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Background: Data comparing the specific reversal agent andexanet alfa with non-specific treatments in patients with non-traumatic intracerebral hemorrhage (ICH) associated with factor-Xa inhibitor (FXaI) use are scarce., Aim: The study aimed to determine the association between the use of andexanet alfa compared with non-specific treatments with the rate of hematoma expansion and thromboembolic complications in patients with FXaI-associated ICH., Methods: We performed an individual patient data analysis combining two independent, prospective studies: ANNEXA-4 (180 patients receiving andexanet alfa, NCT02329327) and TICH-NOAC (63 patients receiving tranexamic acid or placebo ± prothrombin complex concentrate, NCT02866838). The primary efficacy outcome was hematoma expansion on follow-up imaging. The primary safety outcome was any thromboembolic complication (ischemic stroke, myocardial infarction, pulmonary embolism, or deep vein thrombosis) at 30 days. We used binary logistic regression models adjusted for baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively., Results: Among 243 participants included, the median age was 80 (IQR 75-84) years, baseline hematoma volume was 9.1 (IQR 3.4-21) mL and anti-Xa activity 118 (IQR 78-222) ng/mL. Times from last FXaI intake and symptom onset to treatment were 11 (IQR 7-16) and 4.7 (IQR 3.0-7.6) h, respectively. Overall, 50 patients (22%) experienced hematoma expansion (ANNEXA-4: n=24 (14%); TICH-NOAC: n=26 (41%)). After adjusting for pre-specified confounders (baseline hematoma volume, age, calibrated anti-Xa activity, times from last intake of FXaI, and symptom onset to treatment, respectively), treatment with andexanet alfa was independently associated with decreased odds for hematoma expansion (aOR 0.33, 95% CI 0.13-0.80, p = 0.015). Overall, 26 patients (11%) had any thromboembolic complication within 30 days (ANNEXA-4: n=20 (11%); TICH-NOAC: n=6 (10%)). There was no association between any thromboembolic complication and treatment with andexanet alfa (aOR 0.70, 95% CI 0.16-3.12, p = 0.641)., Conclusion: The use of andexanet alfa compared to any other non-specific treatment strategy was associated with decreased odds for hematoma expansion, without increased odds for thromboembolic complications., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.M.S. received research funding from the Swiss Academy of Medical Sciences/Bangerter-Rhyner Foundation and the Swiss Heart Foundation. M.B.G. received grants from Swiss Academy of Medical Sciences/Bangerter-Rhyner Foundation, Insel Gruppe AG, Swiss Stroke Society, European Stroke Organization, U.F. received research support of the Swiss National Science Foundation, and the Swiss Heart Foundation; research grants from Medtronic (and from Stryker, Rapid medical, Penumbra, and Phenox); consultancies for Medtronic, Stryker, and CSL Behring; and participation in an advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera; S.P. received research support from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, European Union, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories, and Werfen; and speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Portola, and Werfen. R.L. has no personal disclosures, but reports institutional fees for consultancy from Bioxodes and Pfizer. D.S. received grants from Alexion/AstraZeneca, personal fees from Bayer, and consultancy fees from VarmX.

Background: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines., Aims: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced)., Summary of Review: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited., Conclusion: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Introduction: Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset., Methods: Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries., Discussion: In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

Background and Aims: Nicardipine has strong, rapidly acting antihypertensive activity. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine after onset of intracerebral hemorrhage on clinical outcomes were determined., Methods: A systematic review and individual participant data analysis of articles before 1 October 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving hyperacute intracerebral hemorrhage adults treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4-6, and hematoma expansion, defined as an increase ≥6 mL from baseline to 24-h computed tomography., Summary of Review: Three studies met the eligibility criteria. For 1265 patients enrolled (age 62.6 ± 13.0 years, 484 women), death or disability occurred in 38.2% and hematoma expansion occurred in 17.4%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio (aOR) 1.12, 95% confidence interval (CI) 1.00-1.26 per 10 mmHg) and hematoma expansion (1.16, 1.02-1.32). Mean hourly systolic blood pressure from 1 h to any timepoint during the initial 24 h was positively associated with death or disability. Later achievement of systolic blood pressure to ≤140 mmHg increased the risk of death or disability (aOR 1.02, 95% CI 1.00-1.05 per hour)., Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h in hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability without increasing serious adverse events.

Background: Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. Thereby, patients with acute ischemic stroke who are on dabigatran treatment may become eligible for thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). In patients on dabigatran with intracerebral hemorrhage idarucizumab could prevent lesion growth., Aims: To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of acute ischemic stroke or intracranial hemorrhage., Methods: Retrospective data collected from German neurological/neurosurgical departments administering idarucizumab following product launch from January 2016 to August 2018 were used., Results: One-hundred and twenty stroke patients received idarucizumab in 61 stroke centers. Eighty patients treated with dabigatran presented with ischemic stroke and 40 patients suffered intracranial bleeding (intracerebral hemorrhage (ICH) in n  = 27). In patients receiving intravenous thrombolysis with rt-PA following idarucizumab, 78% showed a median improvement of 7 points in National Institutes of Health Stroke Scale. No bleeding complications were reported. Hematoma growth was observed in 3 out of 27 patients with ICH. Outcome was favorable with a median National Institutes of Health Stroke Scale improvement of 4 points and modified Rankin score 0-3 in 61%. Six out of 40 individuals (15%) with intracranial bleeding died during hospital stay., Conclusion: Administration of rt-PA after reversal of dabigatran activity with idarucizumab in case of acute ischemic stroke seems feasible, effective, and safe. In dabigatran-associated intracranial hemorrhage, idarucizumab appears to prevent hematoma growth and to improve outcome.

Background and Purpose: On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection., Methods: The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document., Results: This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection., Conclusions: These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

Background Many tertiary care hospitals cannot provide a continuous thrombectomy service due to the lack of a neurointerventionalist. Aims In this study, we present procedural and clinical results of a new concept in which neuroradiologists of a university hospital provide neurointerventional stroke service to a remote hospital ("drive the doctor"). Methods All consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation treated with mechanical thrombectomy after hours at a remote hospital (distance of about 100 km) between 2012 and 2016 were analyzed retrospectively. These patients were compared to a group of patients referred to the above mentioned university hospital for MT over a comparable distance ("drip and ship"). Results A total of 60 patients were treated by "drive the doctor" and 66 patients were treated by "drip and ship." Time from onset to imaging was similar in both groups (77 vs. 70 min, P = 0.6847). However, time from imaging to groin puncture was significantly lower in the "drive the doctor" model (112 vs. 232 min, P < 0.0001). Nonetheless, recanalization rate and clinical outcome were similar in both cohorts. Conclusions "Drive the doctor" is a feasible concept of neurothrombectomy coverage at remote hospitals. The presented data suggest that "drive the doctor" is not inferior compared to established stroke concepts such as "drip and ship" regarding recanalization rate and outcome. However, larger and prospective studies are necessary to confirm this finding.

In the past decade, tissue microarray (TMA) technology has evolved as an innovative tool for high-throughput proteomics analysis and mainly for biomarker validation. Similarly, enormous amount of data can be obtained from the cell line macroarray (CLMA) technology, which developed from the TMA using formalin-fixed, paraffin-embedded cell pellets. Here, we applied CLMA technology in stem cell research and in particular to identify bona fide neogenerated human induced pluripotent stem cell (hiPSC) clones suitable for down the line differentiation. All hiPSC protocols generate tens of clones, which need to be tested to determine genetically stable cell lines suitable for differentiation. Screening methods generally rely on fluorescence-activated cell sorting isolation and coverslip cell growth followed by immunofluorescence; these techniques could be cumbersome. Here, we show the application of CLMA to identify neogenerated pluripotent cell colonies and neuronal differentiated cell products. We also propose the use of the automated image analyzer, TissueQuest, as a reliable tool to quickly select the best clones, based upon the level of expression of multiple pluripotent biomarkers., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2016 The Histochemical Society.)

Background: Although the need for an emergency intervention may merit laboratory measurement of non-vitamin K antagonist oral anticoagulant (NOAC) concentration or anticoagulant activity, NOACs are not supposed to require routine monitoring due to their stable pharmacological profiles compared with warfarin., Aims: To examine situations where NOAC measurement may be useful and to provide information about methodologies available to measure NOAC-related anticoagulation activity., Summary of Review: The routine coagulation tests, including prothrombin time, thrombin time, activated partial thromboplastin time, and international normalized ratio, have variable sensitivities to NOACs. Tests have been developed for use with specific NOACs, e.g. diluted thrombin time or chromogenic factor Xa assays. In emergency situations, such as severe bleeding, stroke, or a requirement for urgent surgery or procedures, there may be a need to assess anticoagulant activity to guide clinical decision making. In cases where neutralization of the anticoagulant effect is warranted, specific reversal agents are likely to become invaluable medical tools. Evidence to date suggests that dosing decisions for NOACs based on clinical features (e.g. age or renal function) can help optimize the benefit-risk balance without assessment of anticoagulant activity in non-emergency routine situations., Conclusions: Regular monitoring of NOAC levels does not provide benefits and cannot be recommended at present. In some specific circumstances, e.g. severe bleeding, before urgent surgery, or before thrombolysis, measurement may be beneficial to assess whether a patient is actively anticoagulated. The availability of NOAC-specific reversal agents may change management practices in emergencies., (© 2016 World Stroke Organization.)

The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16-18 November 2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN)., (© 2016 World Stroke Organization.)

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., (© 2015 World Stroke Organization.)

Background: Hyperthermia is a frequent complication in patients with acute ischemic stroke. On the other hand, therapeutically induced hypothermia has shown promising potential in animal models of focal cerebral ischemia. This Guideline Document presents the European Stroke Organisation guidelines for the management of temperature in patients with acute ischemic stroke., Methods: A multidisciplinary group identified related questions and developed its recommendations based on evidence from randomized controlled trials elaborating the Grading of Recommendations Assessment, Development, and Evaluation approach. This Guideline Document was reviewed within the European Stroke Organisation and externally and was approved by the European Stroke Organisation Guidelines Committee and the European Stroke Organisation Executive Committee., Results: We found low-quality evidence, and therefore, we cannot make any recommendation for treating hyperthermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and hyperthermia; moderate evidence to suggest against routine prevention of hyperthermia with antipyretics as a means to improve functional outcome and/or survival in patients with acute ischemic stroke and normothermia; very low-quality evidence to suggest against routine induction of hypothermia as a means to improve functional outcome and/or survival in patients with acute ischemic stroke., Conclusions: The currently available data about the management of temperature in patients with acute ischemic stroke are limited, and the strengths of the recommendations are therefore weak. We call for new randomized controlled trials as well as recruitment of eligible patients to ongoing randomized controlled trials to allow for better-informed recommendations in the future., (© 2015 World Stroke Organization.)

Background: Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH., Method: A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9-12, and avoidance of corticosteroids., Conclusion: These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome., (© 2014 World Stroke Organization.)

Each year, 1·0-2·0% of individuals with atrial fibrillation and 0·1-0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2-0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offers practical approaches to the management of patients receiving novel oral anticoagulants who present with an ischemic or hemorrhagic stroke. Specifically, we discuss the role of thrombolysis in anticoagulated patients with acute ischemic stroke and factors to consider concerning restarting anticoagulation after acute ischemic and hemorrhagic stroke., (© 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.)

Aims: We analyzed early diffusion-weighted magnetic resonance imaging of patients with acute basilar artery occlusion by applying different lesion scoring systems and determined their predictive value for favorable outcome., Methods: Between 1998 and 2010, patients with confirmed basilar artery occlusion were entered in a local database. magnetic resonance imaging angiography was performed for diagnosis of basilar artery occlusion and/or during initiated recanalization therapy. We analyzed the patients' clinical and radiological baseline data, recanalization, and favorable outcome modified Rankin Scale 0-2 after three-months. Diffusion weighted imaging findings were categorized into lesions in vascular territories as well as by two previously published scores for ischemic damage in the posterior circulation, the Renard score and posterior circulation Acute Stroke Prognosis Early computed tomography Score., Results: Fifty patients with basilar artery occlusion received an early MRI, and in 30 of those, a follow-up MRI was performed. Median time to baseline MRI was 5·5 h (one-hour to 24 h). Median baseline Renard score and posterior circulation Acute Stroke Prognosis Early CT Score were 2·75 (0-10) and 7 (0-10), respectively. Of the patients, 82% received an acute recanalization therapy and in 78% of those, the basilar artery recanalized. Median time to therapy was five-hours (1·25-20 h). 24% of all patients had a favorable outcome (mRS 0-2). Patients with a favorable outcome had a lower Renard score and higher pcASPECTS, a lower rate of complete basilar artery occlusion, a higher Glasgow coma scale on admission, and a higher rate of successful recanalization (all P < 0·05). After logistic regression, the only independent predictor for favorable outcome was a posterior circulation Acute Stroke Prognosis Early CT Score of 8 or more points (odds ratio 3·9, 95% confidence interval 1·4-11·7, P < 0·05)., Conclusion: In patients with acute basilar artery occlusion, posterior circulation Acute Stroke Prognosis Early CT Score of 8 or more points on early diffusion weighted imaging is an independent predictor for favorable outcome., (© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.)

Rationale: Ventilated intensive care patients with ischemic or hemorrhagic strokes have a poor prognosis. Early tracheostomy has led to advantages in selected groups of non-cerebrovascular intensive care patients, including shorter ventilation time, shorter intensive care unit length of stay, and reduced complications. It is completely unclear whether ventilated stroke patients might benefit from early tracheostomy, too., Aim: Stroke-related Early Tracheostomy vs. Prolonged Orotracheal Intubation in Neurocritical care Trial (SETPOINT) is a pilot trial aiming to investigate the safety, feasibility, and potential benefits of early tracheostomy vs. prolonged intubation (and possibly late tracheostomy) in patients with severe ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The primary objective is to compare early tracheostomy and prolonged intubation with respect to the intensive care unit - length of stay and the time until the start of rehabilitation in these patients., Design: SETPOINT is a prospective, randomized, controlled, outcome observer-blinded, monocenter trial. Patients with severe ischemic stroke, intracerebral or subarachnoid hemorrhage requiring intubation and ventilation are eligible. After passing predefined criteria, enrolled patients are randomized to either percutaneous tracheostomy within the first three-days from intubation or to weaning/extubation attempts or percutaneous tracheostomy between days 7 and 14 from intubation (n = 30 per group)., Study Outcomes: The primary end-point is the intensive care unit length of stay. Secondary end-points are functional outcome and mortality at discharge and after six-months, duration to transferability, duration of ventilation, duration and quality of weaning from respirator, need of analgesia and sedation, procedure-related complications, frequency of pneumonia and sepsis, and costs of treatment., Discussion: To clarify the potential benefit of early tracheostomy in critical care ventilated stroke patients, a randomized multicenter trial in a larger patient population is clearly needed. If this monocentric pilot gives promising safety, feasibility, and benefit results, such a multicenter trial will be planned. The results will have a relevant direct impact on the critical care of stroke.

Background: Intracerebral haemorrhage is the most feared complication in patients who are on treatment with vitamin K antagonists. Vitamin K antagonist related intracerebral haemorrhage occurs in about 10% of patients. Intracerebral haemorrhage has the worst prognosis of all subtypes of stroke including spontaneous intracerebral haemorrhage, and a mortality rate of up to about 65%. The higher rate of haematoma expansion due to rebleeding is thought to be responsible for the higher mortality. Current international treatment recommendations include fresh frozen plasma and prothrombin complex concentrate. It is known that these substances lower the international normalised ratio, and thus it is assumed that normalisation of coagulopathy may lead to haemostasis and reduction of rebleeding. However, the issue of whether to use fresh frozen plasma or prothrombin complex concentrate for urgent reversal of vitamin K antagonists is unresolved: safety and efficacy of these treatments have never been studied in a randomised controlled trial. Our questions are: how effective are the two substances in normalisation of the international normalized ratio? How feasible is it to apply either of these treatments in an acute situation? What is the safety profile of each of these substances? Is there a difference in haematoma growth and clinical outcome?, Method: We designed a prospective, randomised, controlled multicentre trial to compare biological efficacy and safety of fresh frozen plasma and prothrombin complex concentrate in vitamin K antagonist related intracerebral haemorrhage. The study is observer-blinded for laboratory, neuroradiological, and clinical outcomes. Patients will be included if a computed tomography scan shows an intraparenchymal or subdural haematoma within 12 h after onset of symptoms, if the patient is on treatment with vitamin K antagonists, and the international normalized ratio is ≥2. Primary endpoint is the normalisation of the international normalized ratio (≤1·2) within three-hours after the start of antagonising therapy. Main exclusion criteria are secondary intracerebral haemorrhage, other known coagulopathies, and known acute ischaemic events., Discussion: We discuss the rationale of our trial on the basis of the current recommendations and specific aspects of trial design as, time window, choice of endpoints, dosing of fresh frozen plasma and prothrombin complex concentrate, monitoring and analysis of safety parameters, and rescue treatment., Conclusion: This will be the first prospective trial comparing fresh frozen plasma and prothrombin complex concentrate in the indication of vitamin K antagonist related intracerebral hemorrhage. Recruitment of subjects started in August 2009. Until now, 19 patients have been included., (International Journal of Stroke © 2011 World Stroke Organization. No claim to original US government works.)

Controversy still exists on surgical management of acute stroke. Even if surgical therapy represents often a life-saving measure, the issue of acceptable outcome remains open. Persuasive evidence for outcome benefit is limited. For large ischaemic strokes, recent convincing data suggest that decompressive surgery significantly reduces mortality and improves outcome quality. On the other hand, despite the long tradition in surgical removal of intracranial haematomas, the recent evidence has not been sufficient to resolve the basic argument whether to operate or not. Most recently, hopeful preliminary data have emerged on new approaches in the treatment of intraventricular haemorrhage. In this article, we review the current neurosurgical options in acute ischaemic and haemorrhagic stroke.

Stroke is potentially preventable through risk factor modification. Over the past decade, there has been considerable interest on microalbuminuria as a risk factor for chronic diseases. The concept of microalbuminuria was originally introduced, about 25 years ago, to clinical practice as a useful marker of nephropathy. Since then various studies reported an association of microalbuminuria with the increased risk of cardiovascular events and all cause of mortality in subjects with or without diabetes. The presence of microalbuminuria was related to left ventricular dysfunction, stroke, and myocardial infarction. Microalbuminuria may be a predictor of stroke but further studies are required. However data on prognostic significance and therapeutic consequence, particularly in haemorrhagic stroke are lacking. This review focuses on the importance of microalbuminuria for cerebrovascular disease, stressing the clinical and therapeutic implications using antihypertensive therapy to control the urinary albumin excretion.

For a long time, patients with severe stroke were facing therapeutic nihilism of the attending physicians. Implementation of do-not-resuscitate-orders may have lead to self-fulfilling prophecies and to a pessimistic overestimation of prognosis of severe stroke syndromes. However, there have been great advances in intensive care management of acute stroke patients and it has been shown that treatment on a specialised neurological intensive care unit improves outcome. In this review, we will present a summary of the current state-of-the-art intensive care management of acute stroke patients. After presenting an overview on general management of stroke intensive care patients, special aspects of neurological intensive care of acute large middle cerebral artery stroke, intracerebral haemorrhage and subarachnoid haemorrhage will be discussed. In part II of the review, surgical management options for acute stroke will be discussed in detail.

The present study applied T2- and diffusion-weighted magnetic resonance imaging to examine if mild cerebral edema and subsequent brain swelling are implicated in the pathophysiology of acute mountain sickness (AMS). Twenty-two subjects were examined in normoxia (21% O2), after 16 hours passive exposure to normobaric hypoxia (12% O2) corresponding to a simulated altitude of 4,500 m and after 6 hours recovery in normoxia. Clinical AMS was diagnosed in 50% of subjects during hypoxia and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). Hypoxia was associated with a mild increase in brain volume (+7.0+/-4.8 ml, P<0.05 versus pre-exposure baseline) that resolved during normoxic recovery. Hypoxia was also associated with an increased T2 relaxation time (T2rt) and a general trend toward an increased apparent diffusion coefficient (ADC). During the normoxic recovery, brain volume and T2rt recovered to pre-exposure baseline values, whereas a more marked reduction in ADC in the splenium of the corpus callosum (SCC) was observed (P<0.05). While changes in brain volume and T2rt were not selectively different in AMS, ADC values were consistently lower (P<0.05 versus non-AMS) and associated with the severity of neurologic symptoms. Acute mountain sickness was also characterized by an increased brain to intracranial volume ratio (P<0.05 versus non-AMS). These findings indicate that mild extracellular vasogenic edema contributes to the generalized brain swelling observed at high altitude, independent of AMS. In contrast, intracellular cytotoxic edema combined with an anatomic predisposition to a 'tight-fit' brain may prove of pathophysiologic significance, although the increase in brain volume in hypoxia was only about 0.5% of total brain volume.

The present study combined molecular and neuroimaging techniques to examine if free radical-mediated damage to barrier function in hypoxia would result in extracellular edema, raise intracranial pressure (ICP) and account for the neurological symptoms typical of high-altitude headache (HAH) also known as acute mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to 12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h, 8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic resonance (EPR) spectroscopy identified a clear increase in the blood and CSF concentration of O2 and carbon-centered free radicals (P<0.05 versus normoxia) subsequently identified as lipid-derived alkoxyl (LO*) and alkyl (LC*) species. Magnetic resonance imaging (MRI) demonstrated a mild increase in brain volume (7.0+/-4.8 mL or 0.6%+/-0.4%, P<0.05 versus normoxia) that resolved within 6 h of normoxic recovery. However, there was no detectable evidence for gross barrier dysfunction, elevated lumbar pressures, T2 prolongation or associated neuronal and astroglial damage. Clinical AMS was diagnosed in 50% of subjects during the hypoxic trial and corresponding headache scores were markedly elevated (P<0.05 versus non-AMS). A greater increase in brain volume was observed, though this was slight, independent of oxidative stress, barrier dysfunction, raised lumbar pressure, vascular damage and measurable evidence of cerebral edema and only apparent in the most severe of cases. These findings suggest that free-radical-mediated vasogenic edema is not an important pathophysiological event that contributes to the mild brain swelling observed in HAH.