Bart van der Worp

Therapeutic hypothermia in acute ischemic stroke

Increased body temperatures are common in the acute phase of stroke. Experimental and clinical studies have suggested that increased body temperatures are related to poor outcome. In animal studies of focal cerebral ischemia, early hypothermia consistently reduced infarct volume. Based on these findings, several Phase II clinical trials have been performed to study physical methods to reduce body temperature in patients with acute stroke. The feasibility and safety of these methods have not yet been established with sufficient certainty. Pharmacological lowering of body temperature may be an attractive alternative approach. In guidelines for the treatment of acute stroke, antipyretics are generally recommended to reduce fever, although their effect on functional outcome is unknown. There is currently no evidence from randomized trials to support routine use of physical or pharmacological cooling in acute stroke. Large randomized clinical trials are needed to study the effect of both physical and medical cooling on functional outcome after stroke.

The European Stroke Organisation Guidelines: a standard operating procedure

In 2008, the recently founded European Stroke Organisation published its guidelines for the management of ischemic stroke and transient ischemic attack. This highly cited document was translated in several languages and was updated in 2009. Since then, the European Stroke Organisation has published guidelines for the management of intracranial aneurysms and subarachnoidal hemorrhage, for the establishment of stroke units and stroke centers, and recently for the management of intracerebral hemorrhage. In recent years, the methodology for the development of guidelines has evolved significantly. To keep pace with this progress and driven by the strong determination of the European Stroke Organisation to further promote stroke management, education, and research, the European Stroke Organisation decided to delineate a detailed standard operating procedure for its guidelines. There are two important cornerstones in this standard operating procedure: The first is the implementation of the Grading of Recommendations Assessment, Development, and Evaluation methodology for the development of its Guideline Documents. The second one is the decision of the European Stroke Organisation to move from the classical model of a single Guideline Document about a major topic (e.g. management of ischemic stroke) to focused modules (i.e. subdivisions of a major topic). This will enable the European Stroke Organisation to react faster when new developments in a specific stroke field occur and update its recommendations on the related module rather swiftly; with the previous approach of a single large Guideline Document, its entire revision had to be completed before an updated publication, delaying the production of up-to-date guidelines. After discussion within the European Stroke Organisation Guidelines Committee and significant input from European Stroke Organisation members as well as methodologists and analysts, this document presents the official standard operating procedure for the development of the Guideline Documents of the European Stroke Organisation.

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

Background: In observational studies, a high body temperature has been associated with unfavorable outcome. In in vitro studies, the fibrinolytic activity of alteplase decreased 5% per degree Celsius reduction in temperature. The modifying effect of body temperature on treatment with alteplase in patients with acute ischemic stroke is unclear. We assessed the influence of baseline body temperature on the effect of alteplase on functional outcome in patients with acute ischemic stroke, included in the Paracetamol (Acetaminophen) in Stroke (PAIS) trial. Methods: PAIS was a randomized, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke. For this study, we selected all patients with ischemic stroke and randomization within 6 h of symptom onset. We estimated the effect of treatment with alteplase on the modified Rankin Scale score at 3 months with ordinal logistic regression, stratified by baseline body temperature. We made adjustments for confounding factors and expressed associations as adjusted odds ratios (aOR) with 95% confidence intervals (CI). We also tested for interaction between treatment with alteplase and body temperature. Results: We included 647 of the 1,400 patients in PAIS in our study. Treatment with alteplase was associated with improved functional outcome at 3 months (aOR 1.51, 95% CI 1.09–2.08). In the 286 patients (44%) with a baseline body temperature of 37.0°C or higher, alteplase was associated with a larger effect (aOR 2.13, 95% CI 1.28–3.45) than in patients with a temperature below 37.0°C (aOR 1.11, 95% CI 0.71–1.69). A test for interaction between body temperature and alteplase did not reach statistical significance (p = 0.18). Conclusion: Patients with ischemic stroke and a high body temperature may have a larger benefit of treatment with alteplase than patients with lower body temperatures. These findings are in line with those from in vitro studies, in which lowering temperature decreased the fibrinolytic activity of the enzyme alteplase. This interaction should be explored further in randomized clinical trials of thrombolytic therapy or modification of body temperature. Trials of therapeutic hypothermia should be controlled for treatment with thrombolytics, and trials of thrombolytic treatment should consider body temperature as a potential effect modifier.

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

BackgroundDuring the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied.AimThe aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments.DesignSeventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.

TriGuard™ HDH embolic deflection device for cerebral protection during transcatheter aortic valve replacement

This study aims to evaluate the safety and performance of the new embolic deflection device TriGuard™HDH in patients undergoing TAVR.

Symptomatic vertebral artery stent fracture: a case report.

Percutaneous transluminal angioplasty (PTA) with stent placement is the preferred treatment modality at present for atherosclerotic stenotic lesions of vertebral artery origin. A complication of stent placement in the vertebral artery origin that has received little attention is the risk of stent fracture. A case with four-vessel pathology treated with PTA and stent placement in the left vertebral artery origin is presented. Symptoms recurred 4 months after stent placement, and arteriogram revealed a fractured stent, which was treated surgically with stent removal and vertebral artery-common carotid artery reimplantation.

Standards of practice in acute ischemic stroke intervention: International recommendations: This article was first published in JNIS. Cite this article as: Pierot L, Jayaraman MV, Szikora I, et al. Standards of practice in acute ischemic stroke intervention: international recommendations. Journal of NeuroInterventional Surgery. Published Online First: 28 August 2018. doi: 10.1136/neurintsurg-2018-014287.

This article was first published in JNIS. Cite this article as: Pierot L, Jayaraman MV, Szikora I, et al. Standards of practice in acute ischemic stroke intervention: international recommendations. Journal of NeuroInterventional Surgery. Published Online First: 28 August 2018. doi: 10.1136/neurintsurg-2018-014287.

Third European Stroke Science Workshop

Lake Eibsee, Garmisch-Partenkirchen, November 19 to 21, 2015: The European Stroke Organization convened >120 stroke experts from 27 countries to discuss latest results and hot topics in clinical, translational, and basic stroke research. Since its inception in 2011, the European Stroke Science Workshop has become a cornerstone of European Stroke Organizations academic activities and major highlight for researchers in the field. Participants include stroke researchers at all career stages who convene for plenary lectures and discussions, thus facilitating crosstalk among researchers from different fields. As in previous years, the workshop was organized into 7 scientific sessions each focusing on a major research topic. All sessions started with a keynote lecture that provided an overview on current developments and set the scene for the following presentations. The latter were short focused talks on a timely topic and included the most recent findings, including unpublished data. A new element at this years meeting was a hot topic session in which speakers had to present a provocative concept or update sharply within 5 minutes. In the following, we summarize the key contents of the meeting. The program is provided in the online-only Data Supplement.