2032Purpose-The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. Methods-A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. Results-Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. Conclusions-Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted.These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

Background— Patients experiencing major bleeding while taking vitamin K antagonists require rapid vitamin K antagonist reversal. We performed a prospective clinical trial to compare nonactivated 4-factor prothrombin complex concentrate (4F-PCC) with plasma for urgent vitamin K antagonist reversal. Methods and Results— In this phase IIIb, multicenter, open-label, noninferiority trial, nonsurgical patients were randomized to 4F-PCC (containing coagulation factors II, VII, IX, and X and proteins C and S) or plasma. Primary analyses examined whether 4F-PCC was noninferior to plasma for the coprimary end points of 24-hour hemostatic efficacy from start of infusion and international normalized ratio correction (≤1.3) at 0.5 hour after end of infusion. The intention-to-treat efficacy population comprised 202 patients (4F-PCC, n=98; plasma, n=104). Median (range) baseline international normalized ratio was 3.90 (1.8–20.0) for the 4F-PCC group and 3.60 (1.9–38.9) for the plasma group. Effective hemostasis was achieved in 72.4% of patients receiving 4F-PCC versus 65.4% receiving plasma, demonstrating noninferiority (difference, 7.1% [95% confidence interval, −5.8 to 19.9]). Rapid international normalized ratio reduction was achieved in 62.2% of patients receiving 4F-PCC versus 9.6% receiving plasma, demonstrating 4F-PCC superiority (difference, 52.6% [95% confidence interval, 39.4 to 65.9]). Assessed coagulation factors were higher in the 4F-PCC group than in the plasma group from 0.5 to 3 hours after infusion start (P<0.02). The safety profile (adverse events, serious adverse events, thromboembolic events, and deaths) was similar between groups; 66 of 103 (4F-PCC group) and 71 of 109 (plasma group) patients experienced ≥1 adverse event. Conclusions— 4F-PCC is an effective alternative to plasma for urgent reversal of vitamin K antagonist therapy in major bleeding events, as demonstrated by clinical assessments of bleeding and laboratory measurements of international normalized ratio and factor levels. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: .

Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

CSL Behring.

Background and Purpose-Intracerebral hemorrhage (ICH) is the most fatal and disabling stroke subtype. Widely used tools for prediction of mortality are fundamentally limited in that they do not account for effects of withdrawal of care and are not designed to predict functional recovery. We developed an acute clinical score to predict likelihood of functional independence. Methods-We prospectively characterized 629 consecutive patients with ICH at hospital presentation. Predictors of functional independence (Glasgow Outcome Score Ն4) at 90 days were used to develop a logistic regression-based risk stratification scale in a random subset of two thirds and validated in the remaining one third of the cohort. Results-At 90 days, 162 (26%) patients achieved independence. Age, Glasgow Coma Scale, ICH location, volume (all PϽ0.0001), and pre-ICH cognitive impairment (Pϭ0.005) were independently associated with Glasgow Outcome Score Ն4. The FUNC score was developed as a sum of individual points (0 -11) based on strength of association with outcome. In both the development and validation cohorts, the proportion of patients who achieved Glasgow Outcome Score Ն4 increased steadily with FUNC score. No patient assigned a FUNC score Յ4 achieved functional independence, whereas Ͼ80% with a score of 11 did. The predictive accuracy of the FUNC score remained unchanged when restricted to ICH survivors only, consistent with absence of confounding by early withdrawal of care. Conclusions-FUNC score is a valid clinical assessment tool that identifies patients with ICH who will attain functional independence and thus, can provide guidance in clinical decision-making and patient selection for clinical trials. (Stroke.

other entities (RWI) can be found at https://professional. heart.org/-/media/phd-files/guidelines-and-statements/ policies-devolopment/aha-asa-disclosure-rwi-policy-5118. pdf?la=en.Beginning in 2017, numerous modifications to AHA/ ASA guidelines have been implemented to make guidelines shorter and enhance user-friendliness. Guidelines are written and presented in a modular knowledge chunk format; each chunk includes a table of recommendations, a brief synopsis, recommendation-specific supportive text, and, when appropriate, flow diagrams or additional tables. Hyperlinked references are provided to facilitate quick access and review. Other modifications to the guidelines include the addition of Knowledge Gaps and Future Research segments in some sections and a web guideline supplement (Online Data Supplement) for useful but noncritical tables and figures.

Purpose— Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment. Methods— A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved. Results— sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.