IV tPA Research Articles

Abstract Number ‐ 241: Simultaneous IV tPA During Thrombectomy Reduces Post‐Procedure Hypoperfusion Volumes in Anterior LVO Patients

Introduction Simultaneous tPA administration during mechanical thrombectomy may induce synergistic benefits (1). We aimed to characterize the hypoperfusion status after thrombectomy according to the timing of tPA administration and the degree of final recanalization. Methods We studied consecutive anterior circulation large vessel occlusion (LVO) stroke patients treated with mechanical thrombectomy who received a CT perfusion (CTP) immediately after endovascular procedure (2). Patients were divided in three groups according to: no iv tPA treatment (non‐tPA), tPA administration before 120 minutes (tPA>120) or iv tPA administration within 120 min (tPA< 120) of groin puncture. The extend of post‐procedure hypoperfusion (volume Tmax>6s) and relative hypoperfusion reduction compared with admission CTP (volume post‐procedure – admission Tmax>6s/admission Tmax>6s) according to final TICI scores were compared between the three study groups. Results One hundred and sixty‐nine patients were included in the study, mean age 72 years and median baseline NIHSS of 15. Thirty (17.8%) patients received iv tPA more than 2h before groin puncture (tPA>120), 32(18.9%) within 2h of the puncture (tPA < 120) and 107(63.3%) were non‐tPA. No difference on stroke severity, pre‐procedure hypoperfusion volume or occlusion location before thrombectomy were detected between groups. The rate of complete recanalization (TICI 3, 38.5%) was also similar in the 3 study groups (p = 0.12). Overall, the post‐procedure hypoperfusion volume was significantly lower in the tPA< 120 group (19.9±4.6cc vs 35.0±5.5, p = 0.04), and the relative hypoperfusion reduction was higher in tPA< 120 (0.86 vs 0.66, p = 0.05) as compared to non‐tPA. No significant differences were detected between non‐tPA and tPA>120 groups. For each final TICI score the post‐procedure hypoperfusion tended to be lower in the tPA< 120‐group, with a stronger reduction in patients with lower degree of recanalization (Figure). Conclusions A reduction of post‐thrombectomy hypoperfusion volumes was detected in patients treated with iv tPA during or shortly before thrombectomy, which could be a surrogate marker of the beneficial effect of tPA on the microcirculation. The specific reperfusion synergistic effect of tPA and mechanical thrombectomy beyond LVO recanalization warrants future studies.

Abstract 147: Reducing The Workflow Times For Reperfusion Therapy For Acute Ischemic Stroke By Using A Task Management Mobile Application For Stroke Care

Background: Since the effectiveness of reperfusion therapy for acute ischemic stroke (AIS) is highly time-dependent, stroke centers are required to carry out quality management (QM) of AIS care and provide treatment promptly. For many hospitals, however, QM are not easy. We have developed a mobile application named Task Calc. Stroke (TCS) to support the hospital's QM while supporting the staffs task processing. This study aims to evaluate the impact of using TCS on the workflow times of reperfusion therapy and clinical outcomes. Methods: We conducted a prospective cohort study at 4 Japanese comprehensive stroke centers for 33 months from June 2018 to December 2020. Patients treated with intravenous tissue plasminogen activator (IV-t PA) / mechanical thrombectomy (MT) were enrolled. The research team visited each facility and trained how to use TCS for AIS care. Each facility begun using TCS after training. We divided the study period into three stages as follows: 1) Pre-intervention stage, 2) Training stage, and 3) Using TCS stage and examined the workflow times such as door-to-needle time (D2N) for IV-tPA and door-to-puncture time (D2P) for MT and clinical outcomes (at discharge modified Rankin Scale score (mRS)). Results: During the study period, 333 cases (165 pre-intervention stage, 80 training stage, and 88 using TCS stage) underwent reperfusion therapy, 250 received IV-tPA, and 156 received MT. For D2N, the geometric mean decreased significantly from 57.7 minutes to 51.3 minutes in the training stage compared to the pre-intervention stage (Exp (β) 0.816: 95% CI 0.691-0.963, P=0.016) and further decreased to 49.7 minutes in the using TCS stage (Exp(β) 0.759: 95% CI 0.65-0. 888, P=0.001). For D2P, it slightly increased from 91.1 to 95.8 minutes in the training stage (Exp(β) 0.939: 95%CI 0.75-01.175, P=0.578), and significantly decreased to 84.2 minutes in the using TCS stage (Exp(β) 0.675: 95%CI 0. 524-0.87, P=0.003). The severity of disability tended to decrease across the mRS range (adjusted common odds ratio, 0.49; 95% CI, 0.22-1.11; P = 0.088) in the TCS using stage. Conclusions: TCS care support hospital's QM to reduce the workflow times of reperfusion therapy and tends to improve clinical outcomes.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Abstract P5: IV Alteplase Benefits Thrombectomy Patients With Incomplete TICI 2 Endovascular Reperfusion but Not Those With Complete TICI 3 Endovascular Reperfusion

Introduction: There is debate regarding how IV tPA influences the efficacy of Endovascular therapy (EVT). One hypothesized potential benefit of thrombolytics is in patients with incomplete endovascular reperfusion. We compared discharge disposition in EVT patients with TICI 2 or TICI 3 reperfusion who received IV tPA with those who did not. Methods: Data from the Providence System Stroke Registry for acute ischemic stroke patients receiving EVT between January 2015 and May 2020 with a TICI 2 or TICI 3 reperfusion grade were used. Patients presenting later than the conventional 4.5 hour IV tPA window were excluded. Multinomial regressions were used to assess if EVT patients with a TICI 2 or TICI 3 who received IV tPA compared to those who did not receive IV tPA had greater odds of being discharged as expired or hospice or other location (acute care or long term care, skilled nursing facility, left against medical advice), compared to home or inpatient rehabilitation (IRF), adjusting for patient age, sex, race and ethnicity, last known well to arrival, NIHSS at admit, and medical history. Adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) are reported. Results: Of 419 EVT patients with TICI 2, 50.1% (n=210) received IV tPA and 49.9% (n=209) did not. Of 771 EVT patients with TICI 3, 48.4% (n=373) received IV tPA and 51.6% (n=398) did not. EVT patients with TICI 2 who were not treated with IV tPA were 59% less likely to be discharged as expired or hospice than home or IRF than those treated with IV tPA (AOR=0.414, 95% CI: 0.203, 0.844), and 63% less likely to be discharged somewhere other than home/IRF (AOR=0.372, 95% CI: 0.217, 0.636) than home/IRF. Among EVT patients with TICI 3, multivariate analyses indicated there was no greater likelihood of being discharged expired or to hospice than home/IRF (AOR=0.682, 95%CI: 0.434, 1.07) or discharged somewhere other than home/IRF (AOR=0.839, 95%CI: 0.592, 1.19) between those who received IV tPA and those who did not. Conclusions: Thrombectomy patients with TICI 2 reperfusion had better discharge outcome if they were treated with IV tPA. However, in completely reperfused patients with TICI 3 reperfusion outcome was not affected by prior IV tPA administration.

Flat panel imaging of occlusion site and collateral scores for emergent large vessel occlusion

IntroductionFlat panel imaging for emergent large vessel occlusion can be acquired prior to mechanical thrombectomy (MT). In this study, we examined patients undergoing MT with computed tomography angiography (CTA) to determine agreement on the site of occlusion and CTA collateral score (CS). MethodsFlat Panel CTA (FP-CTA) was acquired before MT. Time between CTA and FP-CTA acquisition, site of occlusion, and CS were reported. Significant CS change was defined as >2-point change, or any change to/from a malignant profile (CS = 0 to CS > 0, or vice versa). ResultsEleven patients (mean age, 60.8 years; NIHSS, 17; 55.0% female) were included; IV tPA was administered to 7. Intra-reader occlusion site, dichotomous CS, and continuous CS correlation between CTA and FP-CTA were 96.6%, 90.0%, and 86.6%, respectively. Inter-reader correlation for occlusion site was 93% for CTA and 100% for FP-CTA; dichotomous CS correlation was 87% for both CTA and FP-CTA; correlation of continuous CS was 77% for CTA and 87% for FP-CTA. ConclusionStandard CTA and FP-CTA have high intra and inter-reader correlation determining site of occlusion and CS in ELVO setting. This angiographic tool may have potential applications for both triage and patient selection.

Abstract 82: Thrombus Migration is a Common Phenomenon With IV TPA and May Have Negative Effects on Outcome When TPA Treatment is Given Before Endovascular Thrombectomy in Proximal Occlusions

Introduction: There is interest in understanding thrombus dynamics from IV TPA prior to endovascular thrombectomy (EVT) given the possible dichotomy amongst sites of occlusion for IV TPA benefit/harm. Kaesmacher et al reported beneficial 5+% rates of early TICI > 2a reperfusion in distal M1 or M2 MCA occlusions with IV TPA. However in more proximal occlusions this was rare; and potentially harmful worsening of perfusion seen with change of occlusion site. We aimed to examine IV TPA related thrombus dynamics including migration further across both proximal and distal occlusions in a multicenter prospective cohort study INTERRSeCT. Methods: Acute ischemic stroke patients with intracranial occlusion who had baseline CTA and follow-up CTA or initial run angio in INTERRSeCT and IV TPA were reviewed. We evaluated change of occlusion site (COS) and classified patients into 4 categories: Complete Recanalization (CR) of primary occlusive lesion with no remaining thrombus; definite Thrombus Migration (dTM) with primary occlusion site moved to a distal artery and occlusion site patent on baseline CTA; probable Thrombus Migration (pTM) with COS evident but initial occlusion extent not visualized; or No Change of occlusion site (NC). Results: A total of 462 IV TPA patients were enrolled, 41% received EVT. Median time from TPA to follow-up imaging was 133 minutes. COS was seen in 50% of cases with CR in 15% and TM in 35% (dTM 12%, pTM 23%). Distal artery occlusion and longer interval of TPA to imaging were independent predictors for COS. In 62 proximal occlusion (ICA and proximal-mid M1 MCA) patients with follow-up imaging within 60 mins after TPA (receiving EVT in 94%), any TM showed a lower rate of 90-day mRS≤2 than NC (47% vs 78%, adjusted OR 0.21, 95%CI 0.04-0.87). No CR was seen in this early group. Conclusions: Thrombus migration is common after IV TPA. Thrombus instability from IV TPA may worsen clinical outcome in proximal occlusions despite early EVT initiation, possibly due to migration of thrombus to distal arteries accelerating infarction or more challenging thrombectomy due to thrombus dispersion. The benefit of IV TPA prior to EVT at comprehensive stroke centers for ICA or prox-mid M1 occlusions require more study in randomized clinical trials.

Abstract TP64: IV tPA Treatment of Minor Stroke Using MRI Targets Rather Than Clinical Severity

Background: It is unknown whether patients with non-disabling minor acute ischemic stroke (mAIS) at presentation benefit from IV tPA. The CT-based PRISMS trial suggested no benefit, but was inconclusive due to early termination for low enrollment. Conversely, we have observed an increasing trend in IV tPA treatment of mAIS patients screened with MRI. In this study, we sought to determine our IV tPA treatment rate of patients with mAIS and describe the frequency of MRI targets of acute ischemic stroke (AIS) for these patients stratified by clinical severity. Methods: Patients were included in this study if: 1) treated with IV tPA for AIS from 2015-2017, 2) baseline MRI, and 3) NIHSS<6. Baseline MRI was evaluated (2-rater with 3rd tie breaker) for AIS targets on DWI, PWI, GRE, FLAIR, and MRA. Patients were retrospectively categorized as “disabling” vs. “non-disabling” based on NIHSS (“non-disabling” defined as maximum 1 point each for visual fields, facial palsy, sensation, and dysarthria only). Frequency of AIS targets on MRI were compared between the two groups. Results: Of 305 patients treated with IV tPA, 140 (46%) had mAIS (NIHSS<6), 119 of 140 (85%) had baseline MRI, 53 of 119 (45%) were “non-disabling.” There was no difference in presence of these imaging targets between “disabling” vs. “non-disabling” mAIS patients: DWI lesion, 86.4% vs. 88.7%, p=0.705; PWI lesion, 80.3% vs. 79.2%, p=0.685; PWI/DWI mismatch, 62.1% vs. 50.9%, p=0.337; FLAIR HVS, 48.5% vs. 43.4%, p=0.775; MRA LVO, 24.2% vs. 26.4%, p=0.829, MRA LVO location, p=0.91. There was a trend toward greater visualization of GRE thrombus in the “disabling” group: 40.9% vs. 24.5%, p=0.060. “Non-disabling” mAIS patients treated based on MRI target accounted for 17% of all IV tPA-treated patients. Conclusions: In MRI-screened patients with mAIS, there is no difference in frequency of AIS imaging targets in those with “disabling” vs. “non-disabling” deficit. These findings suggest that these MRI targets rather than clinical severity could be used to drive the decision to treat mAIS patients with IV tPA and greatly expand the pool of patients for thrombolytic therapy. The similarities of these imaging targets in mAIS patients with and without disabling deficit can be used to justify an MRI-based treatment trial.

Abstract TP77: Collateral- vs Perfusion-Based Selection Paradigm of Late Window (6-24 hours) Patients With Acute Ischemic Stroke a Comparative Study of Decision Making Using Multi-Phase CTA and CT Perfusion

Purpose: To compare the performance of collateral- vs perfusion-based imaging paradigms in late window stroke patients. Methods: In the prospective international (PRove-IT) study, patients had baseline CT head, multi-phase CTA (mCTA) and CTP. Patients presenting 6-24 hours of onset were included. We retrospectively selected patients for EVT based on 1) Collaterals: ASPECTS ≥5, plus proximal intracranial occlusion, plus good mCTA collaterals; 2) Perfusion: using DEFUSE-3, or DAWN trial criteria. CTP was processed using RAPID software. The performance of each paradigm to predict outcomes was assessed using the area under the receiver operating characteristic curve (AUC) of logistic regression models adjusting for age, NIHSS, sex, onset to CT time, EVT treatment, and interaction of EVT and the imaging paradigm. Results: We included 83 patients; medians of age 71, NIHSS 12, ASPECTS 9, and onset/ last seen well to CT of 576 minutes. Occlusions were: ICA, M1, M2-MCA (81.9 %), distal (8.4%) and none (9.6%). 35 patients received EVT (all without IV tPA), 10 IV tPA, and 38 treated conservatively. TICI 2b-3 was achieved in 71.4% of EVT patients. mRS≤2 at 90 days was achieved in 47% (51.4% with EVT: 72% of TICI2b/3 patients). Table 1 shows 90-day mRS according to the imaging paradigm for the entire cohort. Among 10 patients who were EVT-eligible according to mCTA but not DEFUSE-3, 70% achieved mRS≤2. Among 31 who were EVT-eligible per mCTA but not DAWN, 61% achieved mRS≤2. For 5 patients who were EVT-eligible per DEFUSE-3 but not mCTA, 60% achieved mRS≤2. No patients were EVT-eligible per DAWN but not per mCTA. All paradigms had comparable AUCs for 90-day mRS≤2. In the EVT subgroup, mCTA had AUC of 0.80 vs 0.79 for DAWN, and 0.78 in DEFUSE-3 paradigms. Conclusion: The mCTA-defined collateral paradigm performs similarly well for EVT selection in the late time window. It also may include additional patients with possible benefit from ECT who would have been excluded by CTP-based imaging selection.

Abstract TP307: Clinical and Neuroimaging Criteria to Improve Transfers to Comprehensive Stroke Centers for Endovascular Reperfusion Treatment Evaluation

Transfer protocols from primary (PSC) to comprehensive stroke centers (CSC) are crucial for the success of endovascular treatment (EVT). We aimed to identify clinical and neuroimaging predictors of EVT outcome in patients first assessed at non-capable EVT centers. Methods: Retrospective analysis of consecutive patients included in a prospective, population-based, mandatory registry of acute ischemic strokes (AIS). Inclusion criteria: AIS firstly evaluated at a PSC with suspected large vessel occlusion (LVO) transferred to a CSC for EVT assessment. PSC and CSC-ASPECTS, time-metrics and clinical data were analyzed. Results: Between February 2016 and May 2018, 1185 EVT candidates were transferred from PSC to CSC in our stroke code network (see Graph). Median baseline NIHSS was 13(7-19). 53.4% received iv tPA in the PSC. Upon CSC arrival, LVO was confirmed in 63.1% patients, and 42.8% received EVT. After a median of 130(107-169)min between both CT-acquisitions, the median inter-facilities ASPECTS decay was 1(0-2) and only 11.9% showed a CSC-ASPECTS<6. A ROC curve identified baseline NIHSS>16 as the best cut-off point that predicted CSC-ASPECTS<6(Sensitivity 67%, specificity 75%, AUC 0.7). A logistic regression analysis adjusted by age, time from symptoms to PSC-CT and time from PSC-CT to CSC-CT showed that only a baseline NIHSS>16 independently predicted a CSC-ASPECTS<6(OR 3.8, CI 2.1-6.9, p<0.001). The rate of CSC-ASPECTS<6 increased to 21% among AIS with NIHSS>16, and to 38.1% in patients with NIHSS>16 and PSC-ASPECS≤7. Conclusion: ASPECTS<6 scores are uncommon in CSC even after long transfer times. Except for selected cases (NIHSS>16 or PSC-ASPECTS≤7), confirming ASPECTS upon CSC arrival may not be necessary among AIS transferred from PSC.

Clinical Outcomes of Endovascular Thrombectomy in Tissue Plasminogen Activator versus Non-Tissue Plasminogen Activator Patients at Primary Stroke Care Centers

Background:The effect of intravenous tissue plasminogen activator (IV tPA) administration before endovascular intervention as compared to without at thrombectomy-capable low-volume centers on procedural aspects and patient outcomes has not been investigated.Methods:Retrospective chart review was performed in all consecutive large vessel cerebrovascular accident patients treated with endovascular therapy at two select rural primary stroke centers between 2011 and 2015. Patients’ data regarding age, sex, and medical history, as well as thrombus location by catheter-based cerebral angiography, postprocedural reperfusion status, and clinical outcomes were reviewed. The primary outcome measure of the study was a comparison of modified Rankin scale (MRS) at 90 days in patients’ postendovascular thrombectomy with prior IV tPA administration versus those who underwent thrombectomy and did not qualify for preprocedural IV tPA.Results:After application of the set inclusion and exclusion criteria, data of 46 out of 65 patients were analyzed. Twenty-three patients (50%) received IV tPA before thrombectomy and 23 patients did not qualify for IV tPA (50%). Successful recanalization (thrombolysis in cerebral infarction 2b/3) was achieved in 86% (20/23 patients) of thrombectomy patients without preprocedural IV tPA and 82% (19/23) of patients who received it (odds ratio [OR]: 0.03, confidence interval [CI]: 95% 0.062–0.16, P < 0.0001). MRS of 2 or less at 90 days was 43.4% (10/23) in patients with no preprocedural IV tPA and 39.1% (9/23) in the combined therapy group (OR: 0.84, CI: 0.26–2.70, P = 0.8).Conclusion:Patients undergoing endovascular thrombectomy for large vessel occlusion at select low-volume rural centers showed benefit from this treatment regardless of IV tPA administration. Clinical outcomes and complications at select low-volume thrombectomy-proficient centers are comparable to large volume comprehensive stroke centers as well as the landmark studies proving the efficacy of endovascular treatment.

Abstract TMP5: Acute Ischemic Stroke due to Large Vessel Occlusions: Incremental Benefits of IV tPA Alone and Mechanical Thrombectomy Added to IV tPA

Background: Quantifying the magnitude of benefit of mechanical thrombectomy (MT) add to IV tPA (IVT) versus IV tPA alone vs neither in patients with acute ischemic stroke due to large vessel occlusion (LVO-AIS) is crucial to optimal organization of regional systems of stroke care. But single RCT analysis cannot quantify these effect magnitudes as no IV tPA trial enrolled explicitly-identified LVO patients, and no thrombectomy trial enrolled early IV tPA responders. Methods: We performed a matched patient network analysis of the two NINDS-tPA trials and the SWIFT PRIME trial. Using 1:1 optimal inverse variance matching, with NIHSS ± 1 and age ± 5, triplet matched were made between the NINDS placebo (neither MT or IVT), NINDS tPA (tPA only), and SWIFT PRIME (MT+IVT) treatment groups, ensuring comparable LVO-AIS patients, and 90 day mRS outcomes analyzed. Results: Among 258 triplet matched patients (86 in each treatment arm), baseline characteristics were well balanced for age (MT+IVT 66.6, IVT only 66.5, neither 66.7, p=1.00) and presenting deficit severity (NIHSS 16.3 vs 16.4 vs 16.2, p=0.98). Dramatic early benefits of IVT, leading to foregoing of MT, occurred in 10.1% of patients. The Figure shows final 90 day mRS distributions for the 3 AIS-LVO treatment strategies. Freedom from disability (mRS 0-1) was higher with MT+IVT than IVT alone and neither (47.7% vs 31.4% vs 19.8%), as was functional independence (mRS 0-2, 64.2% vs 37.2% 30.2%), and severe disability/death (mRS 5-6) was lower (11.0% vs 29.1% vs 31.4%). Number needed to treat for 1 improved outcome over the entire mRS range (shift analysis) was 4.9 for IVT alone vs neither and 2.0 for both MT+IVT vs neither. Conclusions: The strategy of IV thrombolysis plus direct mechanical thrombectomy unless immediate dramatic benefit occurs is highly power for LVO-AIS, improving outcomes in 1 of every 2 patients. IVT alone provides benefit in 1 in 5 patients.

Abstract TP239: Initial Results From a Community Emergency Medical System Based Bypass Protocol Using Rapid Arterial Occlusion Scale to Screen for Emergent Large Vessel Occlusion

Introduction: Although mechanical thrombectomy (MT) is the standard of care for patients with acute ischemic stroke due to emergent large vessel occlusion (ELVO), few patients remain eligible for MT due to pre-hospital delays and presentation to non-MT capable hospitals. Emergence of in field screening tools have allowed EMS to reliably identify patients with likely ELVO, thus facilitating their direct triage to MT capable hospitals for prompt thrombectomy. Methods: In collaboration with the Peninsulas EMS Council (PEMS), we implemented a community based pilot program in the Hampton Roads region of Southeastern Virginia to identify patients with ELVO by utilizing the Rapid Arterial oCclusion Evaluation (RACE) scale, a validated in field screening tool. Under this protocol, since March 1 st , 2017, patients with a RACE score of ≥ 5, presenting within 6 hours of last known well would be transported directly to a Comprehensive Stroke Center (CSC) rather than a Primary Stroke Center (PSC), provided the bypass does not prolong the trip by more than 15 minutes. We present the initial results of this study including iv tPA and MT treatment rates, time metrics, and patient outcomes, in comparison to the pre-RACE protocol data. Results: Between March 1 st and June 30 th , 2017, of the 75 brain attacks received in our CSC, 45 patients were screened using the RACE scale by the EMS. 30 patients scored ≥ 5 on the RACE scale (RACE +) and 21 of those bypassed PSCs on their way. RACE + patients had a higher median NIHSS (16 vs. 6, p &lt; .0 5 ), and ischemic strokes (70% vs. 58%), compared to the non-RACE + patients in the preceding 4 months. Improved time metrics (median) were observed for symptom onset to arrival (54 min vs. 81 min), arrival to CT (8.5 min vs. 12 min, p &lt; .05), DTN (36 min vs. 47 min), DTG (94 min vs. 105 min), and arrival to recanalization with MT (142 min vs. 185 min). IV tPA (27% vs. 11%) and MT treatments rates (33% vs. 11%) with TICI ≥ 2b (90% vs. 77%) were higher in the RACE + patients compared to the non-RACE + cohort. Conslusion: Our pilot program employing RACE as an in field screening tool for ELVO and using it to bypass PSCs in favor of CSCs is feasible in the community setting, and demonstrates improved metrics in key domains known to be associated with better outcomes for these patients.

Abstract WMP21: Texture Analysis of Intracranial Thrombus Using CT and CTA Predicts Early Recanalization With Intravenous Alteplase

Objective: In acute ischemic stroke (AIS), thrombus lysis and early restoration of blood flow to ischemic brain is the goal of reperfusion therapy. We hypothesize that image texture analysis of thrombus using non-contrast CT (NCCT) and CTA can predict early recanalization with IV alteplase in AIS patients with ICA/M1 MCA thrombi. Methods: We used a case control design for the study using the whole cohort of the clinical trial of Identifying New approaches to optimize Thrombus characterization for predicting Early Recanalization and Reperfusion with iv tPA using Serial CT angiography (INTERRSeCT). Cases were 31 patients with ICA/M1 MCA thrombi treated with IV alteplase, who achieved early recanalization (as assessed on first angio run in patients undergoing additional IA therapy or on repeat CTA at 4 hrs). Cases were matched with controls (37 patients with ICA/M1 MCA thrombi treated with IV alteplase who did not achieve recanalization). All patients had thin slice NCCT (slice thickness &lt; 2.5 mm) and CTA (≤ 0.625mm). Thrombi in ICA/M1 MCA region were manually contoured from NCCT guided by co-registered CTA. We extracted 378 features (including thrombus length and volume, first order statistics, and image texture features) from each thrombus in both NCCT and CTA images. This was followed by feature selection using linear discriminative analysis. The top 5 features from NCCT and CTA images along with the clot texture difference between NCCT and CTA were used to train a linear support vector machine classifier. Five times 6-fold cross validation was used to evaluate the trained classifier. Results: Receiver operator curves show that thrombus texture from NCCT and CTA are predictive of early recanalization with IV alteplase. Combined NCCT &amp; CTA features and texture difference is the best predictor (AUC: 0.82). Conclusions: Thrombus texture features from NCCT and CTA are strongly predictive of early recanalization with IV alteplase in AIS patients with proximal occlusions.

Abstract WP242: An International Survey of Progressive Stroke System Processes

Introduction: Understanding of high performing stroke systems can help development of regional stroke systems of care and bring meaningful system improvement. We sought to evaluate the current state of advanced systems worldwide to inform the development of a large-scale regional system of care improvement program. Methods: An 81 question, internet-based survey was developed to obtain information on current practices in large and progressive stroke systems. Data was collected from January 2017 - May 2017. Advanced stroke systems were identified by prior knowledge and colleague input. A total of 22 stroke centers from Europe and North America were invited to participate. The survey included questions encompassing center demographics, staffing, acute stroke code processes, Endovascular therapy (EVT) processes, EMS systems, stroke IT, telestroke use, transfer of patients, post-acute patient management and system feedback. Data analysis was conducted using REDCap internal analytic tools; simple counts and averages (mean) were calculated where appropriate. Results: Of the 22 invited centers, 9 (41%; 2 European, 1 Canadian, 6 US) completed the questionnaire, 7 of which were CSCs. Responding centers reported yearly average of 887 ischemic strokes (range 350-1444), and 202 (100-501) primary hemorrhagic strokes. Average annual IV tPA volume was 168 (60-440) and EVT volume was 68 (12-130). At all 9 systems, EMS agencies were trained in identifying potential strokes and reported utilizing an established prehosptial stroke scale. Six systems (66.7%) reported a destination protocol based on stroke severity involving bypass to an EVT-capable center. All 9 centers have developed processes for expedited transfer of stroke patients in need of neurointervention from their non-EVT-capable referral hospital network. For patients with confirmed large vessel occlusion being transferred to the hub hospital, 5 (55.6%) centers reported these patients bypass the ED to go directly to the neurointervention suite. Conclusions: This international survey of progressive stroke systems reveals useful practice patterns and processes that can be adopted by other stroke systems to improve patient care. This information will be integrated into the IMPROVE Stroke program.

Inhibiting 12/15-lipoxygenase to treat acute stroke in permanent and tPA induced thrombolysis models

12/15-Lipoxygenase (12/15-LOX) contributes to the brain damage after middle cerebral artery occlusion (MCAO) in the acute phase of stroke. The aim of this study was to investigate the effects of a 12/15-LOX inhibitor, LOXBlock-1(LB1), in mice using a FeCl3-induced permanent distal MCAO model and FeCl3-induced ischemia/thrombolysis with tPA. In order to induce permanent distal MCAO, 30% FeCl3 was used in C57BL6 mice. LB1 or DMSO treatments were applied intraperitoneally 2 h following MCAO. For FeCl3-induced ischemia/thrombolysis experiments, 10% FeCl3 was preferred so as to obtain reperfusion with tPA in CD1 mice. 4 h following ischemia either LB1 or DMSO and iv tPA was administered. Outcomes were NSS, weight loss, infarct volume, hemorrhage area and reperfusion rate. FeCl3-induced distal MCAO caused an increase in 12/15-LOX signal in the ischemic cortex with an increase in MDA2 and AIF immunoreactivity. LB1 treatment, applied 2 h after ischemia, significantly decreased the infarct volume at 24 h of permanent distal MCAO. Weight loss was also significantly reduced in LB1 treated group. Distal MCAO and tPA application with LB1 or DMSO showed that treatment significantly decreased the infarct volume and the hemorrhage area. The reperfusion rate in the LB1-treated group was surprisingly higher than in the DMSO group and NSS results were significantly improved. These data suggest that LB1 can be used as an adjuvant agent to tPA. This study not only shows the effects of LB1 treatment in distal MCAO but also confirms that FeCl3-induced MCAO model can be a useful tool to screen novel treatment options in stroke.

Current Canadian And American Experiences In The Treatment Of Acute Ischemic Stroke

Stroke remains one of the main public health issues worldwide. It is the third leading cause of death in the United States, with more than 200,000 people dying from strokes each year. Approximately 80% of all acute ischemic strokes are due to intracranial artery occlusion, most commonly thromboembolic clot occlusion. Revascularization of occluded territories is the cornerstone of acute ischemic stroke and Thrombolysis for ischemic stroke has been systematically studied in large randomized trials only since the 1990s. To date, thrombolytic therapy for ischemic stroke has been investigated in 21 randomized controlled clinical trials enrolling more than 7,000 patients. The advent of modern imaging and endovascular tools and technologyhas revolutionized treatment of stroke. In this talk, I will review current clinical trials published in The NEJM (ESCAPE, MR Clean, EXTENDED IA, ….) regarding superiority of the endovascular treatments, especially, the stent retrievers, over Iv tPA. I will also go over all endovascular techniques used in the endovascular treatment of acute stroke using my Canadian and American experiences.

Current Canadian And American Experiences In The Treatment Of Acute Ischemic Stroke

Stroke remains one of the main public health issues worldwide. It is the third leading cause of death in the United States, with more than 200,000 people dying from strokes each year. Approximately 80% of all acute ischemic strokes are due to intracranial artery occlusion, most commonly thromboembolic clot occlusion. Revascularization of occluded territories is the cornerstone of acute ischemic stroke and Thrombolysis for ischemic stroke has been systematically studied in large randomized trials only since the 1990s. To date, thrombolytic therapy for ischemic stroke has been investigated in 21 randomized controlled clinical trials enrolling more than 7,000 patients. The advent of modern imaging and endovascular tools and technology has revolutionized treatment of stroke. In this talk, I will review current clinical trials published in The NEJM (ESCAPE, MR Clean, EXTENDED IA, ….) regarding superiority of the endovascular treatments, especially, the stent retrievers, over Iv tPA. I will also go over all endovascular techniques used in the endovascular treatment of acute stroke using my Canadian and American experiences.

Abstract 112: Recrudescence of Neurological Deficits After Stroke: Clinical-imaging Phenotype, Triggers and Risk Factors

Background: Re-emergence of prior stroke-related deficits or post-stroke recrudescence ( PSR ) has not been adequately studied. Methods: Using preliminary criteria for PSR (transient recurrence or worsening of residual post-stroke deficits; chronic brain infarct or hemorrhage but no acute vascular lesion on MRI including DWI; no severe ipsilateral cerebral artery stenosis; no evidence for seizure), we identified 153 patients (145 prior infarcts, 8 hypertensive ICH) with 164 admissions for PSR from 2000-2015. Clinical-imaging features of PSR were characterized. Triggers of PSR were identified by comparing PSR admissions to adjacent admissions without PSR (n=65). Risk factors for PSR were identified by comparing PSR cases to 1861 controls without PSR in our prospective institutional stroke registry. Results: PSR occurred 3.9±0.6y after stroke, lasted 18.4±20.4 hrs, and 69% resolved on Day 1. Mean age 67±16y, 60% women. Neuro-worsening was usually abrupt, mild, with motor-sensory or language dysfunction. No patient had isolated gaze paresis, hemianopia or neglect. During PSR the NIHSS worsened by mean 2.5±1.9 points; deficits were limited to a single subscale NIHSS item in 38%. The underlying chronic strokes were variably-sized, predominantly affected white-matter tracts, and 73% involved the MCA territory. Infection, hypotension, hyponatremia, insomnia/stress and benzodiazepine use were higher (p&lt;0.05) during PSR as compared to adjacent admissions without PSR. As compared to the ischemic stroke registry controls, the subgroup of 145 cases with PSR after ischemic stroke had more women, African-American and Other races, diabetes, dyslipidemia, smoking, and more severe NIHSS scores at the time of index stroke (all p&lt;0.05). The PSR group had more small-vessel infarcts and more strokes from “other definite” causes. Six patients with PSR received iv tPA without hemorrhagic complications. Conclusion: This detailed characterization of PSR should enable prompt diagnosis and distinguish PSR from mimics such as TIA, migraine, Todd’s paralysis, Uhthoff’s phenomenon, and others. This is the first large comprehensive study of PSR. Prospective studies are required to validate our proposed diagnostic criteria and decipher underlying mechanisms.

Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening

ObjectiveTo determine the effects of a 1-year quality-improvement (QI) process to reduce door-to-needle (DTN) time in a secondary general hospital in which multimodal MRI screening is used before tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke (AIS). MethodsThe QI process was initiated in January 2015. Patients who received intravenous (iv) tPA<4.5h after AIS onset between 26 February 2015 to 25 February 2016 (during implementation of the QI process; the “2015 cohort”) were identified (n=130), and their demographic and clinical characteristics and timing metrics compared with those of patients treated by iv tPA in 2014 (the “2014 cohort”, n=135). ResultsOf the 130 patients in the 2015 cohort, 120 (92.3%) of them were screened by MRI. The median DTN time was significantly reduced by 30% (from 84min in 2014 to 59min; P<0.003), while the proportion of treated patients with a DTN time≤60min increased from 21% to 52% (P<0.0001). Demographic and baseline characteristics did not significantly differ between cohorts, and the improvement in DTN time was associated with better outcomes after discharge (patients with a 0–2 score on the modified rankin scale: 59% in the 2015 cohort vs 42.4% in the 2014 cohort; P<0.01). During the 1-year QI process, the median DTN time decreased by 15% (from 65min in the first trimester to 55min in the last trimester; P≤0.04) with a non-significant 1.5-fold increase in the proportion of treated patients with a DTN time≤60min (from 41% to 62%; P=0.09). ConclusionIt is feasible to deliver tPA to patients with AIS within 60min in a general hospital, using MRI as the routine screening modality, making this QI process to reduce DTN time widely applicable to other secondary general hospitals.

Safety and outcomes of decompressive craniectomy after intravenous tissue plasminogen activator administration for malignant cerebral infarction

Objective: The aim of this study was to evaluate the safety and outcomes of decompressive craniectomy (DC) after intravenous tissue plasminogen activator (IV tPA) administration for malignant cerebral infarction. Methods: We retrospectively reviewed patients who underwent DC for malignant cerebral infarction. We compared fourteen patients who underwent DC after IV tPA administration with another nine patients who underwent DC without prior IV tPA administration. Results: Twenty-three patients underwent DC for malignant hemispheric cerebral infarction in our hospital for five years. Fibrinolysis was performed prior to the DC in fourteen patients (60,9%). The patients characteristics did not differ between the DC patients with and without prior IV tPA administration. The complications that developed after DC were similar in both groups: in patients who underwent DC after IV tPA administration, 9 (64.3%) developed haemorrhagic transformation and 6 (42.9%) developed hydrocephalus. The functional outcome, as the 6-month GOS, was similar in both groups (p = 0.762). ICU mortality (p = 0.329) and hospital mortality after ICU (p= 0.634) were also similar between the two groups. Conclusion: Although the main limitation is that the number of patients in our serie was small, which reduced the statistical power, our study suggest that DC after failure of IV tPA administration for malignant cerebral infarction is safe and did not cause an excess of complications arising from the use of fibrinolytic.