischemic attack (TIA) of undetermined cause for identifying cardioembolic sources (CES). Due to ongoing controversies about this routine strategy, we evaluated its yield in a real-world setting. Methods: In a tertiary medical center, we retrospectively evaluated consecutive patients with ischemic stroke or TIA of undetermined cause, who (after standard work-up) underwent TTE, ambulatory rhythm monitoring, or both. CES were classified as major if probably related to ischemic events and warranting a change of therapy. Results: Between January 2014 and December 2017, 674 patients had ischemic stroke or TIA of undetermined cause. Of all 484 patients (71.8%) who underwent TTE, 9 (1.9%) had a major CES. However, 7 of them had already been identified for cardiac evaluation due to new major electrocardiographic abnormalities or cardiac symptoms. Thus, only 2 patients (0.4%) truly benefitted from unselected TTE screening. Ambulatory rhythm monitoring was performed in 411 patients (61.0%) and revealed AF in 10 patients (2.4%). Conclusion: Detecting a major CES is essential because appropriate treatment lowers the risk of recurrent stroke. Nonetheless, in this real-world study that aimed at routine use of TTE and ambulatory rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause, the prevalence of major CES was low. Most patients with major CES on TTE already had an indication for referral to a cardiologist, suggesting that major CES might also have been identified with a much more selective use of TTE.

Published
2021

33. The additional value of an algorithm for atrial fibrillation at the stroke unit

Author

Gerben J. J. Plas, Marjolein Brusse-Keizer, Matthijs F.L. Meijs, Gerlinde van der Maten, Heleen M. den Hertog, P. J. A. M. Brouwers, and Health Technology & Services Research

Subjects
Male, Cardiac telemetry, UT-Hybrid-D, Action Potentials, Brain Ischemia, Brain ischemia, Electrocardiography, 03 medical and health sciences, 0302 clinical medicine, Heart Rate, Predictive Value of Tests, Risk Factors, Interquartile range, medicine, Humans, ST segment, Telemetry, In patient, Prospective Studies, cardiovascular diseases, Stroke, Aged, Paroxysmal AF, Aged, 80 and over, Observer Variation, business.industry, Transient, Rehabilitation, Reproducibility of Results, Signal Processing, Computer-Assisted, Atrial fibrillation, Middle Aged, Ischemic attack, medicine.disease, Ischemic Attack, Transient, Female, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Algorithm, 030217 neurology & neurosurgery, Algorithms
Abstract

Background and purpose: The rate of newly detected (paroxysmal) atrial fibrillation (AF) during inpatient cardiac telemetry is low. The objective of this study was to evaluate the additional diagnostic yield of an automated detection algorithm for AF on telemetric monitoring compared with routine detection by a stroke unit team in patients with recent ischemic stroke or TIA. Methods: Patients admitted to the stroke unit of Medisch Spectrum Twente with acute ischemic stroke or TIA and no history of AF were prospectively included. All patients had telemetry monitoring, routinely assessed by the stroke unit team. The ST segment and arrhythmia monitoring (ST/AR) algorithm was active, with deactivated AF alarms. After 24 h the detections were analyzed and compared with routine evaluation. Results: Five hundred and seven patients were included (52.5% male, mean age 70.2 ± 12.9 years). Median monitor duration was 24 (interquartile range 22–27) h. In 6 patients (1.2%) routine analysis by the stroke unit team concluded AF. In 24 patients (4.7%), the ST/AR Algorithm suggested AF. Interrater reliability was low (κ, 0.388, p < 0.001). Suggested AF by the algorithm turned out to be false positive in 11 patients. In 13 patients (2.6%) AF was correctly diagnosed by the algorithm. None of the cases detected by routine analysis were missed by the algorithm. Conclusions: Automated AF detection during 24-h telemetry in ischemic stroke patients is of additional value to detect paroxysmal AF compared with routine analysis by the stroke unit team alone. Automated detections need to be carefully evaluated.

Published
2020

34. Path from clinical research to implementation endovascular treatment of ischemic stroke in the Netherlands

Author

Eveline J.A. Wiegers, Kars C.J. Compagne, Paula M. Janssen, Esmee Venema, Jaap W. Deckers, Wouter J. Schonewille, Jan Albert Vos, Geert J. Lycklama à Nijeholt, Bob Roozenbeek, Jasper M. Martens, Jeannette Hofmeijer, Robert-Jan van Oostenbrugge, Wim H. van Zwam, Charles B.L.M. Majoie, Aad van der Lugt, H.F. Lingsma, Yvo B.W.E.M. Roos, Diederik W.J. Dippel, Jelis Boiten, Josje Brouwer, Sanne J. den Hartog, Wouter H. Hinsenveld, Manon Kappelhof, Robert-Jan B. Goldhoorn, Maxim J.H.L. Mulder, Ivo G.H. Jansen, Adriaan C.G.M. van Es, Bart J. Emmer, Jonathan M. Coutinho, Marieke J.H. Wermer, Marianne A.A. van Walderveen, Julie Staals, Sebastiaan F. de Bruijn, Lukas C. van Dijk, H. Bart van der Worp, Rob H. Lo, Ewoud J. van Dijk, Hieronymus D. Boogaarts, J. de Vries, Paul L.M. de Kort, Julia van Tuijl, Jo Jo P. Peluso, Puck Fransen, Jan S.P. van den Berg, Boudewijn A.A.M. van Hasselt, Leo A.M. Aerden, René J. Dallinga, Maarten Uyttenboogaart, Omid Eschgi, Reinoud P.H. Bokkers, Tobien H.C.M.L. Schreuder, Roel J.J. Heijboer, Koos Keizer, Lonneke S.F. Yo, Heleen M. den Hertog, Emiel J.C. Sturm, Paul Brouwers, Marieke E.S. Sprengers, Sjoerd F.M. Jenniskens, René van den Berg, Albert J. Yoo, Ludo F.M. Beenen, Alida A. Postma, Stefan D. Roosendaal, Bas F.W. van der Kallen, Ido R. van den Wijngaard, Joost Bot, Pieter-Jan van Doormaal, Anton Meijer, Elyas Ghariq, Marc P. van Proosdij, G. Menno Krietemeijer, Jo P. Peluso, Rob Lo, Dick Gerrits, Wouter Dinkelaar, Auke P.A. Appelman, Bas Hammer, Sjoert Pegge, Anouk van der Hoorn, Saman Vinke, H. Zwenneke Flach, Naziha el Ghannouti, Martin Sterrenberg, Corina Puppels, Wilma Pellikaan, Rita Sprengers, Marjan Elfrink, Michelle Simons, Marjolein Vossers, Joke de Meris, Tamara Vermeulen, Annet Geerlings, Gina van Vemde, Tiny Simons, Cathelijn van Rijswijk, Gert Messchendorp, Nynke Nicolaij, Hester Bongenaar, Karin Bodde, Sandra Kleijn, Jasmijn Lodico, Hanneke Droste, Maureen Wollaert, Sabrina Verheesen, D. Jeurrissen, Erna Bos, Yvonne Drabbe, Michelle Sandiman, Nicoline Aaldering, Berber Zweedijk, Mostafa Khalilzada, Jocova Vervoort, Eva Ponjee, Sharon Romviel, Karin Kanselaar, Denn Barning, Vicky Chalos, Ralph R. Geuskens, Tim van Straaten, Saliha Ergezen, Roger R.M. Harmsma, Daan Muijres, Anouk de Jong, Olvert A. Berkhemer, Anna M.M. Boers, J. Huguet, P.F.C. Groot, Marieke A. Mens, Katinka R. van Kranendonk, Kilian M. Treurniet, Manon L. Tolhuisen, Heitor Alves, Annick J. Weterings, Eleonora L.F. Kirkels, Eva J.H.F. Voogd, Lieve M. Schupp, Sabine Collette, Adrien E.D. Groot, Natalie E. LeCouffe, Praneeta R. Konduri, Haryadi Prasetya, Nerea Arrarte-Terreros, Lucas A. Ramos, Damage and Repair in Cancer Development and Cancer Treatment (DARE), ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Clinical Neurophysiology, Radiology and Nuclear Medicine, ACS - Microcirculation, Amsterdam Neuroscience - Neurovascular Disorders, Neurology, ACS - Atherosclerosis & ischemic syndromes, MUMC+: MA Neurologie (3), Klinische Neurowetenschappen, MUMC+: Hersen en Zenuw Centrum (3), RS: Carim - B05 Cerebral small vessel disease, Beeldvorming, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, Public Health, Radiology & Nuclear Medicine, and Cardiology

Subjects
Male, SELECTION, medicine.medical_specialty, MEDLINE, ischemia, Rate ratio, THERAPY, symbols.namesake, NUMBER, medicine, Humans, Registries, Poisson regression, Endovascular treatment, Stroke, Aged, Netherlands, Aged, 80 and over, Advanced and Specialized Nursing, implementation science, business.industry, Patient Selection, Standard treatment, MECHANICAL THROMBECTOMY, Endovascular Procedures, Other Research Radboud Institute for Health Sciences [Radboudumc 0], 22/2 OA procedure, Middle Aged, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], stroke, brain ischemia, Clinical trial, Treatment Outcome, Clinical research, INTRAVENOUS T-PA, thrombectomy, Emergency medicine, ONSET, symbols, Female, TRIAL, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

Contains fulltext : 220823.pdf (Publisher’s version ) (Closed access) Before 2015, endovascular treatment (EVT) for acute ischemic stroke was considered a promising treatment option. Based on limited evidence, it was performed in several dedicated stroke centers worldwide on selected patients. Since 2015, EVT for patients with intracranial large vessel occlusion has quickly been implemented as standard treatment in many countries worldwide, supported by the revised international guidelines based on solid evidence from multiple clinical trials. We describe the development in use of EVT in the Netherlands before, during, and after the pivotal EVT trials. We used data from all patients who were treated with EVT in the Netherlands from January 2002 until December 2018. We undertook a time-series analysis to examine trends in the use of EVT using Poisson regression analysis. Incidence rate ratios per year with 95% CIs were obtained to demonstrate the impact and implementation after the publication of the EVT trial results. We made regional observation plots, adjusted for stroke incidence, to assess the availability and use of the treatment in the country. In the buildup to the MR CLEAN (Multicenter Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands), a slow increase of EVT patients was observed, with 0.2% of all ischemic stroke patients receiving EVT. Before the trial results were formally announced, a statistically significant increase in EVT-treated patients per year was observed (incidence rate ratio, 1.72 [95% CI, 1.46-2.04]), and after the trial publication, an immediate steep increase was seen, followed by a more gradual increase (incidence rate ratio, 2.14 [95% CI, 1.77-2.59]). In 2018, the percentage of ischemic stroke patients receiving EVT increased to 5.8%. A well-developed infrastructure, a pragmatic approach toward the use of EVT in clinical practice, in combination with a strict adherence by the regulatory authorities to national evidence-based guidelines has led to successful implementation of EVT in the Netherlands. Ongoing efforts are directed at further increasing the proportion of stroke patients with EVT in all regions of the country.

Published
2020

35. Neurosurgical and Perioperative Management of Chronic Subdural Hematoma

Author

Joukje van der Naalt, Korné Jellema, Rob J. M. Groen, Hester F. Lingsma, Ruben Dammers, Bram Jacobs, Jurre Blaauw, Kuan Hua Kho, Niels A van der Gaag, Heleen M. den Hertog, Molecular Neuroscience and Ageing Research (MOLAR), Neurosurgery, and Public Health

Subjects
medicine.medical_specialty, Decompression, SURGERY, anesthesia, Logistic regression, lcsh:RC346-429, 03 medical and health sciences, GENERAL-ANESTHESIA, 0302 clinical medicine, Chronic subdural hematoma, medicine, Local anesthesia, neurosurgery, RECURRENCE, ELDERLY-PATIENTS, lcsh:Neurology. Diseases of the nervous system, Original Research, business.industry, logistic regression, Confounding, bilateral chronic subdural hematoma, Surgery, Neurology, chronic subdural hematoma, 030220 oncology & carcinogenesis, Radiological weapon, RISK-FACTORS, Neurology (clinical), Neurosurgery, Complication, business, 030217 neurology & neurosurgery, LOCAL-ANESTHESIA
Abstract

Objective: Surgery and specifically burr hole craniostomy is the most common first choice treatment of patients with Chronic Subdural Hematoma (CSDH). However, several aspects of neurosurgical and peri-operative management are still a subject of research, such as how to treat bilateral CSDH and the anesthetic approach. We aim to investigate the effect of the surgical approach to bilateral CSDH and the effect of anesthesia modality on outcome of CSDH patients. Methods: We retrospectively included surgically treated CSDH patients between 2005 and 2019 in three hospitals in the Netherlands. The effect of the surgical approach to bilateral CSDH (unilateral vs. bilateral decompression) and anesthesia modality (general vs. local anesthesia) on outcome (complications, recurrence, and length of hospital stay over 4 days) was studied with logistic regression adjusting for potentially confounding radiological and clinical characteristics. Results: Data of 1,029 consecutive patients were analyzed, mean age was 73.5 years (±11) and 75% of patients were male. Bilateral CSDH is independently associated with an increased risk of recurrence within 3 months in logistic regression analysis (aOR 1.7, 95% CI: 1.1–2.5) but recurrence rate did not differ between primary bilateral or unilateral decompression of bilateral CSDH. (15 vs. 17%, p = 0.775). Logistic regression analysis showed that general anesthesia was independently associated with an increased risk of complications (aOR 1.8, 95% CI: 1.0–3.3) and with a length of hospital admission of over 4 days (aOR 8.4, 95% CI: 5.6–12.4). Conclusions: Bilateral CSDH is independently associated with higher recurrence rates. As recurrence rates in bilateral CSDH are similar for different surgical approaches, the optimal choice for primary bilateral decompression of bilateral CSDH could vary per patient. General anesthesia for surgical treatment of CSDH is associated with higher complication rates and longer hospital admission.

Published
2020

36. Thrombolysis related symptomatic intracranial hemorrhage in estimated versus measured body weight

Author

Hanneke M. Droste, Erik W. van Zwet, Adrien E. Groot, Nyika D. Kruyt, Stephanie I. W. van de Stadt, Marieke J.H. Wermer, Heleen M. den Hertog, T. Truc My Nguyen, Jonathan M. Coutinho, Sander M. Van Schaik, Graduate School, AGEM - Inborn errors of metabolism, Neurology, Amsterdam Neuroscience - Neurovascular Disorders, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, medicine.medical_specialty, thrombolysis, hemorrhagic complications, acute stroke, medicine.medical_treatment, Body weight, Tissue plasminogen activator, Fibrinolytic Agents, Internal medicine, medicine, Humans, intravenous thrombolysis, Dosing, Prospective Studies, Registries, Recombinant tissue plasminogen activator, Lead (electronics), Acute ischemic stroke, Aged, Ischemic Stroke, Aged, 80 and over, tissue plasminogen activator, business.industry, Research, Thrombolysis, Middle Aged, Treatment Outcome, Neurology, Hemorrhagic complication, Cardiology, Administration, Intravenous, Female, business, Intracranial Hemorrhages, intracranial hemorrhage, medicine.drug
Abstract

Background and aim In acute ischemic stroke, under- or overestimation of body weight can lead to dosing errors of recombinant tissue plasminogen activator with consequent reduced efficacy or increased risk of hemorrhagic complications. Measurement of body weight is more accurate than estimation of body weight but potentially leads to longer door-to-needle times. Our aim was to assess if weight modality (estimation of body weight versus measurement of body weight) is associated with (i) symptomatic intracranial hemorrhage rate, (ii) clinical outcome, and (iii) door-to-needle times. Methods Consecutive patients treated with intravenous thrombolysis between 2009 and 2016 from 14 hospitals were included. Baseline characteristics and outcome parameters were retrieved from medical records. We defined symptomatic intracranial hemorrhage according to the European Cooperative Acute Stroke Study (ECASS)-III definition and clinical outcome was assessed with the modified Rankin Scale. The association of weight modality and outcome parameters was estimated with regression analyses. Results A total of 4801 patients were included. Five hospitals used measurement of body weight (n = 1753), six hospitals used estimation of body weight (n = 2325), and three hospitals (n = 723) changed from estimation of body weight to measurement of body weight during the study period. In 2048 of the patients (43%), measurement of body weight was used and in 2753 (57%), estimation of body weight. In the measurement of body weight group, an inbuilt weighing bed was used in 1094 patients (53%) and a patient lift scale in 954 patients (47%). In the estimation of body weight group, policy regarding estimation was similar. Estimation of body weight was not associated with increased symptomatic intracranial hemorrhage risk (adjusted odds ratio = 1.16; 95% confidence interval 0.83–1.62) or favorable outcome (adjusted odds ratio = 0.99; 95% confidence interval 0.82–1.21), but it was significantly associated with longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed (adjusted B = 3.57; 95% confidence interval 1.33–5.80) and shorter door-to-needle times compared to measurement of body weight using a patient lift scale (−3.96; 95% confidence interval −6.38 to −1.53). Conclusion We did not find evidence that weight modality (estimation of body weight versus measurement of body weight) to determine recombinant tissue plasminogen activator dose in intravenous thrombolysis eligible patients is associated with symptomatic intracranial hemorrhage or clinical outcome. We did find that estimation of body weight leads to longer door-to-needle times compared to measurement of body weight using an inbuilt weighing bed and to shorter door-to-needle times compared to measurement of body weight using a patient lift scale.

Published
2020

37. Prediction of Persistent Impaired Glucose Tolerance in Patients with Minor Ischemic Stroke or Transient Ischemic Attack

Author

Diederik W.J. Dippel, Elizabeth Osei, Laus J.M.M. Mulder, Hester F. Lingsma, Susanne Fonville, P. J. A. M. Brouwers, Peter J. Koudstaal, Heleen M. den Hertog, Adrienne A.M. Zandbergen, Neurology, Internal Medicine, and Public Health

Subjects
Blood Glucose, Male, medicine.medical_specialty, Time Factors, Population, Risk Assessment, Decision Support Techniques, Impaired glucose tolerance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Predictive Value of Tests, Recurrence, Risk Factors, Internal medicine, Glucose Intolerance, medicine, Secondary Prevention, Humans, In patient, Prediabetes, Prospective Studies, education, Stroke, Aged, Aged, 80 and over, education.field_of_study, Triglyceride, business.industry, Rehabilitation, nutritional and metabolic diseases, Reproducibility of Results, Atrial fibrillation, Glucose Tolerance Test, Middle Aged, medicine.disease, Prognosis, chemistry, Ischemic Attack, Transient, Cardiology, Surgery, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Body mass index, 030217 neurology & neurosurgery, Biomarkers
Abstract

Background: Impaired glucose tolerance (IGT) in patients with ischemic stroke can return to normal, reflecting an acute stress response, or persist. Persistent IGT is associated with an increased risk of recurrent stroke, other cardiovascular diseases and unfavorable outcome after stroke. We aim to validate our previously developed model to identify patients at risk of persistent IGT in an independent data set, and, if necessary, update the model. Methods: The validation data set consisted of 239 nondiabetic patients with a minor ischemic stroke or TIA and IGT in the acute phase (2-hour post-load glucose levels between 7.8 and 11.0 mmol/l). The outcome was persistent versus normalized IGT, based on repeated oral glucose tolerance test after a median of 46 days. The discriminative ability of the original model was assessed with the area under the ROC curve (AUC). The updated model was internally validated with bootstrap resampling and cross-validated in the development population of the original model. Results: One-hundred eighteen of 239 (49%) patients had persistent IGT. The original model, with the predictors age, current smoking, statin use, triglyceride, hypertension, history of cardiovascular diseases, body mass index (BMI), fasting plasma glucose performed poorly (AUC .60). The newly developed model included only BMI, hypertension, statin use, atrial fibrillation, 2-hour post-load glucose levels, HbA1c, large artery atherosclerosis, and predicted persistent IGT more accurately (internally validated AUC 0.66, externally validated AUC .71). Conclusions: This prediction model with simple clinical variables can be used to predict persistent IGT in patients with IGT directly after minor stroke or TIA, and may be useful to optimize secondary prevention by early identification of patients with disturbed glucose metabolism.

Published
2020

38. 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

39. 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

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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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46. 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

47. 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

48. 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

49. 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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50. 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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