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Background and Purpose: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients., Methods: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days, Outcomes were determined by using utility weighted modified Rankin scale (UW-mRS) at 90 days. To minimize interpretation bias, outcome assessors were blinded to the treatment allocation and clinical data.We adjusted for age, gender, National Institutes of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites) in multivariate regression analysis., Results: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62 ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient (RC)-0.05, p= 0.58), 20-39 cc (RC-0.22, p=0.17), or ≥40 cc (RC-0.34, p= 0.083) compared with no ICH after adjusting for potential confounders. Change in ICH mean volume 26.78 ml ±59.68, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (RC -67.71, p= 0.06)., Conclusions: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Although further studies must be done, our data suggest that strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Clinical practice recommendations guide healthcare decisions. This study aims to evaluate the strength and quality of evidence supporting the American Heart Association (AHA)/American Stroke Association (ASA) guidelines for aneurysmal subarachnoid hemorrhage (aSAH) and spontaneous intracerebral hemorrhage (ICH)., Methods: We reviewed the current AHA/ASA guidelines for aSAH and spontaneous ICH and compared with previous guidelines. Guidelines were classified based on the Class of recommendation (COR) and Level of evidence (LOE). COR signifies recommendation strength (COR 1: Strong; COR 2a: Moderate; COR 2b: Weak; COR 3: No Benefit/Harm), while LOE denotes evidence quality (LOE A: High-Quality; LOE B-NR: Moderate-Quality, Not Randomized; LOE B-R: Moderate-Quality, Randomized; LOE C-EO: Expert Opinion; LOE C-LD: Limited Data)., Results: For aSAH, we identified 84 recommendations across 15 guideline categories. Of these, 31% were classified as COR I, 30% as COR 2a, 17% as COR 2b, and 18% as COR 3. In terms of LOE, 7% were based on LOE A, 10% on LOE B-R, 65% on LOE B-NR, 14% on LOE C-LD, and 5% on LOE C-EO. Compared to previous guidelines, there was a 46% decrease in LOE A, a 45% increase in LOE B, and an 11% decrease in LOE C. For spontaneous ICH, 124 guidelines were identified across 31 guideline categories. Of these, 28% were COR I, 32% COR 2b, and 9% COR 3. For LOE, 4% were based on LOE A, 35% on LOE B-NR, and 42% on LOE C-LD. Compared to previous guidelines, there was a 78% decrease in LOE A, an 82% increase in LOE B, and a 14% increase in LOE C. This analysis highlights that less than a third of AHA/ASA guidelines are classified as the highest class of recommendation, with less than 10% based on the highest LOE., Conclusion: Less than a third of AHA/ASA guidelines on aSAH and spontaneous ICH are classified as the highest class of recommendation with less than 10% based on highest LOE. There appears to be a decrease in proportion of guidelines based on highest LOE in most recent guidelines., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH) is a key predictor of poor prognosis and potentially amenable to treatment. This study aimed to build a classification model to predict HE in patients with ICH using deep learning algorithms without using advanced radiological features., Methods: Data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) was utilized. Variables included in the models were chosen as per literature consensus on salient variables associated with HE. HE was defined as increase in either >33% or 6 mL in hematoma volume in the first 24 h. Multiple machine learning algorithms were employed using iterative feature selection and outcome balancing methods. 70% of patients were used for training and 30% for internal validation. We compared the ML models to a logistic regression model and calculated AUC, accuracy, sensitivity and specificity for the internal validation models respective models., Results: Among 1000 patients included in the ATACH-2 trial, 924 had the complete parameters which were included in the analytical cohort. The median [interquartile range (IQR)] initial hematoma volume was 9.93.mm 3 [5.03-18.17] and 25.2% had HE. The best performing model across all feature selection groups and sampling cohorts was using an artificial neural network (ANN) for HE in the testing cohort with AUC 0.702 [95% CI, 0.631-0.774] with 8 hidden layer nodes The traditional logistic regression yielded AUC 0.658 [95% CI, 0.641-0.675]. All other models performed with less accuracy and lower AUC. Initial hematoma volume, time to initial CT head, and initial SBP emerged as most relevant variables across all best performing models., Conclusion: We developed multiple ML algorithms to predict HE with the ANN classifying the best without advanced radiographic features, although the AUC was only modestly better than other models. A larger, more heterogenous dataset is needed to further build and better generalize the models., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Perihematomal edema (PHE) represents secondary brain injury and a potential treatment target in intracerebral hemorrhage (ICH). However, studies differ on optimal PHE volume metrics as prognostic factor(s) after spontaneous, non-traumatic ICH. This study examines associations of baseline and 24-h PHE shape features with 3-month outcomes., Patients and Methods: We included 796 patients from a multicentric trial dataset and manually segmented ICH and PHE on baseline and follow-up CTs, extracting 14 shape features. We explored the association of baseline, follow-up, difference (baseline/follow-up) and temporal rate (difference/time gap) of PHE shape changes with 3-month modified Rankin Score (mRS) - using Spearman correlation. Then, using multivariable analysis, we determined if PHE shape features independently predict outcome adjusting for patients' age, sex, NIH stroke scale (NIHSS), Glasgow Coma Scale (GCS), and hematoma volume., Results: Baseline PHE maximum diameters across various planes, main axes, volume, surface, and sphericity correlated with 3-month mRS adjusting for multiple comparisons. The 24-h difference and temporal change rates of these features had significant association with outcome - but not the 24-h absolute values. In multivariable regression, baseline PHE shape sphericity (OR = 2.04, CI = 1.71-2.43) and volume (OR = 0.99, CI = 0. 98-1.0), alongside admission NIHSS (OR = 0.86, CI = 0.83-0.88), hematoma volume (OR = 0.99, CI = 0. 99-1.0), and age (OR = 0.96, CI = 0.95-0.97) were independent predictors of favorable outcomes., Conclusion: In acute ICH patients, PHE shape sphericity at baseline emerged as an independent prognostic factor, with a less spherical (more irregular) shape associated with worse outcome. The PHE shape features absolute values over the first 24 h provide no added prognostic value to baseline metrics., 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: KNS reports equity interests in Alva Health.

Background: With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial., Methods: We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110-139 mm Hg versus 140-179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days., Results: Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm 3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00-5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71-1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions., Conclusions: Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 )., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: To summarise evidence of the effects of blood pressure (BP)-lowering interventions after acute spontaneous intracerebral haemorrhage (ICH)., Methods: A prespecified systematic review of the Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE databases from inception to 23 June 2020 to identify randomised controlled trials that compared active BP-lowering agents versus placebo or intensive versus guideline BP-lowering targets for adults <7 days after ICH onset. The primary outcome was function (distribution of scores on the modified Rankin scale) 90 days after randomisation. Radiological outcomes were absolute (>6 mL) and proportional (>33%) haematoma growth at 24 hours. Meta-analysis used a one-stage approach, adjusted using generalised linear mixed models with prespecified covariables and trial as a random effect., Results: Of 7094 studies identified, 50 trials involving 11 494 patients were eligible and 16 (32.0%) shared patient-level data from 6221 (54.1%) patients (mean age 64.2 [SD 12.9], 2266 [36.4%] females) with a median time from symptom onset to randomisation of 3.8 hours (IQR 2.6-5.3). Active/intensive BP-lowering interventions had no effect on the primary outcome compared with placebo/guideline treatment (adjusted OR for unfavourable shift in modified Rankin scale scores: 0.97, 95% CI 0.88 to 1.06; p=0.50), but there was significant heterogeneity by strategy (p interaction =0.031) and agent (p interaction <0.0001). Active/intensive BP-lowering interventions clearly reduced absolute (>6 ml, adjusted OR 0.75, 95%CI 0.60 to 0.92; p=0.0077) and relative (≥33%, adjusted OR 0.82, 95%CI 0.68 to 0.99; p=0.034) haematoma growth., Interpretation: Overall, a broad range of interventions to lower BP within 7 days of ICH onset had no overall benefit on functional recovery, despite reducing bleeding. The treatment effect appeared to vary according to strategy and agent., Prospero Registration Number: CRD42019141136., Competing Interests: Competing interests: TJM reports grants from BHF during the conduct of the study. HA reports grants and personal fees from Daiichi Sankyo, grants and personal fees from Takeda, non-financial support from Phillips, and personal fees from Bayer, Fukuda Denshi, MSD, Teijin and Kyowa Kirin outside the submitted work. KSB reports grants and personal fees from Boehringer Ingelheim and Pfizer/BMS, and personal fees from Servier Canada and Medtronic outside the submitted work. JC reports grants from NHMRC outside the submitted work. SK has a patent Medical Device for acute intracerebral haemorrhage treatment issued. TGR is a National NIHR Senior Investigator; the views expressed in the article are those of the author(s) and not necessarily of NIHR or the Department of Health and Social Care. RASS reports grants from BHF during the conduct of the study, and grants from NHMRC of Australia and The Stroke Association outside the submitted work. JMW reports grants from BHF and UK Medical Research Council (MRC) during the conduct of the study; and grants from Stroke Association, Fondation Leducq, EU Horizon 2020, Alzheimer’s Research UK, Alzheimer’s Society and Chief Scientist Office Scotland outside the submitted work; CSA reports grant funding from Takeda China. PMB reports grant funding from the BHF and UK MRC, and honoraria from DiaMedica, Moleac, Nestle, Phagenesis and Sanofi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background and Purpose: Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT)., Methods: We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume., Results: In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p < 0.001), and 3-month mRS scores (0.44 vs. 0.32, p < 0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p = 0.02), NIHSS (0.64 vs. 0.56, p < 0.001), and 3-month mRS scores (0.43 vs. 0.33, p < 0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts., Conclusions: Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients., (© 2021 European Academy of Neurology.)

Background and Objective: The clinical effect of renal impairment on intracerebral hemorrhage (ICH) is unknown. This study sought to assess whether estimated glomerular filtration rate (eGFR) affects clinical outcomes or modifies the efficacy of intensive systolic blood pressure (BP) control (target, 110-139 mm Hg) against the standard (target, 140-179 mm Hg) among patients with ICH., Methods: We conducted post hoc analyses of ATACH-2, a randomized, 2-group, open-label trial. The baseline eGFR of each eligible patient was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The outcome of interest was death or disability at 90 days. Multivariate logistic regression models were used for analysis., Results: Among the 1,000 patients randomized, 974 were analyzed. The median baseline eGFR was 88 (interquartile range, 68, 99) mL/min/1.73 m 2 ; 451 (46.3%), 363 (37.3%), and 160 (16.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m 2 , respectively. Compared with normal eGFR (≥90 mL/min/1.73 m 2 ), higher odds of death or disability were noted among those with eGFR values of <60 mL/min/1.73 m 2 (adjusted odds ratio [OR], 2.02; 95% confidence interval [CI], 1.25-3.26) but not among those with eGFR values of 60-89 mL/min/1.73 m 2 (OR, 1.01; 95% CI, 0.70-1.46). The odds of death or disability were significantly higher in the intensive arm among patients with decreased eGFR; the ORs were 0.89 (95% CI, 0.55-1.44), 1.13 (0.68-1.89), and 3.60 (1.47-8.80) in patients with eGFR values of ≥90, 60-89, and <60 mL/min/1.73 m 2 , respectively ( p for interaction = 0.02)., Discussion: Decreased eGFR is associated with unfavorable outcomes following ICH. The statistically significant interaction between the eGFR group and treatment assignment raised safety concerns for the intensive BP-lowering therapy among patients with renal impairment., Trial Registration Information: Clinicaltrials.gov identifier: NCT01176565., Classification of Evidence: This study provides Class II evidence that in spontaneous ICH, decreased eGFR identifies patients at risk of death or disability following intensive BP control., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Hematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose an HE shift analysis model as a method to improve the evaluation of candidate ICH therapies., Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on previously established HE definitions, percentile/absolute quartiles of hematoma volume change, and quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored with proportional odds models., Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. With the use of a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.60-0.99). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy (aOR 0.73, 95% CI 0.57-0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (>21.9 mL) were most notable., Conclusions: Our findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies., Trial Registration Information: ClinicalTrials.gov Identifier:NCT01176565., (© 2021 American Academy of Neurology.)

Background To explore how the clinical impact of heart rate (HR) and heart rate variabilities (HRV) during the initial 24 hours after acute intracerebral hemorrhage (ICH) contribute to worse clinical outcomes. Methods and Results In the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial, the HR was recorded for every 15 minutes from baseline to 1 hour and hourly during the initial 24 hours post-randomization. We calculated the following: mean, standard deviation, coefficient of variation, successive variation, and average real variability (ARV). Outcomes were hematoma expansion at 24 hours and unfavorable functional outcome, defined as modified Rankin Scale score 4 to 6 at 90 days. Of the 1000 subjects in ATACH-2, 994 with available HR data were included in the analyses. Overall, 262 experienced hematoma expansion, and 362 had unfavorable outcomes. Increased mean HR was linearly associated with unfavorable outcome (per 10 bpm increase adjusted odds ratio [aOR], 1.31, 95% CI, 1.14-1.50) but not with hematoma expansion, while HR-ARV was associated with hematoma expansion (aOR, 1.06, 95% CI, 1.01-1.12) and unfavorable outcome (aOR, 1.07, 95% CI, 1.01-1.3). Every 10-bpm increase in mean HR increased the probability of unfavorable outcome by 4.3%, while every 1 increase in HR-ARV increased the probability of hematoma expansion by 1.1% and unfavorable outcome by 1.3%. Conclusions Increased mean HR and HR-ARV within the initial 24 hours were independently associated with unfavorable outcome in acute ICH. Moreover, HR-ARV was associated with hematoma expansion at 24 hours. This may have future therapeutic implications to accommodate HR and HRV in acute ICH. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01176565.

Background: High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target., Methods: We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites., Findings: Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group., Interpretation: An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion., Funding: French Health Ministry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To compare the impact of intensive blood pressure (BP) lowering right after intracerebral hemorrhage (ICH) on clinical and hematoma outcomes among patients from different geographic locations, we performed a prespecified subanalysis of a randomized, multinational, 2-group, open-label trial to determine the efficacy of rapidly lowering BP in hyperacute ICH (Antihypertensive Treatment of Acute Cerebral Hemorrhage [ATACH]-2), involving 537 patients from East Asia and 463 recruited outside of Asia., Methods: Eligible patients were randomly assigned to a systolic BP target of 110 to 139 mm Hg (intensive treatment) or 140 to 179 mm Hg (standard treatment). Predefined outcomes were poor functional outcome (modified Rankin Scale score 4-6 at 90 days), death within 90 days, hematoma expansion at 24 hours, and cardiorenal adverse events within 7 days., Results: Poor functional outcomes (32.0% vs 45.9%), death (1.9% vs 13.3%), and cardiorenal adverse events (3.9% vs 11.2%) occurred significantly less frequently in patients from Asia than those outside of Asia. The treatment-by-cohort interaction was not significant for any outcomes. Only patients from Asia showed a lower incidence of hematoma expansion with intensive treatment (adjusted relative risk [RR] 0.56, 95% confidence interval [CI] 0.38-0.83). Both Asian (RR 3.53, 95% CI 1.28-9.64) and non-Asian (RR 1.71, 95% CI 1.00-2.93) cohorts showed a higher incidence of cardiorenal adverse events with intensive treatment., Conclusions: Poor functional outcomes and death 90 days after ICH were less common in patients from East Asia than those outside of Asia. Hematoma expansion, a potential predictor for poor clinical outcome, was attenuated by intensive BP lowering only in the Asian cohort., Clinicaltrialsgov Identifier: NCT01176565., Classification of Evidence: This study provides Class II evidence that, for patients from East Asia with ICH, intensive blood pressure lowering significantly reduces the risk of hematoma expansion., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Endovascular treatment (EVT) is a widely proved method to treat patients diagnosed with intracranial large vessel occlusions (LVOs); however, there has been controversy about the safety and efficacy of incorporating intravenous tissue plasminogen activator (IV tPA) as pretreatment for EVT., Objective: To compare the outcomes of all patients with LVO treated with IV tPA +EVT versus EVT alone within 4.5 hours of stroke onset., Methods: A prospectively collected endovascular database at a comprehensive stroke center between 2012 and 2019 was used to examine variables such as demographics, comorbid conditions, symptomatic/asymptomatic intracerebral hemorrhage (ICH), mortality rate, and good/poor outcomes as shown by the modified Thrombolysis in Cerebral Infarction score and modified Rankin Scale (mRS) assessment at discharge. The outcomes between patients receiving IV tPA+EVT on admission and patients who underwent EVT alone were compared., Results: Of 588 patients with acute ischemic stroke treated with EVT, a total of 189 met the criteria for the study (average age 70.44±12.90 years, 42.9% women). Analysis of 109 patients from the group receiving EVT+IV tPA (average age 68.17±14.28 years, 41.3% women), and 80 patients from the EVT alone group was performed (average age 73.54±9.84 years, 45.0% women). Four patients (5.0%) in the EVT alone group experienced symptomatic ICH versus 15 patients (13.8%) in the IV tPA+EVT group (p=0.0478); significant increases were also noted in the length of stay for patients treated with IV tPA (8.2 days vs 11.0 days; p=0.0056)., Conclusion: IV tPA in addition to EVT was associated with an increase in the rate of ICH in patients with LVO treated within 4.5 hours and in patients' length of stay. Further research is required to determine whether EVT treatment alone in patients with LVO treated within 4.5 hours is a more effective option., Competing Interests: Competing interests: AEH: consultant for Medtronic, Microvention, Penumbra, Stryker, Genentech, Balt, Viz.ai, and GE Healthcare., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Punctate ischemic lesions noted on diffusion-weighted imaging (DWI) are associated with poor functional outcomes after intracerebral hemorrhage (ICH). Whether these lesions increase long-term risk of stroke is poorly understood., Methods: We pooled individual patient data from the ATACH-2 trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage) and the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3). We included subjects with a magnetic resonance imaging scan. The exposure was a DWI lesion. The primary outcome was any stroke, defined as a composite of ischemic stroke or recurrent ICH, whereas secondary outcomes were incident ischemic stroke and recurrent ICH. Using multivariate Cox regression analysis, we evaluated the risk of stroke., Results: Of 505 patients with ICH with magnetic resonance imaging, 466 were included. DWI lesions were noted in 214 (45.9%) subjects, and 34 incident strokes (20 ischemic stroke and 14 recurrent ICH) were observed during a median follow-up of 324 days (interquartile range, 91-374). Presence of a DWI lesion was associated with a 6.9% (95% CI, 2.2-11.6) absolute increase in risk of all stroke (hazard ratio, 2.6 [95% CI, 1.2-5.7]). Covariate adjustment with Cox regression models also demonstrated this increased risk. In the secondary analyses, there was an increased risk of ischemic stroke (hazard ratio, 3.5 [95% CI, 1.1-11.0]) but not recurrent ICH (hazard ratio, 1.7 [95% CI, 0.6-5.1])., Conclusions: In a heterogeneous cohort of patients with ICH, presence of a DWI lesion was associated with a 2.5-fold heightened risk of stroke among ICH survivors. This elevated risk persisted for ischemic stroke but not for recurrent ICH.

Purpose: The spot sign is associated with intracerebral hemorrhage (ICH) expansion and neurological decline. However, the relationship of the spot sign to secondary intraventricular hemorrhage (IVH) has not been well established. The presence of the spot sign in secondary IVH may provide information regarding neurologic outcome in a population with known poor prognosis., Methods: A subset analysis was performed of patients with IVH from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-II) study, a randomized clinical trial examining the effect of intensive blood pressure reduction on hematoma expansion. The presence of the spot sign was determined on CTA and IVH expansion was measured in the first 24 hours. The primary outcome measure was early neurological decline (END), defined as ≥ 2-point decrease in Glasgow Coma Scale (GCS) score or ≥ 4-point increase in NIH Stroke Scale (NIHSS). Secondary outcomes including various radiological and clinical factors were also measured., Results: Of 57 patients included in this analysis, the spot sign was present in 17 (29.8%). The spot sign was a predictor of END in univariate (P < 0.005 for GCS and P = 0.04 for NIHSS) and multivariate analyses using GCS scores (OR=7.2, CI 1.6 - 32.5, P = 0.01). Median 90 day modified Rankin Scale (mRS) scores were significantly different between spot sign-positive and spot sign-negative groups (P = 0.02)., Conclusions: The presence of the spot sign is associated with END in patients with secondary IVH. Identifying this radiologic feature could have important implications for triaging these patients to the appropriate level of care.

Importance: The safety and efficacy of intensive systolic blood pressure reduction in patients with intracerebral hemorrhage who present with systolic blood pressure greater than 220 mm Hg appears to be unknown., Objective: To evaluate the differential outcomes of intensive (goal, 110-139 mm Hg) vs standard (goal, 140-179 mm Hg) systolic blood pressure reduction in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more vs less than 220 mm Hg., Design, Setting, and Participants: This post hoc analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II trial was performed in November 2019 on data from the multicenter randomized clinical trial, which was conducted between May 2011 to September 2015. Patients with intracerebral hemorrhage and initial systolic blood pressure of 180 mm Hg or more, randomized within 4.5 hours after symptom onset, were included., Interventions: Intravenous nicardipine infusion titrated to goals., Main Outcomes and Measures: Neurological deterioration and hematoma expansion within 24 hours and death or severe disability at 90 days, plus kidney adverse events and serious adverse events until day 7 or hospital discharge., Results: A total of 8532 patients were screened, and 999 individuals (mean [SD] age, 62.0 [13.1] years; 620 men [62.0%]) underwent randomization and had an initial SBP value. Among 228 participants with initial systolic blood pressures of 220 mm Hg or more, the rate of neurological deterioration within 24 hours was higher in those who underwent intensive (vs standard) systolic blood pressure reduction (15.5% vs 6.8%; relative risk, 2.28 [95% CI, 1.03-5.07]; P = .04). The rate of death and severe disability (39.0% vs 38.4%; relative risk, 1.02 [95% CI, 0.73-1.78]; P = .92) was not significantly different between the 2 groups. There was a significantly higher rate of kidney adverse events in participants randomized to intensive systolic blood pressure reduction (13.6% vs 4.2%; relative risk, 3.22 [95% CI, 1.21-8.56]; P = .01), but no difference was observed in the rate of kidney serious adverse events., Conclusions and Relevance: The higher rate of neurological deterioration within 24 hours associated with intensive treatment in patients with intracerebral hemorrhage and initial systolic blood pressure of 220 mm Hg or more, without any benefit in reducing hematoma expansion at 24 hours or death or severe disability at 90 days, warrants caution against generalization of recommendations for intensive systolic blood pressure reduction.

Importance: The etiology and significance of diffusion-weighted imaging (DWI) lesions in patients with acute intracerebral hemorrhage (ICH) remain unclear., Objective: To evaluate which factors are associated with DWI lesions, whether associated factors differ by ICH location, and whether DWI lesions are associated with functional outcomes., Design, Setting, and Participants: This analysis pooled individual patient data from 3 randomized clinical trials (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage trial, and Intracerebral Hemorrhage Deferoxamine phase 2 trial) and 1 multicenter prospective study (Ethnic/Racial Variations of Intracerebral Hemorrhage). Patients were enrolled from August 1, 2010, to September 30, 2018. Of the 4782 patients, 1788 who underwent magnetic resonance imaging scans of the brain were included. Data were analyzed from July 1 to December 31, 2019., Main Outcomes and Measures: The primary outcome consisted of factors associated with DWI lesions. Secondary outcomes were poor functional outcome, defined as a modified Rankin score (mRS) of 4 to 6, and mortality, both assessed at 3 months. Mixed-effects logistic regression was used to evaluate the association between exposures and outcomes. Subgroup analyses stratified by hematoma location were performed., Results: After exclusion of 36 patients with missing data on DWI lesions, 1752 patients were included in the analysis (1019 men [58.2%]; mean [SD] age, 60.8 [13.3] years). Diffusion-weighted imaging lesions occurred in 549 patients (31.3%). In mixed-effects regression models, factors associated with DWI lesions included younger age (odds ratio [OR] per year, 0.98; 95% CI, 0.97-0.99), black race (OR, 1.64; 95% CI, 1.17-2.30), admission systolic blood pressure (OR per 10-mm Hg increase, 1.13; 95% CI, 1.08-1.18), baseline hematoma volume (OR per 10-mL increase, 1.12; 95% CI, 1.02-1.22), cerebral microbleeds (OR, 1.85; 95% CI, 1.39-2.46), and leukoaraiosis (OR, 1.59; 95% CI, 1.67-2.17). Diffusion-weighted imaging lesions were independently associated with poor mRS (OR, 1.50; 95% CI, 1.13-2.00), but not with mortality (OR, 1.11; 95% CI, 0.72-1.71). In subgroup analyses, similar factors were associated with DWI lesions in lobar and deep ICH. Diffusion-weighted imaging lesions were associated with poor mRS in deep but not lobar ICH., Conclusions and Relevance: In a large, heterogeneous cohort of prospectively identified patients with ICH, results were consistent with the hypothesis that DWI lesions represent acute sequelae of chronic cerebral small vessel disease, particularly hypertensive vasculopathy. Diffusion-weighted imaging lesions portend a worse prognosis after ICH, mainly deep hemorrhages.

Background and Purpose: We determined the rates and predictors of acute kidney injury (AKI) and renal adverse events (AEs), and effects of AKI and renal AEs on death or disability in patients with intracerebral hemorrhage., Methods: We analyzed data from a multicenter trial which randomized 1000 intracerebral hemorrhage patients with initial systolic blood pressure ≥180 mm Hg to intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure reduction within 4.5 hours of symptom onset. AKI was identified by serial assessment of daily serum creatinine for 3 days post randomization., Results: AKI and renal AEs were observed in 149 patients (14.9%) and 65 patients (6.5%) among 1000 patients, respectively. In multivariate analysis, the higher baseline serum creatinine (≥110 μmol/L) was associated with AKI (odds ratio 2.4 [95% CI, 1.2-4.5]) and renal AEs (odds ratio 3.1 [95% CI, 1.2-8.1]). Higher area under the curve for intravenous nicardipine dose was associated with AKI (odds ratio 1.003 [95% CI, 1.001-1.005]) and renal AEs (odds ratio 1.003 [95% CI, 1.001-1.006]). There was a higher risk to death (relative risk 2.6 [95% CI, 1.6-4.2]) and death or disability (relative risk 1.5 [95% CI, 1.3-1.8]) at 90 days in patients with AKI but not in those with renal AEs., Conclusions: Intracerebral hemorrhage patients with higher baseline serum creatinine and those receiving higher doses of nicardipine were at higher risk for AKI and renal AEs. Occurrence of AKI was associated higher rates of death or disability at 3 months. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT01176565.

Background: We performed this analysis to identify the rates, predictors, and associated outcomes of unexpected neurosurgical evacuation in a multicenter randomized clinical trial, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) 2., Methods: The ATACH 2 trial determined the efficacy of antihypertensive treatment in patients with spontaneous supratentorial intracerebral hemorrhages (ICHs) with a Glasgow Coma Scale (GCS) score of ≥5 and intraparenchymal hematoma volume of <60 cm 3 on initial computed tomographic scan. We determined the proportion of ICH patients requiring unanticipated surgical evacuation and identified baseline factors associated with evacuation., Results: Among the 992 subjects analyzed, 44 (4.4%) subjects required unanticipated surgical evacuation of hematoma. The proportion of subjects with initial GCS score of 13 or less was significantly higher among those who required surgical evacuation (43.2% vs. 26.8%, P < 0.001). In the logistics regression analysis, hematoma volume ≥18 cm 3 (odds ratio, 4.3; 95% confidence interval, 2.1-8.8) and right-sided hematoma (odds ratio, 2.8; 95% confidence interval, 1.3-5.9) were significantly associated with surgical evacuation. Age, location, GCS score strata, and allocated treatment (intensive vs. standard systolic blood pressure reduction) were not associated with surgical evacuation. Among the 44 patients who underwent surgical evacuation, death or disability at 3 months postrandomization was seen in 32 (73%) of 44 subjects., Conclusions: In the large cohort of ATACH 2 subjects with good grade ICH, the rates of unanticipated surgical evacuation were low and were associated with relatively high rates of death or disability at 3 months., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Purpose: Evidence regarding sex differences in clinical outcomes and treatment effect following intracerebral hemorrhage is limited. Using the ATACH-2 trial (Antihypertensive Treatment in Intracerebral Hemorrhage-2) data, we explored whether sex disparities exist in outcomes and response to intensive blood pressure (BP)-lowering therapy., Methods: Eligible intracerebral hemorrhage subjects were randomly assigned to intensive (target systolic BP, 110-139 mm Hg) or standard (140-179 mm Hg) BP-lowering therapy within 4.5 hours after onset. Relative risk of death or disability corresponding to the modified Rankin Scale score of 4 to 6 was calculated, and interaction between sex and treatment was explored., Results: In total, 380 women and 620 men were included. Women were older, more prescribed antihypertensive drugs before onset, and had more lobar intracerebral hemorrhage than men. Hematoma expansion was observed less in women. After multivariable adjustment, the relative risk of death or disability in women was 1.19 (95% CI, 1.02-1.37, P =0.023). The relative risk of death or disability between intensive versus standard BP-lowering therapy was 0.91 (95% CI, 0.74-1.13) in women versus 1.13 (95% CI, 0.92-1.39) in men ( P for interaction=0.11), with inconclusive Gail-Simmon test ( P =0.16)., Conclusions: Women had a higher risk of death or disability following intracerebral hemorrhage. The benefit of intensive BP-lowering therapy in women is inconclusive, consistent with the overall results of ATACH-2. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01176565.

Objective: The aim was to investigate whether intensive blood pressure treatment is associated with less hematoma growth and better outcome in intracerebral hemorrhage (ICH) patients who received intravenous nicardipine treatment ≤2 hours after onset of symptoms., Methods: A post-hoc exploratory analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial was performed. This was a multicenter, international, open-label, randomized clinical trial, in which patients with primary ICH were allocated to intensive versus standard blood pressure treatment with nicardipine ≤4.5 hours after onset of symptoms. We have included 913 patients with complete imaging and follow-up data in the present analysis., Results: Among the 913 included patients, 354 (38.7%) had intravenous nicardipine treatment initiated within 2 hours. In this subgroup of patients treated within 2 hours, the frequency of ICH expansion was significantly lower in the intensive blood pressure reduction group compared with the standard treatment group (p = 0.02). Multivariable analysis showed that ultra-early intensive blood pressure treatment was associated with a decreased risk of hematoma growth (odds ratio, 0.56; 95% confidence interval [CI], 0.34-0.92; p = 0.02), higher rate of functional independence (odds ratio, 2.17; 95% CI, 1.28-3.68; p = 0.004), and good outcome (odds ratio, 1.68; 95% CI, 1.01-2.83; p = 0.048) at 90 days. Ultra-early intensive blood pressure reduction was associated with a favorable shift in modified Rankin Scale score distribution at 3 months (p = 0.04)., Interpretation: In a subgroup of ICH patients with elevated blood pressure given intravenous nicardipine ≤2 hours after onset of symptoms, intensive blood pressure reduction was associated with reduced hematoma growth and improved functional outcome. ANN NEUROL 2020;88:388-395., (© 2020 American Neurological Association.)

Background: It is not clear whether subsets of patients with intracerebral hemorrhage (ICH) benefit from intensive blood pressure (BP) lowering. We evaluated whether white matter hyperintensities (WMH) burden influences response to this therapy., Methods: Retrospective secondary analysis of the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Patients were randomized to intensive (systolic BP target: 110-139 mmHg) versus standard (systolic BP target: 140-179 mmHg) BP treatment with intravenous nicardipine within 4.5 h from onset between May 2011 and September 2015. WMH were rated on magnetic resonance images (fluid-attenuated inversion recovery sequences), defining moderate-severe WMH as total Fazekas scale score ≥ 3 (range 0-6). The main outcome was death or major disability at 90 days (modified Rankin scale ≥ 3). The secondary outcome was ICH expansion, defined as hematoma growth > 33% from baseline to follow-up CT scan. Predictors of the outcomes of interest were explored with multivariable logistic regression., Results: A total of 195/1000 patients had MRI images available for analysis, of whom 161 (82.6%) had moderate-severe WMH. When compared to patients with none-mild WMH, those with moderate-severe WMH did not have an increased risk of death or major disability (adjusted relative risk: 1.83, 95% CI 0.71-4.69) or ICH expansion (adjusted relative risk: 1.14, 95% CI 0.38-3.37). WMH burden did not modify the effect of intensive BP treatment on outcome (all p for interaction ≥ 0.2)., Conclusion: The majority of acute ICH patients have moderate-severe WMH, but advanced small vessel disease burden marked by WMH does not influence ICH-related outcomes or response to intensive BP reduction.

Objective: To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial., Design: Randomized, multicenter, 2 group, open-label clinical trial., Setting: A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany., Patients: A total of 1,000 patients underwent randomization from May 2011 till September 2015., Interventions: We analyzed the effect of intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 4.5 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis. Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage. The primary outcome was death or disability (score 4-6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator., Measurements and Main Results: Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 61.9 ± 13.1 years, 62.5% men) with a mean baseline SBP of 174.7 ± 24.8 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (20.4 vs. 27.9%, relative risk [RR]: 0.7; 95% confidence interval [CI]: 0.55-0.96). The primary endpoint of death or disability was observed in 52.5% (170/324) of subjects receiving intensive SBP reduction and 48.9% (163/333) of subjects receiving standard SBP reduction (RR: 1.1; 95% CI: 0.9-1.2)., Conclusions: Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH., (© 2020 S. Karger AG, Basel.)

Background: Neurological deterioration (ND) has a major influence on the prognosis of intracerebral hemorrhage (ICH); however, factors associated with ND occurring after 24 h of ICH onset are unknown., Methods: We performed exploratory analyses of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial, which compared intensive and standard blood pressure lowering treatment in ICH. NDs were captured on the adverse event case report form. Logistic regression analysis was performed to examine the independent predictors of late ND., Results: Among 1,000 participants with acute ICH, 82 patients (8.2%) developed early ND (≤24 h), and 64 (6.4%) had late ND. Baseline hematoma volume (adjusted OR [aOR] per 1-cm3 increase 1.04, 95% CI 1.02-1.06, p < 0.0001), hematoma volume increase in 24 h (aOR 2.24, 95% CI 1.23-4.07, p = 0.008), and the presence of intraventricular hemorrhage (IVH; aOR 2.38, 95% CI 1.32-4.29, p = 0.004) were independent predictors of late ND (vs. no late ND). Late ND was a significant risk factor for poor 90-day outcome (OR 3.46, 95% CI 1.82-6.56). No statistically significant difference in the incidence of late ND was noted between the 2 treatment groups., Conclusions: Initial hematoma volume, early hematoma volume expansion, and IVH are independent predictors of late ND after ICH. Intensive reduction in the systolic blood pressure level does not prevent the development of late ND., (© 2020 S. Karger AG, Basel.)

Significant hematoma expansion (HE) affects one-fifth of people within 24 hours after acute intracerebral hemorrhage (ICH), and its prevention is an appealing treatment target. Although the computed tomography (CT)-angiography spot sign predicts HE, only a minority of ICH patients receive contrast injection. Conversely, noncontrast CT (NCCT) is used to diagnose nearly all ICH, so NCCT markers represent a widely available alternative for prediction of HE. However, different NCCT signs describe similar features, with lack of consensus on the optimal image acquisition protocol, assessment, terminology, and diagnostic criteria. In this review, we propose practical guidelines for detecting, interpreting, and reporting NCCT predictors of HE. ANN NEUROL 2019;86:480-492., (© 2019 American Neurological Association.)

Background: There is persistent uncertainty over the benefits of early intensive systolic blood pressure lowering in acute intracerebral hemorrhage. In particular, over the timing, target, and intensity of systolic blood pressure control for optimum balance of potential benefits (i.e. functional recovery) and risks (e.g. cerebral ischemia)., Aims: To determine associations of early systolic blood pressure lowering parameters and outcomes in patients with a hypertensive response in acute intracerebral hemorrhage. Secondary aims are to identify the modifying effects of patient characteristics and an optimal systolic blood pressure lowering profile., Methods: Individual participant data pooled analyses of two large, multicenter, randomized controlled trials specifically undertaken to assess the effects of early intensive systolic blood pressure reduction on clinical outcomes in acute intracerebral hemorrhage: the Intensive Blood Pressure in Acute Intracerebral Hemorrhage Trial (INTERACT2) and the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trial. Combined data will include baseline characteristics; systolic blood pressure in the first 24 h; process of care measures; and key efficacy and safety outcomes., Outcomes: The primary outcome is functional recovery, defined by an ordinal distribution of scores on the modified Rankin scale at 90 days post-randomization. Secondary outcomes include various standard binary cut-points for disability-free survival on the modified Rankin scale, and health-related quality of life at 90 days. Safety outcomes include symptomatic hypotension requiring corrective therapy and early neurologic deterioration within 24 h, and deaths, any serious adverse event, and cardiac and renal serious adverse events, within 90 days., Discussion: A pre-determined protocol was developed to facilitate successful collaboration and reduce analysis bias arising from prior knowledge of the findings., Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifiers for INTERACT2 (NCT00716079) and ATACH-II (NCT01176565).

Objective: To determine the association between clinical outcomes and acute systolic blood pressure (SBP) levels achieved after intracerebral hemorrhage (ICH)., Methods: Eligible patients who were randomized to the ATACH-2 (Antihypertensive Treatment in Intracerebral Hemorrhage 2) trial (ClinicalTrials.gov: NCT01176565) were divided into 5 groups by 10-mmHg strata of average hourly minimum SBP (<120, 120-130, 130-140, 140-150, and ≥ 150 mmHg) during 2 to 24 hours after randomization. Outcomes included: 90-day modified Rankin Scale (mRS) 4 to 6; hematoma expansion, defined as an increase ≥6 ml from baseline to 24-hour computed tomography; and cardiorenal adverse events within 7 days., Results: Of the 1,000 subjects in ATACH-2, 995 with available SBP data were included in the analyses. The proportion of mRS 4 to 6 was 37.5, 36.0, 42.8, 38.6, and 38.0%, respectively. For the "140 to 150" group relative to the "120 to 130," the odds ratio (OR), adjusting for sex, race, age, onset-to-randomization time, baseline National Institutes of Health Stroke Scale score, hematoma volume, and hematoma location, was 1.62 (95% confidence interval [CI], 1.02-2.58). Hematoma expansion was identified in 16.9, 13.7, 21.4, 18.5, and 26.4%, respectively. The 140 to 150 (OR, 1.80; 95% CI, 1.05-3.09) and "≥150" (1.98; 1.12-3.51) showed a higher frequency of expansion than the 120 to 130 group. Cardiorenal events occurred in 13.6, 16.6, 11.5, 8.1, and 8.2%, respectively. The 140 to 150 (0.43; 0.19-0.88) and ≥ 150 (0.44; 0.18-0.96) showed a lower frequency of the events than the 120 to 130., Interpretation: Beneficial effects of lowering and maintaining SBP at 120 to 130 mmHg during the first 24 hours on clinical outcomes by suppressing hematoma expansion was somewhat offset by cardiorenal complications. ANN NEUROL 2019;85:105-113., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Purpose of Review: The present review aims to discuss the recent advances in surgical management of spontaneous intracerebral hemorrhage (ICH), safety and efficacy of minimally invasive surgical techniques, and the existing evidence supporting their use., Recent Findings: Newer surgical techniques, collectively referred to as minimally invasive surgery (MIS), have been evaluated and studied in management of ICH. Stereotactic evacuation of intracerebral hemorrhage using aspiration-irrigation technique has showed significant reductions in the hematoma volume with minimal intra-operative bleeding. Catheter-based evacuation in combination with use of recombinant tissue plasminogen activator (rt-PA) produces lysis and drainage of spontaneous ICH and intraventricular hemorrhage (IVH) rapidly with minimal major adverse events. Recent advances in the management of spontaneous ICH highlights potential advantages including safety and efficacy in clot lysis and reduction in hematoma volume especially with image-guided catheter-based drainage and concurrent use of rt-PA. Controlled trials are required to conclusively establish standard surgical techniques and rt-PA dosage, before incorporating minimally invasive surgery plus rt-PA, as a standard of care in patients with spontaneous ICH.

Acute hypertensive response is a common systemic response to occurrence of intracerebral hemorrhage which has gained unique prominence due to high prevalence and association with hematoma expansion and increased mortality. Presumably, the higher systemic blood pressure predisposes to continued intraparenchymal hemorrhage by transmission of higher pressure to the damaged small arteries and may interact with hemostatic and inflammatory pathways. Therefore, intensive reduction of systolic blood pressure has been evaluated in several clinical trials as a strategy to reduce hematoma expansion and subsequent death and disability. These trials have demonstrated either a small magnitude benefit (second intensive blood pressure reduction in acute cerebral hemorrhage trial and efficacy of nitric oxide in stroke trial) or no benefit (antihypertensive treatment of acute cerebral hemorrhage 2 trial) with intensive systolic blood pressure reduction compared with modest or standard blood pressure reduction. The differences may be explained by the variation in intensity of systolic blood pressure reduction between trials. A treatment threshold of systolic blood pressure of ≥180 mm with the target goal of systolic blood pressure reduction to values between 130 and 150 mm Hg within 6 h of symptom onset may be best supported by current evidence.

Importance: Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease., Objectives: To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion., Design, Setting, and Participants: Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses., Main Outcomes and Measures: The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan., Results: A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48)., Conclusions and Relevance: Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01176565.

Background and Purpose: Although the computed tomographic angiography spot sign performs well as a biomarker for hematoma expansion (HE), computed tomographic angiography is not routinely performed in the emergency setting. We developed and validated a score to predict HE-based on noncontrast computed tomography (NCCT) findings in spontaneous acute intracerebral hemorrhage., Methods: After developing the score in a single-center cohort of patients with intracerebral hemorrhage (n=344), we validated it in a large clinical trial population (n=954) and in a multicenter intracerebral hemorrhage cohort (n=241). The following NCCT markers of HE were analyzed: hypodensities, blend sign, hematoma shape and density, and fluid level. HE was defined as hematoma growth >6 mL or >33%. The score was created using the estimates from multivariable logistic regression after final predictors were selected from bootstrap samples., Results: Presence of blend sign (odds ratio, 3.09; 95% confidence interval [CI],1.49-6.40; P =0.002), any intrahematoma hypodensity (odds ratio, 4.54; 95% CI, 2.44-8.43; P <0.0001), and time from onset to NCCT <2.5 hours (odds ratio, 3.73; 95% CI, 1.86-7.51; P =0.0002) were predictors of HE. A 5-point score was created (BAT score: 1 point for blend sign, 2 points for any hypodensity, and 2 points for timing of NCCT <2.5 hours). The c statistic was 0.77 (95% CI, 0.70-0.83) in the development population, 0.65 (95% CI 0.61-0.68) and 0.70 (95% CI, 0.64-0.77) in the 2 validation cohorts. A dichotomized score (BAT score ≥3) predicted HE with 0.50 sensitivity and 0.89 specificity., Conclusions: An easy to use 5-point prediction score can identify subjects at high risk of HE with good specificity and accuracy. This tool requires just a baseline NCCT scan and may help select patients with intracerebral hemorrhage for antiexpansion clinical trials., (© 2018 American Heart Association, Inc.)

Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

Purpose: The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance., Methods: A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%., Results: A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images., Conclusion: Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Objective: To validate various noncontrast CT (NCCT) predictors of hematoma expansion in a large international cohort of ICH patients and investigate whether intensive blood pressure (BP) treatment reduces ICH growth and improves outcome in patients with these markers., Methods: We analyzed patients enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized controlled trial. Participants were assigned to intensive (systolic BP <140 mm Hg) vs standard (systolic BP <180 mm Hg) treatment within 4.5 hours from onset. The following NCCT markers were identified: intrahematoma hypodensities, black hole sign, swirl sign, blend sign, heterogeneous hematoma density, and irregular shape. ICH expansion was defined as hematoma growth >33% and unfavorable outcome was defined as modified Rankin Scale score >3 at 90 days. Logistic regression was used to identify predictors of ICH expansion and explore the association between NCCT signs and clinical benefit from intensive BP treatment., Results: A total of 989 patients were included (mean age 62 years, 61.9% male), of whom 186/869 experienced hematoma expansion (21.4%) and 361/952 (37.9%) had unfavorable outcome. NCCT markers independently predicted ICH expansion (all p < 0.01) with overall accuracy ranging from 61% to 78% and good interrater reliability ( k > 0.6 for all markers). There was no evidence of an interaction between NCCT markers and benefit from intensive BP reduction (all p for interaction >0.10)., Conclusions: NCCT signs reliably identify ICH patients at high risk of hematoma growth. However, we found no evidence that patients with these markers specifically benefit from intensive BP reduction., Clinicaltrialsgov Identifier: NCT01176565., (© 2017 American Academy of Neurology.)

Importance: The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction., Objective: To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign., Design, Setting, and Participants: SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016., Main Outcomes and Measures: Patients in ATACH-II were randomized to intensive (systolic BP target, <140 mm Hg) vs standard (systolic BP target, <180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression., Results: A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51; P = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91; P = .62) in spot sign-positive patients., Conclusions and Relevance: The predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction., Trial Registration: clinicaltrials.gov Identifier: NCT01176565.

Background: Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage., Methods: We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments., Results: Among 1000 participants with a mean (±SD) systolic blood pressure of 200.6±27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard-treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002)., Conclusions: The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .).

We assessed factors associated with mortality and potential targets for intervention in a large national sample of children with nontraumatic intracerebral hemorrhage. Using Healthcare Cost and Utilization Project Kids' Inpatient Database ICD-9-CM code 431 identified children aged 1 to 18 years with nontraumatic intracerebral hemorrhage in 2003, 2006 and 2009. Intracerebral hemorrhage was the primary diagnosis for 1172 children (ages 1-18 years) over the 3-year sample. Factors associated with mortality based on multivariable logistic regression included Hispanic ethnicity (odds ratio 1.9, 95% confidence interval 1.1-3.3), older age (11-18 vs 1-10 years, odds ratio 2.5, 95% confidence interval 1.3-5.0), coagulopathy (odds ratio 3.0, 95% confidence interval 1.6-6.0), and coma (odds ratio 9.0, 95% confidence interval 3.2-24.6). From 2003 to 2009, there was a non-significant decrease in mortality with a significant increase in length of stay from 9 to 11 days (P < .003). In children with intracerebral hemorrhage, coma and coagulopathy had the strongest association with mortality; coagulopathy is a potentially modifiable risk factor., (© The Author(s) 2014.)

Background: The long-term prognostic significance of incidental asymptomatic intracerebral hemorrhages (aICHs) detected on brain magnetic resonance imaging (MRI) is unknown., Methods: We analyzed clinical and baseline MRI data from the cohort of 5888 study participants aged 65 years and older recruited in the Cardiovascular Health Study from 4 US communities. We identified participants who had aICHs on MRI and selected 3 age- and gender-matched controls without aICHs. We compared the rates of cardiovascular events using logistic regression analysis including incident myocardial infarction, stroke, and death between those with and without aICHs., Results: A total of 23 participants had aICHs classified as acute (n = 3), subacute (n = 4), and chronic (n = 16). During 14 years of follow-up, the risk of incident stroke (relative risk [RR], .6; 95% confidence interval [CI], .2-2.0), myocardial infarction (RR, .3; 95% CI, .06-1.4), and death (RR, .6; 95% CI, .2-1.7) was not different between participants with aICHs compared with controls (n = 69). There was no difference between the 2 groups with regard to time to ischemic stroke or time to death by Kaplan-Meier analysis., Conclusions: The risks of stroke, myocardial infarction, and death were similar between persons with aICHs detected on MRI compared with age- and gender-matched controls., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Occurrence of acute renal failure (ARF) is more common in patients with intracerebral hemorrhage (ICH) compared with those with other stroke subtypes. We sought to determine the frequency and effect of ARF on in-hospital outcomes of patients with ICH., Methods: We analyzed data from all patients admitted to the United States' hospitals between 2005 and 2011 with the primary discharge diagnosis of ICH and secondary diagnosis of ARF. The associations of ARF with mortality and discharge outcomes in ICH patients were analyzed after adjusting for potential confounders using logistic regression analyses., Results: Of the 614,454 patients admitted with ICH, 41,694 (6.8%) had ARF. In-hospital dialysis was required in 700 (1.7%) patients. ICH patients with ARF had higher rates of moderate-to-severe disability (49.5% versus 44.2%; P < .0001) and in-hospital mortality (28.7% versus 22.4%; P < .0001) compared with those without ARF. After adjusting for age, gender, and potential confounders defined as statistically significant variables on univariate analysis, ICH patients with ARF had higher odds of moderate-to-severe disability (odds ratio [OR] 1.2; 95% confidence interval [CI], 1.1-1.3; P < .0001) and death (OR, 1.5; 95% CI, 1.4-1.6; P < .0001). The rates of moderate-to-severe disability and death were 37.5% and 50.2% among those who required dialysis, respectively., Conclusions: In patients with ICH, ARF is associated with significantly higher rates of in-hospital mortality and moderate-to-severe disability at the time of discharge., (Copyright © 2015 National Stroke Association. All rights reserved.)

Objective: Postthrombolytic intracerebral hemorrhage (ICH) is an infrequent occurrence in patients with acute ischemic stroke. There is controversy surrounding the value of neurosurgical treatment of symptomatic hematomas in these patients and whether availability of neurosurgical treatment is a necessary prerequisite for administration of thrombolytic agents. We report the frequency and outcomes of patients who undergo craniotomy for postthrombolytic ICH., Methods: Patients with acute ischemic stroke who experienced postthrombolytic ICH were identified using the Nationwide Inpatient Sample from 2002-2010 and International Classification of Diseases, 9th Revision, Clinical Modification codes. Patients were divided into patients who received craniotomy and patients who received medical management alone. Discharge destination and mortality were primary endpoints., Results: An estimated 7607 patients experienced postthrombolytic ICH; 125 (1.6%) patients underwent craniotomy, and 7482 patients (98.4%) received medical treatment alone. Patients in the craniotomy group were younger (53.7 years old ± 36 vs. 72.4 years old ± 29, P = 0.09) and were frequently in the extreme severity All Patient Refined Diagnosis Related Group category compared with patients in the medical management group (92.2% vs. 55.5%, P = 0.001). The mean length of stay was also longer in the craniotomy group (21.5 days vs. 10 days, P < 0.0001). In-hospital mortality was greater in the medical management group (30.5% vs. 24.2%, P = 0.5). After adjusting for age, gender, and All Patient Refined Diagnosis Related Group severity index, the odds ratios of in-hospital mortality, discharge to extended care facility, and discharge to home or self-care were 0.8 (95% confidence interval [CI] 0.3-2.0, P = 0.5), 5.4 (95% CI 0.6-52.0, P = 0.1), and 0.2 (95% CI 0.02-1.8, P = 0.1) for the craniotomy group compared with the medical management group., Conclusions: Emergent craniotomy for postthrombolytic ICH in patients with acute stroke is a salvage treatment offered to a small proportion of patients. Although biases introduced by patient selection cannot be excluded in our analysis, the excessively high rates of death or disability associated with surgical evacuation limit the value of such a procedure in current practice., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: This study aimed to identify the imaging characteristics that can help differentiate intraparenchymal hemorrhage from benign contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients after endovascular treatment., Methods: We reviewed the clinical and imaging records of all acute ischemic stroke patients who underwent endovascular treatment in two hospitals over a 3.5-year period. The immediate post-procedural CT scan was evaluated for the presence of hyperdense lesion(s). The average attenuation of the lesion(s) was measured. Intraparenchymal hemorrhage was defined as a persistent hyperdensity visualized on follow-up CT scan, 24 h or greater after the procedure., Results: Of the 135 patients studied, 74 (55%) patients had hyperdense lesion(s) on immediate post-procedural CT scan. Follow-up scans confirmed the diagnosis of intraparenchymal hemorrhage in 20 of these 74 patients. A receiver operating characteristic analysis showed that the average attenuation of the most hyperdense lesion can differentiate intraparenchymal hemorrhage from contrast extravasation with an area under the curve of 0.78 (p = 0.001). An average attenuation of <50 Hounsfield units (HU) in the most visually hyperattenuating hyperdense lesion had 100 % specificity and 56% sensitivity for identification of contrast extravasations. Petechial hyperdensity was seen in 46/54 (85%) patients with contrast extravasation versus 9/20 (45%) patients with intraparenchymal hemorrhage on the immediate post-procedural CT scan (p < 0.001)., Conclusion: An average attenuation <50 HU of the most hyperattenuating hyperdense parenchymal lesion on immediate post-procedural CT scan was very specific for differentiating contrast extravasation from intraparenchymal hemorrhage in acute ischemic stroke patients after endovascular treatment.

Background: We ascertained the occurrence of global cerebral edema manifesting as increased brain volume in subjects with intracerebral hemorrhage (ICH) and explored the relationship between subject characteristics and three month outcomes., Methods: A post-hoc analysis of a multicenter prospective study that recruited patients with ICH, elevated SBP ≥170 mm Hg, and Glasgow Coma Scale (GCS) score ≥8, who presented within 6 h of symptom onset was performed. Computed tomographic (CT) scans at baseline and 24 h, submitted to a core image laboratory, were analyzed to measure total brain, hematoma, and perihematoma edema volumes from baseline and 24-h CT scans using image analysis software. The increased brain volume was determined by subtracting the hematoma and perihematomal edema volumes from the total brain volume., Results: A total of 18 (44 %) of 41 subjects had increased brain volume that developed between initial CT scan and 24-h CT scan. The median increase in brain volume among the 18 subjects was 35 cc ranging from 0.12 to 296 cc. The median baseline GCS score was 15 in both groups of subjects who experienced increased brain volume and those who did not, and the median hematoma volume was 10.18 and 6.73, respectively. Three of the 18 subjects with increased brain volume underwent concurrent neurological deterioration and one subject died during hospitalization., Conclusions: We found preliminary evidence of increased cerebral brain volume in subjects with good grade and small ICHs, which may be suggestive of global cerebral edema.

Background and Purpose: Acute renal failure (ARF) in setting of acute ischemic stroke (AIS) is associated with worse outcome. We sought to determine the prevalence of ARF and effect on outcomes of patients with AIS., Methods: Data from all patients admitted to US hospitals between 2002 and 2010 with a primary discharge diagnosis of ischemic stroke and secondary diagnosis of ARF were included. The effect of ARF on rates of intracerebral hemorrhage and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis., Results: Of 7,068,334 patients with AIS, 372,223 (5.3%) had ARF during hospitalization. Dialysis was required in 2364 (0.6%) of 372,223 patients. Patients with AIS with ARF had higher rates of moderate to severe disability (41.3% versus 30%; P<0.0001), intracerebral hemorrhage (1.0% versus 0.5%; P<0.0001), and in-hospital mortality (8.4% versus 2.9%; P<0.0001) compared with those without ARF. After adjusting for confounding factors, patients with AIS with ARF had higher odds of moderate to severe disability (odds ratio, 1.3; 95% confidence interval, 1.3-1.4; P<0.0001), intracerebral hemorrhage (odds ratio, 1.4; 95% confidence interval, 1.3-1.6; P<0.0001), and death (odds ratio, 2.2; 95% confidence interval, 2.0-2.2; P<0.0001)., Conclusions: ARF in patients with AIS is associated with significantly higher rates of moderate to severe disability at discharge and in-hospital mortality.

Background and Purpose: Cerebral ischemic events are highly prevalent and associated with high rates of death and disability in patients with infective endocarditis (IE). However, the role of thrombolysis in these patients remains unclear. We sought to determine the rates and outcomes of acute ischemic stroke patients with IE treated with intravenous thrombolysis (IVT)., Methods: We determined the rates of post-thrombolytic intracerebral hemorrhage and favorable outcome among acute ischemic stroke patients with IE treated with IVT. Patients were identified using Nationwide Inpatient Sample data from 2002 to 2010. We compared the rates of various outcomes with ischemic stroke patients without IE treated with IVT., Results: There were 222 patients (mean age 59±18 years; 46% women) who were treated with IVT for acute ischemic stroke associated with IE and 134,048 patients (mean age 69±15 years; 49% women) who were treated for stroke without IE. The rate of post-thrombolytic intracerebral hemorrhage was significantly higher in patients with IE compared with those without IE (20% versus 6.5%; P=0.006). There was a significantly lower rate of favorable outcome in the IE group (10% versus 37%; P=0.01)., Conclusions: High rates of post-thrombolytic intracerebral hemorrhage and low rates of favorable outcome mandate caution in using IVT in acute ischemic stroke patients with IE.

Object: Despite the recognition of racial or ethnic differences in preterm gestation, such differences in the rate of intraventricular hemorrhage (IVH), frequently associated with preterm gestation, are not well studied. The authors performed the current study to identify racial or ethnic differences in the incidence of IVH-related mortality within the national population of the US., Methods: Using the ICD-10 codes P52.0, P52.1, P52.2, P52.3, and P10.2 and the Multiple Cause of Death data from 2000 to 2009, the authors identified all IVH-related mortalities that occurred in neonates and infants aged less than 1 year. The live births for whites and African Americans from the census for 2000-2009 were used to derive the incidence of IVH-related mortality for whites and African Americans per 100,000 live births. The IVH rate ratio (RR, 95% confidence interval [CI]) and annual percent change (APC) in the incidence rates from 2000 to 2009 were also calculated., Results: A total of 3249 IVH-related mortality cases were reported from 2000 to 2009. The incidence rates of IVH were higher among African American infants (16 per 100,000 live births) than among whites (7.8 per 100,000 live births). African American infants had a 2-fold higher risk of IVH-related mortality compared with whites (RR 2.0, 95% CI 1.2-3.2). The rate of increase over the last 10 years was less in African American infants (APC 1.6%) than in white infants (APC 4.3%)., Conclusions: The rate of IVH-related mortality is 2-fold higher among African American than white neonates and infants. Further studies are required to understand the underlying reasons for this prominent disparity in one of the most significant causes of infant mortality.

Background: Given the considerable variation in care of patients with intracerebral hemorrhage (ICH) among centers that results in differences in outcome among these patients, a new intensity of care quality metrics has been proposed. This study aimed to validate the new ICH-specific intensity of care quality metrics., Methods: A total of 50 consecutive patients with ICH who were admitted within 24 hours of symptom onset were identified. Twenty-six quality indicators related to 18 facets of care were incorporated into a metric providing the variable, definition of the variable, and quality parameter. A score of 1 point was assigned if the quality parameter met the threshold for appropriate performance or if the parameter was not applicable, creating a total score of up to 26 points. The predictive validity of the classification scheme was tested by using the bootstrap method., Results: Fourteen of the 50 patients with ICH died during hospitalization (28%). The intensity of care quality metric score ranged from 17 points to 26 points. The mean score was higher in those who survived compared with those who died (23 ± 3 vs 21 ± 2; P = .02). Survival increased with tertile based on higher scores (100%, 67%, and 55%; P = .017). The receiver operating characteristic curve demonstrated a high discriminating ability of intensity of care quality metrics for in-hospital mortality (0.730, 95% confidence interval, 0.591-0.869) and a C-statistic of 0.91 (95% confidence interval, 0.90-0.92)., Conclusions: Correlation of the new ICH-specific intensity of care quality metric with in-hospital mortality supports its broader use for improving and standardizing medical care among patients with ICH., (Copyright © 2013 National Stroke Association. All rights reserved.)