Intracranial Hemorrhage Volume Research Articles

Total intracranial hemorrhage volume measurement summating all compartments best in traumatic and nontraumatic intracranial bleeding.

The ANNEXA-4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. Thirty patients were randomly selected from the ANNEXA-4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty-eight different ANNEXA-4 subjects were also randomly selected to assess intra-rater reliability of total ICrH volume measurement change at baseline and 12-h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA-4. Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

YTHDF2-regulated matrilin-3 mitigates post-reperfusion hemorrhagic transformation in ischemic stroke via the PI3K/AKT pathway.

Hemorrhagic transformation can complicate ischemic strokes after recanalization treatment within a time window that requires early intervention. To determine potential therapeutic effects of matrilin-3, rat cerebral ischemia-reperfusion was produced using transient middle cerebral artery occlusion (tMCAO); intracranial hemorrhage and infarct volumes were assayed through hemoglobin determination and 2,3,5-triphenyltetrazoliumchloride (TTC) staining, respectively. Oxygen-glucose deprivation (OGD) modeling of ischemia was performed on C8-D1A cells. Interactions between matrilin-3 and YTH N6-methyladenosine RNA binding protein F2 (YTHDF2) were determined using RNA immunoprecipitation assay and actinomycin D treatment. Reperfusion after tMCAO modeling increased hemorrhage, hemoglobin content, and infarct volumes; these were alleviated by matrilin treatment. Matrilin-3 was expressed at low levels and YTHDF2 was expressed at high levels in ischemic brains. In OGD-induced cells, matrilin-3 was negatively regulated by YTHDF2. Matrilin-3 overexpression downregulated p-PI3K/PI3K, p-AKT/AKT, ZO-1, VE-cadherin and occludin, and upregulated p-JNK/JNK in ischemic rat brains; these effects were reversed by LY294002 (a PI3K inhibitor). YTHDF2 knockdown inactivated the PI3K/AKT pathway, inhibited inflammation and decreased blood-brain barrier-related protein levels in cells; these effects were reversed by matrilin-3 deficiency. These results indicate that YTHDF2-regulated matrilin-3 protected ischemic rats against post-reperfusion hemorrhagic transformation via the PI3K/AKT pathway and that matrilin may have therapeutic potential in ischemic stroke.

Abstract 2: Intracranial Hemorrhage Managed By A Mobile Stroke Unit

Background: Mobile stroke units (MSUs) improve outcomes in thrombolytic-eligible ischemic stroke patients. Outcomes of MSU management in patients with intracranial hemorrhage (ICH) have not been reported. Methods: We conducted a retrospective review of ICH patients enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management (SM). The primary outcome was utility weighted modified Rankin Scale (uw-mRS) at 90 days; secondary outcomes were hematoma expansion, length of inpatient stay, favorable discharge disposition or 90-day mRS, and mortality. Groups were compared using Chi-square or Fisher’s exact tests for categorical variables, and two sample t-test or Wilcoxon rank sum test for continuous variables. Adjusted analysis was performed to evaluate the relationship between the intervention group and uw-mRS at 90 days. Kaplan-Meier curves and log-rank test were used to compare the survival by 90 days between groups. Results: 201 ICH patients were identified; 102 in the MSU and 99 in the SM groups. MSU patients had more antiplatelet/antithrombotic (AP/AT) use (30.4% vs 15.2%, p=0.016); edema was more frequent in the SM group (72.7% vs 52.0%, p = 0.004). Initial ICH volume was similar between MSU and SM groups (11.50 mL [5.0, 22.0] vs. 9.0 mL [5.0, 20.0], p = 0.62). Anti-hypertensives were given earlier on the MSU (39.0 min [31.00, 45.00] vs 61.0 min [46.50, 75.25], p&lt;0.001), and resulted in shorter time to systolic blood pressure (SBP) &lt; 150mmHg (52 min vs. 121 min, p&lt;0.001). The mean uw-mRS at 90 days was 0.364 ± 0.361 in the MSU and 0.465 ± 0.360 in the SM group (p=0.50, adjusted for AP/AT and edema). There was no difference in hematoma expansion, length of stay, discharge disposition or 90-day mRS. Higher mortality was noted after 5 days post-ictus in the MSU group (26.5% vs. 14.1%, p = 0.04). Conclusion: In ICH patients, MSU management resulted in faster treatment and time to target SBP with similar clinical outcomes except higher late mortality. Further study of the impact of prehospital ICH management including BP reduction and AT/AP reversal are required.

Predictors of Intracranial Hemorrhage Volume Expansion in Patients Receiving Factor Xa Inhibitors in ANNEXA‐4: Time and Severity Matter Most

Background Andexanet alfa, a specific reversal agent for factor Xa inhibitors, resulted in effective hemostasis in 79% of patients with intracranial bleeding in the ANNEXA‐4 (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors) trial (NCT02329327). However, little is known about predictors associated with hematoma expansion in patients with factor Xa inhibitor–associated intracranial hemorrhage (ICrH) receiving andexanet alfa. Methods The ANNEXA‐4 trial was a prospective, single‐arm, open‐label study of andexanet alfa in patients with acute major bleeding within 18 hours after taking a factor Xa inhibitor. Hematoma volumes at baseline and 12 hours after andexanet alfa treatment were measured using a computerized‐assisted volumetric method. Univariable and multivariable logistic regression analyses of clinical and nonclinical parameters were performed to identify factors predictive of different volumes of hematoma expansion. To this end, an ICrH Expansion Scale was developed. Results Overall, 305 ANNEXA‐4 study patients with baseline and follow‐up imaging were included, 15.7% of whom showed evidence of any ICrH expansion ≥6‐mL. Patients with ≥6‐mL ICrH expansion had a significantly ( P&lt; 0.05) higher proportion of ICrH with multiple compartment involvement (36% versus 14.3%); shorter times from symptom onset to baseline computed tomography (median, 1.6 hours [interquartile range (IQR), 1.2–4.3 hours] versus 3.7 hours [IQR, 1.6–7.0 hours]); lower Glasgow Coma Scale scores (14 [IQR, 12–15] versus 15 [IQR, 14–15]); higher systolic blood pressure 15 minutes before andexanet alfa bolus (mean, 151.6 mm Hg [SD, 24.1 mm Hg] versus 143.3 mm Hg [SD, 22.3 mm Hg]); and larger median baseline ICrH volumes (29.3 mL [IQR, 13.3–50.8 mL] versus 8.6 mL [IQR, 2.1–22.4 mL]). Multivariable analysis confirmed shorter symptom onset‐to‐computed tomography time and larger ICrH volume as independent predictors of ≥6‐mL growth and ICrH Expansion Scale change. Lower Glasgow Coma Scale showed a trend ( P = 0.06) as an independent predictor of ≥6‐mL growth but was an independent predictor of ICrH Expansion Scale change. Conclusion Shorter time from symptom onset to computed tomography, larger hematoma volumes, and lower Glasgow Coma Scale score at presentation increased the risk of ICrH expansion in patients with factor Xa inhibitor–associated ICrH treated with andexanet alfa.

Hyponatremia is associated with unfavorable outcomes after reperfusion treatment in acute ischemic stroke.

In patients with acute ischemic stroke, hyponatremia (plasma sodium < 136 mmol/L) is common and associated with unfavorable outcomes. However, data are limited for patients who underwent intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Therefore, our aim was to assess the impact of hyponatremia on postreperfusion outcomes. We analyzed data of consecutive patients who presented with acute ischemic stroke and were treated with IVT and/or EVT at Isala Hospital, the Netherlands, in 2019 and 2020. The primary outcome measure was the adjusted common odds ratio (acOR) for a worse modified Rankin Scale (mRS) score at 3-month follow-up. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, infarct core, and penumbra volumes. Of the 680 patients (median age = 73 years, 49% female, median National Institutes of Health Stroke Scale = 5), 430 patients (63%) were treated with IVT, 120 patients (18%) with EVT, and 130 patients (19%) with both. Ninety-two patients (14%) were hyponatremic on admission. Hyponatremia was associated with a worse mRS score at 3 months (acOR = 1.76, 95% confidence interval [CI] = 1.12-2.76) and in-hospital mortality (aOR = 2.39, 95% CI = 1.23-4.67), but not with symptomatic intracranial hemorrhage (OR = 1.17, 95% CI = 0.39-3.47). Hyponatremia was also associated with a larger core (17.2 mL, 95% CI = 2.9-31.5) and core to penumbra ratio (55.0%, 95% CI = 7.1-102.9). Admission hyponatremia in patients with acute ischemic stroke treated with IVT and/or EVT was independently associated with unfavorable postreperfusion outcomes, a larger infarct core, and a larger core to penumbra ratio. Future studies should address whether correction of hyponatremia improves the prognosis.

Automatic segmentation of intracranial hemorrhage using coarse and fine deep learning models

To save patients’ lives, it is important to go for an early diagnosis of intracranial hemorrhage (ICH). For diagnosing ICH, the widely used method is non-contrast computed tomography (NCCT). It has fast acquisition and availability in medical emergency facilities. To predict hematoma progression and mortality, it is important to estimate the volume of intracranial hemorrhage. Radiologists can manually delineate the ICH region to estimate the hematoma volume. This process takes time and undergoes inter-rater variability. In this research paper, we develop and discuss a fine segmentation model and a coarse model for intracranial hemorrhage segmentations. Basically, two different models are discussed for intracranial hemorrhage segmentation. We trained a 2DDensNet in the first model for coarse segmentation and cascaded the coarse segmentation mask output in the fine segmentation model along with input training samples. A nnUNet model is trained in the second fine stage and will use the segmentation labels of the coarse model with true labels for intracranial hemorrhage segmentation. An optimal performance for intracranial hemorrhage segmentation solution is obtained.

Prognosticators of Functional Outcome After Supratentorial Minimally Invasive Intracranial Hemorrhage Evacuation With Tubular Retractor Systems.

Prognosticators of good functional outcome after minimally invasive surgical (MIS) intracranial hemorrhage (ICH) evacuation are poorly defined. This study aims to investigate clinical and radiographic prognosticators of poor functional outcome after MIS evacuation of ICH with tubular retractor systems. Single-center retrospective review of adult (age ≥18 years) patients who underwent surgical evacuation of a spontaneous supratentorial ICH evacuation using tubular retractors from 2013 to 2022 was performed. Clinical and radiographic factors, such as antiplatelet/anticoagulant use, initial NIH Stroke Scale, ICH score, premorbid modified Rankin Scale (mRS), intraventricular hemorrhage (IVH) severity according to the modified Graeb scale, and preoperative/postoperative ICH volume, were collected. The main outcome was poor functional outcome, defined as mRS score of 4-6 within 1 year postoperatively. Eighty-eight patients were included. Clinical follow-up data were available for 64 (73%) patients. Of those, 43 (67%) had a poor functional outcome. On multivariate Cox regression, postoperative ICH volume ≥15 mL (hazard ratio [HR] = 2.46 [95% CI: 1.25-4.87]; P = .010) and higher modified Graeb score (HR = 1.04 [95% CI: 1-1.1]; P = .035] significantly increased the risk of poor functional outcome. Elevated postoperative ICH volume was predicted by the presence of lobar ICH (vs nonlobar, OR = 3.32 [95% CI: 1.01-11.55]; P = .043) and higher preoperative ICH volume (OR = 1.05 [1.02-1.08]; P < .001). A minimum of 60% ICH evacuation yielded an improvement in mRS 4-6 rates (HR 0.3 [95% CI: 0.1-0.8], P = .013). In patients without IVH and with a >80% ICH evacuation, the rate of mRS 4-6 was 42% compared with 67% in the whole patient sample ( P = .017). Increased IVH volumes and residual postoperative ICH volumes are associated with poor functional outcome after MIS ICH evacuation. Postoperative ICH volume was associated with lobar ICH location as well as preoperative ICH volume. These factors may help to prognosticate patient outcomes and improve selection criteria for MIS ICH evacuation techniques.

Clinical characteristics and outcomes of patients with intracerebral hemorrhage after acute myocardial infarction

Data regarding patients with intracranial hemorrhage (ICH) following acute myocardial infarction (AMI) is scarce. This study aims to investigate the incidence, clinical characteristics, prevention, treatment, and prognosis of ICH in patients with AMI.Among 5257 patients with AMI, 14 cases (0.27%) experienced ICH following AMI, including 11 males and three females. In-hospital mortality occurred in eight patients (57.1%), all of whom experienced sudden loss of consciousness. Six patients (42.6%) were classified as high or very high risk according to CRUSADE score, and seven patients (50.0%) were classified as high risk according to Academic Research Consortium for High Bleeding Risk (ARC-HBR). The CRUSADE and ARC-HBR scores can complement each other in risk assessment. All in-hospital deaths occurred within four days of ICH onset; The volume of ICH in patients who died in the hospital was significantly higher than in those who survived and were discharged, with 30 ml possibly serving as a threshold.The incidence of ICH following myocardial infarction is low; however, the mortality rate is extremely high, presenting considerable challenges for clinical treatment. Prevention, early detection, and prompt symptomatic management are essential for improving patient outcomes.

Neurosurgical Consequences of e-Scooter Use: Strategies to Prevent Neurological Injury.

Rideshare electric scooter accidents have led to increasing emergency department (ED) visits and neurosurgical consultations. This study categorizes e-scooter-related injuries requiring neurosurgical consultation at a single level 1 trauma center. Patients who required neurosurgical consultation from June 2019 to June 2021 with a positive finding on computed tomography imaging were selected for review of patient and injury characteristics, resulting in a sample size of 50 cases. Average patient age was 36.9 (15-69) years, and 70% were male. Seventy-four percent of patients were under the influence of alcohol and 12% illicit drugs. None (0%) were helmeted. Seventy-eight percent of accidents occurred between 6:00 pm and 6:00 am. Twenty-two percent of patients required surgical intervention by craniotomy/craniectomy, and 4% required intracranial pressure monitor placement. Average intracranial hemorrhage volume was 17.8 cc (trace to 125). Volume of hemorrhage was associated with the need for an intensive care unit (ICU) stay (odds ratio [OR] = 1.01; p = 0.04), need for surgical intervention (OR = 1.007; p = 0.0001), and mortality (1.816; p < 0.001) and trended toward, but did not reach significance for, overall poor outcome (OR = 1.63; p = 0.06). Sixty-two percent of this patient pool required ICU admission. Average length of ICU stay was 3.5 days (0-35), and average length of hospital stay was 8.3 days (0-82). Mortality in this series was 8%. Lower admission Glasgow Coma Scale (OR = 0.974; p < 0.001) and increased volume of hemorrhage (OR = 1.816; p < 0.001) were associated with increased risk of mortality in the linear regression analysis. Electric scooters have become prevalent in most urban centers, and accidents are a potential source of severe intracranial injury requiring extended ICU and hospital stays, surgical intervention, and sometimes resulting in long-term morbidity and/or mortality. Injuries often occur in the evening hours and are often associated with alcohol/drug use and lack of helmet use. Policy changes to help mitigate the risk of these injuries are recommended.

Abstract Number ‐ 246: Quantification of Hemorrhage Volume for Prediction of Complications of Aneurysmal Subarachnoid Hemorrhage

Introduction Aneurysmal subarachnoid hemorrhage (aSAH) can lead to life‐threatening complications such as vasospasm and hydrocephalus. The incidence of these events is influenced by the volume of intracranial hemorrhage. The Fisher score is a subjective adjudication of SAH volume. We developed an objective semi‐automated method to quantify the volume of intracranial hemorrhage. Moreover, we evaluated the association of aSAH volume with vasospasm and hydrocephalus. Methods A custom semi‐automated image segmentation algorithm quantifying aSAH volume was implemented in MATLAB. The volume of hemorrhage was retrospectively measured from non‐contrast brain CT scans with Fisher grade ≥ 2. The algorithm utilized region‐growing and 3D k‐means clustering. Performance was validated against the average of two sets of hemorrhage volumes manually measured. These measurements were obtained from two independent raters who selected regions of interest spanning areas of hemorrhage. The association between blood volume and clinical outcome (hydrocephalus or vasospasm) was evaluated using ROC analysis. Results Fifty‐seven patients were included in this study and 10 patients were used for validation of our method. The ICC between raters for manual measurements of hemorrhage in the validation group was 0.988 (CI: (0.911, 0.997), p &lt; 0.001). Validation of semi‐automated versus manual methods resulted in an ICC of 0.961 (CI: (0.756, 0.991), p &lt; 0.001). Bland‐Altman analysis revealed that the algorithm slightly underestimated blood volume (mean difference = ‐4.11 mL). Hemorrhage volume discriminated for the development of vasospasm (AUC = 0.781) and hydrocephalus (AUC = 0.776). Conclusions Volume of hemorrhage is a key factor that influences the incidence of complications in aSAH. We developed and validated a semi‐automated algorithm for quantifying the volume of aSAH. Vasospasm and hydrocephalus were associated with greater amounts of intracranial blood. Objective measurements of aSAH volume can aid in adjudicating risk of complications among patients with aSAH.

A Radiologist Approach to Acute Parenchymal Hemorrhages: How to Intercept Shrouded Dragons

Primary intracranial hemorrhage (ICH) or hemorrhagic strokes etiology is unknown in the initial stage. The location, size and morphology are three important factors when reading the scan of intracranial hemorrhage. Clinical ICH score correlates with a 30 day mortality which takes into consideration admission Glasgow coma scale,&gt;80 years old, ICH volume, infratentorial and presence of intraventricular hemorrhage. Management includes finding the cause of hemorrhage or symptomatic management.

The comprehensive comparison of imaging sign from CT angiography and noncontrast CT for predicting intracranial hemorrhage expansion: A comparative study.

Expansion of intracranial hemorrhage (ICH) is an important predictor of poor clinical outcomes. Various imaging markers on non-contrast computed tomography (NCCT) or computed tomographic angiography (CTA) have been reported as predictors of ICH expansion. We aimed to compare the associations between various CT imaging markers and ICH expansion. Patients with spontaneous ICH who underwent initial NCCT, CTA, and subsequent NCCT between January 2016 and December 2019 were retrospectively identified. ICH expansion was defined as a volume increase of > 33% or > 6 mL. We analyzed the presence of imaging markers such as the black hole sign, blend sign, island sign, or swirl sign on initial NCCT or spot sign on CTA. An alternative free-response receiver operating characteristic curve analysis was performed using a 4-point scoring system based on the consensus of the reviewers. The predictive value of each marker was assessed using univariate and multivariate logistic regression analyses. A total of 250 patients, including 60 (24.0%) with ICH expansion, qualified for the analysis. Among the patients with spontaneous ICH, 118 (47.2%) presented with a black hole sign, 52 (20.8%) with a blend sign, 93 (37.2%) with an island sign, 79 (31.6%) with a swirl sign, and 56 (22.4%) with a spot sign. In univariate logistic regression, the initial ICH volume (P = .038), initial intraventricular hemorrhage (IVH) presence (P < .001), swirl sign (P < .001), and spot sign (P < .001) were associated with ICH expansion. Multivariate analysis confirmed that the presence of initial IVH (odds ratio, 4.111; P = .002) and spot sign (odds ratio, 109.5; P < .001) were independent predictors of ICH expansion. Initial ICH volume, IVH, swirl sign, and spot sign are associated with ICH expansion. The presence of spot signs and IVH were independent predictors of ICH expansion.

Antiplatelet Medications and Intracranial Hemorrhage in Patients with Primary Brain Tumors

Background: Intracranial hemorrhage (ICH) frequently complicates the clinical course of patients with brain tumors. These bleeding events carry significant morbidity and portend poor survival outcomes. The frequent need to prescribe antiplatelet medications, including aspirin and P2Y12 inhibitors, further complicates the risk of hemorrhage in this patient population with concurrent cardiovascular or cerebrovascular indications. The impact of these agents on rates of ICH in the general population has previously been studied and remains equivocal. Whether antiplatelet medications increase the risk of ICH in primary brain tumors remains undefined, and there is limited evidence to guide their use in this setting. Aims: We investigated whether patients with primary brain tumors receiving antiplatelet medications had an increased risk of ICH compared to a matched cohort. Methods: This study was a retrospective matched cohort study of patients with diagnosis of primary brain tumor treated at our center between 2010-2021. Patients with metastatic brain disease were excluded. Patients treated with antiplatelet medications (aspirin and P2Y12 inhibitors) were matched with patients not receiving these agents. Matching was performed using a scoring algorithm that ranked controls according to cancer type, exposure to anticoagulation, age, sex, and year of diagnosis. The primary end point of the study was the cumulative incidence of ICH at 1 year after tumor diagnosis. Radiologic images of bleeding events were assessed by a neuroradiologist blinded to the study cohort allocation. ICH was defined as trace (< 1 cm3), measurable (1 - 10 cm3), or major (symptomatic or > 10 cm3), with bleed volumes defined by the ½ ABC method. Results: The study population included 398 patients with primary brain tumors. 134 patients were exposed to antiplatelet medications. Of these 134 patients, 123 were exposed to aspirin alone, 10 were exposed to dual antiplatelet therapy (aspirin and P2Y12 inhibitor), and 1 received P2Y12 inhibitor alone. The most common malignancy in the study cohort was glioma (78%). The cumulative incidence of ICH at 1 year was 10.8% (95% CI, 5.2 - 16.3) in those receiving antiplatelet agents compared with 13.6% (95% CI, 9.0 - 18.2) in the control population (P = 0.48, Gray test). The cumulative incidence of major ICH at 1 year was 7.2% (95% CI, 2.6 - 11.7) in those receiving antiplatelet agents compared to 4.8% (95% CI, 2.0 - 7.5) among controls (P = 0.48, Gray test) (Figure 1). The distribution of ICH volume size was similar in the 2 groups (Table 1). The combined use of antiplatelet medication with anticoagulation did not increase the risk of total ICH compared to patients that did not receive either (HR 1.53, 95% CI 0.74 - 3.17) but did increase the risk of major ICH compared with patients that did not receive either (HR 3.41, 95% CI 1.04 - 11.19, P = 0.043). Median overall survival in patients exposed to antiplatelet medications was 28.3 months (95% CI, 19.6 - 47.9) compared to 20.8 months in those not exposed (95% CI, 16.6 - 30.6, P = 0.09). Conclusions: In patients with primary brain tumors, administration of antiplatelet medications was not associated with an increased incidence of ICH. However, there was an increased risk of major ICH for patients exposed to both antiplatelet medication and anticoagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Integral neuroimaging criteria for predicting the outcome of the acute period of spontaneous supratentorial intracerebral hemorrhage on the background of conservative therapy

The aim of the study was to develop criteria for predicting the outcome of the acute period of spontaneous supratentorial intracerebral hemorrhage (SSICH) on the background of conservative therapy, taking into consideration the lesion localization in conjunction with neuroimaging parameters of the quantitative severity assessment of the damage to cerebral structures. Materials and methods. Prospective cohort examination of 314 patients in acute period of SSICH on the ground of conservative treatment. Clinical and neurological examination consisted of using the Full Outline of Unresponsiveness coma scale and NIHHS, neuroimaging with the help of computed tomography with detection of SSICH localization, volume of intracranial hemorrhage, secondary intraventricular hemorrhage and midline shift. Disease acute period outcome was evaluated on the 21st day by the Rankin scale. Results. It was detected that integrated neuroimaging SSICH’s type considering its localization and quantitative severity estimation of cerebral structure injury was closely associated with the disease acute period outcome on the ground of conservative therapy (χ2 Pearson = 308.6, Р &lt; 0.0001). Thus, mortality rate was the highest in patients with posteromedial type of thalamic hemorrhage (50.0 %), global type of thalamic hemorrhage (91.7 %) and massive type of striatocapsular hemorrhage (89.8 %). Unfavorable functional outcome as the modified Rankin scale score 4–5 on 21st disease day predominated among patients with posterolateral types of thalamic hemorrhage (76.5 %) and striacapsular hemorrhage (64.3 %). Whereas the frequency of favorable outcome was the highest among patients with anterior/dorsal type of thalamic hemorrhage (100.0 %), posteromedial (88.0 %), middle (95.0 %), lateral types of striatocapsular hemorrhage (61.9 %) and lobar (74.5 %) hemorrhage. Conclusions. Posteromedial type of thalamic hemorrhage, global type of thalamic hemorrhage and massive type of striatocapsular hemorrhage are the predictors of lethal outcome of the acute period of SSIСH on the background of conservative therapy. Criteria for unfavorable short-term functional outcome are posterolateral types of thalamic and striatocapsular hemorrhage, while anterior/dorsal type of thalamic hemorrhage, posteromedial/middle type of striatocapsular hemorrhage and lobar hemorrhage are associated with favorable outcome of the acute period of the disease.

Radiographic Predictors of Shunt Dependency in Intracranial Hemorrhage With Intraventricular Extension.

BackgroundIntracranial hemorrhage (ICH) may be complicated by intraventricular hemorrhage (IVH) and hydrocephalus, which can require the placement of a ventriculoperitoneal shunt (VPS). ICH and IVH risk scores using radiographic and clinical characteristics have been developed but utilization for assessment of future need for VPS placement is limited.MethodsThis is a single-institution retrospective review for patients with primary ICH with IVH from 2018-2020. Initial CTs and charts were analyzed to determine ICH, IVH, LeRoux and Graeb scores, Evans’ index, ICH and IVH volumes, and comorbidities. Outcomes including Glasgow coma scale (GCS), National Institute of Health Stroke Scale (NIHSS), length of stay, and shunt placement were evaluated with bivariate correlations, t-tests, chi-squared tests, and receiver operating characteristic (ROC) curves (p=0.05).ResultsA total of 130 patients were included of which 102 underwent full treatment beyond hospital day one. VPS placement was significantly associated with longer length of stay (p<0.001), discharge NIHSS (p=0.001), arrival Evans’ index (p<0.001), IVH (p=0.033), LeRoux (p=0.049), but not comorbidities, ICH score, or admission GCS. When treated beyond hospital day one, Evans’ index (p<0.001), IVH volume (p=0.029), Graeb (p=0.0029), IVH (p=0.004), Slice (p=0.015), and Leroux scores (p=0.006) were associated with shunt placement of which an Evans’ index of 0.31 or greater had highest sensitivity and specificity (area under the ROC curve (AUC) 0.81, sensitivity 81%, specificity 0.76).ConclusionsThe higher the Evans’ index, Graeb, IVH, Slice, and LeRoux scores on admission, the higher the risk of shunt dependency in patients undergoing full treatment beyond hospital day one. Admission imaging scores significantly predict the development of shunt dependence and may be considered in treatment.

Dose-dependent benefits of iron-magnetic nanoparticle-coated human umbilical-derived mesenchymal stem cell treatment in rat intracranial hemorrhage model

BackgroundThis study tested whether two doses of human umbilical-derived mesenchymal stem cells (hUC-MSCs) were superior to one dose for protecting the brain against intracranial hemorrhage (ICH) induced by intracranial injection collagenase and the capacity of ironic-magnetic-nanoparticles (Ir-MNa) coated hUC-MSCs tracked by MRI.Methods and resultsAdult male SD rats (n = 40) were equally categorized into group 1 (sham-operated-control), group 2 (ICH), group 3 [ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an extracorporeal magnet over rat head (eCMag)/administered by left internal carotid artery (LICA) at post-3 h ICH], and group 4 (ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an eCMag/administered post-3 h ICH by LICA and 24 h by IV) and euthanized by day 28. The result showed that by day 28 after ICH induction the neurological function was severely impaired in group 2 than in group 1 that was significantly improved in group 3 and further significantly improved in group 4, whereas ICH volume exhibited an opposite pattern of neurological impairment among the groups (all p < 0.0001). Brain MRI demonstrated that by 4 h after ICH, Ir-MNa-coated hUC-MSCs were abundantly identified in ischemic area in group 4. The protein expressions of inflammatory (TNF-α/MMP-9/IL-1ß/iNOS)/oxidative-stress (NOX-1/NOX-2/oxidized protein)/apoptotic (caspase-3/mitochondrial Bax/PARP)/fibrotic (Smad3/TGF-ß)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an identical pattern of neurological impairment among the groups (all p < 0.0001). The cellular expressions of inflammation (CD68+/CD11b+)/brain edema (AQP4+) biomarkers exhibited an identical pattern, whereas the neuronal-myelin (Doublecortin+/NeuN/nestin) biomarkers displayed an opposite pattern of neurological impairment (all p < 0.0001).ConclusionTwo doses of hUC-MSCs were superior to just one dose for protecting the brain against ICH-induced damage and Ir-MNa-coated hUC-MSCs offered a well adopted method for tracking hUC-MSCs homing into the brain.

Abstracts from The 39th Annual Symposium of the National Neurotrauma Society, including the AANS/CNS Joint Section on Neurotrauma and Critical Care

Abstracts from The 39^th Annual Symposium of the National Neurotrauma Society, including the AANS/CNS Joint Section on Neurotrauma and Critical Care

Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. This single-center retrospective cohort study included patients ≥ 18years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0mL NR vs. 1mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis

BackgroundThere is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban. ObjectiveThe objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban. MethodsThis retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration. ResultsIn total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159). Conclusion and relevanceThis study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed.