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The diagnostic performance of an artificial intelligence (AI) clinical decision support solution for acute intracranial hemorrhage (ICH) detection was assessed in a large teleradiology practice. The impact on radiologist read times and system efficiency was also quantified. A total of 61 704 consecutive noncontrast head CT examinations were retrospectively evaluated. System performance was calculated along with mean and median read times for CT studies obtained before (baseline, pre-AI period; August 2021 to May 2022) and after (post-AI period; January 2023 to February 2024) AI implementation. The AI solution had a sensitivity of 75.6%, specificity of 92.1%, accuracy of 91.7%, prevalence of 2.70%, and positive predictive value of 21.1%. Of the 56 745 post-AI CT scans with no bleed identified by a radiologist, examinations falsely flagged as suspected ICH by the AI solution ( n = 4464) took an average of 9 minutes 40 seconds (median, 8 minutes 7 seconds) to interpret as compared with 8 minutes 25 seconds (median, 6 minutes 48 seconds) for unremarkable CT scans before AI ( n = 49 007) ( P < .001) and 8 minutes 38 seconds (median, 6 minutes 53 seconds) after AI when ICH was not suspected by the AI solution ( n = 52 281) ( P < .001). CT scans with no bleed identified by the AI but reported as positive for ICH by the radiologist ( n = 384) took an average of 14 minutes 23 seconds (median, 13 minutes 35 seconds) to interpret as compared with 13 minutes 34 seconds (median, 12 minutes 30 seconds) for CT scans correctly reported as a bleed by the AI ( n = 1192) ( P = .04). With lengthened read times for falsely flagged examinations, system inefficiencies may outweigh the potential benefits of using the tool in a high volume, low prevalence environment. Keywords: Artificial Intelligence, Intracranial Hemorrhage, Read Time, Report Turnaround Time, System Efficiency Supplemental material is available for this article. © RSNA, 2024.

Background: Elevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation., Methods: This retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records., Results: A total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3-6) in 31 patients (26.96%) and good (mRS 0-2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054-21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330-0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118-1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850-0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736., Conclusions: High BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation., (© 2024. The Author(s).)

Purpose To explore the potential benefits of deep learning-based artifact reduction in sparse-view cranial CT scans and its impact on automated hemorrhage detection. Materials and Methods In this retrospective study, a U-Net was trained for artifact reduction on simulated sparse-view cranial CT scans in 3000 patients, obtained from a public dataset and reconstructed with varying sparse-view levels. Additionally, EfficientNet-B2 was trained on full-view CT data from 17 545 patients for automated hemorrhage detection. Detection performance was evaluated using the area under the receiver operating characteristic curve (AUC), with differences assessed using the DeLong test, along with confusion matrices. A total variation (TV) postprocessing approach, commonly applied to sparse-view CT, served as the basis for comparison. A Bonferroni-corrected significance level of .001/6 = .00017 was used to accommodate for multiple hypotheses testing. Results Images with U-Net postprocessing were better than unprocessed and TV-processed images with respect to image quality and automated hemorrhage detection. With U-Net postprocessing, the number of views could be reduced from 4096 (AUC: 0.97 [95% CI: 0.97, 0.98]) to 512 (0.97 [95% CI: 0.97, 0.98], P < .00017) and to 256 views (0.97 [95% CI: 0.96, 0.97], P < .00017) with a minimal decrease in hemorrhage detection performance. This was accompanied by mean structural similarity index measure increases of 0.0210 (95% CI: 0.0210, 0.0211) and 0.0560 (95% CI: 0.0559, 0.0560) relative to unprocessed images. Conclusion U-Net-based artifact reduction substantially enhanced automated hemorrhage detection in sparse-view cranial CT scans. Keywords: CT, Head/Neck, Hemorrhage, Diagnosis, Supervised Learning Supplemental material is available for this article. © RSNA, 2024.

Purpose To develop and evaluate a semi-supervised learning model for intracranial hemorrhage detection and segmentation on an out-of-distribution head CT evaluation set. Materials and Methods This retrospective study used semi-supervised learning to bootstrap performance. An initial "teacher" deep learning model was trained on 457 pixel-labeled head CT scans collected from one U.S. institution from 2010 to 2017 and used to generate pseudo labels on a separate unlabeled corpus of 25 000 examinations from the Radiological Society of North America and American Society of Neuroradiology. A second "student" model was trained on this combined pixel- and pseudo-labeled dataset. Hyperparameter tuning was performed on a validation set of 93 scans. Testing for both classification ( n = 481 examinations) and segmentation ( n = 23 examinations, or 529 images) was performed on CQ500, a dataset of 481 scans performed in India, to evaluate out-of-distribution generalizability. The semi-supervised model was compared with a baseline model trained on only labeled data using area under the receiver operating characteristic curve, Dice similarity coefficient, and average precision metrics. Results The semi-supervised model achieved a statistically significant higher examination area under the receiver operating characteristic curve on CQ500 compared with the baseline (0.939 [95% CI: 0.938, 0.940] vs 0.907 [95% CI: 0.906, 0.908]; P = .009). It also achieved a higher Dice similarity coefficient (0.829 [95% CI: 0.825, 0.833] vs 0.809 [95% CI: 0.803, 0.812]; P = .012) and pixel average precision (0.848 [95% CI: 0.843, 0.853]) vs 0.828 [95% CI: 0.817, 0.828]) compared with the baseline. Conclusion The addition of unlabeled data in a semi-supervised learning framework demonstrates stronger generalizability potential for intracranial hemorrhage detection and segmentation compared with a supervised baseline. Keywords: Semi-supervised Learning, Traumatic Brain Injury, CT, Machine Learning Supplemental material is available for this article. Published under a CC BY 4.0 license. See also the commentary by Swimburne in this issue.

We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome.

Background: Prehospital triage and treatment of patients with acute coma is challenging for rescue services, as the underlying pathological conditions are highly heterogenous. Recently, glial fibrillary acidic protein (GFAP) has been identified as a biomarker of intracranial hemorrhage. The aim of this prospective study was to test whether prehospital GFAP measurements on a point-of-care device have the potential to rapidly differentiate intracranial hemorrhage from other causes of acute coma., Methods: This study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in the northern vicinity of Stuttgart, Germany. Patients who were admitted to the emergency department with the prehospital diagnosis of acute coma (Glasgow Coma Scale scores between 3 and 8) were enrolled prospectively. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min) shortly after hospital admission., Results: 143 patients were enrolled (mean age 65 ± 20 years, 42.7% female). GFAP plasma concentrations were strongly elevated in patients with intracranial hemorrhage (n = 51) compared to all other coma etiologies (3352 pg/mL [IQR 613-10001] vs. 43 pg/mL [IQR 29-91.25], p < 0.001). When using an optimal cut-off value of 101 pg/mL, sensitivity for identifying intracranial hemorrhage was 94.1% (specificity 78.9%, positive predictive value 71.6%, negative predictive value 95.9%). In-hospital mortality risk was associated with prehospital GFAP values., Conclusion: Increased GFAP plasma concentrations in patients with acute coma identify intracranial hemorrhage with high diagnostic accuracy. Prehospital GFAP measurements on a point-of-care platform allow rapid stratification according to the underlying cause of coma by rescue services. This could have major impact on triage and management of these critically ill patients., (© 2024. The Author(s).)

A 63-year-old male patient with a history of hypertension presented to the emergency department with a one-day history of dizziness, nausea, and vomiting.

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association between levels of GFAP in the bloodstream and the occurrence of sICH., Methods: Between June 2019 and May 2023, 142 consecutive AIS patients undergoing EVT at Stroke Center and 35 controls from the Physical Examination Center were retrospectively included. The levels of GFAP in the bloodstream were quantified using enzyme-linked immunosorbent assay prior to endovascular treatment (T1) and 24 h after the procedure (T2). The identification of sICH was based on the Heidelberg Bleeding Classification., Results: Serum GFAP levels at T1 in AIS patients were significantly higher than those in the controls (0.249 [0.150-0.576] versus 0.065 [0.041-0.110] ng/mL, p = 0.001), and there was a notably elevation in GFAP levels at T2 compared to T1 (3.813 [1.474, 5.876] versus 0.249 [0.150-0.576] ng/mL, p = 0.001). Of the 142 AIS patients, 18 (14.5%) had sICH after EVT. Serum GFAP levels at T2 showed significant associations with sICH in both the unadjusted model (OR 1.513, 95% CI 1.269-1.805, p = 0.001) and multivariable adjusted model (OR 1.518, 95% CI 1.153-2.000, p = 0.003). Furthermore, the addition of GFAP at T2 to conventional model resulted in a significant enhancement of risk reclassification for sICH (integrated discrimination improvement [IDI] 0.183, 95% CI 0.070-0.295, p = 0.001)., Conclusion: Serum GFAP levels were notably increased in AIS patients 24 h after EVT. Elevated GFAP levels were correlated to an elevated risk of sICH. GFAP could potentially serve as a dependable indicator for sICH in AIS individuals who treated with EVT., Competing Interests: The authors declare no conflict of interest., (© 2024 Li et al.)

Background: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs)., Hypothesis: An externally validated model improves ICH risk stratification., Methods: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register., Results: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets., Conclusions: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Purpose: The Treat Stroke to Target trial has confirmed the benefit of targeting low-density lipoprotein cholesterol (LDL-C) of <1.8 mmol/L in patients who had an ischaemic stroke (IS). However, haemorrhagic risk brought by this target level (<1.8 mmol/L) or even lower level (<1.4 mmol/L) of LDL-C should also be concerned. In this study, we aimed to demonstrate whether low LDL-C could increase the intracranial haemorrhage risk following IS., Methods: Patients who had an IS from China Stroke Center Alliance programme with complete baseline information were prospectively enrolled. 793 572 patients who had an IS were categorised into 6 groups according to LDL-C level (<1.40 mmol/L, 1.40-1.79 mmol/L, 1.80-2.59 mmol/L, 2.60-2.99 mmol/L, 3.00-4.89 mmol/L, ≥4.90 mmol/L). The study outcome was defined as intracranial haemorrhage identified during hospitalisation. Logistic regression model was used to examine the association between different LDL-C levels and risk of intracranial haemorrhage., Results: Compared with patients of LDL-C=1.80-2.59 mmol/L, both subgroups of LDL-C<1.40 mmol/L and LDL-C=1.40-1.79 mmol/L showed significantly higher risk of intracranial haemorrhage (OR=1.26, 95% CI=1.18 to 1.35; OR=1.22, 95% CI=1.14 to 1.30, respectively). Interaction effect was found to exist between the subgroups of intravenous thrombolytic therapy (p=0.04), rather than the subgroups of age, sex and body mass index. Moreover, the sensitivity analyses indicated that even patients who had an IS with minor stroke still suffered from the increased intracranial haemorrhage risk related to low LDL-C level., Conclusions: Among patients who had an IS, the low LDL-C level (<1.4 mmol/L or <1.8 mmol/L) at baseline is associated with increased risk of intracranial haemorrhage during acute stage. While actively lowering LDL-C level for patients who had an IS, clinicians should also concern about the haemorrhagic risk associated with low LDL-C level., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications., Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4., Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log 10 S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7-6.9, p  = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3-7.1, p  < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 ( p  = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 ( p  < 0.0001) for symptomatic brain edema., Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TH Nothing to report; JS Nothing to report; AB Nothing to report; LW Nothing to report; VS Nothing to report; CI Nothing to report; TP Nothing to report; MA reports honoraria and board involvements outside the submitted work; UF reports grants, consulting fees, honoraria and board involvements, outside the submitted work; LB Nothing to report; GM Nothing to report; KN Nothing to report; TK Nothing to report; CC reports fees outside the submitted work; GK reports grants outside the submitted work; JM Nothing to report; AB Nothing to report; EP Nothing to report; GN Nothing to report; CF reports a patent Use of GFAP for identification of intracerebral Hemorrhage US20150247867 licensed to Banyan Biomarkers; AL reports grants and fees outside the submitted work.; KS Nothing to report; LS Nothing to report; AvE reports grants, fees, honoraria and board involvements, outside the submitted work; MA Nothing to report; MKv reports grants from the Swiss National Science Foundation (142422), the Swiss Heart Foundation, the Göhner Foundation and the Swiss Seaside Foundation as well as non-financial support from Roche diagnostics during the conduct of the study and is involved in the Advisory Board of AstraZeneca, Bayer, Amgen, BMS/Pfizer and Medtronic outside the submitted work., (© European Stroke Organisation 2022.)

Background The association between cancer types and specific bleeding events in patients with atrial fibrillation has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. We investigated the rate of any bleeding, intracranial hemorrhage, major bleeding, and gastrointestinal bleeding according to cancer types in patients with atrial fibrillation. We also tested the predictive value of HAS-BLED, ATRIA, and ORBIT bleeding risk scores. Methods and Results Observational retrospective cohort study including hospitalized patients with atrial fibrillation and cancer from the French National Hospital Discharge Database (Programme de Medicalisation des Systemes d'Information) from January 2010 to December 2019. Major bleeding was defined according to Bleeding Academic Research Consortium definitions. Patients with HAS-BLED ≥3, ATRIA ≥5, or ORBIT ≥4 were classified as at high bleeding risk. Receiver operating characteristic analysis for each score against any bleeding, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage was performed. Areas under the curve (AUCs) were then compared. We included 399 344 patients. Mean age was 77.9±10.2 years, and 63.2% were men. The highest intracranial hemorrhage rates were found in leukemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year), and pancreas cancer (1.41%/year). Receiver operating characteristic analysis showed that ORBIT score predicted best for any bleeding. In addition, ORBIT score ≥4 had the highest predictivity for major bleeding (AUC, 0.805), followed by HAS-BLED ≥3 and ATRIA ≥5 (AUCs, 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for intracranial hemorrhage (AUCs, 0.744 and 0.742 for continuous scores, respectively), better than ATRIA (AUC, 0.635). For gastrointestinal bleeding, ORBIT ≥4 had the highest predictivity (AUC, 0.756), followed by the HAS-BLED ≥3 (AUC, 0.702) and ATRIA ≥5 (AUC, 0.662). Conclusions Some cancer types carry a greater bleeding risk in patients with atrial fibrillation. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up.

Background: Blood pressure (BP) fluctuates significantly in patients with atrial fibrillation (AF); office BP measurements seem insufficient to assess AF patient risk accurately. We hypothesized that home BP could better predict the risk of stroke/systemic embolic events (SEE) and major bleeding in patients with AF than office BP., Methods: In this prespecified subcohort study of the ANAFIE (All Nippon AF in the Elderly) Registry, we evaluated the impact of home BP on the risk of stroke/SEE, major bleeding, intracranial hemorrhage, all-cause death, and net cardiovascular outcome (a composite of stroke/SEE and major bleeding). At enrollment, home BP was measured twice in the morning and evening for 7 days., Results: In total, 4933 elderly patients (aged ≥75 years) with nonvalvular AF participated. Incidences of net cardiovascular outcome, stroke/SEE, major bleeding, and intracranial hemorrhage increased significantly with increasing home systolic BP (H-SBP). Compared with H-SBP <125 mm Hg, ≥145 mm Hg was associated with increased risk of these events. The association between H-SBP and the events was observed only in patients with ≥20 H-SBP measurements., Conclusions: In elderly patients with nonvalvular AF, high H-SBP (≥145 mm Hg) was a significant predictor of stroke/SEE, major bleeding, and intracranial hemorrhage risk. Strict BP control guided by the increasing number of home BP measurements may provide an accurate clinical outcome risk assessment., Registration: URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000024006.

Aims: The aim of this study is to perform a systematic review and meta-analysis on the epidemiology of cerebral microbleeds (CMBs) and the risk of intracranial haemorrhage (ICH) and ischaemic stroke (IS) in patients with atrial fibrillation (AF)., Methods and Results: PubMed and EMBASE databases were systematically searched from inception to 6 March 2021. All studies reporting the prevalence of CMBs and incidence of ICH and IS in AF patients with and without CMBs were included. Meta-analysis was conducted using random-effect models; odds ratios (ORs), 95% confidence intervals (CIs), and prediction intervals (PIs) were calculated for each outcome. Subgroup analyses were performed according to the number and localization of CMBs. A total of 562 studies were retrieved, with 17 studies finally included in the meta-analysis. Prevalence of CMBs in AF population was estimated at 28.3% (95% CI: 23.8-33.4%). Individuals with CMBs showed a higher risk of ICH (OR: 3.04, 95% CI: 1.83-5.06, 95% PI 1.23-7.49) and IS (OR: 1.78, 95% CI: 1.26-2.49, 95% PI 1.10-2.87). Patients with ≥5 CMBs showed a higher risk of ICH. Metaregression showed how higher of prevalence of diabetes mellitus in AF cohort is associated with higher prevalence of CMBs., Conclusions: Cerebral microbleeds are common in patients with AF, found in almost one out of four subjects. Cerebral microbleeds were associated with both haemorrhagic and thromboembolic events in AF patients. Moreover, the risk of ICH increased consistently with the burden of CMBs. Cerebral microbleeds may represent an important overlooked risk factor for both ICH and IS in adults with AF., Competing Interests: Conflict of interest: S.B. received research grants from MSD, outside the scope of this study. All remaining authors have declared no conflicts of interest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Objective: Cerebral hyperperfusion syndrome (CHS) is a rare but potentially devastating complication after carotid endarterectomies (CEA). Its symptoms range from new-onset unilateral headache (HA) to intracranial hemorrhage (ICH). Risk factors for CHS in the literature to date have not yet yielded a consensus. This study examines intraoperative and postoperative blood pressure variations as potential risk factors for HA., Methods: A single-center retrospective review at a tertiary care center from January 2010 to November 2019 was performed. Inclusion criteria were all patients undergoing CEA for symptomatic or asymptomatic carotid disease. Patients with incomplete charts were excluded. Primary endpoints were new-onset unilateral HA or postoperative ICH. Data on intraoperative and postoperative mean arterial pressure (MAP), systolic blood pressure (SBP), the mode of endarterectomy, shunt placement, and contralateral carotid status were collected., Results: There were 735 patients who met the inclusion criteria: 430 patients underwent modified eversion CEA (59%) and 305 patients for patch angioplasty (42%). The incidence of HA was 19% (n = 142) in our total cohort. Of the 19% with HA, 1.5% (n = 11) demonstrated no relief with analgesics and strict blood pressure control; noncontrast head computed tomography scans were performed subsequently. One patient (0.1%) had an ipsilateral ICH. Univariate analysis demonstrated that greater intraoperative MAP peak had the highest risk for HA (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.007-1.022; P = .0002), followed by intraoperative MAP variability (OR, 1.011; 95% CI,1.005-1.018; P ≤ .0008), and peak intraoperative SBP (OR, 1.01; 95% CI, 1.004-1.015; P = .0011). An unpaired Student t test identified change in intraoperative MAP (P < .005), change in the SBP (P < .005), and peak SBP (P < .001) were significantly associated with HA. Interestingly, there was no significant difference between postoperative MAP variability and HA (P = .1). The mode of endarterectomy showed no statistically significant difference in risk for developing HA (OR, 1.165; 95%; 95% CI, 0.801-1.694; P = .42)., Conclusions: Greater intraoperative variability in blood pressures are significantly associated with a higher risk of HA. Adhering to stricter intraoperative blood pressure parameters and limiting blood pressure variability may be beneficial at decreasing the incidence of CHS and its complications., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Intracranial hemorrhage (ICH) is a rare but fatal central nervous system complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, factors that are predictive of early mortality in patients who develop ICH after undergoing allo-HSCT have not been systemically investigated. From January 2008 to June 2020, a total of 70 allo-HSCT patients with an ICH diagnosis formed the derivation cohort. Forty-one allo-HSCT patients with an ICH diagnosis were collected from 12 other medical centers during the same period, and they comprised the external validation cohort. These 2 cohorts were used to develop and validate a grading scale that enables the prediction of 30-day mortality from ICH in all-HSCT patients. Four predictors (lactate dehydrogenase level, albumin level, white blood cell count, and disease status) were retained in the multivariable logistic regression model, and a simplified grading scale (termed the LAWS score) was developed. The LAWS score was adequately calibrated (Hosmer-Lemeshow test, P > .05) in both cohorts. It had good discrimination power in both the derivation cohort (C-statistic, 0.859; 95% confidence interval, 0.776-0.945) and the external validation cohort (C-statistic, 0.795; 95% confidence interval, 0.645-0.945). The LAWS score is the first scoring system capable of predicting 30-day mortality from ICH in allo-HSCT patients. It showed good performance in identifying allo-HSCT patients at increased risk of early mortality after ICH diagnosis. We anticipate that it would help risk stratify allo-HSCT patients with ICH and facilitate future studies on developing individualized and novel interventions for patients within different LAWS risk groups., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Brain arteriovenous malformations (bAVM) are an important cause of intracranial hemorrhage (ICH), especially in younger patients. The pathogenesis of bAVM are largely unknown. Current understanding of bAVM etiology is based on studying genetic syndromes, animal models, and surgically resected specimens from patients. The identification of activating somatic mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene and other mitogen-activated protein kinase ( MAPK ) pathway genes has opened up new avenues for bAVM study, leading to a paradigm shift to search for somatic, de novo mutations in sporadic bAVMs instead of focusing on inherited genetic mutations. Through the development of new models and understanding of pathways involved in maintaining normal vascular structure and functions, promising therapeutic targets have been identified and safety and efficacy studies are underway in animal models and in patients. The goal of this paper is to provide a thorough review or current diagnostic and treatment tools, known genes and key pathways involved in bAVM pathogenesis to summarize current treatment options and potential therapeutic targets uncovered by recent discoveries.

Background: Highly accurate detection of intracranial hemorrhages (ICH) on head computed tomography (HCT) scans can prove challenging at high-volume centers. This study aimed to determine the number of additional ICHs detected by an artificial intelligence (AI) algorithm and to evaluate reasons for erroneous results at a level I trauma center with teleradiology services., Methods: In a retrospective multi-center cohort study, consecutive emergency non-contrast HCT scans were analyzed by a commercially available ICH detection software (AIDOC, Tel Aviv, Israel). Discrepancies between AI analysis and initial radiology report (RR) were reviewed by a blinded neuroradiologist to determine the number of additional ICHs detected and evaluate reasons leading to errors., Results: 4946 HCT (05/2020-09/2020) from 18 hospitals were included in the analysis. 205 reports (4.1%) were classified as hemorrhages by both radiology report and AI. Out of a total of 162 (3.3%) discrepant reports, 62 were confirmed as hemorrhages by the reference neuroradiologist. 33 ICHs were identified exclusively via RRs. The AI algorithm detected an additional 29 instances of ICH, missed 12.4% of ICH and overcalled 1.9%; RRs missed 10.9% of ICHs and overcalled 0.2%. Many of the ICHs missed by the AI algorithm were located in the subarachnoid space (42.4%) and under the calvaria (48.5%). 85% of ICHs missed by RRs occurred outside of regular working-hours. Calcifications (39.3%), beam-hardening artifacts (18%), tumors (15.7%), and blood vessels (7.9%) were the most common reasons for AI overcalls. ICH size, image quality, and primary examiner experience were not found to be significantly associated with likelihood of incorrect AI results., Conclusion: Complementing human expertise with AI resulted in a 12.2% increase in ICH detection. The AI algorithm overcalled 1.9% HCT., Trial Registration: German Clinical Trials Register (DRKS-ID: DRKS00023593)., Competing Interests: The authors have declared that no competing interests exist.

Background: Defects in the RYR1 (OMIM#180901) gene lead to Ryanodine receptor type 1-related myopathies (RYR1-RM); the most common subgroup of congenital myopathies., Methods: Congenital myopathy presents a diagnostic challenge due to the need for multiple testing modalities to identify the many different genetic etiologies. In this case, the patient remained undiagnosed after whole-exome sequencing (WES), chromosomal microarray, methylation analysis, targeted deletion and duplication studies, and targeted repeat expansion studies. Clinical whole-genome sequencing (WGS) was then pursued as part of a research study to identify a diagnosis., Results: WGS identified compound heterozygous RYR1 intronic variants, RNA sequencing confirmed both variants to be pathogenic causing RYR1-RM in a phenotype of severe congenital hypotonia with respiratory failure from birth, neonatal brain hemorrhage, and congenital heart disease involving transposition of the great arteries., Conclusion: While there is an ongoing debate about the clinical superiority of WGS versus WES for patients with a suspected genetic condition, this scenario highlights a weakness of WES as well as the added cost and delay in diagnosis timing with having WGS follow WES or even ending further genetic testing with a negative WES. While knowledge gaps still exist for many intronic variants, transcriptome analysis provides a way of validating the resulting dysfunction caused by these variants and thus allowing for appropriate pathogenicity classification. This is the second published case report of a patient with pathogenic intronic variants in RYR1-RM, with clinical RNA testing confirming variant pathogenicity and therefore the diagnosis suggesting that for some patients careful analysis of a patient's genome and transcriptome are required for a complete genetic evaluation. The diagnostic odyssey experienced by this patient highlights the importance of early, rapid WGS., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To investigate the effects of rivaroxaban and warfarin on gastrointestinal and intracranial hemorrhage in patients with AF, we searched PubMed, Embase, and Medline from the establishment of databases up to 2020. We finally included 38 observational studies involving 1 312 609 patients for the assessment of intracranial hemorrhage, and 33 observational studies involving 1 332 956 patients for the assessment of gastrointestinal bleeding. The rates of intracranial hemorrhage were 0.55% in the rivaroxaban group versus 0.91% in the warfarin group (OR 0.59; 95% CI 0.53-0.66; p < .00001, I2 = 78%). The rates of gastrointestinal bleeding were 2.63% in patients with rivaroxaban versus 2.48% in those with warfarin (OR 1.06; 95% CI 0.96-1.17; p < .00001, I2 = 94%). Rivaroxaban could significantly reduce the risk of intracranial hemorrhage in patients with AF than warfarin, but the risk of gastrointestinal bleeding remained controversy due to no statistical significant difference. Notably, a subgroup analysis demonstrated that patients in rivaroxaban group with severe chronic renal diseases or undergoing hemodialysis exposed to less gastrointestinal hemorrhage risk than the group from warfarin., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90-day mortality. There were 1889 patients (90.6%) who had 90-day follow-up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57-3.17) but reduced risk of 90-day mortality (OR, 0.58; 95% CI, 0.39-0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90-day mortality (OR, 0.68; 95% CI, 0.45-1.04). Conclusions Alteplase reduced 90-day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.

Background Outcomes after stroke as a result of large-vessel occlusion in patients with prestroke disability were compared between endovascular therapy (EVT) and medical management. Methods and Results Of 2420 patients with acute stroke with large-vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients with prestroke modified Rankin Scale scores 2 to 4 with occlusion of the internal carotid artery, or M1 of the middle cerebral artery were analyzed. The primary effectiveness outcome was the favorable outcome, defined as return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage. A total of 339 patients (237 women; median 85 [interquartile range (IQR), 79-89] years of age; median prestroke modified Rankin Scale score of 3 [IQR, 2-4]) were analyzed. EVT was performed in 175 patients (51.6%; mechanical thrombectomy, n=139). The EVT group was younger ( p <0.01) and had lower prestroke modified Rankin Scale scores ( p <0.01) than the medical management group. The favorable outcome was seen in 28.0% of the EVT group and in 10.9% of the medical management group ( p <0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 3.01; 95% CI, 1.55-5.85; mixed effects multivariable model with inverse probability of treatment weighting). Symptomatic intracranial hemorrhage rates were similar between the EVT (4.0%) and medical management (4.3%) groups ( p =1.00). Conclusions Patients who underwent EVT showed better functional outcomes than those with medical management. Given proper patient selection, withholding EVT solely on the basis of prestroke disability might not offer the best chance of favorable outcome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02419794.

Delayed intracerebral hemorrhage (DICH) secondary to ventriculoperitoneal (VP) shunt is considered to be a potentially severe event. This study aimed to investigate the association between a ratio of postoperative neutrophil-to-lymphocyte ratio to preoperative neutrophil-to-lymphocyte ratio (NLRR) and DICH secondary to VP shunt. We performed a retrospective review of patients who underwent VP shunt between January 2016 and June 2020. Multivariable logistic regression analysis was used to assess the association of DICH and NLRR. Then patients were divided into two groups according to the optimal cut-off point of NLRR, propensity score matching (PSM) method was performed to reconfirm the result. A total of 130 patients were enrolled and DICH occurred in 29 patients. Elevated NLRR and history of craniotomy were independent risk factors for DICH secondary to VP shunt. The optimal cut off point of NLRR was 2.05, and the sensitivity was 89.7%, the specificity was 63.4%. Patients with NLRR > 2.05 had much higher incidence of DICH (40.6% vs 4.5%). Our finding suggested that DICH following VP shunt was not a rare complication and elevated NLRR could independently predict DICH. Inflammatory responses might play an important role in the development of DICH following VP shunt.

To date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42-20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

Background: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant., Objectives: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma., Methods: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy., Results: Fourteen patients presented with ICH (6.8%, 3.8-11.1%) and three (1.5%, 0.3-4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0-2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8-98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7-88.3) of the cohort., Conclusions: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

Anticoagulants prevent thrombosis and death in patients with atrial fibrillation and venous thromboembolism (VTE) but also increase bleeding risk. The benefit/risk ratio favors anticoagulation in most of these patients. However, some will have a bleeding complication, such as the common trip-and-fall brain injury in elderly patients that results in traumatic intracranial hemorrhage. Clinicians must then make the difficult decision about when to restart the anticoagulant. Restarting too early risks making the bleeding worse. Restarting too late risks thrombotic events such as ischemic stroke and VTE, the indications for anticoagulation in the first place. There are more data on restarting patients with spontaneous intracranial hemorrhage, which is very different than traumatic intracranial hemorrhage. Spontaneous intracranial hemorrhage increases the risk of rebleeding because intrinsic vascular changes are widespread and irreversible. In contrast, traumatic cases are caused by a blow to the head, usually an isolated event portending less future risk. Clinicians generally agree that anticoagulation should be restarted but disagree about when. This uncertainty leads to long restart delays causing a large, potentially preventable burden of strokes and VTE, which has been unaddressed because of the absence of high quality evidence. Restart Traumatic Intracranial Hemorrhage (the "r" distinguished intracranial from intracerebral) (TICrH) is a prospective randomized open label blinded end-point response-adaptive clinical trial that will evaluate the impact of delays to restarting direct oral anticoagulation (1, 2, or 4 weeks) on the composite of thrombotic events and bleeding in patients presenting after traumatic intracranial hemorrhage.

Background and Purpose: Indirect consequences of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic include those related to failure of patients to seek or receive timely medical attention for seemingly unrelated disease. We report our experience with stroke code imaging during the early pandemic months of 2020., Materials and Methods: Retrospective review of stroke codes during the 2020 pandemic and both 2020 and matched 2019 prepandemic months was performed. Patient variables were age, sex, hospital location, and severity of symptoms based on the NIHSS. We reviewed the results of CT of the head, CTA, CTP, and MR imaging examinations and classified a case as imaging-positive if any of the imaging studies yielded a result that related to the clinical indication for the study. Both year-to-year and sequential comparisons were performed between pandemic and prepandemic months., Results: A statistically significant decrease was observed in monthly stroke code volumes accompanied by a statistically significant increased proportion of positive imaging findings during the pandemic compared with the same months in the prior year ( P < .001) and prepandemic months in the same year ( P < .001). We also observed statistically significant increases in average NIHSS scores ( P = .045 and P = .03) and the proportion of inpatient stroke codes ( P = .003 and P = .03)., Conclusions: During our pandemic period, there was a significantly decreased number of stroke codes but simultaneous increases in positivity rates, symptom severity, and inpatient codes. We postulate that this finding reflects the documented reluctance of patients to seek medical care during the pandemic, with the shift toward a greater proportion of inpatient stroke codes potentially reflecting the neurologic complications of the virus itself., (© 2021 by American Journal of Neuroradiology.)

Background: Parvimonas micra (P. micra) is a gram-positive anaerobic coccus that is detected widely on the skin, in the oral mucosa and in the gastrointestinal tract. In certain circumstances, P. micra can cause abdominal abscesses, bacteraemia and other infections. To the best of our knowledge, there have been no case reports describing the biological characteristics of P. micra-related pneumonia. These bacteria do not always multiply in an aerobic organ, such as the lung, and they could be easily overlooked because of the clinical mindset., Case Presentation: A 35-year-old pregnant woman was admitted to the emergency department 4 weeks prior to her due date who was exhibiting 5 points on the Glasgow coma scale. A computed tomography (CT) scan showed a massive haemorrhage in her left basal ganglia. She underwent a caesarean section and brain surgery before being admitted to the ICU. She soon developed severe pneumonia and hypoxemia. Given that multiple sputum cultures were negative, the patient's bronchoalveolar lavage fluid was submitted for next-generation sequencing (NGS) to determine the pathogen responsible for the pneumonia; as a result, P. micra was determined to be the causative pathogen. Accordingly the antibiotic therapy was altered and the pneumonia improved., Conclusion: In this case, we demonstrated severe pneumonia caused by the anaerobic organism P. micra, and the patient benefited from receiving the correct antibiotic. NGS was used as a method of quick diagnosis when sputum culture failed to distinguish the pathogen.

Aims: Although atrial fibrillation (AF) catheter ablation (AFCA) is an effective rhythm control strategy, there is limited data on whether ischaemic stroke (IS) or intracranial haemorrhage (ICH) decreases after AFCA compared with medical therapy or non-AF population. We explored the IS and ICH risk after AFCA or medical therapy in the AF population and matched non-AF population., Methods and Results: We compared 1629 patients with AFCA (Yonsei AF ablation cohort), 3258 with medical therapy [Korean National Health Insurance (NHIS) database], and 3258 non-AF subjects (NHIS database) following a 1:2:2 propensity score matching. All AFCA patients underwent regular rhythm follow-ups for 51 ± 29 months. Among the AFCA group, the incidence rate ratio (IRR) of ISs was significantly higher in patients with sustained AF recurrences after the last ablation (0.87%) than in those remaining in sinus rhythm (0.24%, P = 0.017; log rank P = 0.003). The IRR of ISs was significantly higher in the medical therapy (1.09%) than AFCA (0.30%, P < 0.001, log rank P < 0.001 vs. medical therapy) or non-AF groups (0.34%, P < 0.001, log rank P < 0.001 vs. medical therapy; P = 0.673, log rank P = 0.874 vs. AFCA). The IRR of ICHs was 0.17% in the medical therapy, 0.06% in the AFCA (P = 0.023, log rank P = 0.042 vs. medical therapy), and 0.12% in the non-AF group (P = 0.226, log rank P = 0.241 vs. medical therapy; P = 0.172, log rank P = 0.193 vs. AFCA)., Conclusion: Post-procedural AF control influences the risk of ISs. Atrial fibrillation catheter ablation significantly reduces the risk of both ISs and ICHs to the extent of the non-AF population compared to the medical therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: The objective is to analyze the clinical diagnosis and treatment of children with rescindable posterior encephalopathy syndrome (PRES) and intracranial hemorrhage (ICH) to improve the pediatrician's understanding of PRES combined with ICH in children., Patient Concerns and Diagnosis: After liver transplantation, the patient developed symptoms of epilepsy and coma. Meanwhile, massive necrosis of acute cerebral infarction and small hemorrhage was observed in the left cerebellar hemisphere and left occipital lobe, respectively. The above symptoms were initially diagnosed as PRES., Interventions and Outcomes: After adjusting the anti-rejection drug regimen, it was found that the child's neurological symptoms were relieved, and the limb motor function gradually recovered during follow-up. Imaging examination showed significant improvement on abnormal signals in brain., Conclusion: In general, children with PRES may further develop ICH and contribute to a poor prognosis. Early diagnosis, detection of risk factors and timely adjustment of medication regimen are the keys to prevent irreversible brain damage., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: This study aims to determine whether door-to-needle times (DNT) for reversal of anticoagulant-associated intracerebral haemorrhage (ICH) (1) have improved over time, (2) differ between warfarin and dabigatran and (3) are comparable to ischaemic stroke (IS) thrombolysis DNT, and (4) whether reversal is monitored., Methods: Retrospective review of all warfarin- and dabigatran-associated ICH presenting to Christchurch Hospital over a 15-year period. DNT data from 2013-2018 were compared between warfarin-related ICH (WRICH), dabigatran-related ICH (DRICH) and IS thrombolysis., Results: 172 WRICH were identified. Over time there were significant reductions in door-to-first-reversal-agent (r=-0.21, p=0.01), scan-to-first-reversal-agent (r=-0.27, p=0.001) and scan-to-prothrombin-complex-concentrate (PCC) (r=-0.33, p=0.001) times. In the 2013-2018 cohort, WRICH had significantly slower DNT, door-to-scan time and scan-to-needle time compared to DRICH and IS thrombolysis (all p<0.001). There was no statistical difference between DRICH and IS. Median DNT was 183 minutes for WRICH, 72 minutes for DRICH and 52 minutes for IS. Median time to repeat international normalised ratio was 231 minutes, and the median time to repeat thrombin clotting time was 825 minutes., Conclusion: Door-to-any-reversal-agent and scan-to-PCC times have improved over time, but they remain significantly longer than IS thrombolysis times. Monitoring of reversal is inadequate, particularly for WRICH receiving PCC., Competing Interests: Nil.

Background: In patients on anticoagulant treatment, the major bleeding (MB) definition released by the International Society of Thrombosis and Haemostasis (ISTH) is widely accepted. However, this definition identifies MBs with highly variable short-term risk of death., Objectives: The study aims were to derive and validate a classification of ISTH-defined MBs for the risk of short-term death., Methods: Consecutive patients admitted for ISTH-defined MB occurring while on treatment with oral anticoagulants were included in the study and divided into a derivation and a validation cohort. Death within 30 days was the primary study outcome., Results: Among 1077 patients with MB, 64/517 and 63/560 patients in the derivation and validation cohort died, respectively. In the derivation cohort, Glasgow coma scale (GCS) <14 and shock were predictors of death; critical site bleeding and hemoglobin decrease ≥2 g/dL, or transfusion ≥ 2 units were not. GCS <14 (hazard ratio [HR], 8.67; 95% confidence interval [CI], 3.93-19.13) was predictor of death in intracranial hemorrhage (ICH) and shock at admission (HR, 4.84; 95% CI, 2.01-11.70) and pericardial bleeding (HR, 11.37; 95% CI, 1.33-97.31) in non-ICH MBs. The predictive value of GCS <14 in ICH and shock and pericardial bleeding in non-ICH MBs was confirmed in the validation cohort. None of the patients with isolated ocular or articular bleeding died. A prognostic classification of ISTH-defined MBs for the risk of short-term death is proposed as "serious," "severe," and "life-threatening" (ICH with GCS <14 or non-ICH with shock) MBs., Conclusion: According to our study, ISTH-defined MBs can be stratified for the risk of death within 30 days., (© 2020 International Society on Thrombosis and Haemostasis.)

Pilocytic astrocytomas comprise the most common central nervous system tumour during childhood and have an excellent response to surgical treatment in this population. The tumour incidence decreases with age, whereas more aggressive behaviour tends to increase. Haemorrhage as a presenting feature of pilocytic astrocytomas is a rare phenomenon, especially in the adult population. We present a case of a 55-year-old patient with progressive headaches and dizziness. MRI confirmed a sellar and predominantly retrochiasmal suprasellar lesion with heterogeneous signal, enhancement and blood products. Management via transsphenoidal approach was performed, and histopathology revealed the unexpected diagnosis of haemorrhagic pilocytic astrocytoma. Haemorrhagic pilocytic astrocytoma is an infrequent entity in the adult population and it is essential to recognise the peculiarities regarding diagnostic evaluation and management, which differ from the paediatric population. During adulthood, this tumour carries an overall unfavourable prognosis, with higher rates of progression and recurrence., Competing Interests: Competing interests: RH, senior author of the above-mentioned manuscript, is consultant for Covidien, Stryker, Codman and MicroVention., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Brainstem hemorrhage is presumed to be invariably associated with a poor prognosis in people with spontaneous hypertensive cerebral hemorrhage. The optimal timing of tracheostomy placement in brainstem hemorrhage patients, who generally require endotracheal intubation for airway protection, remains uncertain. Our research aim was to analyze the impact of early tracheostomy versus late tracheostomy on brainstem hemorrhage patients related outcomes and prognostic factors at 30 days. We identified early tracheostomy and how it could benefit the patients with brainstem hemorrhage and ameliorate the predictors of functional recovery at 30 days. Data on 136 patients with brainstem hemorrhage and Glasgow Coma Scale score ≤ 8, were retrospectively collected from 2012 to 2019. Patients were divided into the early tracheostomy group and the late tracheostomy group. Patients in the early tracheostomy group had a significantly lower neurosurgical intensive care unit stay (both overall and survival) compared with the late tracheostomy group (15.6 days vs. 19.0 days, P = 0.041, overall and 14.5 vs. 19.5 days, P = 0.023, survival). Also, the good outcomes (modified Rankin Score ≤ 3) were higher in the early tracheostomy group ( P = 0.036). Multivariate analysis demonstrated that less hemorrhagic volume, high Glasgow Coma Scale score on admission, young age, and early tracheostomy were significantly associated with a better 30-day functional outcome. In conclusion, an early tracheostomy in patients with brainstem hemorrhage can reduce neurosurgical intensive care unit stay, and in addition to improvements in prognosis at 30 days., Competing Interests: All authors declare no conflicts of interest., (© 2020 Ding et al. Published by IMR press.)

Purpose: This study aimed to identify independent predictors for the risk of hemorrhagic transformation (HT) in arterial ischemic stroke (AIS) patients., Methods: Consecutive patients with AIS due to large artery occlusion in the anterior circulation treated with mechanical thrombectomy (MT) were enrolled in a tertiary stroke center. Demographic and medical history data, admission lab results, and Circle of Willis (CoW) variations were collected from all patients., Results: Altogether, 90 patients were included in this study; among them, 34 (37.8%) had HT after MT. The final pruned decision tree (DT) model consisted of collateral score and platelet to lymphocyte ratios (PLR) as predictors. Confusion matrix analysis showed that 82.2% (74/90) were correctly classified by the model (sensitivity, 79.4%; specificity, 83.9%). The area under the ROC curve (AUC) was 81.7%. The DT model demonstrated that participants with collateral scores of 2-4 had a 75.0% probability of HT. For participants with collateral scores of 0-1, if PLR at admission was <302, participants had a 13.0% probability of HT; otherwise, participants had an 75.0% probability of HT. The final adjusted multivariate logistic regression analysis indicated that collateral score 0-1 (OR, 10.186; 95% CI, 3.029-34.248; p < 0.001), PLR (OR, 1.005; 95% CI, 1.001-1.010; p = 0.040), and NIHSS at admission (OR, 1.106; 95% CI, 1.014-1.205; p = 0.022) could be used to predict HT. The AUC for the model was 0.855, with 83.3% (75/90) were correctly classified (sensitivity, 79.4%; specificity, 87.3%). Less patients with HT achieved independent outcomes (mRS, 0-2) in 90 days (20.6% vs. 64.3%, p < 0.001). Rate of poor outcomes (mRS, 4-6) was significantly higher in patients with HT (73.5% vs. 19.6%; p < 0.001)., Conclusion: Both the DT model and multivariate logistic regression model confirmed that the lower collateral status and the higher PLR were significantly associated with an increased risk for HT in AIS patients after MT. PLR may be one of the cost-effective and practical predictors for HT. Further prospective multicenter studies are needed to validate our findings., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Feng et al.)

Background: Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic., Methods: Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic., Results: A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 ( P =0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city ( P <0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale., Conclusions: Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.

Objective: Altered mental status (AMS) is one of the most common symptoms in the febrile elderly. Brain imaging tests are an important tool for diagnosing AMS patients. However, these may be prescribed unnecessarily in emergency departments, particularly for febrile patients with AMS for whom infection is suspected, leading to excessive radiation risk and cost. In this study, we investigated the factors that can predict clinically significant abnormal brain imaging (ABI) in the febrile elderly with AMS., Methods: This retrospective multicenter study was conducted from July 2016 to June 2019. Febrile patients over the age of 65 years with AMS who visited the emergency department of two tertiary university hospitals were enrolled. Medical records were reviewed, and laboratory results were obtained. Brain imaging results with a formal reading by a radiologist were obtained., Results: In all, 285 patients were enrolled, and 47 (16.49%) showed ABI. The most common diagnoses in patients admitted to the emergency department were intracranial hemorrhage and ischemic stroke for ABI, and pneumonia and urinary tract infection for non-ABI. In multivariate logistic regression analyses, higher systolic blood pressure (odds ratio [OR], 1.017; 95% confidence interval [CI], 1.006-1.028), lower body temperature (OR, 0.578; 95% CI, 0.375-0.892), the presence of lateralizing sign (OR, 45.676; 95% CI, 5.015-416.025), and lower Glasgow Coma Scale (OR, 0.718; 95% CI, 0.617-0.837) were significantly associated with ABI., Conclusion: Lower Glasgow Coma Scale, the presence of lateralizing sign, higher systolic blood pressure, and lower body temperature are significantly associated with ABI in febrile elderly patients with AMS., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Competing Interests: Nil.

Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non-traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d´Hebron (VdH = 76). Plasmatic levels of MMP-1, -2, -7, -9, -10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0.05-0.2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0.14 ml in haemorrhage (combined β = 0.14, 95% CI = 0.08-0.21). Likewise, mice receiving TIMP-1 (0.2 mg/Kg) showed a shorter bleeding time (p < 0.01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH.

Background: Despite many effective strategies for the prevention of recurrent stroke, individuals who survive an initial stroke have been shown to be at high risk of recurrent stroke. The aim of this study was to investigate the current status of stroke recurrence after first-ever stroke using a population-based stroke registry in Japan., Methods and results: As part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based stroke registry study that covers approximately 1.4 million residents of Shiga Prefecture, Japan. A total of 1,883 first-ever stroke survivors at 28 days was registered in 2011 and followed-up until the end of 2013. Recurrence was defined as any type of stroke after 28 days from the onset of an index event. Two-year cumulative recurrence rates were estimated using cumulative incidence function methods. Over a mean 2.1-year follow-up period, 120 patients experienced recurrent stroke and 389 patients died without recurrence. The 2-year cumulative recurrence rate was higher in patients with index ischemic stroke (6.8%) than in those with index hemorrhagic stroke (3.8%)., Conclusions: Two-year cumulative recurrence rate after first-ever stroke remained high, particularly among patients with ischemic stroke, in the present population-based registry study in a real-world setting in Japan. Further intensive secondary prevention strategies are required for these high-risk individuals.

Objective: This study aimed to analyze the risk factors of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) for idiopathic Parkinson's disease (PD)., Methods: Patients who received DBS from March 2014 to December 2016 were retrospectively analyzed. The hemorrhage index was derived by combining the hemorrhagic volume and clinical manifestations of ICH. All patients with IHC were followed up for 2 years., Results: Computed tomography showed 13 events of ICH in 11 patients (nine cases in the subthalamic nucleus), including eight cases with symptomatic hemorrhage (seven cases in the subthalamic nucleus). Hemorrhage was characterized by intracranial hematoma in the electrode puncture tract. Male sex and hypertension were significant risk factors for ICH. Hemorrhage in the preferred puncture side was significantly higher than that in the non-preferred puncture side. The mean hemorrhage index was 2.23 ± 0.83 in 11 patients, and no permanent neurological impairment was found during the 2-year follow-up. The effect of DBS on motor symptoms was similar in patients with and without ICH., Conclusion: Male sex and hypertension are risk factors of ICH after DBS in PD. The risk of hemorrhage on the first puncture site is significantly higher than that on the second puncture site.

Objective: To improve the understanding of the association between electrocardiographic (ECG) abnormalities and clinical outcomes of patients with all types of intracranial hemorrhage (ICH)., Methods: A retrospective cohort study was conducted in a tertiary healthcare hospital on patients with ICH without cardiac disease or renal disease requiring dialysis. Demographic and clinical data were collected from hospital records. ECG record were obtained within 24 hours of presentation and prior to treatment. Records were interpreted for this study by a cardiologist blinded to other data., Results: Assessment of 291 patients (228 adults and 63 children) showed that subdural hemorrhage was the most common type of ICH (31.6%) followed by intraparenchymal hemorrhage (23.0%). ECG records were available for 98 patients. ECG abnormalities were most commonly nonspecific ST-segment changes (32.6%). In adults, history of neurological disease was associated with atrioventricular block (p=.004) and QTc prolongation (p=.041). Pediatric patients exhibited associations between ST-segment changes (p=.045) and sinus tachycardia (p=.027) and type of ICH. However, ECG changes were not statistically associated with clinical outcomes in adults or children., Conclusion: Significant ECG changes frequently occurred in patients with all types of ICH but did not consistently predict the outcome in this study. Close observation of patients is still recommended to detect ECG changes that could affect the treatment.

Background: Stroke has become the leading cause of death in China. This study aimed to assess the age-period-cohort (APC) effects on the long-term trends of type-specific stroke morbidity and mortality in China between 1993 and 2017., Methods and results: The data were obtained from the Global Burden of Disease 2017 (GBD 2017) and were analyzed with the age-period-cohort framework. The net drifts of mortality were below 0 (hemorrhagic stroke [HS]: males: -1.620%, females: -3.531%; ischemic stroke [IS]: males: -1.041%, females: -3.002%), and the local drift values were below 0 in all age groups and for both genders. The net drifts of HS incidence were below 0 (males: -1.412%, females: -2.688%), while those of IS were above 0 (males: 1.425%, females: 1.117%). Period effect of mortality showed similar monotonic downward patterns for both genders, with a faster decrease for females than for males. Period effect of incidence showed a declined trend of incidence for HS, but an elevated trend for IS in both genders. After controlling for age and period effects, cohort effects on incidence found a monotonic decline trend for HS, while for IS, an elevated trend was found at first to peak during the 1950-1970 s, then declined steadily afterwards. Cohort effects on mortality showed a monotonic declined trend., Conclusions: By using Age-Period-Cohort (APC) analysis, a disparity between HS and IS was identified. Different prevention and control strategies should be used depending on the subtypes of stroke.

Antiplatelet agents have been administered to patients with acute ischemic stroke after endovascular therapy. This study was designed to provide initial data to compare thromboelastography (TEG) with the conventional coagulation test (CCT) to analyze the coagulation function of antiplatelet drugs in such patients.The present retrospective cohort study included 240 patients who received endovascular therapy from September 2012 to December 2017. The baseline and clinical characteristics of these patients were collected with respect to TEG (parameters: R, K, maximal amplitude (MA), and α angle) and CCT (parameters: PT, activated partial thromboplastin time (APTT), fibrinogen (FIB), international normalized ratio (INR), and platelet count (PLT)) on day 5 after aspirin and clopidogrel post-endovascular interventions. The correlation and agreement of these 2 detecting methods were analyzed. Additionally, the area under the receiver operating characteristic curve (AUROC) was used to analyze the effectiveness of these 2 methods in detecting unfavorable clinical outcomes, including symptomatic intracranial hemorrhage and early neurological deterioration.The 3 pairs of parameters (R and APTT, K and APTT, and α angle and FIB) were in agreement for identifying hypercoagulability, while R and APTT, K and APTT, K and PLT, and α angle and PLT were in agreement for identifying hypocoagulability. The AUROC of parameter R for detecting symptomatic intracranial hemorrhage was 0.817, while that of parameter FIB for predicting early neurological deterioration was 0.887.Parameter FIB derived from CCT might be advantageous for evaluating early neurological deterioration, while parameter R detected by TEG might be superior for evaluating symptomatic intracranial hemorrhage.