Intracranial Hemorrhage In Patients Research Articles

Abstract 51: Apoe Epsilon 4 And Risk Of Bleeding Patients With Brain Arteriovenous Malformations. A Combined Genetic Study In The Uk Biobank And All Of Us

Background: Patients with brain arteriovenous malformation (AVM) are at risk of intracranial hemorrhage (ICH). The epsilon 2 and 4 alleles within the APOE gene are well-described genetic risk factors for spontaneous, non-traumatic intraparenchymal hemorrhages. We tested the hypothesis that the APOE epsilon variants lead to higher risk of ICH in patients with AVMs. Methods: We conducted a two-stage (discovery and replication) genetic association study using individual-level data from the UK Biobank and the All of Us Research Program. We ascertained AVMs and ICH using validated ICD-9/10 codes. Genome-wide array genotyping was completed using the UK Biobank Axiom Array in the UK Biobank, and Illumina’s Global Diversity Array in All of Us. We used genotypic data on the APOE variants rs429358 and rs7412 to ascertain the epsilon 2 and 4 status. Within each study, we tested for association between APOE epsilon variants and ICH risk using multivariable logistic regression. Results: The discovery phase included 189 UK Biobank participants with an AVM (mean age 57 years, female sex 49%), including 37 (19.6%) that sustained an ICH. After adjusting by age, sex, and race/ethnicity, APOE epsilon 4 was associated with a higher risk of ICH (OR 4.20; 95%CI 1.99-9.25; p<0.001) whereas epsilon 2 was not (p>0.05). These results were replicated in 228 participants with AVMs enrolled in All of Us (mean age 56 years, female sex 66%), including 31 (13.6%) who sustained an ICH, where APOE epsilon 4 was associated with a higher risk of ICH (OR 2.73; 95%CI 1.05-7.22; p=0.038) whereas epsilon 2 was not (p>0.05). Conclusion: Among study participants with AVMs enrolled in two large population studies, the APOE epsilon 4 variants were associated higher risk of sustaining a brain bleed. These results point to shared pathophysiology with spontaneous intraparenchymal hemorrhages and provide support for further research focused on evaluating the role of APOE in risk stratification strategies.

Utility of infrascanner device in the diagnosis of intracranial hemorrhage in patients presenting to the emergency department

Utility of infrascanner device in the diagnosis of intracranial hemorrhage in patients presenting to the emergency department

Abstract TP3: Network-wide Incidence Of Intracranial Hemorrhage In Patients With Acute Ischemic Stroke Receiving Tenecteplase

Background: Intravenous tenecteplase (TNK) is currently being used as a thrombolytic agent in acute ischemic stroke (AIS) and has has been shown to be non-inferior to intravenous alteplase according to recent studies. Intracranial hemorrhage (ICH) as a complication of alteplase is approximately at 6%. The aim of our study was to determine the rate of significant ICH in patients receiving TNK indicated for AIS in a real world setting. Methods: A network-wide (3 CSCs, 6 PSCs), multicenter retrospective chart review of patients receiving TNK from February 2020 to January 2022 was performed using the Get With The Guidelines database. TNK bolus dose of 0.25mg/kg was used according to a network-wide policy. ICH was categorized using ECASS-3 criteria. Fisher exact test statistic was used to determine if a significant association existed between the presence of ICH and baseline ASPECTS score, endovascular treatment (EVT), and IV eptifibatide use. A benchmark less than 2% PH-2 incidence was set based on historical alteplase related PH-2 rates within our network. Social science statistics software was used for data analysis. Results: Out of 180 patients who received TNK, 25 subjects (13.89%) developed hemorrhagic transformation. Mean age was 71.88 (95% CI 65.54, 78.22). Forty-eight percent of subjects were female. Median ASPECTS score was 8 (95% CI 7.54, 8.78). Median 90 day mRS was 3 (95% CI 2.1, 3.9). Hemorrhagic transformation was classified as HI-1 in 5% (n=9), HI-2 in 1.7% (n=3), PH-1 in 3.8% (n=7), and PH-2 in 3.3% (n=6) subjects. No significant difference between subjects with other subtypes versus PH-2 was identified when adjusting for ASPECTS score >=7 versus <7 (Fisher value=1), EVT versus no EVT (Fisher value=0.65), or use of IV eptifibatide (Fisher value=0.06). Conclusion: Tenecteplase is associated with higher rates of PH-2 intracranial hemorrhage when compared with our benchmark rates of alteplase-related PH-2. This study is significantly limited by small sample size, retrospective nature, and uncontrolled variables. Larger, prospective studies are needed to validate our results.

Abstract TMP83: Optimal Timing For Resumption Of Anticoagulation After Intracranial Hemorrhage In Patients With Mechanical Heartvalves

Introduction: Anticoagulation in patients with acute intracranial hemorrhage (ICH) and mechanical heart valves (MHV) is often held to mitigate the risk of ICH expansion or recurrence; however there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation after ICH remains uncertain. Methods: We retrospectively studied ICH patients with MHV at two academic hospitals from April, 2000-August, 2018. The primary outcome was a composite endpoint of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post-ICH. The exposure was timing of re-initiation of anticoagulation classified as early if therapeutic anticoagulation was resumed up to 7 days after ICH; late if ≥7 and up to 30 days after ICH; and never if not resumed or resumed after 30-days post-ICH. Cox proportional hazard models were built adjusted for age, sex, and covariates significantly different in univariate analysis at a pre-specified p-value threshold of 0.05. Results: We identified 184 patients with ICH and MHV (65 anticoagulated early, 100 resumed late, 19 not resumed by day 30 post-ICH). We observed 12 AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation in the cohort was 12.7 days. Patients resumed early versus late were more likely to have atrial fibrillation (62% versus 42%), and less likely to be reversed (75% versus 94%), to undergo hematoma evacuation (23% versus 43%), have midline shift (27% versus 52.9%), and to have intracerebral involvement (26% versus 49%). There was no significant difference in the hazard of AIS, new or symptomatic ICH expansion, or the composite outcome among those resumed early versus late. Patients not resumed within 30 days post-ICH had a significantly higher risk of AIS compared to those resumed within 30 days (HR 15.9; 95% C.I.1.9-129.7, p=0.0098). Discussion: In this study of ICH patients with MHV, there was no difference in the 30-day thrombotic and hemorrhagic brain-related outcomes in patients anticoagulated within 7 days versus 7-30 days. Withholding anticoagulation within the first 30 days was associated with a significantly higher risk of AIS. Our findings provide a discrete time window to guide resumption of anticoagulation in MHV patients with ICH.

Abstract WMP35: Distinct Multivariate Models Predict 3 Month Disability Outcomes From Day 4 Modified Rankin Scale In Patients With Acute Cerebral Ischemia Vs Patients With Intracranial Hemorrhage

Background: Long-term disability after stroke is standardly assessed 3m post-onset, using the modified Rankin Scale (mRS), but clinical trial patients lost to follow-up require imputation of likely outcome. An early post-onset, e.g. day 4, mRS is often available but its utility to forecast outcome in ischemic and in hemorrhagic stroke patients has not been delineated. Methods: We analyzed all patients with acute cerebral ischemia (ACI) and with intracranial hemorrhage (ICH) enrolled in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of ordinal day 4 mRS, alone and as part of multivariate models, in predicting ordinal day 90 mRS was assessed using Spearman correlation coefficients (r s ) and kappa (chance corrected agreement) statistics. Results: Among the 1206 acute cerebral ischemic patients, age was 70.9, 45.5 % were female, and initial NIHSS was 9.28 ± 8.28. In univariate analysis, day 4 mRS and day 90 mRS correlated strongly, r s = 0.76, weighted kappa = 0.71 increasing in multivariate analysis to r s = 0.78 and weighted kappa = 0.76 (Figure 1A). Among the 367 intracranial hemorrhage patients, age was 65.4, 32.7% were female, and initial NIHSS was 18.3 ± 11. In univariate analysis, day 4 mRS and day 90 mRS also correlated moderately r s = 0.64, weighted kappa = 0.63, increasing in multivariate analysis to r s = 0.81 and weighted kappa = 0.78 (Figure 1B). In the multivariate predictive models, day 4 mRS was the most determinative variable along with age and initial NIHSS for both ICH and ACI. Conclusion: For both acute cerebral ischemia and intracranial hemorrhage patients, long-term, 3m mRS disability outcomes can be predicted well using mRS assessment on day 4, alone and even more accurately in combination with baseline prognostic variables. Age and baseline NIHSS exert more additional influence on 3m mRS outcome in ICH than ACI, likely reflecting the better functional recovery among ICH than ACI stroke survivors.

Diagnostic performance of dynamic 3D magnetic resonance angiography in daily practice for the detection of intracranial arteriovenous shunts in patients with non-traumatic intracranial hemorrhage.

Identification of treatable causes of intracranial hemorrhage (ICH) such as intracranial arteriovenous shunt is crucial to prevent recurrence. However, diagnostic approaches vary considerably across centers, partly because of limited knowledge of the diagnostic performance of first-line vascular imaging techniques. We assessed the diagnostic performance of dynamic three-dimensional magnetic resonance angiography (dynamic 3D MRA) in daily practice to detect intracranial arteriovenous shunts in ICH patients against subsequent digital subtraction angiography (DSA) as reference standard. We reviewed all adult patients who underwent first-line dynamic 3D MRA and subsequent DSA for non-traumatic ICH between January 2016 and September 2021 in a tertiary center. Sensitivity, specificity, accuracy, positive and negative predictive values of dynamic 3D MRA for the detection of intracranial arteriovenous shunt were calculated with DSA as reference standard. Among 104 included patients, 29 (27.9%) had a DSA-confirmed arteriovenous shunt [19 pial arteriovenous malformations, 10 dural arteriovenous fistulae; median onset-to-DSA: 17 (IQR: 3-88) days]. The sensitivity and specificity of dynamic 3D MRA [median onset-to-dynamic 3D MRA: 14 (3-101) h] for the detection of intracranial arteriovenous shunt were 66% (95% CI: 48-83) and 91% (95% CI: 84-97), respectively. The corresponding accuracy, positive and negative predictive values were 84% (95% CI: 77-91), 73% (95% CI: 56-90), and 87% (95% CI: 80-95), respectively. This study suggests that although first-line evaluation with dynamic 3D MRA may be helpful for the detection of intracranial arteriovenous shunts in patients with ICH, additional vascular imaging work-up should not be withheld if dynamic 3D MRA is negative. Comparative prospective studies are needed to determine the best imaging strategy to diagnose arteriovenous shunts after non-traumatic ICH.

Wrong Cohort to Reduce "Unnecessary" Computed Tomography Imaging

We commend the authors on studying a robust database of over 1000 patients taking direct oral anticoagulants (DOACs) who sustained minor head trauma in their article in the current Journal of Emergency Medicine entitled “Analysis of Clinical and Laboratory Risk Factors of Post-Traumatic Intracranial Hemorrhage in Patients on DOACs With Mild Traumatic Brain Injury: An Observational Multicenter Cohort.” The methodology was sound. We agree with excluding patients who arrived 48 h after their trauma (asymptomatic after 48 h would not require head imaging), those that took their last dose of DOAC 24 h prior to the head trauma (need for imaging does not need to factor in the risk of anticoagulation), and those that arrived with focal deficits (immediate imaging required). There was 6.8% of the cohort that sustained an intracranial hemorrhage (ICH), and 1.5% required neurosurgery or died. These numbers are consistent with prior studies. Analysis of Clinical and Laboratory Risk Factors of Post-Traumatic Intracranial Hemorrhage in Patients on Direct Oral Anticoagulants with Mild Traumatic Brain Injury: An Observational Multicenter CohortJournal of Emergency MedicinePreviewAssessing the risk of intracranial hemorrhage (ICH) in patients with a mild traumatic brain injury (MTBI) who are taking direct oral anticoagulants (DOACs) is challenging. Currently, extensive use of computed tomography (CT) is routine in the emergency department (ED). Full-Text PDF

Analysis of Clinical and Laboratory Risk Factors of Post-Traumatic Intracranial Hemorrhage in Patients on Direct Oral Anticoagulants with Mild Traumatic Brain Injury: An Observational Multicenter Cohort

BackgroundAssessing the risk of intracranial hemorrhage (ICH) in patients with a mild traumatic brain injury (MTBI) who are taking direct oral anticoagulants (DOACs) is challenging. Currently, extensive use of computed tomography (CT) is routine in the emergency department (ED). ObjectiveThis study aims to investigate whether the clinical and laboratory characteristics presented at the ED evaluation can also estimate the risk of post-traumatic ICH in DOAC-treated patients with MTBI. MethodsA retrospective observational study was conducted in three EDs in Italy from January 1, 2016 to March 15, 2020. All patients treated with DOACs who were evaluated for an MTBI in the ED were enrolled. The primary outcome of the study was the presence of post-traumatic ICH in the head CT performed in the ED. ResultsOf 930 patients on DOACs with MTBI who were enrolled, 6.8% (63 of 930) had a post-traumatic ICH and 1.5% (14 of 930) were treated with surgery or died as a result of the ICH. None of the laboratory factors were associated with an increased risk of ICH. On multivariate analysis, previous neurosurgical intervention, major trauma dynamic, post-traumatic loss of consciousness, post-traumatic amnesia, Glasgow Coma Scale score of 14, and evidence of trauma above the clavicles were associated with a higher risk of post-traumatic ICH. The net clinical benefit provided by risk factor assessment appears superior to the strategy of performing CT on all DOAC-treated patients. ConclusionsAssessment of the clinical characteristics presented at ED admission can help identify DOAC-treated patients with MTBI who are at risk of ICH.

The emergent neurosurgical outcome of spontaneous intracranial hemorrhage in patients with chronic liver disease.

The influence of chronic liver disease (CLD) on emergent neurosurgical outcomes in patients with spontaneous intracerebral hemorrhage (ICH) remains unclear. CLD is usually associated with coagulopathy and thrombocytopenia, which contribute to a high rebleeding rate and poor prognosis after surgery. This study aimed to confirm the outcomes of spontaneous intracranial hemorrhage in patients with CLD after emergent neurosurgery. We reviewed the medical records of all patients with spontaneous ICH from February 2017 to February 2018 at the Buddhist Tzu Chi Hospital, Hualien, Taiwan. This study was approved by the Review Ethical Committee/Institutional Board Review of Hualien Buddhist Tzu Chi Hospital (IRB111-051-B). Patients with aneurysmal subarachnoid hemorrhage, tumors, arteriovenous malformations, and those younger than 18 years were excluded. Duplicate electrode medical records were also removed. Among the 117 enrolled patients, 29 had CLD and 88 did not. There were no significant differences in essential characteristics, comorbidities, biochemical profile, Glasgow coma scale (GCS) score at admission, or ICH sites. The length of hospital stay (LOS) and length of intensive care unit stay (LOICUS) are significantly longer in the CLD group (LOS: 20.8 vs. 13.5 days, P = 0.012; LOICUS: 11 vs. 5 days, P = 0.007). There was no significant difference in the mortality rate between the groups (31.8% vs. 28.4%, P = 0.655). The Wilcoxon rank-sum test for liver and coagulation profiles between survivors and the deceased revealed significant differences in the international normalized ratio (P = 0.02), including low platelet counts (P = 0.03) between survivors and the deceased. A multivariate analysis of mortality found that every 1 mL increase in ICH at admission increased the mortality rate by 3.9%, and every reduction in GCS at admission increased the mortality rate by 30.7%. In our subgroup analysis, we found that the length of ICU stay and LOS are significantly longer in patients with CLD who underwent emergent neurosurgery: 17.7 ± 9.9 days versus 7.59 ± 6.68 days, P = 0.002, and 27.1 ± 7.3 days versus 16.36 ± 9.08 days, P = 0.003, respectively. From our study's perspective, emergent neurosurgery is encouraged. However, there were more prolonged ICU and hospital stays. The mortality rate of patients with CLD who underwent emergent neurosurgery was not higher than that of patients without CLD.

Intraventricular hemorrhage following thrombolytic therapy with streptokinase: A case series

Streptokinase is a widely used medication for the purpose of thrombolysis in case of acute coronary artery thrombosis despite being high risks of bleeding complications. The main reason behind it may be that it is one of the immediate lifesaving measure in cases of myocardial infarction. Keeping in mind, the post-thrombolytic measures in all such patients are need of an hour prevent such complicators. We hereby report three such cases of intracranial hemorrhage in patients undergoing thrombolytic therapy.

Challenges in Perioperative management of spontaneous acute subdural hematoma in haemophilia patients

Intracranial hemorrhage in patients with hemophilia is associated with high mortality and morbidity. We report a case of 15 years old boy with haemophilia A, who presented with a spontaneous acute subdural hematoma and underwent craniotomy for clot evacuation. The patient also received Factor VIII infusions peri-operatively along with other measures, to decrease blood loss. The patient presented with signs of raised intracranial pressure and received mannitol intra-operatively and postoperatively to prevent brain edema. Hypertonic saline (3 ml/kg of 3% solution) was also given over 30 minutes for brain relaxation. Recommendations for peri-operative preparation and management of haemophilia, especially in the setting of emergency major surgery were also reviewed.

The independent risk factors for abnormal head computed tomography in patients with hepatic encephalopathy

It's known that head computed tomography (CT) is used excessively to exclude intracranial hemorrhage in patients with hepatic encephalopathy (HE) in the emergency department. However, the independent risk factors for abnormal head CT in patients with HE have not been studied extensively to date. In this retrospective study, patients with an ammonia level of >90 U/L who were clinically considered HE and had head CT were included. The characteristics of patients with abnormal head CT and independent risk factors for abnormal CT were investigated. Three hundred seventy-eight patients were included in the study. CT findings of 18 (4.8%) of the patients were abnormal: 12 had intracranial hemorrhage, 1 had an ischemic stroke, and 5 had an intracranial mass. Intracranial hemorrhage (odds ratio [OR] 12.5), history of recent trauma (OR 23.4), history of active malignancy (OR 10.3), thrombocyte count <100.000/μL (OR 4.3), and international normalized ratio ≥1.5 (OR 3.2) were found to be independent risk factors for abnormal head CT. Head CT scan may be considered in patients with HE if any of the following are present: intracranial bleeding history, recent trauma history, active malignancy, platelet count <100,000/μL, and international normalized ratio >1.5.

788: ANDEXANET ALFA (ANDEXXA) REVIEW OF EFFICACY, SAFETY, AND TIME TO PATIENT ADMINISTRATION

Introduction: The 2022 Management of Patients with Spontaneous Intracranial Hemorrhage guideline recommends the use of andexanet alfa as an option for patients taking apixaban or rivaroxaban to reverse the anticoagulant effects. In the ANNEXA-4 trial, 82% of the patients evaluated achieved either excellent or good hemostatic efficacy 12 hours after the andexanet alfa infusion. The use of andexanet alfa is restricted at our institution to the treatment of intracranial hemorrhage in patients previously on rivaroxaban or apixaban asordered by neurocritical care providers. The primary objectives for this evaluation were to determine the hemostatic efficacy 24 hours post andexanet alfa infusion and the time from andexanet alfa order to administration. Secondary endpoints included the rate of thromboembolic events, 30-day mortality, and adherence to prescribing restriction protocol. Methods: This was a single-center, retrospective medication use evaluation that assessed patients prescribed andexanet alfa from November 2018 to December 2021. Results: A total of 30 patients were prescribed andexanet alfa with 26 patients included in the analysis. Four patients were excluded due to the drug being ordered but not administered. Most patients were on apixaban prior to admission for atrial fibrillation indication (n=22, 85%). All included patients received low dose andexanet alfa, with the most common indication for reversal being intracranial hemorrhage (n=25, 96%).One patient received andexanet alfa for hemoperitoneum bleed reversal indication. Hemostatic efficacy was assessed and 61.5% achieved a rating of good or excellent as defined by the ANNEXA-4 trial. The average time from andexanet alfa order to administration was 53.2 minutes and the average door to needle time was 2.5 hours. Adverse events, including thromboembolic events and inpatient mortality, occurred in 0 and. Conclusions: In our study, patients admitted with intracranial hemorrhages secondary to apixaban or rivaroxaban use who received andexanet alfa for emergent reversal had excellent hemostatic outcomes with a low rate of adverse events. Most patients received andexanet alfa within an hour of order entry into the electronic health record and adhered to institutional prescribing restrictions.

1085: HYPERCHLOREMIA AND ACUTE KIDNEY INJURY IN PATIENTS WITH NONTRAUMATIC INTRACRANIAL HEMORRHAGE

Introduction: Hypertonic saline (HTS) is commonly used in patients with non-traumatic intracranial hemorrhage (ICH) as a prophylactic and therapeutic option for intracranial hypertension and/or cerebral edema. Hyperchloremia is often resulted an adverse event due to the accompanying chloride load. Among patients with subarachnoid hemorrhage, traumatic brain injury, and acute ischemic stroke, previous literature has demonstrated an association between hyperchloremia and acute kidney injury (AKI) incidence, length of stay (LOS), and even mortality. We sought to investigate this relationship in patients with non-traumatic ICH. Methods: This was a single-center, retrospective, cohort study comparing patients with and without hyperchloremia in the first 7 days of hospitalization. This was defined as a serum chloride level above 115 mEq/L. Primary outcome was incidence of AKI in the first 10 days of hospitalization, defined by having met any of either AKIN or RIFLE criteria. Secondary outcomes included ICU and hospital LOS, disposition status, and in-hospital mortality. All adult patients with non-traumatic ICH were included. Those who had CKD stage 3 or higher, baseline SCr > 2 mg/dL or chloride > 115 mEq/L, mannitol administration, and LOS < 72 hours were excluded. Results: A total of 133 patients were analyzed, 54 of which were in the hyperchloremia group. Baseline characteristics were similar between groups, except for chloride, Modified Early Warning score (MEWS), and ICH score. Incidence of AKI was found in 32.9% and 35.2% of the non-hyperchloremia and hyperchloremia groups, respectively (p=0.785). Patients with hyperchloremia had longer ICU LOS (7 vs. 5 days, p=0.006), lower rate of independent disposition (18.5% vs. 44.3%, p=0.001), and higher rate of mortality (38.9% vs. 15.2%, p=0.002). A logistic regression analysis was run to predict mortality risk using AKI, hyperchloremia, ICH score, and MEWS. ICH score was the only significant predictor of mortality (OR 2.25 (95% CI 1.40 -3.64), p=0.01). Conclusions: In non-traumatic ICH patients, we found no significant difference with AKI development between non-hyperchloremia and hyperchloremia groups. Baseline ICH score was predictive of mortality risk. Study limitations were its observational nature and lack of propensity score matching.

Preoperative antiplatelet therapy may be a risk factor for postoperative ischemic complications in intracranial hemorrhage patients

Background and purpose Spontaneous intracranial hemorrhage (ICH) patients are still at risk of postoperative ischemic complications (PICs) after surgery. In addition, the proportion of patients receiving antiplatelet therapy (APT) in ICH patients increased significantly with age. This study aims to evaluate the impact of preoperative antiplatelet therapy on PICs in ICH patients. Methods This is a cohort study that retrospectively analyzed the data of ICH patients who underwent surgical treatment. PICs rate was compared between patients with preoperative ATP and those without preoperative ATP. Univariate and multivariate analyses were conducted to evaluate the impact of preoperative APT on PICs. In addition, Kaplan-Meier method was used for survival analysis and the impact of PICs on patients’ postoperative outcomes was evaluated. Results A total of 216 patients were included in this study. There were 47 patients (21.76%) with preoperative APT; 169 patients (78.24%) without preoperative APT. The incidence of PICs in the APT group was significantly higher when compared with that in the nAPT group (36.17% vs. 20.71%, p = 0.028＜0.05). Furthermore, significant differences were both observed in multivariate analysis (p = 0.035＜0.05) and survival analysis (log rank χ2 = 5.415, p = 0.020＜0.05). However, there was no significant difference between the outcomes of patients suffering from PICs and that of patients not suffering from PICs (p = 0.377 > 0.05). Conclusions In conclusion, preoperative APT may be a risk factor for PICs in ICH patients undergoing surgical treatment significantly.

Stains therapy and the risk of all bleeding and intracranial hemorrhage: A meta-analysis of randomized controlled studies.

Statins had been used as a cornerstone in the primary and secondary prevention of cardiovascular disease. Widespread attention had been given to the risk of bleeding, especially intracranial hemorrhage (ICH) in patients receiving statins therapy. This study aimed to determine whether statins treatment was associated with the risk of bleeding and ICH in randomized controlled trials (RCTs). Electronic databases were searched for studies up to September 8, 2022. Articles from RCTs were included in the meta-analysis if they reported the bleeding events associated with the treatment of statins or placebo/nonstatin treatment. The risk ratios (RR) of total bleeding and ICH were pooled from the number of patients with each outcome in the statins and control groups from the included studies. Twenty-nine studies comprising 145,929 individuals (2437 incident bleeding cases) were included in the meta-analysis. After a median follow-up duration of 3.65 years, statins treatment was not associated with the risk of all bleeding (RR=1.03, 95% CI 0.93-1.15). Furthermore, in 26 studies comprising 144,177 participants, after a median follow-up duration of 3.95 years, statins treatment was not associated with the risk of ICH (RR=1.05, 95% CI 0.84-1.31). Although in the subgroup analysis with patients with prior stroke, statins treatment showed an increased risk of ICH (RR=1.47, 95% CI 1.07-2.01), sensitivity analysis showed that the result was unstable, which may be mainly driven by the SPARCL study. Statins therapy is not associated with the risk of all bleeding and ICH. Although a mildly increased risk of ICH in patients with prior stroke is observed, which may be caused by chance finding and warrant further documentation.

Adverse Cardiovascular Events in Non-Traumatic Intracranial Hemorrhage and Ischemic Stroke Survivors.

We aimed to evaluate different measures of adverse cardiovascular events between non-traumatic intracranial hemorrhage (ICrH) and ischemic stroke (IS) survivors with and without atrial fibrillation (AF). Using a national hospitalization database we compared incidences and risks of all-cause in-hospital death, cardiovascular death, non-cardiovascular death, MACE-HF (in-hospital cardiovascular death, myocardial infarction, IS or new-onset heart failure [HF]) between ICrH and IS survivors with and without AF. Propensity-score matching was also performed. We identified 40,523 survivors of IS and 12,028 survivors of an ICrH without AF, and 20,449 IS survivors and 3574 ICrH survivors with AF. In unadjusted, adjusted and matched analyses, ICrH patients without AF had a higher risk of all-cause in-hospital death (Hazard Ratio (HR; for matched analyses) 1.80; 95% confidence interval (CI) 1.74-1.86), cardiovascular death (HR; 2.79; CI 2.64-2.94), MACE-HF (HR 1.97; CI 1.89-2.06) and new cerebrovascular events (HR 1.75; CI 1.57-1.96) but with lower risk of myocardial infarction (HR 0.81; CI 0.70-0.94), major bleeding (HR 0.92; CI 0.87-0.98) and new onset HF (HR 0.85; CI 0.79-0.91) compared to IS survivors without AF. Similar results were found for ICrH and IS survivors with AF except for myocardial infarction (HR 1.05; CI 0.79-1.34) and new onset HF (HR 0.94; CI 0.84-1.06) that were similar between the two groups. Adverse cardiovascular events are more frequent in ICrH survivors compared to IS survivors. New onset HF is a relatively frequent event after ICrH, especially in those patients with comorbid atrial fibrillation.

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

The value of the optic nerve sheath diameter measured using computerized brain tomography in the evaluation of mortality status in patients admitted to the emergency department with intracranial hemorrhage

Background/Aim: The optic nerve sheath diameter (ONSD) measurement is a non-invasive method that can be obtained from computerized tomography (CT) images. It can therefore be a useful diagnostic tool in determining prognosis in the emergency department. The aim of this study was to investigate the relationship between ONSD and mortality status in patients with intracranial hemorrhage who presented to the emergency department by measuring ONSD on computerized brain tomography images taken during admission. Methods: This retrospective cohort study was carried out in the emergency department of a tertiary hospital between December 1, 2018 and December 1, 2020 and included intracranial hemorrhage patients and patients with normal brain CT scans that had been obtained for any reason. Bilateral ONSDs were measured in both the intracranial hemorrhage and control groups. We first evaluated whether ONSD would differ between the two groups after which the relationship between ONSD and mortality was analyzed in the patient group who presented with bleeding. Results: Intracranial hemorrhage was present in half the cases and midline shift in 21.5%. A statistically significant increase in ONSD was observed in cases with intracranial hemorrhage (P &lt; 0.001). Similarly, a statistically significant increase in ONSD was found in cases with midline shifts and mortality (P &lt; 0.001). A cut-off value of 4.19 mm for mean optic nerve diameter exhibited 100% sensitivity and 70% specificity in terms of hemorrhage detection (area under the curve [AUC]: 0.952; P &lt; 0.001). A cut-off value of 6.03 mm for ONSD exhibited 76% sensitivity and 74% specificity in terms of hemorrhage detection (AUC: 0.730; P = 0.001). The odds ratio for prediction of mortality based on a regression analysis was 8.838 in cases with intracranial hemorrhage (P &lt; 0.001). Conclusion: ONSSD measured on CT images is a promising tool for prediction of intracranial hemorrhage, midline shift, and mortality status.

Effect of Statin Therapy on Mortality and Recurrence of Intracerebral Hemorrhage in Patients With Spontaneous Intracerebral Hemorrhage.

Statins can play an essential role in the tertiary and primary prevention of cardiovascular events by reduction of cholesterol in a stroke patient. This meta-analysis aims to assess statin therapy's effect on mortality and recurrence of Intracranial Hemorrhage (ICH) in patients with spontaneous ICH. The current meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A systematic search was performed using PubMed, EMBASE, and Cochrane Library to identify studies assessing the use of statins in patients with ICH. The primary outcome assessed in the current meta-analysis was a hemorrhagic stroke. The secondary outcomes included cardiac-related events and all-cause mortality. A total of 9 studies were included in the current meta-analysis enrolling 49027 patients, with 8094 patients on statin therapy and 40933 patients in the control group. The risk of recurrent ICH was significantly lower in patients receiving stains (RR: 0.81, 95% CI: 0.67-0.99, p-value: 0.02) compared to placebo. However, no significant differences were observed regarding all-cause mortality (RR: 0.80, 95% CI: 0.53-1.20, p-value: 0.27) and cardiovascular events (RR: 1.24, 95% CI: 0.88-1.74). In ICH patients, statins can reduce the risk of recurrent ICH in patients with a history of ICH. However, statins had no significant effect on all-cause mortality and cardiovascular events.