Thrombolytic Treatment Research Articles

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p ≤ 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954–1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932–0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989–0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p ≤ 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9–96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis

Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.

Abstract Number: LBA7 Outcomes of Endovascular Thrombectomy Versus Medical Treatment in Ischemic Strokes Secondary to Medium Vessel Occlusion

Introduction Acute ischemic stroke (AIS) from arterial occlusions are treated with emergent endovascular thrombectomy (EVT) when clinically appropriate. Clinical outcomes of EVT in medium vessel occlusion (MVO) compared to large vessel occlusion (LVO) have neither been well established nor compared to alternate medical management. Our aim was to evaluate outcomes of patients with AIS secondary to MVO undergoing EVT. Methods We conducted a retrospective chart review of patients presenting to our comprehensive stroke center with MVO‐associated AIS undergoing EVT or aggressive intra‐arterial thrombolytic treatment with concurrent administration of IV eptifibatide. We assessed occlusion site, NIHSS (presentation, 7 day or discharge, 3 months), modified Rankin Scale (baseline, 90‐day), and intracranial hemorrhage (ICH) rate. MVO was defined as occlusion of pure M2 middle cerebral artery without M1 segment involvement, anterior cerebral artery A1 segment or more distal, and posterior cerebral artery P1 segment or more distal. Mann‐Whitney U test, Fisher exact test statistic, and T‐test statistic were used for analysis. Social science statistics software was used for data analysis. Results From August 2020 to December 2021, out of 175 patients who underwent EVT, 50 had MVO (n = 33 M2 occlusion, n = 12 M3 occlusion, n = 1 for P1, P2, A1, A2, A3 each). Twelve subjects with MVO received aggressive medical management with concurrent IV eptifibatide. Subjects between arms were similar at baseline (median NIHSS 11 [95% CI 10.75, 14.32]; mean age 71.5 [95% CI 69.24, 73.77]; male 48.39% [n = 30]). The difference between initial NIHSS and discharge NIHSS was statistically significant in the EVT arm (Z‐Score = 4.03; p‐value < .00001) but not in the medical arm (Z‐score = 1.96; p‐value 0.05). Hemorrhagic transformation occurred in 28% (n = 14) of EVT arm and 16.67% (n = 2) of medical arm. This was not statistically significant (Fisher value: 0.71). Median 90 day mRS was 1 (95% CI [0.89, 2.11]). The difference between 90 day mRS was not significantly different (Z‐score = ‐1.20; p‐value 0.23). Conclusions In our patient cohort, endovascular therapy was safe in medium vessel occlusion and may have more favorable clinical outcomes as illustrated by higher delta NIHSS in the endovascular thrombectomy group. Larger, prospective studies are needed to validate our results.

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

Serum asprosin levels in patients with acute ischemic stroke

Objective: This study aimed to investigate the association between serum asprosin and the incidence, severity, etiological subtypes and thrombolysis therapy of acute ischemic stroke (AIS). Methods: A total of 130 patients with AIS were included; 50 patients matched for age, sex, and vascular risk factors, and 50 healthy subjects matched only for age and sex were used as the control group. The National Institutes of Health Stroke Scale was used to estimate the severity of stroke. Scores >6 were considered to indicate a moderate-to-severe stroke. The AIS group was divided into 3 etiological subtype groups according to the Toast classification method. The thrombolytic and non-thrombolytic groups were divided according to whether emergency thrombolytic treatment was performed. Results: The asprosin level was significantly higher in the AIS group than in the control group (p<0.001). Further, the asprosin level was higher in the moderate-to-severe stroke group than in the minor stroke group (p<0.001). Logistic regression analysis showed that asprosin was an independent risk factor for AIS and AIS severity. The areas under the receiver operating characteristic curve of serum asprosin for predicting AIS and moderate-to-severe stroke were 0.671 (95% confidence interval: 0.587–0.755; p<0.001) and 0.778 (95% confidence interval: 0.698–0.858; p<0.001), respectively. There was no statistically significant difference in serum asprosin levels in the etiological subtype of AIS and thrombolytic therapy or not. Conclusion: Serum asprosin levels are positively associated with the incidence and severity of AIS and can be used as biomarkers for predicting the occurrence of AIS. Serum asproisn levels may not be used to differentiate between different etiologic subtypes of acute ischemic cerebral infarction and thrombolytic therapy or not.

Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial.

Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130-140mm Hg within 1h; maintained for 72h) or guideline-recommended (systolic target <180mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30,2018. All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24-36h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24-36h. Mean achieved systolic blood pressures over 1-24h were 141mm Hg and 149mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24-36h (0.3 [IQR 0.0-16.6] in the intensive group and 0.9 [0.0-12.5] in the guideline group; log Δmean-0.17, 95% CI-0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Intensive blood pressure lowering treatment to a systolic target <140mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.

A case of successful intraventricular thrombolysis and external ventricular drain treatment in primary intraventricular hemorrhage

Intraventricular hemorrhage (IVH), accounting for about 45% of acute spontaneous intracranial hemorrhage (ICH), is often associated with obstructive hydrocephalus and poor functional outcomes [1] [2]. Obstructive hydrocephalus and increased intracranial pressure are common after IVH because of an obstruction of normal cerebrospinal fluid (CSF) flow and absorption by blood clots. An external ventricular drain (EVD) - a temporary system that permits drainage of cerebral spinal fluid (CSF) from the ventricles to an external closed system) has been indicated for patients with IVH with hydrocephalus and neurologic decline [3]. However, the treatment with EVD alone is often not sufficiently effective due to a likely potential obstruction of the catheter by blood clots. Intraventricular fibrinolysis (IVF) via the extra-ventricular drain has been known to speed clot resolution and maintain the EVD functionality [4]. However, it is also possible that the risk of hemorrhage, infection, and CFS pleocytosis may be increased with IVF therapy, but these have not been demonstrated so far. We report a clinical case of primary IVH with acute obstructive hydrocephalus, successfully treated with a combination of EVD and direct intraventricular injection of rt-PA into the lateral ventricles. This treatment contributes to confirm that combination of EVD and thrombolysis could be considered as a treatment option for selected patients.

Endovascular thrombectomy for basilar artery occlusion stroke: Analysis of the German Stroke Registry-Endovascular Treatment.

Acute ischemic stroke due to basilar artery occlusion (BAO) causes the most severe strokes and has a poor prognosis. Data regarding efficacy of endovascular thrombectomy in BAO are sparse. Therefore, in this study, we performed an analysis of the therapy of patients with BAO in routine clinical practice. Patients enrolled between June 2015 and December 2019 in the German Stroke Registry-Endovascular Treatment (GSR-ET) were analyzed. Primary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3), substantial neurological improvement (≥8-point National Institute of Health Stroke Scale [NIHSS] score reduction from admission to discharge or NIHSS score at discharge ≤1), and good functional outcome at 3 months (modified Rankin Scale [mRS] score of 0-2). Out of 6635 GSR-ET patients, 640 (9.6%) patients (age 72.2 ± 13.3, 43.3% female) experienced BAO (median [interquartile range] NIHSS score 17 [8, 27]). Successful reperfusion was achieved in 88.4%. Substantial neurological improvement at discharge was reached by 45.5%. At 3-month follow-up, good clinical outcome was observed in 31.1% of patients and the mortality rate was 39.2%. Analysis of mTICI3 versus mTICI2b groups showed considerable better outcome in those with mTICI3 (38.9% vs. 24.4%; p=0.005). The strongest predictors of good functional outcome were intravenous thrombolysis (IVT) treatment (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.76-5.23) and successful reperfusion (OR 4.92, 95% CI 1.15-21.11), while the effect of time between symptom onset and reperfusion seemed to be small. Acute reperfusion strategies in BAO are common in daily practice and can achieve good rates of successful reperfusion, neurological improvement and good functional outcome. Our data suggest that, in addition to IVT treatment, successful and, in particular, complete reperfusion (mTICI3) strongly predicts good outcome, while time from symptom onset seemed to have a lower impact.

Application of an Artificial Neural Network to Identify the Factors Influencing Neurorehabilitation Outcomes of Patients with Ischemic Stroke Treated with Thrombolysis.

The administration of thrombolysis usually reduces the risk of death and the consequences of stroke in the acute phase. However, having received thrombolysis administration is not a prognostic factor for neurorehabilitation outcome in the subacute phase of stroke. It is conceivably due to the complex intertwining of many clinical factors. An artificial neural network (ANN) analysis could be helpful in identifying the prognostic factors of neurorehabilitation outcomes and assigning a weight to each of the factors considered. This study hypothesizes that the prognostic factors could be different between patients who received and those who did not receive thrombolytic treatment, even if thrombolysis is not a prognostic factor per se. In a sample of 862 patients with ischemic stroke, the tested ANN identified some common factors (such as disability at admission, age, unilateral spatial neglect), some factors with higher weight in patients who received thrombolysis (hypertension, epilepsy, aphasia, obesity), and some other factors with higher weight in the other patients (dysphagia, malnutrition, total arterial circulatory infarction). Despite the fact that thrombolysis is not an independent prognostic factor for neurorehabilitation, it seems to modify the relative importance of other clinical factors in predicting which patients will better respond to neurorehabilitation.

Abstract TP38: Gender Disparities In Ischemic Stroke Thrombolytic Treatment In Nebraska Hospitals

Introduction: Mission: Lifeline Stroke Nebraska was a 4-year program to enhance stroke systems of care in Nebraska. With 68% of hospitals in Nebraska participating in GWTG-Stroke, analysis of stroke treatment data can be accomplished on disparities across the state. Methods: De-identified data was accessed through AHA GWTG-Stroke registry to assess stroke outcomes of patients at 49 participating NE hospitals in 2020. Data were analyzed based on AHA specified Mission: Lifeline reporting, achievement, and pre-hospital measures. The purpose of analysis was to describe patient characteristics and determine differences in IV thrombolytic treatment and mean patient NIH stroke score (NIHSS) upon admission. Percentages and counts were reported for categorical variables. The mean, standard deviation (SD) and median were reported for continuous variables. The Kruskal-Wallis rank sum, Wilcoxon sign rank, T-tests, chi-square and one-way ANOVA tests were used, where appropriate, to assess differences in stroke outcomes by age, gender, and race/ethnicity. Results: Of the 3,952 patient encounters registered in GWTG-Stroke from 01/01/2020 to 12/31/20, 2670 (67.5 %) were patients 18+ at time of admission with clinical diagnosis of ischemic stroke. Statistically significant differences in age, NIHSS at admission, and treatment with thrombolytics by gender were observed. Compared to males, females were older (72.7 vs. 68.1 years), had a lower mean NIHSS at admission (5.8 vs. 6.0), and a smaller proportion of females received thrombolytic treatment (42% vs. 58%). Conclusions: Overall, females were less likely to receive IV thrombolytic treatment compared to males. Women in the study were older with lower NIHSS than males. Results from this analysis align with those from the study “The Impact of Sex and Gender on Stroke” (Rexrode, et al.,2022) indicating that females may present different signs of a stroke than males. Our data showed the NIHSS scores to be lower for females possibly leading to lower frequency of treatment. As a part of the Mission: Lifeline initiative, this information was shared with hospitals and providers across the state. These results led to public awareness and education targeted to women, including a local podcast and social media.

Abstract WP190: Central Retinal Artery Occlusion: Do Patient Presentation Patterns Complicate Use Of Potential Treatments?

Introduction: For patients diagnosed with central retinal artery occlusion (CRAO), timely screening for underlying risk factors to prevent secondary stroke and other cardiovascular events is required. Given the profound impact on vision, there is also great interest in the potential to treat CRAO. Thrombolytic therapy is the current standard of care in acute ischemic cerebral stroke, but the window for administration is short. As part of a larger pilot to investigate the prospect of intravenous thrombolysis for patients presenting with acute CRAO in our institution, we set out to evaluate the specific presentation patterns of this population within our system. Methods: Retrospective study performed on 804 patients correctly diagnosed with CRAO from 2011-2020. From this cohort of patients, we identified 484 for whom we could accurately determine the time of first symptoms, the time of first contact with the healthcare system, and the time of evaluation by an ophthalmologist. Results: While 18.0% (87/484) of patients waited over 24 hours from time of vision loss to contact the health care system, 50.2% of patients did connect in under 4.5 hours (243/484). However, only 16.7% (81/484) of patients saw an ophthalmologist within that window, and 35.5% (172/484) did not have any ophthalmologic evaluation within 24 hours of vision loss. Conclusion: Half of CRAO patients within our institution connect with the health care system within a potential window for intravenous thrombolytic treatment, but the majority do not receive ophthalmic diagnosis within that time frame. In conclusion, public health education efforts to speed up presentation times and system-based strategies to decrease the time to ophthalmic diagnosis are needed if thrombolytic treatment either via compassionate use or within a clinical trial setting is to be more widely offered.

Abstract WP230: Human Peripheral Blood Gene Expression Associated With 90day Ischemic Stroke Outcomes

Objective: Identifying the molecular underpinnings associated with long-term functional outcome after ischemic stroke (IS) could guide search for treatments for improved outcome. Thus, we identified early peripheral immune gene expression (GE) responses associated with 90-day IS outcome, as measured by the Barthel Index (BI). Methods: RNA from 108 samples from three peripheral blood draws (≤3h – before thrombolytic treatment; 5h and 24h - post-treatment) from 36 CLEAR-trial subjects was analyzed on Affymetrix arrays. We performed Analysis of Covariance accounting for treatment (tPA or tPA+eptifibatide), hypercholesterolemia, hypertension, diabetes, age, sex and BI. Genes whose partial correlation with BI was significant ( P &lt;0.005) were identified. Results: There were 206, 865, and 209 genes that significantly correlated with 90-day BI at ≤3h, 5h and 24h post ictus , respectively. The gene lists at all three time-points were enriched in B-cell specific genes (hypergeometric probability p&lt;0.05), while the 5h gene list was also enriched in neutrophil-specific genes, and the 24h gene list was also enriched in monocyte-specific genes. B Cell Receptor Signaling pathway was predicted activated in subjects with better 90-day outcome at the ≤3h time-point, while ICOS-ICOSL Signaling in T Helper Cells and Role of NFAT in Regulation of the Immune Response were predicted activated at the 24h time-point.Immune-related pathways were enriched at three time-points including B cell-related, IL-7, and T cell signaling pathways. Apoptosis was suppressed in patients with better 90-day outcome at 3h and 24h post ictus . Among the genes associated with the 90-day BI were genes important for stroke and repair after stroke, such as KCNG1 , Potassium voltage-gated channel subfamily G member 1, which like other potassium channels could modulate stroke outcome. KCNG1 expression was positively correlated with 90-day BI at ≤3h and 5h. TERML4 , implicated in inflammatory response and human coronary arterial calcification had expression that positively correlated with BI at all three time-points. Conclusion: The findings expand our understanding of the early molecular biology associated with long-term stroke outcome and may serve as potential targets to improve outcome.

Abstract TMP37: Gene Expression May Predict Symptom Onset Time In Acute Ischemic Stroke

Introduction: Imprecise timing of symptom onset (SO) in patients with acute ischemic stroke (AIS) may impact eligibility for reperfusion therapy. Unreliable “last-known-well” (LKW) estimates may reduce the use of thrombolytic or endovascular treatments. A blood biomarker that serves as a “stroke clock” could minimize uncertainty and augment treatment rates. Methods: The single-center VuEssence Stroke Trial (VEST) evaluated gene expression biomarkers in adult ED patients with suspected AIS, a LKW time &lt; 24hrs, and timing of SO accurate within a 0-3 hour time frame. At ED presentation and before reperfusion treatment, whole blood was collected in PAXgene RNA tubes for RNA-sequencing and gene expression analysis. Researchers blinded to molecular results adjudicated final diagnosis (AIS vs stroke mimic) and estimated time of SO based on times of witnessed onset (WO), LKW, and symptom discovery (SD). The confirmed AIS subgroup with WO timing, or ≤60 minutes between LKW and SD, was analyzed. Results: Of AIS patients, 56 met criteria (52% men, mean age 71.6). The average time from SO was 148 minutes (range 48-490). After RNA-sequencing, linear regression showed 684 genes with a significant linear time-related expression change in reference to time from SO (&lt;0.2 Benjamini-Hochberg p-adjusted). A subgroup of 210 genes with &lt;0.004 p-values and linear coefficients &gt;0.25 were used to generate multiple classifiers of up to 12 genes that identified AIS &lt;2.5 hrs from SO. Each gene is used in at least one classifier with other genes selected to maximize a measure of accuracy. The top panels showed both high sensitivity and specificity ( table ). Conclusion: Using a biological “stroke clock” biomarker instead of SO timing may streamline evaluations of suspected AIS, augment reperfusion therapy rates, and improve outcomes. VEST identified time-related gene expression changes that may accurately classify AIS &lt;2.5 hrs from SO. These gene panels will require further validation.

Abstract TP144: VARIANCE-S: Variability Of Assessed Bp Readings In Acute Neuro-intervention Cases And Its Effect On Outcomes Pertaining To Sex Differences

Introduction: Sex differences exist in thrombolytic stroke treatment and outcome and likely in endovascular thrombectomy (EVT). Previous analysis has shown a significant correlation of blood pressure variability (BPV) and sex. The purpose of this study was to assess sex differences in a sample of patients with good recanalization post-with EVT and examine the impact of BPV. Methods: We conducted a retrospective analysis of prospectively collected data from an IRB approved Stroke Registry of two academic Comprehensive Stroke Centers in Southern California between 2017 and 2022. Patients were included if they had 1) anterior circulation ischemic stroke due to large vessel occlusions (LVO) and 2) underwent successful EVT defined as a TICI 2b or 3 result. Male and female subjects were compared for age, sex, Hispanic ethnicity, initial NIHSS, history of HTN, current antihypertensive use, symptom onset to groin puncture time, door to groin puncture time, and symptomatic ICH (sICH), BPV, onset to groin, and door to groin . Good outcome was defined as mRS 0-2. Chi squared a t-test were used as appropriate. Results: We included 131 females and 124 males. There was a significant difference between males and females in: 1) history of a fib (76% v 64%, p=0.42); 2) atrial fibrillation during admission (36% v 50%, p=0.01); 3) age (male 67 v female 73 years, p&lt;0.001); 4) post-EVT SBP (137mmHg v 144mmHg, p-0.02). There was a significant difference in onset to groin (p=0.41), but no significant difference in door to groin (p=0.59). When adjusting for time of onset, there was no significant difference in thrombolysis prior to EVT between groups. There was no significant difference in sICH (6 male v 4% female, p=0.50), 90 day mRS (p=0.81); or discharge disposition (p=0.56). BPV was significantly correlated with sex but not significant for any interaction effect with the variables assessed. Conclusion: This study found no significant sex differences in outcome in this sample. The systems of care provided by an academic, CSC ensure that all patients’ care is expedited and provides the best opportunity for a good outcome in both sexes. Studies of sex differences in EVT treatment and outcome in multiple stroke care settings are vital to reduce disparities in care.

Abstract WP161: Does History Of Atrial Fibrillation (Afib) Impact TICI Scores In Acute Ischemic Stroke Patients Receiving Endovascular Treatment With Or Without Iv Thrombolytics? Results From A Large Health System In Six Western States Of The United States

Introduction: Despite the importance of Afib in stroke, it is unclear whether patients with acute ischemic stroke (AIS) and Afib have a different response to reperfusion with IV thrombolysis (IVT) and/or endovascular treatment (EVT) compared to non-Afib patients. Patients with AIS due to Afib may have difficulty achieving favorable TICI scores (The thrombolysis in cerebral infarction).This study aimed to compare the TICI scores in patients with and without a history of Afib treated with EVT and/or IVT. Methods: Data on consecutive AIS patients (a multi-state health system’s stroke registry) treated with EVT and/or IVT for five years (2018 -2022) were evaluated. Patients were stratified into two groups, 1- EVT only with or without a history of Afib; 2- IVT plus EVT with or without a history of Afib.Multivariable mixed effect logistic regressions were performed to evaluate if patients with AFib showed a difference in TICI scores (favorable outcome : TICI: 2b-3) within the two treatment groups adjusting for patient age, sex, race and ethnicity, NIHSS on admission, blood glucose on admission, SBP on admission and history of diabetes, CAD/prior MI, carotid stenosis, smoking, dyslipidemia, heart failure, or being overweight. Results: The cohort consists of 3311 patients with a median age at arrival 73 years and median NIH Stroke scale 16, who were 51.7% females, 68% white, 23.9% diabetes mellitus, 51.6% dyslipidemia , 20.5% CAD , 13.6% smoking, 53.6% overweight, 14.9% HF.In group 1 (EVT) :2350 patients:37.3% had Afib and 93.6% achieved a score of TICI 2b-3 .In group 2 (EVT+IVT): There were 961 patients, 28.7% having Afib with 94.9% achieving TICI 2b-3. After adjustment, there was no difference in the TICI scores between two groups . Conclusions: In this study, atrial fibrillation did not significantly impact TICI scores in AIS patients treated with EVT. The study also supports the efficacy of EVT in combination with IVT in the population with Afib.

Abstract TP98: Deep Learning-based Automatic Ischemic Core Estimation Based On Non-contrastenhanced Computed Tomography

Background/Purpose: With the spread of thrombus retrieval procedures, the demand for immediate diagnosis and severity assessment of ischemic stroke is increasing, but current standard method using ASPECTS is semi-quantitative, and has low consistency among physicians. We develop and validate the fully automatic machine learning-based ischemic core segmentation model based only on non-contrast-enhanced computed tomography (NCCT). Materials and Methods: This multicenter retrospective study included patients with anterior circulation acute ischemic stroke who received both CT and MRI before thrombolysis or recanalization treatment between 2013 to 2019. The ischemic core on CT was manually delineated referencing the DWI and ADC map. A deep learning-based ischemic core segmentation model was developed using the derivation cohort data from 3 institutions (n=313), and the model performance was validated on the external validation cohort data from 3 institutions (n=106). Results: On the validation cohort, the median time between CT and MRI was 18 min. The ischemic core volume calculated by the DL model was significantly correlated with the reference standard (Pearson r=0.91, p&lt;.001). The correlation was significant both in early time window (&lt;4.5hr from onset; Pearson r=0.91, p&lt;.0.01) and the late time window (&gt;4.5hr from onset; Pearson r=0.93, p&lt;0.01). The median difference between model and reference standard was 4.7 mL (IQR, 0.8-12.4 mL). The DL model displayed high accuracy on discriminating large ischemic core (&gt;70mL) with a sensitivity of 84.2%, specificity of 97.7%, and AUC of 0.91. Conclusions: A segmentation model of cerebral ischemic core volume of the anterior circulation based on NCCT using deep learning showed good correlation with the correct labels generated with reference to MRI.

Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial

There is increasing interest in replacing alteplase with tenecteplase as the preferred thrombolytic treatment for patients with acute ischaemic stroke. We aimed to establish the non-inferiority of tenecteplase to alteplase for these patients. In this multicentre, prospective, open-label, blinded-endpoint, randomised controlled, non-inferiority trial, adults with an acute ischaemic stroke who were eligible for standard intravenous thrombolysis but ineligible for endovascular thrombectomy were enrolled from 53 centres in China and randomly assigned (1:1) to receive intravenous tenecteplase (0·25 mg/kg, maximum dose of 25 mg) or intravenous alteplase (0·9 mg/kg, maximum dose of 90 mg). Participants had to be able to receive treatment within 4·5 h of stroke, have a modified Rankin Scale (mRS) score of no more than 1 before enrolment, and have a National Institutes of Health Stroke Scale score of 5-25. Patients and treating clinicians were not masked to group assignment; clinicians evaluating outcomes were masked to treatment type. The primary efficacy outcome was the proportion of participants who had a mRS score of 0-1 at 90 days, assessed in the modified intention-to-treat population (all randomly assigned participants who received the allocated thrombolytic), with a non-inferiority margin of 0·937 for the risk ratio (RR). The primary safety outcome was symptomatic intracranial haemorrhage within 36 h, assessed in all participants who received study drug and had a safety assessment available. The trial is registered with ClinicalTrials.gov, NCT04797013, and has been completed. Between June 12, 2021, and May 29, 2022, 1430 participants were enrolled and randomly assigned to tenecteplase (n=716) or alteplase (n=714). Six patients assigned to tenecteplase and seven to alteplase did not receive study product, and five participants in the tenecteplase group and 11 in the alteplase group were lost to follow-up at 90 days. The primary outcome in the modified intention-to-treat population occurred in 439 (62%) of 705 in the tenecteplase group versus 405 (58%) of 696 in the alteplase group (RR 1·07, 95% CI 0·98-1·16). The lower limit of the RR's 95% CI was greater than the non-inferiority margin. Symptomatic intracranial haemorrhage within 36 h was observed in 15 (2%) of 711 in the tenecteplase group and 13 (2%) of 706 in the alteplase group (RR 1·18, 95% CI 0·56-2·50). Mortality within 90 days occurred in 46 (7%) individuals in the tenecteplase group versus 35 (5%) in the alteplase group (RR 1·31, 95% CI 0·86-2·01). Tenecteplase was non-inferior to alteplase in people with ischaemic stroke who were eligible for standard intravenous thrombolytic but ineligible for or refused endovascular thrombectomy. National Science and Technology Major Project, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Abstract 118: Expanded Tele-stroke Coverage In Community Hospitals Improves Care For Stroke Patients And Reduces Transfers

Background: Minor ischemic strokes and transient ischemic attacks account for more than a third of ER stroke admissions (21% and 15%, respectively). Most small community hospitals lack adequate coverage by stroke service necessitating transfer of stroke patients to comprehensive stroke centers. Methods: We studied the effect of implementing telestroke service in all regional hospitals and emergency departments affiliated with Promedica Toledo Hospital, a comprehensive stroke center (CSC). This service is carried out by stroke-trained advanced practice providers under supervision of vascular neurologists. Coverage included acute ED assessments of stroke patients, inpatient telestroke consults and follow ups. We propose that this comprehensive telestroke service will improve care of stroke patients presenting to community hospitals, decrease the number of transfers to CSC. It will improve numbers and timing of IV thrombolysis. Results: The total stroke alerts from affiliated locations before implementing telestroke service (2018 and 2019 and first half of 2020), and after implementing the service (since July 2020, 2021, and 2022) were 4817 and 4900, respectively. In pre-telestroke years, about 43% of patients were transferred to the CSC for acute stroke care while during post-telestroke years were 28% with 34.8% reduction on transfers. Among transferred patients, stroke mimickers' percentage decreased from 21% to 8%. There was a 14.5% increase in the number of IVT patients after implementing telestroke service but door to needle time did not change. Conclusion: This is the first reported experience of utilizing stroke-trained APPs to expand telestroke coverage for both ED and inpatient services at community hospitals. There was a decrease in number of transfers to CSC, keeping patients at their local communities. It also increased the number of IV thrombolytic treatments and reduced the number of stroke mimickers' transfers.

Abstract WP87: Sex-based Variation In Acute Stroke Care Via Telestroke

Objective: Assess for treatment differences by sex and their potential contributors among telestroke evaluations. Background: Studies have shown sex differences in stroke care. Female patients have both lower thrombolytic treatment rates with OR as low as 0.57 reported and worse outcomes. With improved access to care through telestroke and updated standards of care, there is potential to reduce or alleviate these disparities. Methods: Acute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 203 facilities (23 states) from January 1, 2021 to April 30, 2021 were extracted from the Telecare TM database. The encounters were reviewed for age, sex, last known normal (LKN), arrival time, consult call time, needle time, thrombolytics candidate, premorbid modified Rankin Score (p-mRS), NIHSS score, screen time, stroke risk factors (hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary artery disease and previous stroke), antithrombotic use, admitting diagnosis of stroke, and reason not treated with thrombolytic. The treatment rates, Door-to-needle (DTN) times, and variables of treatment were compared for females and males. Results: There were 18,783 (10,073 female and 8,710 male) total patients included. Of the total, 6.9% of females received thrombolytics compared to 7.9% of males (OR 0.86, 95% CI 0.75-0.97, p=0.006). Median DTN times were shorter for males (38 minutes) than females (41 minutes), p&lt;0.001. Male patients were more likely to have an admitting diagnosis of stroke, p &lt;0.001. Female patients &lt;50 and ≥80 years of age were treated at a higher rate than males, while males 50-79 were treated at a higher rate than females. Multivariate analysis of the 50-79 age group did not show a difference in the thrombolytics treatment rates (female 7.6% and male 8.3%, p= 0.752), but did show males had higher rates of all stroke risks factors. Conclusion: While the overall lower treatment rate for females in univariate analysis was consistent with previous studies, the difference was not seen in multivariate analysis. The treatment differences between males and females were negated once the significant sex-based differences in stroke risk factors are taken into consideration.

Abstract WMP8: Tenecteplase Versus Alteplase For Acute Ischemic Stroke: Treatment Outcomes From A Large Northwest Us Stroke Registry

Introduction: The American Stroke Association Guidelines on acute ischemic stroke (AIS) thrombolytic treatment endorse the use of tenecteplase (TNK) weakly (IIb) based on moderate quality (B-R) evidence. The use of alteplase for AIS is strongly recommended (I) with high quality (A) of evidence. Despite this, many healthcare systems have transitioned to the use of TNK based on limited clinical trial data. Our study presents real world outcome data comparing AIS patients treated with TNK vs alteplase. Methods: Data were retrospectively abstracted from AIS patients treated with IV thrombolytic (IVT) or IVT and endovascular therapy (EVT) discharged between 1/1/2019-6/30/2022 . Patients were grouped into alteplase w/wo thrombectomy and TNK w/wo thrombectomy. Primary outcomes were discharge disposition, complications (sICH, serious systemic hemorrhage), door to needle and door to device times, treatment complications and post-EVT TICI score. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) are reported for likelihood to receive IVT within 45 minutes and 30 minutes of arrival for the IVT group, adjusting for sex, race, admit NIHSS, and previous stroke. Results: 3733 patients were included in the IVT group: 90.7% received alteplase, 9.3% received TNK. 814 patients received IVT and EVT: 90% received alteplase and 10% received TNK. In the IVT group, the median [Q1, Q3] DTN for alteplase was 48 [35, 66] minutes TNK was 45.5 [34.75, 63.25] (p=0.067). There was no significant difference in the likelihood of receiving IVT within 45 minutes and 30 minutes between the two drugs. Patients with higher admit NIHSS were more likely to receive IVT within 45 minutes (AOR 1.031 95% 1.021, 1.041 p&lt;0.0001) and within 30 minutes (AOR 1.025 95% 1.013, 1.037 p&lt;0.0001). There were no significant differences found in median DTN, DTD or TICI score for patients receiving both IVT and EVT. There were no significant differences in complications for any group. Conclusion: In our study there were no differences in benefit, risk, or treatment logistics between alteplase and tenecteplase when used in treating acute ischemic stroke. Recanalization of large vessel occlusion prior to endovascular thrombectomy was not analyzed but will be the subject of study in this cohort.