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Background: The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a potential predictor of malignant edema formation in patients with acute ischemic stroke., Aims: We aimed to evaluate the added value of the CSF/ICV ratio in a model to predict malignant edema formation in patients who underwent endovascular treatment., Methods: We included patients from the MR CLEAN Registry, a prospective national multicenter registry of patients who were treated with endovascular treatment between 2014 and 2017 because of acute ischemic stroke caused by large vessel occlusion. The CSF/ICV ratio was automatically measured on baseline thin-slice noncontrast CT. The primary outcome was the occurrence of malignant edema based on clinical and imaging features. The basic model included the following predictors: age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT score, occlusion of the internal carotid artery, collateral score, time between symptom onset and groin puncture, and unsuccessful reperfusion. The extended model included the basic model and the CSF/ICV ratio. The performance of the basic and the extended model was compared with the likelihood ratio test., Results: Malignant edema occurred in 40 (6%) of 683 patients. In the extended model, a lower CSF/ICV ratio was associated with the occurrence of malignant edema (odds ratio (OR) per percentage point, 1.2; 95% confidence interval (CI) 1.1-1.3, p  < 0.001). Age lost predictive value for malignant edema in the extended model (OR 1.1; 95% CI 0.9-1.5, p  = 0.372). The performance of the extended model was higher than that of the basic model ( p  < 0.001)., Conclusions: Adding the CSF/ICV ratio improves a multimodal prediction model for the occurrence of malignant edema after endovascular treatment.

Background: Early prediction of malignant infarction may guide treatment decisions. For patients who received endovascular treatment, the risk of malignant infarction is unknown and risk factors are unrevealed., Aims: The objective of this study is to estimate the incidence of malignant infarction after endovascular treatment in patients with an occlusion of the anterior circulation, to identify independent risk factors, and to establish a model for prediction., Methods: We analyzed patients who received endovascular treatment for a large vessel occlusion in the anterior circulation within 6.5 h after symptom onset, included in the Dutch MR CLEAN Registry between March 2014 and June 2016. We compared patients with and without malignant infarction. Candidate predictors were incorporated in a multivariable binary logistic regression model. The final prediction model was established using backward elimination. Discrimination and calibration were evaluated with the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow test., Results: Of 1445 patients, 82 (6%) developed malignant infarction. Independent predictors were lower age, higher National Institutes of Health Stroke Scale (NIHSS), lower alberta stroke program early CT score (ASPECTS), internal carotid artery occlusion, lower collateral score, longer times from onset to groin puncture, and unsuccessful reperfusion. The AUROC of a prediction model combining these features was 0.83 (95% confidence interval (CI): 0.79-0.88) and the Hosmer-Lemeshow test indicated appropriate calibration (P = 0.937)., Conclusion: The risk of malignant infarction after endovascular treatment started within 6.5 h of stroke onset is approximately 6%. Successful reperfusion decreases the risk. A prediction model combining easily retrievable measures of age, ASPECTS, collateral status, and reperfusion shows good discrimination between patients who will develop malignant infarction and those who will not.

Background: The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients., Methods: We performed a search and review of the literature, and conducted a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation., Results: The survey and workshop identified a number of barriers to patient recruitment and retention, from patients' incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments by health services only when delivered within clinical trials. The literature review revealed that few methods have been formally evaluated. The top five priorities for evaluation identified in the workshop were as follows: short and illustrated patient information leaflets, nonwritten consent, reimbursement for new interventions only within a study, and monetary incentives to institutions taking part in research (for recruitment); and involvement of patient groups, remote and central follow-up, use of mobile devices, and reminders to patients about their consent to participate (for retention)., Conclusions: Many interventions have been used with the aim of improving recruitment and retention of patients in stroke studies, but only a minority has been evaluated. We have identified methods that could be tested, and propose that such evaluations may be nested within on-going clinical trials., (© 2016 World Stroke Organization.)

Rationale: In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37.0 °C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1.43; 95% confidence interval: 1.02-1.97). This relation was also found in the patients with a body temperature of 36.5 °C or higher (odds ratio 1.31; 95% confidence interval 1.01-1.68). These findings need confirmation., Aim: The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36.5 °C or above on functional outcome., Design: The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0.05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36.5 °C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register., Study Outcomes: The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression., Discussion: If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background and Purpose: In patients with space-occupying middle cerebral artery infarction, surgical decompression strongly reduces risk of death and increases the chance of a favorable outcome. This comes at the expense of an increase in the risk of survival with (moderately) severe disability. We assessed quality of life, depression, and caregiver burden in these patients., Summary of Review: We systematically reviewed the literature by searching MEDLINE, EMBASE, and PsycINFO up to March 2014. We included randomized controlled trials, cohort studies, case-control studies, and case series with quality of life, depression, or caregiver burden as primary or secondary outcome. Seventeen articles reporting on 459 patients were included. At final follow-up at 7 to 51 months, 1344 patients (30%) had died, and 34 (11%) were lost to follow up. Data on 291 patients were available, of whom 81 of 213 survivors (39%) achieved good functional outcome at final follow-up (modified Rankin Scale ≤ 3). Mean quality of life was 46% to 67% of the best possible score when based on questionnaires or visual analogue scales. At final follow-up, 143 of 189 patients (76%) would in retrospect again choose for surgical decompression. Severe depressive symptoms were present in 14 of 113 patients (16%). Three studies investigated caregiver burden and reported substantial burden. Patients more than 60 years old had a lower quality of life in comparison with younger patients., Conclusions: Most patients treated with surgical decompression for space-occupying infarction have a reasonable quality of life at long-term follow-up and are satisfied with the treatment received. Severe depressive symptoms are uncommon., (© 2014 World Stroke Organization.)

Background: Carotid endarterectomy and carotid artery stenting are frequently complicated by hemodynamic instability., Aims: The study aims to compare the incidence of hemodynamic complications between carotid artery stenting and carotid endarterectomy in the International Carotid Stenting Study (ISRCTN25337470)., Methods: Patients with symptomatic carotid stenosis were randomly allocated to carotid artery stenting or carotid endarterectomy. The occurrence of peri-procedural hemodynamic depression (severe bradycardia, asystole, or hypotension requiring treatment) and hypertension requiring treatment was assessed in a per-protocol analysis. We compared the rate of hemodynamic complications, determined independent predictors thereof, and assessed their relation with the composite outcome of all-cause death, stroke, and myocardial infarction within 30 days of treatment., Results: A number of 766 carotid artery stenting and 819 carotid endarterectomy patients had a single completed intervention. Hemodynamic depression occurred in 13.8% after carotid artery stenting and in 7.2% after carotid endarterectomy (relative risk 1.9, 95% confidence interval 1.4-2.6, P < 0.0001). Hypertension requiring treatment occurred less often after carotid artery stenting than after carotid endarterectomy (relative risk 0.2, 95% confidence interval, 0.1-0.4, P < 0.0001). In carotid artery stenting patients, a history of cardiac failure was the trongest independent predictor of hemodynamic depression (relative risk 2.4, 95% confidence interval 1.3-4.8, P = 0.009). There was no statistically significant association between hemodynamic complications and the occurrence of the composite outcome., Conclusion: Hemodynamic depression occurs more often after carotid artery stenting and severe hypertension more often after carotid endarterectomy, but these complications are not responsible for the excess of major perioperative events after carotid artery stenting., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background: Hypothermia is a promising experimental treatment for acute ischemic stroke. Human trials are still at an early stage, with the focus now on using hypothermia in awake patients. Pethidine (meperidine) is the principle agent used to control shivering in humans; however, whether it has any modulating effects on the neuroprotective efficacy of hypothermia is unknown., Aim: The aim of this study was to determine if pethidine influences the neuroprotective effect of hypothermia in experimental stroke., Methods: Seventy-two male spontaneously hypertensive rats were anesthetized with isoflurane and randomly assigned to either normothermia (37. 4 °C rectal temperature); hypothermia (33 °C maintained for 130 mins); normothermia plus pethidine (2.5 mg/kg); or hypothermia plus pethidine. Temporary (90 mins) endovascular occlusion of the middle cerebral artery was induced blinded to treatment allocation and was confirmed with laser Doppler flowmetry. Pethidine and cooling were started immediately after vessel occlusion. Animals in the normothermia group had active temperature management using a heat lamp and fan. Assessments of outcome were carried out 24 after the induction of injury., Results: Thirteen animals met our prespecified criteria for exclusion, and data for 59 rats were presented here. Hypothermia was associated with a 63% reduction in infarct size, and pethidine had no significant impact on the efficacy of hypothermia. No effects were observed in neurobehavioral outcome or edema volume across experimental groups., Conclusions: The effects of hypothermia in a model of focal ischemia are not affected by administration of pethidine., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.