European Cooperative Acute Stroke Study Research Articles

Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study

BACKGROUND Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. METHODS This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China. RESULTS The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90. CONCLUSIONS It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China. Clinical Trial Registration Information NCT04915729 ( https://clinicaltrials.gov/study/NCT04915729 )

Hypoperfusion intensity ratio and hemorrhagic transformation in patients with successful recanalization after thrombectomy.

Hemorrhagic transformation remains a potentially devastating complication of acute ischemic stroke. We aimed to evaluate whether the hypoperfusion intensity ratio (HIR), a parameter derived from CT perfusion imaging, is associated with the development of hemorrhagic transformation in patients with anterior large-artery occlusion who had undergone thrombectomy. We retrospectively reviewed data from consecutive acute ischemic stroke patients who had achieved successful recanalization (thrombolysis in cerebral infarction score ≥ 2b) between January 2020 and December 2023. HIR was defined as the ratio of the volume of lesions with a time-to-maximum (TMax) > 6 s to those with a Tmax > 10 s delay. The primary outcome, based on the European Cooperative Acute Stroke Study, was hemorrhagic transformation (HT), diagnosed by follow-up imaging assessment in 24 h windows, and radiologically classified as hemorrhagic infarction (HI) and parenchymal hematoma (PH). The secondary outcome was a 3-month mRS score of ≥3. Among 168 patients, 35/168 developed hemorrhagic transformation HT; 14/168 developed hemorrhagic infarction HI, and 21/168 developed parenchymal hematoma PH. After adjusting the latent covariates, increased hypoperfusion intensity ratio (per 0.1, adjusted OR [aOR] 1.68, 95% CI 1.26-2.25), ASPECTS (aOR 0.44, 95% CI 0.27-0.72), onset-to-puncture (aOR 1.01, 95% CI 1.00-1.02), and cardioembolism (aOR 5.6, 95% CI 1.59-19.7) were associated with hemorrhagic transformation in multivariable regression. The receiver operating characteristic curve indicated that HIR can predict HT accurately (area under the curve = 0.81; 95% CI, 0.738-0.882; P < 0.001) and predict PH (area under the curve = 0.801; 95% CI, 0.727-0.875; P < 0.001). Upon admission, hypoperfusion intensity ratio, an imaging parameter, predicted hemorrhagic transformation after reperfusion therapy in this patient population.ABBREVIATIONS: HT = hemorrhagic transformation; HIR = hypoperfusion intensity ratio; LVO = left vessel occlusion; EVT = endovascular thrombectomy; AIS = arterial ischemic stroke; OTP = onset-to-puncture; HI = hemorrhagic infarction; PH = parenchymal hematoma.

Impact of Sex on Thrombectomy Outcomes in Ischemic Stroke: A Propensity Score‐Matched Study, Systematic Review, and Meta‐Analysis

Background Women are underrepresented in stroke thrombectomy trials, and the impact of sex differences in outcomes after stroke thrombectomy is unclear. We performed a multicenter propensity matching study to define sex‐related differences in outcome after endovascular thrombectomy and integrated results in a meta‐analysis. Methods We included patients with anterior circulation large vessel occlusion consecutively treated with thrombectomy at 2 Comprehensive Stroke Centres (2016–2023). Selection criteria reflected international guidelines. Through systematic review we selected all studies reporting endovascular thrombectomy outcomes in anterior circulation large vessel occlusion stroke, applying propensity score matching. MEDLINE, EMBASE, and Cochrane CENTRAL were searched up to August 15, 2023 according to predefined protocol (OSF.io/je3da). Data were extracted by 2 independent raters, pooled estimates calculated according to random‐effect modeling meta‐analysis and reported as odds ratio (OR) and standard 95% CI. Outcomes were good functional outcome, defined as modified Rankin Scale score 0–2 at 90 days after stroke, and symptomatic intracranial hemorrhage, adjudicated according to European Cooperative Acute Stroke Study II criteria. Results After matching, 698 patients (349 women versus 349 men) had similar cardiovascular risk factors, baseline features, and treatment approach. No significant differences were found for good functional outcome (OR = 0.89, 95% CI = 0.66–1.2) and symptomatic intracranial hemorrhage (OR = 1.00, 95% CI = 0.44–2.26) in the cohort study by sex. Systematic review identified 3 studies (n = 3706), all of high quality. No differences emerged in rates of good functional outcome (OR = 1.00, 95% CI = 0.79–1.21) or symptomatic intracranial hemorrhage (OR = 0.85, 95% CI = 0.60–1.19) depending on sex. Conclusion Women receiving endovascular thrombectomy for anterior circulation large vessel occlusion related stroke have similar rates of good functional outcome and symptomatic intracranial hemorrhage compared to men.

ASSOCIATION OF THE TYPE OF INTRACEREBRAL HEMORRHAGE WITH SERIOUS COMPLICATIONS AND PREDICTIVE FACTORS FOR HEMORRHAGIC TRANSFORMATION AFTER THROMBOLYTIC TREATMENT IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Background: Accurate classification of postthrombolytic intracerebral hemorrhage (ICH) subtypes is vital for predicting stroke outcomes and managing ICH. Currently, the recommended classification criteria are the European Cooperative Acute Stroke Study III criteria, including two primary categories: hemorrhagic infarction (HI) and parenchymal hematoma (PH). Objectives: The primary objective of this study was to assess the contribution of various ICH subtypes to serious complications, with the secondary aim to identify associated predictors.Methods: The study examined medical records of patients with acute ischemic stroke receiving thrombolysis at Saraburi Hospital from 2014 to 2022. The logit model with the margins command assessed the association of ICH subtypes with serious complications, and multinomial logistic regression identified potential predictors for HI and PH. Results: Among 345 patients, HI-1, HI-2, PH-1 and PH-2 had prevalence rates of 3.2, 7.8, 4.9 and 7.5%, respectively, while 76.5% did not have ICH. PH-2 demonstrated the strongest correlation with inhospital mortality (adjusted risk ratio [RR] 2.83, 95% CI 1.56-5.13), invasive mechanical ventilator requirement (adjusted RR 3.93, 95% CI 2.09-7.39) and hematoma evacuation (adjusted RR 4.58, 95% CI 1.17-17.95) compared with patients of non-ICH. HI demonstrated a significant prolongation of hospitalization. (adjusted RR 3.30, 95% CI 1.53-7.12). Multinomial logistic regression analysis revealed that prior use of antiplatelet drugs, antihypertensive treatment before rt-PA, white blood cell count ≥11,750 cells/mm3 and baseline Alberta stroke program early CT scores ≤7 were independent predictors for PH. The adjusted odds ratios were 3.06 (95% CI, 1.23-7.57), 6.95 (95% CI, 2.62-18.45), 6.01 (95% CI, 2.17-16.65) and 5.01 (95% CI, 2.00-12.60), respectively. Conclusion: The PH-2 subtype was associated with the highest mortality, while our study demonstrated that the HI subtype, previously considered relatively benign with successful early recanalization, showed a significant prolongation of hospitalization compared with that of patients of non-ICH. High-risk patients of ICH require intensive monitoring to reduce complications.

Prognosis and Prediction of Asymptomatic Intracranial Hemorrhage After Endovascular Thrombectomy: A Multi-Center Study.

The impact of asymptomatic intracranial hemorrhage (aICH) on functional outcomes after endovascular thrombectomy (EVT) remains unclear, and tools for forecasting this complication are lacking. We aim to evaluate the clinical relevance of aICH and establish a prediction model. Data of patients who received EVT for acute anterior-circulation large vessel occlusion in 3 comprehensive hospitals were retrospectively analyzed. Asymptomatic intracranial hemorrhage was defined as any hemorrhage detected after EVT that did not fulfill the definition of symptomatic intracranial hemorrhage in the European Cooperative Acute Stroke Study. Logistic regression models were performed to assess the impact of aICH on 90-day functional outcomes and identify the predictors of aICH, which were then used to establish a prediction model. The discrimination, calibration, and clinical utility of the model were evaluated. This study included 460 patients, among whom 152 (33.0%) developed aICH after EVT. Asymptomatic intracranial hemorrhage was negatively associated with 90-day excellent outcomes (adjusted odds ratio [OR]: 0.414, 95% confidence interval [CI]: 0.230-0.745, p=0.003) and good outcome (adjusted OR: 0.603, 95% CI: 0.374-0.971, p=0.037), but not with mortality (adjusted OR: 1.110, 95% CI: 0.611-2.017, p=0.732) after adjusted for other predictors of functional outcome. Pre-stroke anticoagulant therapy (OR: 2.233, 95% CI: 1.073-4.647, p=0.032), Alberta stroke program early CT score (OR: 0.842, 95% CI: 0.754-0.939, p=0.002), site of occlusion (internal carotid artery occlusion as the reference; M1 segment of middle cerebral artery occlusion, OR: 2.827, 95% CI: 1.409-5.674, p=0.003; tandem occlusion, OR: 3.928, 95% CI: 1.752-8.806, p=0.001), intravenous thrombolysis (OR: 2.091, 95% CI: 1.362-3.209, p=0.001), and successful recanalization (OR: 0.383, 95% CI: 0.213-0.689, p=0.001) were identified as the predictors of aICH, which were incorporated into a nomogram model. The area under the receiver operating characteristic curve of the model was 0.707 (95% CI: 0.657-0.757), and the calibration plot demonstrated good consistency between actual observed and predicted probability of aICH. Decision curve analysis showed that patients might benefit from the model. Asymptomatic intracranial hemorrhage was negatively associated with favorable functional outcome after EVT. We established a nomogram model for predicting aICH, which requires external clinical validation. The impact of asymptomatic intracranial hemorrhage after endovascular thrombectomy on mid-term functional outcome has been controversial. We found that asymptomatic intracranial hemorrhage may also decreased the likelihood of 90-day favourable functional outcome after endovascular thrombectomy, supporting the notion that asymptomatic intracranial hemorrhage at the acute stage may not be benign. Moreover, we established a prediction model for this complication, which may improve clinical evaluation and management of patients who would receive endovascular thrombectomy for large vessel occlusion.

Abstract 234: Antithrombotic use in Emergent Cervical Carotid Artery Stenting in Thrombectomy

Introduction Current literature suggests a benefit in functional outcomes and reperfusion rates when carotid artery stenting (CAS) and mechanical thrombectomy (MT) are performed emergently. However, rates of symptomatic intracranial hemorrhages have been inconclusive. Antithrombotic protocols used in CAS and MT tend to be heterogenous among physicians. There is no standardized data on antithrombotic therapy use during CAS and MT procedures with less associated rates of symptomatic hemorrhagic transformation. We aimed to compare the efficacy and safety of antithrombotic use in patients requiring CAS and MT. Additionally, we sought to analyze clinical and mortality outcomes in CAS and MT retrospectively at our institution. Methods We searched for patients who underwent emergency cervical ICA stent placement and intracranial thrombectomy with stent‐retriever and/or aspiration devices in our institution between 2019‐2023. Clinicoangiographic and antithrombotic data were analyzed. Good clinical outcomes were a &lt; 4 points of NIHSS at 24 hours, mRS (0‐3) at 90 days, and disposition to home or inpatient rehabilitation. Characteristics of hemorrhagic transformation (HT) according to the European Cooperative Acute Stroke Study (ECASS). Clinical, radiographic, and mortality outcomes were described. Results Twenty‐seven patients were treated. The mean age was 64 years, nine females: mean occlusion time 400 minutes, mean fluoro time 32 minutes. Fourteen patients received IV tissue‐type plasminogen (tPA) activator. The admission NIHSS score mean was 16. Stent placement was feasible in all cases. Thrombolysis in Cerebral Infarction score of 2B was achieved in 18 patients (66.7%); the rest had a TICI 3 score. Twelve patients had improved 4 NIHSS points between admission and 24 hours. Dual antiplatelet therapy with aspirin and clopidogrel was used in 15 patients before stenting. While six patients received aspirin and ticagrelor, and the rest received eptifibatide drip. Seven (26%) patients had symptomatic intracranial hemorrhages. Antithrombotic type of treatment had no significant association with bad outcomes (p‐value: 0.872), neither did IV tPA use (p‐value: 0.853). Fourteen patients had good clinical outcomes (mRS 0‐3) at discharge, while eight died. At 90 days follow‐up, the median mRS was 3. Conclusion Our analysis suggests no significant association between symptomatic hemorrhagic transformation with IV tPA or heterogenous antithrombotic use. Our retrospective study has several limitations, including sample size and heterogeneous pathology. Larger studies are needed to stratify symptomatic hemorrhages' high‐risk profile in CAS and MT.

A Comparative Study of Hemorrhagic Conversion Patterns After Stroke Thrombolysis With Alteplase Versus Tenecteplase.

Tenecteplase is the thrombolytic drug of choice for acute ischemic stroke (AIS) as it has unique pharmacologic properties, along with results demonstrating its non-inferiority compared to alteplase. However, there are contradictory data concerning the risk of intracranial hemorrhage. The purpose of the study was to report the rate and patterns of symptomatic intracranial hemorrhage (sICH) in AIS patients after thrombolysis with tenecteplase compared to alteplase. This is a retrospective cohort study with data collected 90 days before and after the change from alteplase to tenecteplase from 15 Texas stroke centers. The primary endpoint is the incidence of sICH according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) and European Cooperative Acute Stroke Study III (ECASS-3) criteria. The secondary endpoints are the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBC). A total of 431 patients were eligible for thrombolytic therapy. Half of the cohort received alteplase (n=216), and the other half received tenecteplase (n=215). The average age of the alteplase group was 62.94 years old (SD=15.12) and 64.45 years old (SD=14.51) for the tenecteplase group. Seven patients in the alteplase group (3.2%) and 14 (6.5%) in the tenecteplase group had sICH, with an odds ratio of 1.44 (95% CI 0.60-3.43; P=0.41). An increased National Institutes of Health Stroke Scale (NIHSS) score on arrival (1.06; 95% CI 1.0004-1.131; P=0.04) was a statistically significant predictor of sICH. Tenecteplase was associated with a statistically significant increase in HBC-3 (P=0.040) over alteplase. Compared with alteplase, our study revealed a higher rate of sICH with tenecteplase that was not statistically significant and a higher rate of HBC-3 hemorrhages that was statistically significant. The proposed mechanism of bleeding is hemorrhagic conversion in clinically silent infarcts and contusions underlying the lesions. Further studies are needed to confirm our findings and determine predictive risk factors.

Impact of lipid profiles on parenchymal hemorrhage and early outcome after mechanical thrombectomy.

We aimed to investigate the association of lipid parameters with parenchymal hemorrhage (PH) and early neurological improvement (ENI) after mechanical thrombectomy (MT) in stroke patients. We retrospectively analyzed consecutive patients who underwent MT between January 2019 and February 2022 at a tertiary stroke center. PH was diagnosed and classified as PH-1 and PH-2 according to the European Cooperative Acute Stroke Study definition. ENI was defined as a decrease in the National Institutes of Health Stroke Scale (NIHSS) score by ≥8 or an NIHSS score of ≤1 at 24 h after MT. Among 155 patients, PH occurred in 41 (26.5%) patients, and 34 (21.9%) patients achieved ENI. In multivariate analysis, lower triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) value (OR = 0.51; 95% CI 0.30-0.89; p = 0.017) and higher HDL-C level (OR = 5.83; 95% CI 1.26-26.99; p = 0.024) were independently associated with PH. The combination of TG <0.77 mmol/L and HDL-C ≥ 0.85 mmol/L was the strongest predictor of PH (OR = 10.73; 95% CI 2.89-39.87; p < 0.001). A low HDL-C level was an independent predictor of ENI (OR 0.13; 95% CI 0.02-0.95; p = 0.045), and PH partially accounts for the failure of ENI in patients with higher HDL-C levels (estimate: -0.05; 95% CI: -0.11 to -0.01; p = 0.016). The combination of lower TG level and higher HDL-C level can predict PH after MT. Postprocedural PH partially accounts for the failure of ENI in patients with higher HDL-C levels. Further studies into the pathophysiological mechanisms underlying this observation are of interest.

Pre-treatment risk markers for hemorrhagic transformation in posterior circulation acute ischemic stroke treated with reperfusion therapy.

Hemorrhagic transformation (HT) is an uncommon complication of posterior circulation acute ischemic stroke (PCS) compared to anterior circulation stroke. Nevertheless, it remains a major concern especially following reperfusion therapy. This study aimed at identifying potential predictive factors associated with HT in PCS. Consecutive patients, from a multicenter cohort, with PCS treated by IVT or EVT or the combination of both, were included from December 2015 to May 2019. The European Cooperative Acute Stroke Study criteria was used to identify HT. Potential risk factors were analyzed using univariate and multivariable testing models. A total of 96 patients were included in our study. Median age was 66 (57-83) years, 54 patients (56%) were male and median baseline NIHSS was 8 (4-14). 77 patients (80%) received IVT and 54 patients (56%) benefited from EVT. HT occurred in 19 patients (20%), while sHT occurred in 3 patients (3%). HT was found to be associated with poor functional status at 3months in univariate analysis (p = 0.0084). Multivariable analysis confirmed that higher baseline NIHSS (OR 1.1008; 95% CI [1.0216-1.1862]; p = 0.0117) and lobar topography of ischemia (OR 4.4275; 95% CI [1.3732-14.2753]; p = 0.0127) were independent predictors of the occurrence of HT. HT is associated with increased morbidity in patients with PCS; higher NIHSS and lobar ischemia were independent predictors of HT in our population. Easy-to-use predictive markers may help to tailor therapeutic management of patients with PCS.

Increased Serum EphrinA1 Is Associated with Parenchymal Hematoma after Ischemic Stroke

Introduction: Previous preclinical studies reported that the level of serum EphrinA1 was associated with blood-brain barrier disruption; however, its role in predicting parenchymal hematoma (PH) after ischemic stroke is underexplored. We aimed to explore the association between the level of serum EphrinA1 and PH in patients with ischemic stroke. Methods: Patients with ischemic stroke after onset from West China Hospital, Sichuan University, were prospectively enrolled between January 2017 and December 2019. The level of serum EphrinA1 at baseline was measured after admission. PH was diagnosed as hematoma within the infarct territory detected on the brain CT/MRI scans within 7 days after onset but not on the initial scan according to European Cooperative Acute Stroke Study (ECASS) III criteria. The association between the level of serum EphrinA1 and PH after ischemic stroke was assessed by multiple logistic regression analysis. Results: A total of 667 patients were included in the final analysis. The mean age was 67.20 ± 14.31 years, and 57.87% (368/667) were males. Of the 667 patients, 65 (9.75%) patients had PH. The median of EphrinA1 on admission was 82.83 ng/mL (IQR, 70.11–93.75 ng/mL). Compared with patients without PH, those with PH had a higher level of serum EphrinA1 (p = 0.024). Patients were divided into 3 categories based on EphrinA1 tertiles (T1, <79.11 ng/mL, n = 223; T2, 79.11–93.75 ng/mL, n = 222; and T3, >93.75 ng/mL, n = 222). After adjusting for age, sex, atrial fibrillation, smoking, statins, antiplatelets, Trail of Org 10172 in Acute Stroke Treatment (TOAST) classification and National Institutes of Health Stroke Scale (NIHSS) score ≥15, patients in the second and third EphrinA1 tertiles showed a significant increase in PH compared with those in the lowest tertile (OR 2.44, 95% CI: 1.10–5.40, p = 0.028; OR 2.61, 95% CI: 1.19–5.74, p = 0.017, respectively). Additionally, adjusting for reperfusion therapy (thrombolysis and/or endovascular therapy), only patients in the highest group (tertile 3) had a significantly higher risk of PH compared to the lowest group (OR 2.30, 95% CI: 1.03–5.13, p = 0.042). Conclusion: Higher serum EphrinA1 is independently associated with a higher risk of PH after ischemic stroke. Future studies with larger sample sizes are needed to validate our findings and elucidate the potential role of EphrinA1 in PH.

Risk factors and predictors of intracranial hemorrhage after mechanical thrombectomy in acute ischemic stroke: insights from the Stroke Thrombectomy and Aneurysm Registry (STAR)

BackgroundReducing intracranial hemorrhage (ICH) can improve patient outcome in acute ischemic stroke (AIS) intervention. We sought to identify ICH risk factors after AIS thrombectomy.MethodsThis is a retrospective review of the...

Increased blood pressure variability during general anaesthesia is associated with worse outcomes after mechanical thrombectomy: a prospective observational cohort study

ObjectivesOptimal periprocedural blood pressure (BP) management during mechanical thrombectomy (MT) for acute ischaemic stroke is still controversial. The aim of this study was to investigate the association between intraprocedural BP...

Diagnostic performance of intraoperative cone beam computed tomography compared with postoperative magnetic resonance imaging for detecting hemorrhagic transformation after endovascular treatment following large vessel occlusion

ObjectivesEarly detection of hemorrhagic transformation (HT) in patients with large vessel occlusion (LVO) after endovascular treatment is important for postoperative patient management. We investigated the diagnostic performance of intraoperative cone beam computed tomography (CBCT) with reference standard magnetic resonance imaging (MRI) for detecting HT. Materials and methodsConsecutive patients with LVO treated by endovascular treatment who underwent intraoperative CBCT and postoperative MRI were included. Two observers evaluated all images for the presence of HT. Sensitivity and specificity for detecting HT were calculated with MRI as reference standard. The observers classified HT according to the European Cooperative Acute Stroke Study (ECASS). Inter-method and inter-rater agreement for the detection of HT and for the ECASS classification were assessed using kappa or weighted Brennan-Prediger (wBP) statistics. ResultsImages of 106 procedures (94 for anterior circulation) were analyzed. The sensitivity and specificity for detecting HT on CBCT were 0.77 and 0.83, respectively, for all procedures and 0.83 and 0.8, respectively, for anterior circulation. The inter-method agreement for HT detection (κ = 0.63 overall, κ = 0.69 anterior circulation) and ECASS classification (wBP = 0.67 overall, wBP = 0.77 anterior circulation) were substantial. The inter-rater agreement for HT detection (κ = 0.87 overall, κ = 0.85 anterior circulation) and for ECASS classification (wBP = 0.95 overall, wBP = 0.92 anterior circulation) were almost perfect. ConclusionsThe diagnostic performance of CBCT for the detection of HT in stroke patients treated for LVO was acceptable with excellent inter-rater agreement. Intraoperative CBCT may be useful to trigger early interventions if HT is detected, although detailed classifications of HT may be difficult.

Higher serum albumin-corrected calcium levels are associated with revascularization and poor outcome after mechanical thrombectomy

BackgroundSerum calcium abnormalities have been determined to be associated with the risk and outcome of stroke. The aim of the present study was to examine the associations of serum calcium with vascular recanalization, symptomatic intracranial haemorrhage and functional outcome in stroke patients after mechanical thrombectomy.MethodsA total of 192 patients treated with mechanical thrombectomy for anterior circulation large vessel occlusion were consecutively included from August 2017 to June 2021. Serum calcium levels were measured on admission, and albumin-corrected calcium levels were calculated for subsequent analysis. Successful arterial revascularization was defined as a modified Thrombolysis in Cerebral Infarction scale score ≥ 2b. Symptomatic intracranial haemorrhage was assessed according to the European Cooperative Acute Stroke Study (ECASS) III criteria. Poor functional outcome was defined as a modified Rankin Scale score > 2 at 3 months.ResultsPatients with poor outcomes had higher albumin-corrected calcium levels than patients with good outcomes before (2.20 (2.10, 2.30) mmol/L vs. 2.13 (2.04, 2.24) mmol/L, P = 0.002), and after adjusting for other factors (AOR 95% CI, 1.812 (1.253, 2.621), P = 0.002). Patients with unsuccessful recanalization had higher albumin-corrected calcium levels than those with recanalization (2.26 (2.09, 2.46) mmol/L vs. 2.17 (2.07, 2.27) mmol/L, P = 0.029), and after adjusting for other factors (AOR 95% CI, 2.068 (1.214, 3.524)), P = 0.008). No association was found between albumin-corrected calcium and symptomatic intracranial haemorrhage.ConclusionsHigher serum albumin-corrected calcium levels are independently associated with revascularization and poor outcome in stroke patients after mechanical thrombectomy.

Fibroblast Growth Factors are Associated with Parenchymal Hemorrhagic Infarction Following ELVO

ObjectiveThe goal of this study was to analyze possible associations between fibroblast growth factors (FGFs) and hemorrhagic conversion (HC) in patients with acute ischemic stroke that underwent mechanical thrombectomy (MT).BackgroundEmergent Large Vessel Occlusion (ELVO), often treated with MT, can lead to further complications such as HC. Little is known about predicting the risk and extent of HC. FGF‐21 and 23 are angiogenic proteins of the endocrine subfamily and are independent factors for overall risk of stroke and intracranial hemorrhage (PMID: 33967812). Comorbidities such as diabetes, obesity, hypertension, and hypercholesterolemia are also known to increase risk of HC and affect FGF levels.MethodsThe Center for Advanced Translational Stroke Science at the University of Kentucky utilizes the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (www.clinicaltrials.gov NCT03153683) for collection of systemic (i.e. proximal to thrombus) arterial blood during a MT procedure. Blood samples collected from 61 patients were sent to Olink Proteomics for proteomic analysis. The European Cooperative Acute Stroke Study (ECASS II) grading system was used to differentiate between the types of HT: Hemorrhagic Infarction (HI 1 and 2) and Parenchymal Hemorrhagic Infarction (PH 1 and 2). Logistic regressions were used to determine the association of FGF with the subtypes of hemorrhagic conversion. Data analyses were performed using IBM SPSS Statistics.ResultsFGF‐21 and FGF‐23 were significantly higher in patients with HI versus PH‐type HC (p=0.043 and p=0.004 respectively). Logistic regression yielded a significant model for only FGF‐21 (χ2= 5.196, p=0.023). Increasing levels of FGF‐21 were associated with a decreased likelihood of having PH‐type HC. Most patients receiving TPA had decreased levels of FGF‐21 (p=0.04). Various comorbidities were tested but were not found to be significant.DiscussionThe data provides an indication that lower levels of FGF‐21 increase the odds for a worse type of hemorrhagic transformation. Lower levels of FGF‐21 are reported in patients with hypercholesterolemia and hypertension. Our study found TPA correlated with lower levels of FGF‐21. Taken together, patients with comorbidities that decrease FGF‐21 levels, such as hypertension and hypercholesterolemia, and those who receive TPA should be monitored more carefully following thrombectomy. FGF‐21 should be evaluated further as a potential biomarker for hemorrhagic transformation to administer adjunctive therapies to MT.

Comparison of Different Dosages of Alteplase in Atrial Fibrillation-Related Acute Ischemic Stroke After Intravenous Thrombolysis: A Nationwide, Multicenter, Prospective Cohort Study in Taiwan.

BackgroundInsufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses.Methods and ResultsThis multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk‐scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non‐AF group, the AF group exhibited a 2‐ to 3‐fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk [RR], 2.10 [95% CI, 1.35–3.26]). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke‐Monitoring Study standards did not significantly differ between the AF and non‐AF groups. In addition, the low‐dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 [95% CI, 1.63–4.96]). A validation study confirmed these findings after adjustment for scores determined using different stroke risk‐scoring tools.ConclusionsDifferent alteplase dosages did not affect functional status at 90 days in the AF and non‐AF groups. Thus, the adoption of low‐dose alteplase simply because of AF is not recommended.

The Relationship between Intracranial Hemorrhage after Intravenous Thrombolytic Therapy and the Need for Antihypertensive Treatment During and after Infusion in Acute Ischemic Stroke

Background: This study aims to determine which factors increase the risk of intracerebral hemorrhage after tissue plasminogen activator (tPA) treatment in patients with acute ischemic stroke and to investigate whether there is a relationship between the need for antihypertensive therapy during and after tPA infusion and the risk of intracerebral hemorrhage. Materials and Methods: Consecutive patients who applied to our stroke center with acute ischemic stroke and received IV tPA treatment in the first 4.5 h between 2012 and 2020 were included in the study. The demographic data of patients, stroke risk factors, drugs used before the stroke, neurological examinations, cranial computed tomographys (CTs) before and after tPA, antihypertensive usage during IV tPA and in the 24-h period after treatment, hospital mortality rates, and modified Rankin Scale scores in the 3rd month were evaluated retrospectively. Patients with intracerebral bleeding were divided into groups according to bleeding subtypes and whether they were symptomatic. Results: Intracranial bleeding was detected in 48 of 214 patients included in this study. Nineteen of these (8.8%) were classified as symptomatic intracerebral hemorrhage according to the National Institute of Neurological Disorders and Stroke and 14 (6.5%) according to the definition of the European Cooperative Acute Stroke Study. In the multiple logistic regression analysis, intracranial bleeding was significantly associated with 24th h systolic blood pressure and the need for antihypertensive usage. Conclusions: Blood pressure regulation should be done carefully during tPA infusion and in the first 24 h. In addition, cranial CT scanning in patients who need antihypertensive usage may enable earlier detection of intracranial bleeding.

Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network.Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality.Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05).Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Lower uric acid level may be associated with hemorrhagic transformation after intravenous thrombolysis.

Previous studies have shown that uric acid (UA) is a powerful water-soluble antioxidant and free radical scavenger for humans. However, the relationship between serum uric acid (SUA) and hemorrhagic transformation (HT) is still controversial. To address this challenge, we aimed to explore the association between serum UA and HT in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). A retrospective analysis was conducted in patients with anterior circulation AIS who underwent IVT at Affiliated Hospital of Qingdao University from 2016 to 2021. HT was evaluated by CT or MRI within 7days after admission. Baseline demographic, clinical, and laboratory data were compared between the HT and non-HT groups, and between different types of HT groups which were documented according to the European Cooperative Acute Stroke Study III Classification (ECASS III). A total of 727 AIS patients were enrolled, including 112 patients who experienced HT (HT group) and 615 patients who did not experience HT (non-HT group). Patients with HT had significantly lower UA levels compared to those without HT (253.65 ± 97.75 vs 315.97 ± 96.42, p < 0.001); however, there was no significant difference for UA levels in different types of HT (p = 0.907). After adjusting confounders, patients in the fourth UA quartile showed a significant decrease in HT compared with those in the first quartile (OR 0.266, 95% CI 0.107-0.661, p = 0.006). The best cutoff value was identified as 218.5μmol/L after analysis. These findings suggest that low levels of UA may be associated with HT after IVT.

A New Classification System for Postinterventional Cerebral Hyperdensity: The Influence on Hemorrhagic Transformation and Clinical Prognosis in Acute Stroke.

Background Postinterventional cerebral hyperdensity (PCHD) is commonly seen in acute ischemic patients after mechanical thrombectomy. We propose a new classification of PCHD to investigate its correlation with hemorrhagic transformation (HT). The clinical prognosis of PCHD was further studied. Methods Data from 189 acute stroke patients were analyzed retrospectively. According to the European Cooperative Acute Stroke Study criteria (ECASS), HT was classified as hemorrhagic infarction (HI-1 and HI-2) and parenchymal hematoma (pH-1 and pH-2). Referring to the classification of HT, PCHD was classified as PCHD-1, PCHD-2, PCHD-3, and PCHD-4. The prognosis included early neurological deterioration (END) and the modified Rankin Scale (mRS) score at 3 months. Results The incidence of HT was 14.8% (12/81) in the no-PCHD group and 77.8% (84/108) in the PCHD group. PCHD was highly correlated with HT (r = 0.751, p < 0.01). After stepwise regression analysis, PCHD and the National Institutes of Health Stroke Scale (NIHSS) score at admission were found to be independent factors for END (p < 0.001, p = 0.015, respectively). The area of curves (AUC) of PCHD, the NIHSS at admission, and the combined model were 0.810, 0.667, and 0.832, respectively. The optimal diagnostic cutoff of PCHD for END was PCHD > 2. PCHD, the NIHSS score at admission, and good vascular recanalization (VR) were independently associated with 3-month mRS (all p < 0.05). The AUC of PCHD, the NIHSS at admission, good VR, and the combined model were 0.779, 0.733, 0.565, and 0.867, respectively. And the best cutoff of PCHD for the mRS was PCHD > 1. Conclusion The relationship of PCHD and HT suggested PCHD was an early risk indicator for HT. The occurrence of PCHD-3 and PCHD-4 was a strong predictor for END. PCHD-1 is considered to be relatively benign in relation to the 3-month mRS.