Case series of intravenous thrombolysis for acute ischemic stroke in confirmed COVID-19 patients: single-centre experience

Background Coronavirus disease 2019 (COVID-19) not only caused a large surge of respiratory infections, it also had a potential association with and increases the risk of stroke. The pandemic has certainly provided new challenges and opportunities in the management of acute ischemic stroke (AIS); however, data regarding outcomes of intravenous tissue plasminogen activator (IV TPA) administration in stroke patients with COVID-19 remains limited. Case presentation Three AIS patients with confirmed COVID-19 treated using IV tPA. One case had excellent outcome, while the other cases showed unfavorable results. The risk–benefit ratio of IV TPA in COVID-19 remains unclear. Conclusion In this article, we discuss the possible explanation behind these different outcomes. Although IV tPA could not cure COVID-19, we suggest that its administration should not be delayed in AIS patients with COVID-19.

Mechanical Thrombectomy With and Without Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis Using Nested Knowledge

Background: Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform.Methods: The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0–2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure.Results: We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]).Conclusions: Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.

Quantification of clot spatial heterogeneity and its impact on thrombectomy

BackgroundCompositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis.MethodsWe collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann–Whitney test and an artificial neural network (ANN) model.ResultsFor cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration.ConclusionsClot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.

Mechanical thrombectomy versus intravenous alteplase alone in acute isolated posterior cerebral artery occlusion: a systematic review

BackgroundAcute isolated posterior cerebral artery occlusions (aPCAOs) were excluded or under-represented in major randomized trials of mechanical thrombectomy (MT). The benefit of MT in comparison to intravenous tissue plasminogen activator (alteplase; IV-tPA) alone in these patients remains controversial and uncertain.MethodsWe performed a systematic search of PubMed, MEDLINE, and EMBASE databases for articles comparing MT with or without bridging IV-tPA and IV-tPA alone for aPCAO using keywords (‘posterior cerebral artery’, ‘thrombolysis’ and ‘thrombectomy’) with Boolean operators. Extracted data from patients reported in the studies were pooled into groups (MT vs IV-tPA alone) for comparison. Estimated rates for favorable outcome (modified Rankin scale score 0–2), symptomatic intracranial hemorrhage (sICH), and mortality were extracted.ResultsSeven articles (201 MT patients, 64 IV-tPA) were included, all retrospective. There was no statistically significant difference between pooled groups in median age, median presentation National Institutes of Health Stroke Scale (NIHSS) score, PCAO segment, and median time from symptom onset to puncture or needle. The recanalization rate was significantly higher in the MT group than the IV-tPA group (85.6% vs 53.1%, p<0.00001). Odds ratios for favorable outcome (OR 1.5, 95% CI 0.8 to 2.5), sICH (OR 1.1, 95% CI 0.2 to 5.5), and mortality (OR 1.4, 95% CI 0.5 to 3.6) did not significantly favor any modality.ConclusionsWe found no significant differences in odds of favorable outcome, sICH, and mortality in MT and IV-tPA in comparable aPCAO patients, despite superior MT recanalization rates. Equipoise remains regarding the optimal treatment modality for these patients.

Abstract 1122‐000067: Radial Versus Femoral Artery Access for Mechanical Thrombectomy Following IV tPA Administration

Introduction : The transradial artery (TRA) approach for neuroendovascular procedures has been demonstrated as a safe and effective alternative to the transfemoral artery (TFA) approach. The present study compares the efficiency and periprocedural outcomes of the TRA and TFA approach for acute stroke interventions in patients receiving intravenous alteplase. Methods : The study was designed as a retrospective analysis of patients who underwent acute mechanical thrombectomy at a large cerebrovascular center between January 2014 and March 2021. Intervention cohorts (TRA and TFA) were compared on baseline characteristics, periprocedural efficiency/efficacy, and in‐hospital outcomes. Results : A total of 314 patients underwent acute mechanical thrombectomy following IV tPA via TRA (6.7%, 21/314) or TFA (93.3%, 293/314) approach. The overall complication rate appeared higher in TFA (6.8%, 20/314) compared to TRA (4.8%,1/21) patients. Access site complications were present in 4.1%(12/293) of TFA patients and 0.0%(0/21) of TRA patients. The average length of stay (days ± standard deviation) was significantly greater in TFA (8.8 ± 8.5) vs. TRA (4.8 ± 2.9) patients (P = 0.02). Linear regression analysis found femoral access (p = 0.046), Medicaid (p = 0.004) insurance, and discharge NIHSS >10 (p = 0.045) as predictors of increased length of stay. However, when time to initial physical/occupation session was added to the model, access site was no longer significant. Conclusions : The TRA (vs. TFA) approach for acute stroke interventions following IV tPA administration may potentially reduce periprocedural complications and hospital length of stay. The reduction in length of stay with TRA access appears to be associated with earlier initiation of therapies.

Abstract 1122‐000234: Hemorrhagic Conversion in Patients Undergoing MT with Concurrent IA tPA with or Without IV tPA/Anticoagulation

Introduction : Introduction There is a growing body of literature on concurrent use of MT and IA tPA use in acute large vessel occlusion ischemic stroke, but few address the risk of IA tPA use in patients also receiving IV tPA or baseline anticoagulation1,23. This cohort study aims to assess the rate of improved functional outcome and complications in patients receiving MT plus IA tPA with or without IV‐tPA or baseline anticoagulation. Methods : In this single institution, retrospective cohort study, medical records of 114 patients undergoing MT who received concurrent IA‐tPA were identified and reviewed. Parameters such as age, sex, admission/discharge mRS scale and NIHSS score, INR, history of anticoagulation use, concomitant IV‐tPA and complications such as any hemorrhage and in hospital death were reviewed. Patients were divided into two groups and two subgroups. First group included patients treated with IA‐tPA who also received IV‐tPA, had an INR above 1.7 or were on anticoagulation therapy. The second group was composed of patients who only received concurrent IA‐tPA. The primary outcomes were hemorrhage, all cause mortality, and good functional outcome (modified Rankin scale equal to or less than 2). The results were calculated and t‐test for two samples analysis was conducted with one‐tail p‐value (<0.05). Results : 74 patients were included in the first group receiving IA‐tPA with either IV‐tPA, or elevated INR or anticoagulated while 40 patients were in the only concurrent IA‐tPA group. 72% versus 60% of the groups respectively have an mRS less or equal to 2 on discharge, p‐value 0.07. 41% of the first group had some type of bleeding on repeat imaging compared to 25% in the IA‐tPA only group, p‐value 0.03. In a subgroup analysis, IV‐tPA alone without prior anticoagulation treatment or an elevated INR, when given in conjunction with IA‐tPA, was an independent risk factor that increased rate of bleeding, 42% versus 25% with a p‐value of 0.04 with an attributable risk of 32%. There was no difference in in‐hospital death rate between the groups. Conclusions : This study shows that in patients receiving MT with concurrent IA tPA with elevated INR>1.7, treatment with anticoagulation at baseline, or concomitant IV‐tPA use increases the risk of hemorrhagic conversion. Therefore, there is a need for careful selection of patients receiving concurrent IA‐tPA. Further investigation is warranted to elucidate which patient groups might maximally benefit from IA‐tPA.

Abstract 1122‐000091: Predictors of Symptomatic Hemorrhagic Transformation After Mechanical Thrombectomy in Acute Ischemic Stroke

Introduction : Mechanical thrombectomy (MT) has become the current standard of care for large vessel occlusion stroke but is associated with an increased risk of intracranial hemorrhage (ICH). Although several studies have investigated the risk factors, there is still limited, not well‐established data. This study aims to evaluate the risk factors of HT after MT. Methods : We retrospectively reviewed all MT patients who were treated at a single comprehensive stroke center from 12/2016 to 7/2019. Variables included initial NIHSS, blood glucose, initial systolic blood pressure, age, gender, IV tPA, time from door to recanalization, and TICI score. Outcome measures were HT on post‐procedure or 24‐hour post‐tPA head CT/MRI as well as modified Rankin scale (mRS) upon discharge. Results : Among 74 patients (68.8 ± 14 years, men 47.3%), 9 (12.2%) experienced hemorrhagic transformation after thrombectomy. Average admitting NIHSS was significantly higher in the HT group (22 vs 16.8, p = 0.041). TICI 3 after MT was protective for HT (OR 0.078, 95% CI 0.009‐0.663). IV tPA (OR 3.86, 95% CI 1.448‐10.326) was associated with good neurological outcome at discharge (mRS < = 2), but HT was not (OR 0.114, 95% CI 0.013‐0.964). Patients with mRS < = 2 upon discharge were younger (65.2±12 vs 71.9±15, p = 0.04) and had lower initial BG (124±45.8 vs 157±69.6, P = 0.02). Conclusions : TICI 3 score, decreased NIHSS, and lower BG were associated with less HT and better outcomes in our MT cohort. Admitting NIHSS > = 20 may be a reasonable threshold to predict HT after MT. Our findings are consistent with the TICI‐ASPECTS‐glucose (TAG) score to predict sICH; however, we used initial NIHSS as a surrogate for ASPECTS. Further studies may utilize additional quantitative measures such as CTP data to predict HT.

Abstract 1122‐000168: Hyperacute Stenting and Angioplasty for Isolated Non‐tandem Cervical ICA Strokes within the First 48 Hours

Introduction : Acute stroke that involves complete and isolated occlusion of extracranial cervical ICA segment with no intracranial clot burden account for a minority of stroke cases. Since endarterectomy is not recommended in the hyperacute phase (first 48 hours), management of these strokes includes administration of IV‐tPA as part of standard medical therapy. This makes endovascular intervention with acute carotid artery stenting (CAS) with or without balloon angioplasty a viable treatment option during the hyperacute phase of the disease. We aim to present our two‐decade long experience of endovascular management of complete and isolated cervical ICA occlusive strokes in the hyperacute phase, and attempt to evaluate the clinical efficacy and safety of this treatment modality. Methods : A prospectively maintained database was retrospectively searched for patients who presented from Jan 2000 – Dec 2020 with acute cervical ICA stroke confirmed on angiography. Only patients who had 100% occlusion of cervical ICA segment and who underwent acute CAS within the first 48 hours of symptom onset were included. Patients who had an intracranial or tandem lesion or those with <100% EC‐ICA stenosis were excluded. Information on demographics, co‐morbidities, procedural details, and complications was recorded. Rate of adequate revascularization and follow up were also recorded. Results : A total of 46 patients with acute cervical ICA occlusive stroke were included in the study. Mean age was 68.9 years, and 32 (69.6%) were male. Median NIH Stroke Scale at admission was 8 (IQR 7) with a perfusion deficit seen in 78.3% of cases. IV‐tPA was administered in 41.3% of cases with median time from symptom onset to puncture 14.4 hours. Stenting was performed in all patients with pre‐ and/or post‐angioplasty done in 78.3% of cases. Successful recanalization was achieved in 82.6% cases. One patient (2.2%) suffered a symptomatic intracerebral hemorrhage (sICH) post‐procedure. Outcome measures were reported as stable or improved NIHSS at discharge in 86.9% of cases, with good outcome (functional independence at 90‐day‐mRS <2) at 78.3% and a mortality rate of 6.5%. Conclusions : Emergent stenting and angioplasty for acute cervical ICA occlusive strokes within the first 48 hours (hyperacute phase) can be performed successfully with good clinical outcomes and an impressive rate of recanalization.

Abstract 1122‐000137: Characteristics and Utilization of Acute Reperfusion Therapy after Transfer of In‐Hospital LVO Strokes

Introduction : Acute repercussion therapy for acute ischemic stroke is a crucial tool in the tertiary care setting for patients presenting with large vessel occlusion (LVO). While strokes that present from the community have favorable outcomes compared to in‐hospital strokes, it is unclear if this is because of greater access to endovascular therapy. We aim to characterize the utilization of endovascular reperfusion therapy for in‐house LVO and compare outcomes of in‐house LVOs to those presenting from the community. Methods : From the period of December 2013 to December 2019, all stroke patients with an LVO who presented to a primary stroke center (“spoke” hospital) who were transferred to a comprehensive stroke center (“hub”) were analyzed. Univariate and multivariate analyses were performed to compare baseline characteristics and clinical outcomes. Results : A total of 181 in‐house strokes were transferred from a peripheral center to our comprehensive stroke center. About 16% (29) received IV‐tPA at the OSH and 2 additional patients received IV‐tPA at the CSC [17%; n = 31]. 163 patients harbored an intracranial acute vessel occlusion. Anterior LVO (ICA, M1,M2) and basilar artery occlusion was observed in 64% (n = 116) patients and 6% (n = 11) patients, respectively [Total LVO‐ 70%; n = 127]. 20% (n = 27) of LVO received IV‐tPA and 72% (n = 91) of LVO underwent thrombectomy. Reasons for not receiving included symptoms improved (25%), repeat imaging made reperfusion inadvisable (72.2%) and poor baseline (2.8%). Rates of mRS 0–2 in patients with ICA/M1/M2 receiving EVT were 13% (13/100) and the mortality rate was 45% (46/103). Rates of mRS 0–2 were significantly lower [13% vs 38%, p<0.01] and mortality was significantly higher [45% vs 18%, p<0.01] amongst anterior LVO in‐house transfer patients receiving EVT compared to all anterior LVO patients receiving EVT in the given time period. Conclusions : A relatively large proportion of in‐house LVO stroke patients underwent thrombectomy (70%). Most common cause of not receiving thrombectomy was imaging findings showing completed or large infarct. Compared to their community stroke counterparts, in‐house LVO strokes had lower efficacy outcomes and higher mortality. Further study in required to understand these findings.

P.117 Pediatric acute ischemic stroke protocols

Background: Approximately 1,000 children present with AIS annually in North America. Most suffer from long-term disability. Childhood AIS is diagnosed after a median of 23 hours post-symptom onset, limiting thrombolytic treatment options that may improve outcomes. Pediatric stroke protocols decrease time to diagnosis. AIS treatment is not uniform across Canada, nor are pediatric stroke protocols standardized. Methods: We contacted neurologists at all 16 Canadian pediatric hospitals regarding their AIS management. Results: Response rate was 100%. Seven centers have an AIS protocol and two have a protocol under development. Seven centers do not have a protocol – two redirect patients to adult neurology, and five use a case-by-case approach for management. Analysis of the seven AIS protocols reveals differences: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (n=1) versus age-independent 0.9 mg/kg (n=6), with maximum doses 75 mg (n=1) or 90 mg (n=6); 2) IV-tPA lower age cut-off: 2 years (n=4) versus 3, 4 or 10 years (n=1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (n=3), <5 (n=1), or <6 (n=3); 4) Pre-treatment neuroimaging: CT (n=3) versus MRI (n=4); 5) Intra-arterial tPA use (n=3). Conclusions: The seven Canadian pediatric AIS protocols show prominent differences. We plan a teleconference discussing a Canadian pediatric AIS consensus approach.