IV tPA Research Articles

Abstract W P14: Endovascular Treatment for M2 Occlusions. A Descriptive Multicenter Experience on Behalf of the Catalan Stroke Code and Reperfusion Consortium (Cat-SCR).

Background: Patients with M2-MCA occlusion are not always considered for endovascular treatment. We aimed to study patients with an M2 occlusion treated with endovascular procedures. Methods: We studied patients prospectively included in the SONIIA register (January 2011-December 2012), a mandatory and externally audited register that monitors quality of reperfusion therapies in Catalonia under routine practice conditions. Baseline characteristics including NIHSS and occlusion location were collected. Complete recanalization was defined as a post-procedure TICI>2a, dramatic recovery: NIHSS drop>10 points or NIHSS<2 and good outcome as mRS<3 at 3 months. 24 hours CT scan determined the presence of hemorrhagic transformation (ECASS criteria) and infarct volume. Results: Of the 571 registered patients that received endovascular treatment, 65 (11.4%) presented an M2 occlusion on initial angiogram: mean age 66±15, female 47.7% median pre-procedure NIHSS 16(IQR:6). Mean time from symptom onset to groin puncture was 289±195 minutes, 35 patients (54%) received iv tPA before the procedure. Patients were treated with mechanic thrombectomy (n=49, 75.4%), ia tPA (n=3, 4.6%), both (n=7, 10.8%) or only diagnostic angiogram (n=6, 9.2%) according to interventionalist preferences. Patients who achieved complete recanalization (78.5%) had more often dramatic improvement (48% Vs 14.8%, p=0.023) smaller infarct volumes (8 vs. 82cc, p=0.013) and better outcome (66.3% Vs 30%; p=0.032) than those who did not recanalize. Rate of SICH was 9%. Independent predictors of dramatic improvement was complete recanalization (OR: 0,169 p=0.03 CI95%: 0.034-0.838) adjusted for age and baseline NIHSS Independent predictors of good outcome at 3 months were age (OR 1.067 p=0.033 CI95%: 1.005-1132) and baseline NIHSS (OR: 1.162 p=0.007 CI95%: 1.041-1.297) Conclusion: Endovascular treatment of M2 MCA occlusion seems safe. Induced recanalization may double the chances to achieve a favourable outcome

Organizational changes aiming to reduce iv tPA door-to-needle time

To assess time trends in intravenous thrombolytic (iv tPA) treatment in a general local hospital during a period with organizational changes, especially how movement of treatment start from the emergency room (ER) to the CT laboratory, and changing method of administration of acute antihypertensive medication influenced on door-to-needle time (DNT). All stroke patients treated with iv tPA have been prospectively enrolled in the Safe Implementation of Treatments in Stroke (SITS) registry. Data from 2007 to 2011 were reviewed. Safety was evaluated by the incidence of symptomatic intracerebral hemorrhage (SICH). Predictors of DNT were assessed by multivariable regression. Two hundred and forty-three patients were treated with iv tPA. The annual treatment rate reached 21.9% of patients with ischemic strokes admitted to the hospital. Median DNT decreased from 36 to 28 min (P ≤ 0.001). The incidence of SICH remained low and was throughout the period 2.5%. Treatment start in the CT laboratory vs in the ER was associated with a reduction in median DNT (P = 0.007). Acute antihypertensive treatment and treatment with warfarin were associated with increased DNT (P = 0.024 and P = 0.003, respectively). Age, gender, baseline NIHSS, onset-to-door time, comorbidity, and method of administration of acute antihypertensive treatment did not influence DNT significantly. Streamlining of iv tPA logistics can reduce median DNT to <30 min in a general local hospital. Moving treatment start from the ER to the CT laboratory contributed to reduce DNT. Our organizational model was resistant to influence on DNT by patient age, gender, stroke severity, and time to hospital arrival. The incidence of SICH remained low.

Abstract 244: Why Registries Matter: Impact of a Comprehensive Telestroke Data Collection Process on Clinical Quality Improvement

Introduction: Evaluating patient care within a telestroke network is challenging due to lack of appropriate data. The AHA/ASA’s Target Stroke helps address QI programming in larger hospitals, typically PSCs, but may not be appropriate for smaller facilities that lack specialty knowledge and data collection tools. Telestroke has only heightened this need for smaller facilities to measure and track performance to ensure quality care. Goal: In an effort to narrow this disparity and incorporate similar data-driven QI projects in our partner sites and therefore network as a whole, the Providence Telestroke Network sought to develop a novel comprehensive registry. Clinical performance measures, such as IV tPA treatment rates, door to CT and door to needle times, were collected to inform our quality improvement processes. Methods: The Providence Telestroke Network consists of two PSC hubs and 17 partner sites. Network participants utilize the American Stroke Association’s Get With The Guidelines (GWTG) data collection tool to capture stroke quality measures. Once entered, quality data from all sites are consolidated into a single cloud-based registry. For patients that transfer, clinical information from the partner hospital is automatically matched to the corresponding hub record within the registry. Aggregate patient information is then summarized for quality reviews and performance improvement planning. Results: The registry includes information on 1264 patients who received a neurologic consult by hub-based neurologists, of which 37% (n=470) received a formal telemedicine consult and 20% (n=274) resulted in a transfer to our hub facility for a higher level of care. We identified several partner sites that had patient arrival to initiation of IV tPA (door to needle) times in excess of the recommended goal of 60 minutes and door to CT times in excess of the recommended goal of 25 minutes. Initial data review at the start of network participation also found overall treatment rates at the spokes were between 0 to 6%. Quality improvement processes and ED staff education from our hub PSCs were provided to partner facilities to improve door to CT and door to needle times as well as overall IV tPA treatment rates. Door to CT times were changed by up to 54% and door to needle times were changed by up to 24%. IV tPA treatment rates in the partner sites increased by 5-32%. Implications: Our comprehensive registry enabled us to identify quality improvement opportunities at partner hospitals and implement appropriate QI processes. As a result, significant improvement in acute stroke care metrics were realized in our partner facilities.

Abstract WP25: Concomitant IV tPA Does Not Increase Harm to Patients Who Receive Simultaneous Mechanical Thrombectomy and Emergent Carotid Artery Stent Treatment

Background: Stenting of the cervical internal carotid artery (ICA) may be performed acutely in patients undergoing endovascular intervention for stroke due to occlusion of the intracranial ICA or MCA. It is unclear if pre-intervention IV tPA increases complications of carotid artery stenting (CAS) in this group. Hypothesis: We assessed the hypothesis that pre-intervention IV tPA does not increase the risk of complications in acute ischemic stroke patients (AIS) who require concurrent mechanical thrombectomy and emergent CAS. Methods: Patients undergoing both mechanical thrombectomy and CAS within 24 hours of stroke onset were identified from the Merci Registry, a prospective database of AIS patients treated with the Merci Retriever. Those receiving IV tPA were compared with those that did not for associations with functional independence (mRS 0-2) and risk of symptomatic intracerebral hemorrhage (sICH). The primary endpoint for this study was the percentage of patients with mRS 0-2 at 90 days. Secondary endpoints included 90-day mortality and sICH. Outcomes were compared with Fisher’s exact test. Results: 103 patients were included. Thirty received IV tPA (mean age 59.1, time to treatment 6.3 hrs, median NIHSS 18) and 74 did not (mean age 66.1, time to treatment 9.8 hrs, median NIHSS 16). Although numerically higher, there was no significant difference in sICH at 24 hours, occurring in 18.2% (4/22) of IV tPA patients and 7.3% (4/55) of patients without IV tPA (p=0.22) [sICH data was not available on 28 patients]. At 90 days, 40% of the IV tPA group (12/30) was functionally independent while 30.6% (22/73) was functionally independent in the non-IV tPA group (p=0.36). There was no difference in 90-day mortality between the two groups (26.7% vs. 34.7%, p=0.67). Conclusions: This study demonstrates that concomitant IV tPA use in acute stroke patients who had simultaneous mechanical thrombectomy and CAS did not significantly affect patient outcomes or increase complications. Although neither result was statistically significant, there was a trend toward improved functional outcomes at 90 days in the IV tPA treated group despite a trend toward increased rates of sICH.

Abstract WP52: A Novel CT-angiogram Based Recanalization Grading System (TICI-CTA) Correlates With Early Neurologic Response After Intravenous tPA Therapy

Introduction: Noninvasive imaging tools to assess the degree of recanalization are limited. CT-angiography (CTA) may be ideal for assessment of recanalization in view of excellent visualization of thrombus and distal vasculature; however no scoring system is available to evaluate extent of recanalization. We sought to derive a score and test it’s correlation to early neurologic response (24 hours NIHSS) within a research study having a post tPA CTA. Method: The TICI-CTA score was defined by debulking of thrombus of proximal intracranial arterial occlusive lesion (PIAOL) and forward filling of distal arterial tree.(see graphic) Data is from INTERRSeCT, an ongoing multi-center study evaluating thrombus characteristics and recanalization in acute stroke. Results: From 166, 78 patients treated with IV tPA were evaluated. The cohort had 48% males. The median time from symptom onset to baseline CTA was 114 min, and onset to IV tPA bolus was 148 min. Proximal intracranial sites of occlusions were: carotid-T 6.4%, M1-MCA 26.9%, distal MCA 58.9%, PCA 6.4%, and vertebral 1.3%. The symptom onset to follow-up post treatment CTA was 373 min. The recanalization grading TICI-CTA in post iv tPA CTA was: TICI-CTA 0 in 30 (38.4%), TICI-CTA 1A/1B in 3 (3.8%); TICI-CTA 2A/2B/2C in 17 (21.7%); and TICI-CTA 3 in 28 (35.8%). We noted a significant positive correlation between TICI-CTA score and absolute change in NIHSS from baseline to 24 hours (r=0.26, p=0.02). A positive correlation was also noted between TICI-CTA score and proportional change in NIHSS from baseline to 24 hrs (r=0.34, p&lt;0.01). Conclusion: The TICI-CTA score based on comparison of pre and post treatment CTA correlates with early neurologic response, thus showing content validity. Further validation is needed. This grading score could be used to evaluate the recanalization efficacy of novel lytics and combination therapies in phase 2 proof of concept or as a predefined CTA sub-study in a pivotal Phase 3 clinical trial.

Abstract TP70: Safety of IV tPA Administration with CT Evidence of Prior Infarction

Background: Prior stroke within 3 months excludes patients from thrombolysis, however patients may have CT evidence of prior infarct often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pre-treatment head CT is a predictor of hemorrhagic complications following administration of IV tPA. Methods: We retrospectively analyzed the database of consecutive patients treated with IV tPA at our institution from 2009-2011. Pre-treatment CTs were reviewed without knowledge of subsequent hemorrhagic transformation (HT) for evidence of any prior infarct. Further independent review determined if any HT was present on repeat CT or MRI. Symptomatic ICH (sICH) was defined as the presence of parenchymal hematoma (PH-1 or PH-2) and neurological deterioration by ≥ 4 points within 36 hours. Results: Of 212 IV tPA treated patients, 72 (34%) had evidence of prior infarct on pre-treatment CT. Any HT was found in 16%, sICH occurred in 2.4% of the total population, and both events never occurred in the areas of prior infarcts. Patients with prior infarcts on CT were older (median age 72 vs 65; p=0.001), were more likely to have a history of hypertension (85% vs 71%; p=0.024), were on antiplatelet agents prior to admission (49% vs 31%; p=0.007) and had higher pre-treatment NIHSS scores (median 10 vs 7; p=0.023). Patients with prior infarcts on CT did not experience more HT (p=0.3956) nor sICH (p=0.2207), even after stratifying for prior lacunar or cortical stroke appearances (p=0.301). More patients with prior infarcts on CT had microbleeds on follow-up MRI (25% vs 11%; p=0.033), and patients with prior infarcts and microbleeds experienced more HT (63% vs. 10%; p&lt;0.0001) but did not have more sICH (p=0.4784). Conclusions: Visualization of prior infarcts on pre-treatment CT does not predict an increased risk of sICH and should not be viewed as a contraindication for systemic tPA treatment after clinically evident strokes within 3 months were excluded. A subgroup of patients with prior infarcts and subsequently discovered cerebral microbleeds show a propensity to develop asymptomatic HT.

Abstract TP347: Improving Performance in Target Time Compliance for Acute Stroke using Structured Feedback to Providers

Introduction: Time targets for rapid assessment and treatment of acute stroke patients were established in 2005 by the Brain Attack Coalition, including door-to-needle time &lt;60 minutes. At a Primary Stroke Center in Honolulu, HI, we sought to improve compliance with target times by providing structured and meaningful feedback to a multidisciplinary group of acute stroke providers. Hypothesis: We hypothesized that delivering direct, structured feedback to providers would improve compliance with target times for rapid evaluation and treatment of acute stroke patients. Methods: Utilizing a FOCUS-PDCA framework, a quality assurance project was developed to analyze performance measures and identify barriers to timely administration of IV tPA. Onset-to-door, door-to-stroke-code-activation, door-to-CT-onset, door-to-CT-completion, and door-to-lab-result times were monitored for each IV tPA administration at a single Primary Stroke Center during 2009-2012. Through a series of monthly multidisciplinary stroke team meetings, a simple yet comprehensive reporting tool was developed in 2010, utilizing the “traffic light” concept. This feedback mechanism included a case-by-case analysis of compliance to enhance communication among members of the multidisciplinary stroke team. Results: There were 128 stroke code activations with 10 IV tPA administrations in 2009, 147 activations with 21 tPA administrations in 2010, 183 activations with 31 tPA administrations in 2011, and 151 activations with 30 tPA administrations in 2012 year-to-date. During this period, door-to-needle time &lt;60 minutes compliance rates improved from 22.2% in 2009 to 64.7% in 2010 and 53.8% in 2011. In 2012 year-to-date, the compliance rate with the door-to-needle target time has improved to 71.4%. Conclusion: The care of the acute stroke patient is a multidisciplinary endeavor. Feedback to providers involved in the stroke code process is an effective way to improve performance. Developing a simple reporting tool proved an efficient, sustainable way to promote awareness and enhance engagement in performance improvement throughout a multidisciplinary system of care.

Abstract WP279: Can We Reduce Door-to-Needle Times and Improve Outcome by Giving tPA on the CT Suite?

Objectives: The time to administration of intravenous (iv) tPA has a relevant impact on patients outcome. Our treatment protocol has been modified in order to improve our latency times by starting iv tPA bolus in the computed tomography room (CT-tPA). We aimed to evaluate the impact of CT-tPA on door-to-needle times and functional outcome in patients with acute ischemic stroke. Material and methods: We consecutively evaluated 70 patients treated in accordance with the CT-tPA protocol from June 2011 to June 2012. Those patients were compared to 130 patients from the previous year who received iv tPA bolus in the Stroke Unit (conventional protocol). Demographic data, baseline stroke severity, and inpatient latency times were evaluated. The primary outcome was the modified Rankin scale (mRS) at 3 months. Functional independency was considered when mRS≤2. Results: Two-hundred patients were evaluated, with mean age of 74.4±11.5 years and median NIHSS of 13 (IQR 11). There was no difference in baseline clinical characteristics at admission between CT-tPA and conventional protocol. The door-to-CT times were similar in both groups. Mean door-to-needle time was 57.1 min in the conventional protocol, and was reduced to 53.4 after CT-tPA protocol implantation. We analyzed the number of patients who received iv tPA bolus bellow 30 and 50 minutes in each group. The CT-tPA group had 9% more patients treated in &lt;30 min (16% vs. 25%) and 11% more treated in &lt;50 min-window (50% vs. 61%) after arrival to the emergency department. Clinically, there was a trend toward a better functional outcome in the CT-tPA protocol, with an increase of 10.7% of patients with mRS≤ 2 at 3 months compared with the conventional protocol (56.9% vs 46.2%). We also observed a reduction of 3-months mortality in patients treated according to the CT-tPA protocol (19% vs. 23%). The application of CT-tPA was not associated with the increase of ICH nor with tPA protocol violations. Conclusions: The CT-tPA protocol reduces door-to-needle times, increasing the number of patients treated bellow the &lt;50 and &lt;30 minutes time-window. We hypothesized that this time-reduction would improve functional outcome in a larger number of patients.

Abstract TP66: Quantitative Proteomic Profile of Tissue Plasminogen Activator (tPA) Responders

Background: The utilization of IV tPA continues to be low after more than a decade of FDA approval. We aim to widen the therapeutic window for tPA by understanding clinical thrombolysis response. Besides its intended role in clot lysis, tPA is also a pleiotrophic signaling protease in the blood, whose efficacy may potentially be monitored by proteomic profiles directly in stroke patients. Method/Results: To study thrombolysis response, we mapped quantitative profiles of all proteins pre and post IV tPA administration in plasma of stroke patients with good clinical outcome at 3 months. Plasma was sampled from stroke patients immediately before and 6-12hrs after tPA administration (n=28). Quantitative changes of proteins pre and post tPA were mapped by isotopic methods and analyzed on LC-MS. While both intra- and extracellular proteins were found, most were known plasma proteins, as seen on IPA analysis (Figure). Of 191 proteins found, 48 changed significantly post tPA (fold ratio in parenthesis). Compared to pre-tPA levels, we found significantly increased post-tPA levels of thrombolysis-related proteins such as fibrinogen gamma chain (↑11x), α-2-antiplasmin (↑4x), and a decrease in factor X (↓7x) etc. Changes were also found in factors outside of standard thrombolytic pathways, such as α-2-macroglobulin (↑2.3x); CD14 (↓2x) and GPX3 glutathione peroxidase 3 (↓2x) etc. Conclusion: In order to study thrombolysis response and monitor thrombolysis efficacy at the bedside, we mapped quantitative protein fold changes of IV tPA responders and found a coordinated change not only in reported thrombolysis pathways, but also in other enzymatic pathways in patient plasma. These early results are a step toward attempts to monitor clinical thrombolysis response in acute stroke patients in real time. Further studies are under way to compare plasma profiles of tPA-treated stroke patients with respect to different clinical outcome and imaging findings of reperfusion.

Abstract TMP77: Baseline Nihss-adjusted Time Window For Iv Tpa In Acute Stroke

Background: Updated metaanalysis have shown that beneficial effect of iv tPA on functional outcome decreases progressively overtime until 4.5 h. However, given the differential pattern of arterial occlusion, stroke severity and speed of ischemic lesion growth among candidates for reperfusion, the time window should be adjusted accordingly. We aim to identify time windows for different categories of stroke severity and occlusion location. Methods: Were included patients treated according to the criteria of the European Summary of Product Characteristics for alteplase treatment &lt; 4.5h in a Universitary Hospital from 2001- 2011. Patients were grouped according to NIHSS severity in minor NIHSS ≤ 8, moderate stroke NIHSS 9-15, severe stroke NIHSS ≥ 16. We sequentially analyzed time-to-treatment to achieve favorable outcome as mRS ≤ 2 at 3 months. Results: 640 patients were included, of whom 123 patients (19.22%) with minor stroke, 205 (32.5%) with moderate stroke and 312 (48.75%) with severe stroke. The rate of favorable outcome was 79.8%, 62.5%, 24.2% respectively. In patients with minor stroke time-to-treatment did not predict outcome (OR 1.005, 95% CI: 0.997- 1.012; p = 0.264). After adjusting for age and occlusion location only age was a independent variable (OR 1.198; 95% CI: 1.054-1.336; p= 0.001). In patients with moderate stroke time-to-treatment ≤ 240 minutes predict favorable outcome (OR 0.041, 95% CI 0.160- 0.962; p= 0.041), although only age and occlusion location, were independent predictors: (OR 1.061, 95% CI 1.024- 1.098; p= 0.001) and (OR 2.968, 95% CI 1.293- 6.614; p= 0.010), respectively. In patients with severe stroke time-to-treatment ≤ 90 minutes predict favorable outcome (OR 0.428, 95% CI 0.186-0.985; p= 0.046). Adjusting for proximal occlusion, age and time-to-treatment before 90 minutes were independent variables: age (OR 1.045, 95% CI 1.014-1.077, p= 0.004) and time-to-treatment (OR 0.267, 95% CI 0.088- 0.809, p= 0.020) Conclusions: The impact of time-to-treatment on favorable outcome varies widely depending on baseline stroke severity. The window for favorable outcome was &lt;90min for severe strokes and extends to &lt;240min in moderate stokes. However, time-to-treatment appeared unrelated to functional outcome in minor stroke.

Accuracy of Pre-Hospital Identification of Stroke (P04.059)

Objective: Determine accuracy of emergency medical service (EMS) identification of stroke. Background Activation of stroke systems by EMS may expedite time to intervention for stroke patients. Gropen et al. reported on sensitivity and impact of EMS identification of stroke. We additionally explored specificity and predictive values (PV) of EMS and emergency department (ED) evaluations. Design/Methods: We reviewed records of all patients transported by EMS to the Loyola University ED between 10/1/2010 and 6/30/2011. EMS impressions, ED physician diagnosis (DX), and neurology discharge diagnosis (DDX) were compared to determine sensitivity, specificity, and PV of EMS and ED identification of stroke. For patients with EMS impression of stroke, or DDX of stroke, additional parameters explored included: age, iv tPA administration, Cincinnati Stroke Scale (CSS), NIHSS, and time from ED arrival to neurology consult. Results: 5300 EMS patient records were included: 84 had EMS impression of stroke, with 49 true positives (TP), 35 false positives (FP), 47 false negatives (FN), and 5169 true negatives (TN); sensitivity was 51.04%, specificity 99.33%, positive PV 58.33%, and negative PV 99.10% (p Conclusions: EMS identifies stroke with high specificity, though lesser sensitivity. Pre-hospital stroke team activation may therefore help in decreasing the time to treatment. Improving the sensitivity of EMS and ED identification of stroke is needed for early identification of additional possible stroke patients. Disclosure: Dr. Wild has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Hyman has nothing to disclose. Dr. Venizelos has nothing to disclose. Dr. Cichon has nothing to disclose. Dr. Schneck has nothing to disclose.

Decompressive craniectomy after intravenous tissue plasminogen activator administration for stroke

ObjectiveIntravenous tissue plasminogen activator (IV tPA) is an approved treatment for acute ischemic stroke. However, the effects of decompressive craniectomy (DC) after IV tPA administration for ischemic stroke are still largely unknown. The aim of this study was to investigate the safety and outcomes of DC after IV tPA administration. MethodsWe retrospectively reviewed patients who underwent DC for malignant hemispheric infarction. We compared 20 patients who underwent DC after IV tPA administration with another 20 patients who underwent DC without prior IV tPA administration. ResultsThe patient characteristics did not differ between the DC patients with and without prior IV tPA administration. New intracranial bleeding or worsening of pre-existing ICH occurred in two patients (10%) in each group. Furthermore, the rates of an mRS score of 4–6, 5 or 6, and 6 did not differ significantly between the two groups. ConclusionDC may be a safe and useful surgical procedure for space-occupying edema after IV tPA administration for acute stroke.

Treatment of Intracerebral Hemorrhage with Tranexamic Acid After Thrombolysis with Tissue Plasminogen Activator

Thrombolytic treatment with intravenous tissue plasminogen activator (i.v. tPA) is the only FDA-approved therapy for acute ischemic stroke. There are risks associated with thrombolytics, including intracranial and extracranial hemorrhage and hypersensitivity reactions. Established treatment for post-tPA hemorrhage includes administration of blood products including cryoprecipitate, fresh frozen plasma, and platelets which have poorly established efficacy. Tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) have been studied as hemostatic therapies in post-operative hemorrhage, menorrhagia, intracranial hemorrhage (ICH), subarachnoid hemorrhage, and trauma patients. There is no reported literature on the use of TXA to reverse thrombolytic therapy with tPA. This is a case report of a Jehovah's Witness patient who was unwilling to receive blood products after developing symptomatic ICH following i.v. tPA. He consequently received TXA for reversal of thrombolytic therapy. The patient received a total of 1.675 g of i.v. TXA within 3 h of finishing the iv tPA. Repeat brain imaging with computed tomography and magnetic resonance imaging revealed no further expansion of hemorrhages. TXA is an inexpensive medication which competitively inhibits the activation of plasminogen and can be given to reverse thrombolysis in the setting of hemorrhage after i.v. thrombolytic therapy.

Abstract 132: In-hospital Versus Out-of-hospital Code Stroke: Iv Tpa Rate And Clinical Outcomes.

Background: Patients with Code Stroke alert in the hospital may have different risk factors, demographics and differential diagnoses than patients who are admitted with Code Stroke Alert to the ED. Hospitals and health care systems use considerable resources to provide 24/7 acute stroke care access to in-hospital Code Stroke alerts. Most of the utility analyses are based on data from out-of-hospital stroke. We analyzed the frequency of IV tPA use and the likelihood of home discharge in patients with Code Stroke alert in the hospital versus out-of-hospital. Methods: All adult patients with Code Stroke alerts in the UCSD SPOTRIAS Database from 2004 to 2011, excluding patients transferred from acute care facilities; grouped into 1: out-of-hospital Code Stroke alerts (EMS or ED) and 2: in-hospital (all inpatient units) and analyzed by baseline demographics; time to treatment decision; frequency of IV tPA use; diagnosis (Acute Ischemic Stroke, SAH, ICH, TIA, mimic, unknown); discharge disposition (home versus other), 90 day modified Rankin Scale (mRS) and adjusted for multiple co-variables. Results: We identified 2,699 Code Stroke alerts; 2,498 in group 1 and 201 in group 2. Patients in group 2 were younger (63.6±15.5 vs 66.8±16.8 years of age, p=0.005), more likely to have diabetes (27.9 vs 21.3%, p=0.03), had higher baseline NIHSS (11.6±11.6 vs 9.0±10.0, 0.007) and likelihood to have a pre-stroke mRS &gt;1 (35.8 vs 27.4%, p=0.01); had fewer acute ischemic strokes (38.8 vs 46.6%), but more stroke mimics (39.8 vs 29.5%), p=0.01,had shorter time from stroke onset to treatment decision (202.2±282.3 vs 275.2±423.1 min, p&lt;0.0001) and were less likely to receive IV tPA (10.0 vs 16.0%, p=0.03). The time from onset to IV tPA treatment in Group 2 was 162.9±69.8 min; vs 150.1±106.0, p=0.07. Multivariable logistic regression analysis adjusting for age, history of diabetes and admission NIHSS show that the rates of being discharge home (OR=0.83, 95%CI = 0.59, 1.17, p=0.29) and having a 90-day mRS of 0-1 (OR-1.35, 95% CI = 0.64, 2.86), p=0.44) are similar in the two groups. Conclusion: In-hospital are less likely to lead to IV tPA treatment than out-of-hospital Code Stroke alerts. Patient outcome based on discharge disposition and 90-day mRS is not significantly different from out-of-hospital Code Stroke.

Abstract 2706: Patients with the Malignant Profile Within 3 Hours of Symptom Onset have Very Poor Outcomes Following IV tPA Therapy

Background: The “Malignant profile” is an MRI pattern that is associated with poor outcomes (mRS 5-6) following reperfusion in the 3-6 hr time window. The aim of this study was to estimate the incidence and prognostic implications of the Malignant profile, as identified by CT perfusion (CTP), in patients treated with tPA &lt;3 hrs from stroke onset. Methods: Consecutive patients treated with iv tPA at the Stanford Stroke Center from May 2009 to May 2011 who had CTP performed prior to tPA therapy, and within 3 hrs of symptom onset, were included. Perfusion data were acquired in cine mode on 16 and 64-row CT scanners; 2 separate scans were done yielding either 4 cm or 8 cm coverage depending on the scanner type. The incidence of the Malignant profile, based on the previously published definition of a Tmax &gt;8 sec perfusion lesion &gt; 85 mL, was assessed using a fully automated software program (RAPID). This program also estimates the infarct core based on cerebral blood flow (rCBF) and cerebral blood volume (rCBV) thresholds &lt;30% of the contralateral hemisphere. Poor outcome was defined as a mRS of 5-6 at 30 days. A receiver operating characteristic (ROC) curve analysis was done to identify Tmax and core volume thresholds that optimally define the Malignant profile (high specificity for poor outcome). Results: 121 patients were treated with iv tPA. Of these, 42 patients had an interpretable CTP performed within 3 hrs of symptom onset. Mean age was 75±14 years and median (IQR) NIHSS was 13 (6-19). Five patients (11%) met the pre-specified criteria for the Malignant profile and all 5 died during the acute hospitalization. ROC analysis determined that the optimized criteria were either a PWI Tmax &gt;8 sec lesion &gt;86 mL or an infarct core &gt;53 mL (both criteria had 100% specificity and 56% and 67% sensitivity respectively). The optimized criteria identified 6 patients as Malignant (14%). The poor outcome rate in these patients was 100% vs. 8.3% in the 36 patients non-malignant patients (p&lt;0.001). Conclusion: The incidence of the Malignant Profile is about 10-15% in tPA eligible patients imaged within 3 hrs of symptoms onset. The clinical outcome of these patients is very poor despite iv tPA therapy. This finding is consistent with data from patients treated with iv tPA in the 3-6 hr window. Further study is warranted to verify if CTP can reliably identify a subgroup of patients who do not benefit from iv tPA within 3 hours.

Abstract 2703: In-hospital Versus Out-of-hospital Stroke Treated With Iv Tpa And 3 Month Outcomes.

Background: Most hospitals set up Code Stroke alert teams in the Emergency Departments. Expanding sufficient Code Stroke coverage to in-hospital areas requires additional resources, often through Neuro-hospitalist teams. Most data on outcomes after stroke are based on out-of-hospital stroke. We evaluated the outcomes of patients with stroke that occurs in the hospital versus out-of-hospital. Methods: We included all adult patients with Code Stroke alerts, diagnosis of acute ischemic stroke, who had 90-days post Code Stroke modified Rankin Scale from the UCSD SPOTRIAS database (2004 to 2011) and excluded patients transferred from acute care facilities. The patients were grouped into 1: out-of-hospital Code Stroke alerts (EMS or ED) and 2: in-hospital (all inpatient units) and analyzed by baseline demographics, time to treatment decision, frequency of IV tPA use, 90-day modified Rankin Scale (mRS) and adjusted for multiple co-variables. Symptomatic intracranial hemorrhage (SICH) was defined as ≥4 point increase in NIHSS and ICH that was deemed the cause of the clinical change. Results: We identified 590 Code Stroke alerts; 563 in group 1 and 27 in group 2. Baseline demographics were balanced, except group 2 patients younger (64.26±16 vs 70.2±15.5 years of age, p=0.0497) and were more likely to be Hispanic (29.6 vs 14.2%, p=0.047). IV tPA was given in 13/27 (48.2%) patients in Group 2 and 266/563 (47.3%) in Group 1 (NS). Anticoagulation was the reason for exclusion in 4/14 (28.6%) of patients in Group 2 vs 18/266 (6.5%) (p=0.017). The frequency of other diagnoses and reasons for exclusion were similar between groups. The time from stroke onset to tPA treatment in group 2 was 135.1±57.9 vs 151.4±121.2 min (NS). A 90-day mRS of 0 or 1 was achieved in 9/27 (33.3%) patients in Group 2 and 221/563 (39.3%) patients in Group 1 (NS); in tPA treated patients: Group 2 3/13 (23.1%), Group 1 83/266 (31.2%) (NS). SICH occurred in the tPA treated patients: Group 2 1/13 (7.7%); Group 1 9/266 (3.4%) (NS). Conclusion: We identified a relatively small group of ischemic stroke patients with in-hospital onset. In those patients, however, rates of tPA use and outcomes were similar to out-of-hospital stroke.

Abstract 73: Results of DEFUSE 2: Clinical Endpoints

Background: The aim of DEFUSE 2 was to determine if there is a differential response to reperfusion following endovascular therapy according to predefined baseline MRI profiles. Methods: This prospective cohort study was conducted at 9 stroke centers. Consecutive patients, scheduled to undergo acute endovascular therapy within 12 hours of stroke onset, were enrolled if they had an NIHSSS&gt;5 and could undergo an MRI with perfusion (PWI) and diffusion-weighted imaging (DWI) immediately before the intervention. A fully automated image analysis program (RAPID) was used to determine lesion volumes. Patients were classified as Target Mismatch (TMM) if they met these criteria: a ratio of PWI(Tmax&gt;6s) over DWI volume &gt;1.8, DWI &lt;70ml, and a PWI(Tmax&gt;10s) volume &lt;100ml. An early follow-up MRI was obtained &lt;12 hours after endovascular therapy. Early reperfusion was defined as a &gt;50% reduction in Tmax&gt;6s volume between baseline and early follow-up. Favorable clinical response was defined as a ≥8 point improvement on the NIHSSS or an NIHSSS of 0-1 at 30 days. Results: This abstract represents a preliminary analysis of 86 of 101 patients who were treated with endovascular therapy (final results will be presented). The baseline characteristics of patients with TMM (n=70) were: mean age 67, median NIHSS 15, treated with iv tPA 43%, mean time from symptom onset to endovascular treatment 6.7 hrs, mean DWI volume 18 ml, and Tmax&gt;6s volume 82 ml. Early reperfusion was achieved in 64% of the TMM population and favorable clinical response was more common in TMM patients with early reperfusion than in TMM patients who did not reperfuse (69% vs 24%; p&lt;0.001). The baseline characteristics of patients without TMM (n=16) were: mean age 59, median NIHSS 19, treated with iv tPA 81%, mean time from symptom onset to endovascular treatment 5.4 hrs, mean DWI volume 76 ml, and Tmax&gt;6s volume 115 ml. Early reperfusion was achieved in 53% of the patients without TMM but was not associated with favorable clinical response in this population (44% had favorable clinical response with reperfusion vs 86% without reperfusion; p=0.15). The odds ratio for favorable clinical response associated with reperfusion was higher in TMM patients (7.0; 95% CI 2.3-21) than in those without TMM (0.1; 95% CI 0.1-1.6) (p&lt;0.01 for difference between odds ratios). These odds ratios remained similar after adjustment for differences in baseline characteristics (OR 7.8 vs. 0.2; p&lt;0.01 for difference between odds ratios). Conclusion: Early reperfusion following endovascular therapy is associated with substantial clinical benefits in patients with the Target Mismatch profile on baseline MRI. There is no association between reperfusion and favorable clinical outcomes in patients without Target Mismatch. These findings support the use of PWI/DWI selection criteria to identify a patient subgroup that is most likely to benefit from endovascular reperfusion therapy.

Abstract 3977: Neuroprotective Effects of Echogenic Liposomes-Mediated Xenon Delivery in a Rat Embolic Stroke Model Combined With Tissue Plasminogen Activator Thrombolysis

BACKGROUND: Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. Intravenous (iv) tissue plasminogen activator (tPA) in combination with the neuroprotective gas, xenon (Xe), is a promising strategy for ischemic stroke treatment. However, Xe delivery by inhalation may reduce oxygen uptake and tPA activity. We have developed novel Xe-containing echogenic liposomes (Xe-ELIP). In this study, we investigated the therapeutic effect of Xe-ELIP in a rat embolic stroke model. METHODS: Xe-ELIP was prepared by the pressurized-freeze method. Thrombotic strokes were induced in male Sprague-Dawley rats (n=16) by injecting a 13mm long blood clot into the middle cerebral artery (MCA). In the treatment group, tPA (10mg/kg) was infused intravenously at 2 hours after the onset occlusion. Xe-ELIP was administrated into the common carotid artery just before iv tPA. Continuous wave ultrasound (1 MHz, 50% duty cycle, 0.5 W/cm 2 ) was applied to trigger Xe release from ELIP during the 5 min of Xe-ELIP administration. Behavioral tests (limb placement, grid walking and beam walking) were conducted three days after the thrombotic stroke. Two mm-thick coronal brain sections were cut and stained with TTC to determine infarct size. RESULTS: The thrombotic stroke control group without any treatment exhibited the largest damage and infarct size (17±5% of the whole brain); tPA treatment reduced the damage and the infarct size to 5.2±0.4% of (p=0.025 vs stroke). tPA treatment in combination with Xe-ELIP further reduced the infarct size to 1.5±0.4% (p=0.05 vs tPA group) ( Fig 1a, 1b). Behavioral deficit correlated with the infarct volume reduction. Regional blood flow velocity monitored by a laser Doppler flow meter was the same in both tPA and tPA+Xe-ELIP treatment groups. CONCLUSIONS: This study has demonstrated a significant neuroprotective effect of ELIP-encapsulated xenon released by application of 1 MHz ultrasound. Xe-ELIP can be used in combination with tPA without affecting tPA thrombolytic activity.

Abstract 2968: Outcomes Of Young Acute Ischemic Stroke Over The Last Decade: Insights From Nationwide Inpatient Sample

Background: The burden of young ischemic stroke has increased over the years. However, outcomes of young patients with acute ischemic stroke (AIS) remain unknown. Over the last decade, with increasing utilization rate of iv tpa, our objective was to evaluate trends in survival and discharge outcomes of young AIS patients in the United States. Methods: Data from the Nationwide Inpatient Sample for the years 2001 through 2009 were reviewed. Hospitalizations with a discharge diagnosis of an acute ischemic stroke (ICD-9 codes: 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 424.01, 434.11, 434.91 and 436) were included. Nationwide estimates of deaths and discharge destination were calculated for each year within the young AIS subset. The Cochrane Armitage test was used to assess trend across the years Results: From 2001 through 2009, there were an estimated 4,917,217 admissions for acute ischemic stroke. Out of that, 204,703 (4.16%) were young patients with AIS. Thrombolysis in young ischemic stroke increased from 354 (1.84% of young AIS) in 2001 to 1237 (4.97%) in 2009 (p&lt;0.0001). There was a progressive decrease in mortality in young AIS patients, from 6.81% in 2001 to 5.43% in 2009 (trend p= 0.027). Discharge to home or home with home health did not show any significant change (trend p= 0.52). Discharge to rehabilitation facilities showed significant increase over the years, 3.42% in 2002 to 12.7% in 2009 (trend p &lt;0.0001). Discharge to other facilities other than rehabilitation showed significant decrease over the years, 29.1% in 2001 to 17.8% in 2009 (trend p&lt;0.0001). Rate of intracranial hemorrhage, 2.70% in 2001 to 2.69% in 2009, did not show any significant change despite increasing use of iv tpa (trend p=0.39). Conclusion: Over the last decade, deaths from AIS among young patients have decreased. The increase in rehabilitation placement and decrease in nursing home discharges suggest improving neurologic outcomes. Modern treatments such as stroke units, thrombolysis, and mechanical thrombectomy may be responsible for the reductions in mortality and morbidity.

Abstract 3531: Clinical Outcomes Following Endovascular Stroke Treatment Facilitated via Telestroke Evaluation

BACKGROUND: Most stroke patients present to small community hospitals without established stroke pathways or interventional stroke treatment capability. The advent of 2 way audiovisual telestroke systems gives such patients the opportunity to be assessed rapidly by stroke neurologists. Patients who are not candidates for systemic IV tPA or have failed thrombolytic treatment can be identified and transferred to a comprehensive stroke center for potential endovascular treatment. We compared the clinical outcomes of patients undergoing endovascular stroke treatment at University of Pittsburgh Medical Center triaged either through telestroke or non-telestroke means. METHODS: Prospective data including demographics, co-morbidities, baseline Alberta Stroke Program Early CT (ASPECT) and National Institute of Health Stroke Scale (NIHSS) score, intervention modality (pharmacological, mechanical or both), time to treatment, clinical outcome, and hemorrhage and mortality rates were compared. Favorable outcome was defined as modified rankin score (mRS) of 2 or less. RESULTS: Between 3/2007 and 5/2011, thirty four patients underwent endovascular stroke treatment following telestroke evaluation versus 354 patients who were triaged through other means. Baseline characteristics were similar between the groups. Time to endovascular treatment (595 vs. 767 minutes; p = 0.5), pretreatment with systemic tPA (51.6 vs. 56.9%, p=0.6), recanalization (TIMI ≥ 2; 91.2% vs. 84.8%; p = 0.31), favorable outcome (modified rankin score ≤ 2; 50% vs. 40.4%; p = 0.29) and mortality rates (28.1% vs. 34.9%, p=0.44) were comparable. Multivariate logistic regression model identified young age (OR 0.91, CI 0.88-0.95, p&lt;0.01), successful recanalization (OR 3.3, CI 1.8-6.2, p&lt;0.01), and baseline ASPECT score (OR 6.5, CI 2.4-17.4, p&lt;0.01) as predictors of favorable outcome. CONCLUSION: The results of this study suggest that telestroke guided endovascular stroke treatment is feasible and the outcomes are similar to those patients who were triaged by traditional means. Future randomized studies which specifically compare triage via telemedicine vs. telephone or direct emergency department presentation are needed to substantiate these findings.