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Abstract 426: Inhibition of RIPK3/MLKL-dependent Necroptosis by SAP-12 in Ischemic Brain
- Qing Guo and
- Jun Xie
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 39, Issue Suppl_11 May 2019

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Introduction: RIPK3 (receptor-interacting protein kinase 3)/MLKL (mixed lineage kinase domain-like protein)-dependent necroptosis plays a significant role in ischemic neuronal cell death. We found that AATF (apoptosis antagonizing transcription factor) was secreted extracellularly without a classical N-terminal signal peptide by cortical neurons following acute ischemic stroke. Secreted AATF binds to cell surface TRL4 receptors and blocks TRL4-mediated neuroinflammation. By using in vitro GST fusion protein based assays and several molecular deletion mutants of AATF, we identified a region corresponding to the amino acid sequence between AATF179 and AATF279 that was responsible for interacting with TLR-4. A small AATF core peptide, termed SAP-12, was identified to interact specifically with TLR-4 and confers potent neuroprotective actions in primary neuronal cultures. Here, we investigated whether SAP-12 can be targeted to the brain to reduce ischemic brain injury in vivo by blocking neuronal necroptosis.Methods: SAP-2 is conjugated with a protein transduction domain of HIV TAT protein to deliver SAP-12 across the blood-brain-barrier into the brain after intraperitoneal injections. Middle cerebral artery occlusion (MCAO) was used to induce cerebral ischemia.Results: SAP-12 administered intraperitoneally can be delivered to the brain parenchyma without affecting the integrity of the blood brain barrier. SAP-12 significantly reduced TNF-α levels and brain infarct size. SAP-12 markedly decreased RIPK3- and MLKL-dependent necroptosis in ischemic brains. Of importance, SAP-12 had a much greater potency and broader effective dose range than the full length secreted AATF in vivo.Conclusions: SAP-12 can be targeted to the brain parenchyma following intraperitoneal administration where it functions as a potent blocker of RIPK1- and MLKL-mediated necroptosis in ischemic brain. SAP-12 may represent a potential strategy for new drug development in ischemic stroke.
Abstract 13074: High Detection Rates of Atrial Fibrillation in Patients After a Cerebrovascular Event by Systematic ECG Monitoring With an Implanted Device: SPIDER-AF Study
- Franz Goss,
- Karin Rybak,
- Ralph Bosch,
- Markus Seige,
- Winfried Haerer,
- Bernd Schütz,
- Rolf Mitusch,
- Michael Müller,
- Ullus Heinrich,
- Reinhard Stöhring,
- Oliver Turschner,
- Andreas Knapp,
- Martin Jauernig and
- Michael Drexler
Circulation Volume 138, Issue Suppl_16 November 2018

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Introduction: Atrial fibrillation (AF) is associated with a substantial increase in the risk of stroke and cardiovascular morbidity. Therefore, early detection of AF to initiate appropriate therapy in patients at risk is crucial and may improve outcome. An implantable loop recorder (ILR) can monitor the heart rhythm for up to three years, modern devices provide dedicated algorithms to detect AF. In the case of an arrhythmia, an ECG is automatically recorded and transmitted to the treating physician.Objectives: We aimed to investigate the AF detection rate in patients in sinus rhythm and no history of AF after a recent cerebrovascular event by systematic continuous screening in the ambulatory setting.Methods: Observational study in patients with no prior diagnosis of AF, who had (presumably thromboembolic) transient ischemic attack (TIA) or stroke within 12 months and were implanted an ILR in the last 6 months. Follow-up visits every 3 months for 1 year overall.Results: In 34 outpatient cardiology centers in Germany, a total of 500 patients were documented (mean age 63.1 ± 12.7 years, 177 patients > 70 years; 60.8 % males). The qualifying event was a TIA in 27.3% or a stroke in 72.7% with typical thromboembolic pattern in NMR or CT imaging.Arterial hypertension was present in 71.4%, diabetes mellitus in 23.0%, coronary heart disease in 13.2%, carotid artery stenosis <70% in 22.6%, respectively.Actual mean screening period with the Reveal LinQ device (Medtronic) was 149 ± 130 days. AF was newly detected during follow-up by the device in 26.4% (25.1 % with prior stroke, 29.9% TIA), after a median interval of 118 days. Of these patients, 97.0% had paroxysmal and 3.0% persistent AF. Most AF patients were asymptomatic (78.7%). CHA2DS2Vasc in AF 4.1, in sinus rhythm 3.8 respectively.Conclusions: In patients in sinus rhythm and no history of AF after a recent cerebrovascular event, during 1-year follow-up in a quarter of patients AF could be newly detected by means of systematic continuous screening with an implantable ECG device. As AF diagnosis usually leads to immediate secondary prevention with long-term anticoagulation, such screening may substantially reduce the risk of recurrent stroke and progression of cardiovascular morbidity.
Abstract 112: Brain Selective Hypothermia With Intra-arterial Cold Infusions Plus Early Normobaric Hyperoxygenation for Neuroprotection in Experimental Acute Ischemic Stroke
- Yi Wang,
- Xueyu Yang,
- Kristin Patzwaldt,
- Salvador Castaneda,
- Manuela Martella,
- Leticia Quintanilla-Fend,
- Bernd Pichler,
- Ulf Ziemann and
- Sven Poli
Stroke Volume 50, Issue Suppl_1

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Introduction: Characterized by strong and brain-selective cooling performance paired with only minor (systemic) adverse effects, intra-arterial cold infusions (IACI) into brain-supplying arteries have been reported as neuroprotective in experimental acute ischemic stroke (AIS). Combining normobaric hyperoxygenation (NBHO) with IACI might potentiate neuroprotection by increasing oxygen supply and, at the same time, reducing metabolism during ischemia and mitigating oxidative stress during reperfusion.Methods: To investigate potentially synergistic effects, we tested NBHO+IACI vs. NBHO vs. IACI vs. controls in a transient (60 minutes) filament middle cerebral artery occlusion (MCAO) rat model (n = 16 per group). NBHO (100 % oxygen) was initiated 10 minutes after MCAO, continuous IACI (0 °C, 12 mL) into the internal carotid artery were started two minutes prior to reperfusion, both treatments were stopped (simultaneously) after 65 and 15 minutes. Infarct and edema growth were estimated by MRI incl. perfusion, diffusion and T2 during ischemia, at 24 hours and two weeks. Neurological tests were performed for functional outcome. NeuN, IB4 and GFAP staining was used to illustrate selective neuron loss (SNL), microglia activation and gliosis at two weeks. Effect of arterial on penumbral oxygenation was evaluated with pre/post-treatment blood gas analyses and MBA1 staining at 24 hours.Results: In accordance with previous studies, NBHO reduced infarct growth (primary endpoint; T2 infarct at two weeks minus perfusion ischemic core during MCAO) by 50 % vs. controls. Cerebral edema, penumbral oxygenation and functional outcome as well as SNL, microglia activation and gliosis were also improved or reduced. In contrast, IACI were not beneficial and no synergistic neuroprotection was found for NBHO+IACI.Conclusions: Our findings confirm strong NBHO-mediated neuroprotection in AIS, while IACI were not neuroprotective. Longer duration of brain-selective hypothermia might be the key, but IACI volume is the limiting factor. MRI, functional and histological results will be discussed in the context of current literature.
Abstract 113: Late Window Transfer Patients had Favorable Outcomes Following Thrombectomy in DEFUSE 3
- Amrou Sarraj,
- Michael Mlynash,
- Jeremy Heit,
- Michael Marks,
- Maarten Lansberg and
- Gregory Albers
Stroke Volume 50, Issue Suppl_1

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Background: Although the treatment benefit of endovascular thrombectomy (EVT) was maintained in transfer patients in the early window trials, overall rates of functional independence were lower in both the EVT and control groups among transfer patients. We hypothesized that the imaging-based selection criteria employed in DEFUSE 3 would lead to comparable outcome rates and treatment efficacy in transfer vs. direct admission patients.Methods: DEFUSE 3 patients were stratified based on if they presented directly to the study site or were transferred from a primary center. The primary and secondary efficacy and safety outcomes of DEFUSE 3 were compared.Results: Of 182 patients randomized, 121 (66%) were transfers and 61 (34%) direct. The 2 groups had similar baseline characteristics, other than transfers had 30 min longer median times from last known well time to arrival at the study site. The primary efficacy outcome (mRS shift at day 90) did not differ in the direct vs. transfer groups, OR 2.9, 95% CI 1.2-7.2, P=0.014 for direct and OR=2.6, 95% CI 1.3-4.8, P=0.009 for transfer (Fig 1). The overall rate of functional independence (mRS 0-2 at day 90) in the EVT group did not differ (44% direct, 45% transfer) nor did the treatment effect: RR 2.0 (0.9-4.4) direct vs. 3.1 (1.6-6.1) for transfer. EVT reperfusion rates were identical (mTICI≥2b 76%) in both groups. The rates of death and SICH did not differ. Transfer patients had more favorable collateral profiles (based on the hypoperfusion intensity ratio) median (IQR) for transfer 0.35 (0.18-0.47) vs. 0.42 (0.25-0.56) for direct, p=0.050.Conclusions: In late window patients selected by penumbral mismatch criteria, both the favorable outcome rates and treatment effects did not decline in transfer patients. These results have healthcare implications indicating transferring potential candidates for late window thrombectomy to EVT centers is associated with substantial clinical benefits and should be strongly encouraged.
Abstract 145: Advanced Neuroimaging in Stroke Patient Selection for Mechanical Thrombectomy: A Systematic Review and Meta-analysis
- Georgios Tsivgoulis,
- Aristeidis H Katsanos,
- Peter D Schellinger,
- Martin Köhrmann,
- Valeria Caso,
- Lina Palaiodimou,
- Georgios Magoufis,
- Adam Arthur,
- Urs Fischer and
- Andrei V Alexandrov
Stroke Volume 50, Issue Suppl_1

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Introduction: There is clinical equipoise regarding the use of advanced imaging for selecting acute ischemic stroke (AIS) patients eligible for mechanical thrombectomy (MT) during the first 6 hours from symptom onset. However, accumulating evidence indicates that advanced neuroimaging represents an invaluable and time independent prognostic factor.Methods: We performed a systematic review and meta-analysis of available randomized clinical trials (RCTs) to evaluate the impact of patient selection with advanced neuroimaging on the 3-month: 1. functional independence (FI, mRS: 0-2), 2. favorable functional outcome [FFO, modified Rankin Scale scores (mRS): 0-1], 3. all-cause mortality and 4. functional improvement (assessed with ordinal analysis of the mRS-scores).Results: Among the 10 eligible RCTs (1979 total patients, mean age: 67 years), 5 studies reported the use of advanced imaging. Studies using advanced neuroimaging showed higher treatment effects of MT on 3-month FI (OR=3.79, 95%CI: 2.71-5.28 vs. OR=1.76, 95%CI: 1.39-2.24; p for subgroup differences<0.001), FFO (OR=3.16, 95%CI: 1.94-5.14 vs. OR=1.75, 95%CI: 1.30-2.34; p for subgroup differences=0.04) and functional improvement (cOR=2.77, 95%CI: 2.04-3.76 vs. 1.60, 95%CI: 1.32-1.95; p for subgroup differences: 0.003) compared to studies using conventional neuroimaging. Including only studies in the early (0-8hrs) time window advanced imaging selection was associated with better 3-month FI rates (p for subgroup differences: 0.04) compared to conventional imaging selection. No difference in the mortality (p for subgroup differences: 0.27) and sICH rates (p for subgroup differences 0.93) was found between the two groups. No evidence of heterogeneity was documented in all the aforementioned subgroups (I²<30%, p for Cochran Q>0.17 for all analyses).Conclusions: Our findings indicate that AIS patient selection for MT based on advanced neuroimaging appears to be associated with improved clinical outcomes, including lower mortality rates. The use of advanced neuroimaging for both the selection and prediction of prognosis for MT candidates should not depend on the elapsed time from symptom onset.
Abstract 146: Endovascular Treatment May Still Benefit Patients With Low Baseline Alberta Stroke Program Early CT Score
- Manon Kappelhof,
- Ivo G Jansen,
- Albert J Yoo,
- Ludo F Beenen,
- Stefan D Roosendaal,
- Maxim J Mulder,
- Jasper Martens,
- Alida A Postma,
- Diederik W Dippel,
- Hester Lingsma,
- Wim H van Zwam,
- Olvert A Berkhemer,
- Henk A Marquering,
- Charles B Majoie
Stroke Volume 50, Issue Suppl_1

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Introduction: We aimed to investigate the outcome of endovascular treatment (EVT) for acute ischemic stroke in patients with low Alberta Stroke Program Early CT Score (ASPECTS).Methods: This study reports on MR CLEAN Registry patients with available baseline ASPECTS (N=1423). ASPECTS was trichotomized in 0-4, 5, and 6-10 in order to create low ASPECTS groups of similar size. Primary outcome was modified Rankin Scale score (mRS) at 90 days. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Benefit of reperfusion (defined as extended thrombolysis in cerebral infarction [eTICI] score 2B-3) was assessed by multivariable ordinal logistic regression analysis, including an interaction term of reperfusion and ASPECTS, and it was expressed as an adjusted common odds ratio (acOR). A comparison with the MR CLEAN trial control arm was made to assess benefit of EVT.Results: Higher trichotomized ASPECTS was associated with improved mRS (acOR 1.4, 95%CI 1.2-1.7). For ASPECTS 0-4 (n=93) successful reperfusion was not associated with improved mRS (acOR 1.4, 95%CI 0.6-2.9). ASPECTS 5 (n=63) and ASPECTS 6-10 subgroups (n=1267) however, did show significant benefit of reperfusion (acOR 3.9, 95%CI 1.3-11.8; acOR 2.7, 95%CI 2.2-3.3, respectively)(Fig1). Interaction between trichotomized ASPECTS and reperfusion was not significant (p=0.13). Comparison with the MR CLEAN trial control group showed that trichotomized ASPECTS did not modify the effect of EVT (p=0.14). Patients with lower trichotomized ASPECTS had a higher risk of mortality (aOR 0.9, 95%CI 0.9-1.0), but not of sICH (aOR 1.0, 95%CI 0.9-1.1).Conclusion: ASPECTS does not modify effect of reperfusion or EVT on functional outcome after acute ischemic stroke. Patients with ASPECTS 5 or higher seem to benefit from successful reperfusion.
Abstract 161: Interfacility Transfer for Mechanical Thrombectomy - Direct to Neuroangiography or CT Angiography First?
- Kelley A Humbert,
- Michele Sellers,
- Elizabeth Neuhaus-Booth,
- Steven R Messé,
- Bryan A Pukenas and
- Brett L Cucchiara
Stroke Volume 50, Issue Suppl_1

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Objective: Faster time to mechanical thrombectomy (MT) is associated with better outcome in acute stroke. In patients transferred from other hospitals where a routine CT has already ruled out hemorrhage, transfer direct to angiography (DTA) suite may reduce door to groin time compared to transfer to CT angiography (CTA) first. However, this may result in unnecessary catheter angiography if many patients would have been excluded based on CTA results. We sought to determine how often CTA and repeat head CT changed the decision to proceed to MT.Methods: An internal transfer database at a comprehensive stroke center (CSC) was used to identify patients transferred from outside facilities for consideration of mechanical thrombectomy from July 2016 to May 2017. Detailed clinical and radiographic data was extracted using a standard case report form.Results: Of 187 patients transferred for MT, 171 underwent CT +/- CTA on arrival, 5 went DTA, and 11 were admitted without imaging or intervention. Among those undergoing CT +/- CTA on arrival, MT was aborted in 110 (64%) patients. Of these, 87 (79%) were aborted directly based on imaging findings, with absence of proximal large vessel occlusion (LVO) amenable to MT being the most common reason (69%), followed by rapid clinical improvement or mild deficit (7%). MT was aborted based on imaging findings in 36% of patients with NIHSS≥10 on arrival at CSC, and in 29% of patients with NIHSS≥15. In patients with outside hospital CTA demonstrating proximal LVO (n=48), MT was aborted in 48% on CSC arrival, mostly based on imaging findings (48%) or dramatic clinical improvement (31%). Use of tPA did not substantively modify any of these findings. CSC arrival to groin puncture tended to be shorter in the patients going DTA compared to CTA (median 39 v 54 min, p=0.06).Conclusions: While transfer DTA may be associated with faster door to groin puncture times, this might result in many patients undergoing unnecessary catheter angiography who would have been excluded based on CT +/- CTA findings. Even in transferred patients with severe stroke deficits on arrival, imaging excludes about 1/3 of patients from MT.
Abstract TMP1: Time From Image Acquisition to Interventional Team Notification: A New Target for Enhancing Acute Stroke Workflow
- Kurt Yaeger,
- Hazem Shoirah,
- Akila Pai,
- J Mocco and
- Johanna T Fifi
Stroke Volume 50, Issue Suppl_1

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Background: Reducing time to reperfusion for emergent large vessel occlusion (ELVO) has consistently shown to correlate with favorable outcome after ischemic stroke. However, there are many barriers to the efficient delivery of care. We hypothesize that the time from radiological image acquisition to interventional neuroradiology (INR) team activation makes up a significant, yet modifiable period of time within the acute stroke workflow.Methods: An institutional, prospectively-maintained registry was queried for patients who underwent endovascular thrombectomy (EVT) for ELVO during the one-year period between August 1, 2017 and July 31, 2018. Patients were excluded if imaging was obtained after activation of the INR team, or if times were not recorded. We calculated the time from image acquisition, defined as time of first CT imaging, to INR notification.Results: The time from initial CT acquisition to INR activation was available in 151 out of 183 patients (83%) who underwent thrombectomy during this one-year period. The team was notified after imaging in 62 patients (34%). The remainder either underwent imaging after INR notification (49%) or times were not recorded (17%). On average, this time was calculated to be 50.8 minutes (range 1-310 mins, SD 63 mins), and made up on average 11% of the total time from presentation to final reperfusion (range 0.4-55%, SD 7.0%). When broken down between stroke codes with rapid (≤30 min) and delayed (>30 mins) notification times, the overall time to reperfusion increased from 168 minutes to 307 minutes (p<0.001). The proportional time delay as caused by lagging imaging notification increased from an average of 9% to 26% of the total time delay until reperfusion, in rapid and delayed cases respectively (p<0.001).Discussion: We have identified delays in the time between initial CT imaging acquisition to notification of the INR team, and further observe that delays in this time period lead to proportionally greater delays in overall time to reperfusion. Imposing a more efficient communication process to reduce this time would decrease overall time to reperfusion, including automating neuroradiological interpretations, enhancing stroke team mass notification, and streamlining the chain of communications.
Abstract TMP12: Pre Procedure Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) Does Not Reduce the Risk of Distal Embolization with Mechanical Thrombectomy in Acute Ischemic Stroke: A Diffusion Weighted Magnetic Resonance Imaging (MRI) Study
- Emrah Aytac,
- Ahmer Asif,
- Erdem Gurkas,
- Humera Ahsan,
- Premkumar N Chandrasekaran,
- Brandi R French and
- Adnan I Qureshi
Stroke Volume 50, Issue Suppl_1

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Background: It has been hypothesized that intravenous recombinant tissue plasminogen activator (rt-PA) prior to mechanical thrombectomy reduces the risk of intraprocedural distal embolization in acute ischemic stroke patients.Methods: We analyzed the diffusion-weighted imaging (DWI) acquired with 1.5- or 3- Tesla magnetic resonance imaging (MRI) scans obtained within 24 hours of mechanical thrombectomy in consecutive acute ischemic stroke patients. DWI was performed with single-shot echo-planar technique at b values of 0-1000 s/mm². An independent physician identified distal embolization related foci of restricted diffusion on ipsilateral and contralateral hemispheres. Distal embolization was defined as discrete foci of restricted diffusion independent of the primary area of infarction on MRI. Patients were stratified based on whether they had or did not receive intravenous rt-PA prior to thrombectomy.Results: Distal embolization was seen in 48 of 50 patients (mean age ± SD; 62.9 ± 15.5 years) who underwent mechanical thrombectomy (mean number 9.1; range 0-22). The mean number of distal embolization was not significantly different between patients who had and those who did not receive intravenous rt-PA prior to mechanical thrombectomy (9.5 ± 6.2 versus 8.7 ± 6.5; p=0.67 by ANOVA). There was no difference in mean number of ipsilateral hemispheric distal embolization between the two groups (8.5 ± 6.4 versus 7.6 ± 6.4, p=0.61 by ANOVA). There was no relationship between mean number of emboli and age of the patient (regression coefficient 0.004; p=0.94) or time interval between symptom onset and thrombectomy (regression coefficient -0.02; p=0.67) on linear regression analyses.Conclusion: Although distal embolization is very common after thrombectomy, we did not find any evidence that intravenous rt-PA prior to procedure reduces the risk of intraprocedural distal embolization.
Abstract TMP86: Improved Outcomes After Mechanical Thrombectomy for In-Hospital Strokes
- Jasmina Ehab,
- Abdelrahman Beltagy,
- Nicholas Hilker,
- Nicole Slye,
- Henian Chen,
- William S Burgin,
- David Z Rose and
- Swetha Renati
Stroke Volume 50, Issue Suppl_1

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Background: Most stroke patients have their stroke in the community setting, however a significant minority occur while hospitalized for another condition. Prior studies have noted worse outcomes for in-hospital strokes(IHS) compared to community-onset strokes(COS). IHS are also less likely to receive intravenous thrombolytic therapy. The increased use of mechanical thrombectomy(MT) and distinct eligibility criteria from thrombolysis provide additional therapy options for these patients. We present one of the first comparison of outcomes looking specifically at MT for IHS versus COS.Methods: We performed an IRB-approved, retrospective cross-sectional study on patients who underwent MT at our center for acute ischemic stroke between Jan 2012 and Nov 2017. Variables reviewed included patient demographics, vascular risk factors, symptom recognition time, treatment time, and disability as measured by the Modified Rankin Scale(mRS). Statistical analyses were performed using logistic regression to assess the relationship between IHS versus COS.Results: We studied 334 patients (290 COS and 44 IHS) who were treated with MT for acute ischemic stroke. Patients who presented in-hospital were younger (60.7 vs. 70.4 years; p<0.001). IHS were more likely to have a history of coronary artery disease (48% vs. 25%; p<0.003) and tobacco use (32% vs. 16%; p<0.032), conversely, they had a lower rate of atrial fibrillation (20% vs. 42% p<0.005). No significant difference was noted in history of diabetes, hypertension, and dyslipidemia. IHS treated with MT had lower use of intravenous thrombolysis (14% vs 34%; p<0.006). Patients with IHS had a significantly shorter mean symptom recognition to femoral stick time (p<0.039). In addition, IHS patients had significantly better outcomes at discharge as measured by mRS 0-3 (mRS range, 0-6; lower scores indicating less disability). After adjustment for age and stroke severity (National Institute of Health Stroke Scale) IHS continued to have better outcomes at discharge as measured by mRS 0-3; AOR=4.832; 95% Cl, (1.207-19.348); P< 0.026.Conclusion: In conclusion, time from symptom recognition to MT is faster for IHS vs. COS. In addition, IHS had less disability after mechanical thrombectomy for large vessel occlusion.
Abstract TP129: The Combination of Tissue Plasminogen Activatorand Vepoloxamer Results in Sustained Neuroprotection in Aged Rats After Embolic Stroke
- Chunyang Wang,
- Zheng Gang Zhang,
- Michael Chopp,
- Martin Emanuele and
- Li Zhang
Stroke Volume 50, Issue Suppl_1

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Stroke is a leading cause of death and disability worldwide, mainly affecting the elderly. To date, tissue plasminogen activator (tPA), the only FDA approved treatment agent, is of limited use in stroke patients mainly due to its narrow therapeutic window and hemorrhage complication. Vepoloxamer is a highly purified proprietary amphipathic copolymer, which has potent anti-thrombotic and rheological properties for treating various thrombotic disorders. In an effort to increase the efficacy and safety of tPA thrombolytic therapy, the present study evaluated the neuroprotective effect of combination treatment with Vepoloxamer and a low dose of tPA in aged rats after embolic middle cerebral artery occlusion (MCAO). Male aged rats (18 month) subjected to MCAO were randomly divided into the following groups (n=10/group): tPA alone (5mg/kg, IV) at 2h; tPA (5mg/kg, IV) at 2h in combination withVepoloxamer (300mg/kg at 2h, IV; followed by a 12h IV infusion of 100 mg/kg/hr starting at 10h); or saline at 2h as control. An array of behavioral tests were performed weekly for 4 weeks. Infarct volume was measured 4 weeks after MCAO. The combination treatment with tPA and Vepoloxamer significantly (p<0.05) reduced infarct volume (20±3%) compared with rats treated with saline (31±2%) or tPA alone (32±2%). In addition, the rats treated with tPA in combination with Vepoloxamer exhibited sustained improvements in neurological function up to 4 weeks starting at 1d after MCAO, when compared with rats treated with saline or tPA monotherapy. However, tPA monotherapy failed to reduce neurological functional deficits compared with the saline control. The combination of tPA and Vepoloxamer did not increase the mortality rate nor the incidence of cerebral hemorrhage compared with saline or tPA monotherapy. In conclusion, our data demonstrated that the adjuvant treatment with Vepoloxamer and tPA amplifies the therapeutic efficacy of low-dose tPA in aged rats after embolic stroke without increasing the incidence of hemorrhagic transformation.
Abstract TP271: Long-term Results of an EMS-driven Rapid Arterial oCclusion Evaluation (RACE) Protocol for Triage of Acute Strokes
- Ehad Afreen,
- Alicia C Castonguay,
- Julie Shawver,
- Hisham Salahuddin,
- Andrea Korsnack,
- Giana Dawod,
- Syed F Zaidi and
- Mouhammad A Jumaa
Stroke Volume 50, Issue Suppl_1

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Background and Purpose: We previously reported on the successful implementation of a EMS-driven bypass protocol using the Rapid Arterial oCclusion Evaluation (RACE) score for triage of acute strokes. Here, we describe the long-term results of our RACE alert protocol.Methods: Patients with a RACE score >5, who are last seen normal within 12 hours, wakeup with stroke symptoms, or have unknown time of symptoms onset were directly transferred as RACE alerts (RA) to our two stroke centers (one primary with interventional capabilities and one comprehensive) with interventional capacity in Lucas County, Ohio. Data including baseline demographics, RACE score, diagnosis, treatments and procedures, and clinical and angiographic outcomes were captured in a prospective database.Results: From July 2015 to July 2018, 511 RAs were triaged. Median age of RA patients was 73 (IQR 63-82), 55.8% were female, and median RACE score was 7 (IQR 5-8). Median time from 911 dispatch to ER was 31 minutes (IQR 22-38) and onset to arrival was 85 minutes (IQR 47-307). Of the 511 RAs, 52.3% were diagnosed with an ischemic stroke, 13.5% intracerebral hemorrhage, 6.5% transient ischemic attack, 12.9% seizure, and 7.8% encephalopathy. The rate of IV-tPA use was 24.5% and median door to needle time was 33 min (IQR 24-48). The rate of mechanical thrombectomy (MT) was 24.3%, with median door to puncture and door to revascularization times of 64 (IQR 48.5-78.5) and 91 minutes (IQR 79.3-114.8), respectively. The majority of occlusions were MCA (73.2%). Successful revascularization (TICI≥2b) was achieved in 84.7%. Ninety-day favorable outcome (mRS 0-2) and mortality was 47.2% and 25.4% in patients who underwent MT.Conclusions: Our results show the long-term feasibility and efficiency of an EMS-driven early stroke triage protocol using the RACE score.
Abstract TP40: Outcomes of Thrombectomy in Basilar Artery Occlusions: A Single Center Study
- Angela M Hawkins,
- Harold Morris,
- Karin Olds,
- Coleman Martin,
- Naveed Akhtar and
- William Holloway
Stroke Volume 50, Issue Suppl_1

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Background: Basilar artery occlusion (BAO) remains a devastating ischemic stroke subtype leading to high mortality rates and poor outcomes. Recently, mechanical retrieval therapy (MER) became a standard of care and a influential predictor of favorable outcomes in anterior circulation stroke patients. However, the use of MER in AIS patients with BAO is not established.Purpose: Our hospital sees over 1600 stroke patients a year with over 18% of stroke patients receiving MER therapy compared to the national average of 4.3%. We sought to evaluate our BAO patients who received MER therapy for efficacy and outcomes.Methods: Patients presenting to our facility between January 1, 2015 and June 30, 2018 were studied in a retrospective chart review. AIS patients who had BAO were evaluated for types of treatment, age, outcomes, recanalization rate TICI score of >2b, and disability or mortality after stroke. Of the 4,212 stroke patients presenting at our facility in the timeframe, 441 underwent MER therapy with 20 patients having a primary occlusion of basilar artery. Data was analyzed and compared to meta-analysis data.Results: Our patients with BAO had a (mRS) modified Rankin Score (0-2) of 81.8% (95% CI 7.8%, 96.8%) compared to the national average of 42.0% (95% CI 36%, 48%). Reperfusion scores (TICI >2b) in our patients was 90.9 % (95% CI 57.1%, 99.5%), while the reperfusion scores (TICI >2b) in the comparison group as 81% (95% CI 73%, 87%). Our sICH rate was 0.0% (95% CI 0.0%, 31.1%) while the comparison group was 4% (95% CI 2.0%, 8.0%). Our overall mortality rate of our BAO patients was 5.1%, with the comparison group’s mortality rate at 30.1%. There was no significance noted in patients’ ages or in the use of thrombolytics between the two groups.Conclusion: Patients presenting with stroke caused by BAO who receive MER at our facility have more favorable outcomes than those in the systematic review. Potential reasons include shorter time to recanalization, improved catheters and technology, experienced staff and strict attention to seamless transitions of care. MER therapy can be a safe treatment modality for patients with BAO. Further clinical trials are needed to show MER efficacy in patients experiencing a BAO.
Abstract TP493: Impact of Extended Window Protocol for Acute Stroke Treatment (EPAST) Implementation on Stroke Treatment Rates and Quality Indicators in Emergency Room
- Jon Aagesen,
- Nataliya Omelchenko and
- Jeffery Adkins
Stroke Volume 50, Issue Suppl_1

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Background and Purpose: Acute ischemic strokes remain one of the main causes of morbidity and mortality in the United States (US). With a stroke occurring every 40 seconds, the interest in advancing stroke care is critical to improving survival and reduces the loss of function (Taylor, Uchino, Hussain, & Carlson, 2014). Presently, 12% of acute ischemic strokes evaluated in US Emergency Departments (ED) receive stroke intervention (Lin et al., 2015). The purpose of the extended window protocol for acute stroke treatment (EPAST) study was to evaluate it’s impact on stroke patients’ treatment rates and quality indicators (door to the needle (DTN) and door to groin (DTG) times). Patient outcome was measured by the change in the modified Rankin Score (mRS). The investigation also assessed a new nursing process, which extended the assessment and screening window for acute stroke patients presenting within the emergency department (Omelchenko & Cerone, 2017).Methods: A chi-square test of independence, an Independent t-test and Mann-Whitney U test were used for data analysis (Sheskin, 2011).Results: The study examined the stroke alerts during January-February 2017 to establish a baseline (n=8) vs. total stroke alerts during January-February 2018 identified as the sample (n=9). Study showed number of alerts at X² (1) = .118, p = 0.732. The DTN baseline was 72.50 minutes vs. sample time of 64.75 minutes. t (7.031) = .374, p = 0.720. DTG baseline was 90.50 minutes vs. sample time of 70.00 minutes, t (2) = .179, p = 0.874. The mRS baseline median was 4.50 vs. sample median of 2.67 (p< 0.05).Conclusion: EPAST project showed overall improvements in the stroke process quality indicators such as DTN and DTG with the average improvement of 11% and 22% respectively. Study also showed positive trends in overall stroke treatment rates, as it included additional patients who would be excluded in the past. Study was limited by small sample size. Additional studies are recommended in the future.
Abstract TP523: A Randomized Controlled Trial Evaluating the Effectiveness of Pretreatment With the Free Radical Scavenger, Edaravone, Before Carotid Artery Stenting
- Takenobu Kunieda,
- Kosuke Miyake,
- Hiroki Sakamoto,
- Masataka Nakamura,
- Satoshi Kaneko and
- Hirofumi Kusaka
Stroke Volume 50, Issue Suppl_1

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Objective: Cerebral hyperperfusion syndrome (CHS) is likely to occur after carotid revascularization in patients with severe hemodynamic failure. It is important to control cerebral hyperperfusion phenomenon (CHP) to prevent the development of CHS. To determine whether pretreatment with the free radical scavenger, edaravone, could prevent the onset of CHP after carotid artery stenting (CAS).Methods: Patients with severe carotid artery stenosis were randomized to receive either pretreatment with edaravone immediately before CAS or the common CAS procedure. Cerebral blood flow (CBF) was assessed in the affected middle cerebral artery (MCA) region and in the ipsilateral cerebellum using single-photon emission computed tomography (SPECT) of the brain before and immediately after CAS. Cerebrovascular reactivity (CVR) in the MCA region was also evaluated using the stereotactic extraction estimation based on the Japanese extracranial-intracranial bypass trial (SEE-JET) program and classified as reduced when it was <18.4%. The ratio of MCA to cerebellar activity was defined as the CBF in the affected MCA region divided by the CBF in the ipsilateral cerebellar hemisphere. CHP was defined as an increase in the ratio of MCA to cerebellar activity after CAS ≥10%.Results: Of the 52 patients recruited in this study, 26 were assigned to the pretreatment with edaravone group and 26 were assigned to the treatment as the usual group. Eleven patients showed reduced CVR. CHP occurred in 0 of 6 patients in the edaravone group and in 4 of 5 patients in the usual group (0% vs. 80%, p=0.0152). However, there was no significant difference in the overall patient population between the two groups.Conclusion: Pretreatment with edaravone could reduce the incidence of CHP after CAS in patients with reduced CVR.
Abstract TP54: Result of Clinical Trial Using Tron Fx, New Stent Retriver for Acute Ischemic Stroke
- Nobuyuki Sakai,
- Hirotoshi Imamura,
- Yasushi Matsumoto
Stroke Volume 50, Issue Suppl_1

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Objective: To show safety and efficacy of mechanical thrombectomy (MT) for acute stroke using TRON-FX in Japanese approving trial.Material and Methods: This trial is multi center, prospective, single arm, registry study of new stent retriever, TRON-FX, Biomedical Solutions, Tokyo, Japan. TRON-FX have 2 size variation, 4mm diameter/20mm length and 2/15, smallest in the world. Inclusion criteria are 1) acute ischemic stroke (AIS) aged 20-85, 2) from onset to start MT within 8 hours, 3) IV rt-PA is ineligible or ineffective, 4) confirm occlude ICA, M1/M2/M3, VA, BA, and P1/P2. 5) NIHSS score 8 or more. Primary endpoint is immediate post procedural recanalization (up to 3 times by TRON-FX)and symptomatic intracranial hemorrhage (ICH) at 24 hours. Secondary endpoints are 1) good neurological outcome (mRS 0-2) at 90days, 2) symptomatic and asymptomatic ICH at 24 hours, 3) Mortality within 90days and 4) device-related or procedure-related serious adverse events at day 90.Results: 50 patients enrolled and first patient in was 2017/9/27 and last patient in was 2017/11/5. All patient followed 90 days. Median age is 75, raged 44-86, male gender is 62% (31/50), occluded vessels are ICA(2) 4%, MCA/M1(23) 46%, MCA/M2M3(26) 52%, BA(3) 6%, PCA(1) 2%, IV rt-PA failed(37) 74%, median baseline NIHSS score is 17, ranged 8-29, and median mRS prior to stroke 0. The primary endpoint, recanalization TICI 2b or better was 40(80%), and symptomatic ICH was 1(2%). More over, the secondly endpoint, 1) mRS 0-2 at 90 days was 25/47(53.2%), 2) symptomatic and asymptomatic ICH was 15(30%), 3) mortality was 4(8%) and 4) no device-related or procedure-related serious adverse event.Conclusions: TRON FX approving trial in Japan has proved great efficacy and safety of this thrombectomy device with high recanalization rate with less intracranial hemorrhage, especially for distal and small vessel. Clinical Trial gov. IDNCT02964702
Abstract TP59: Experience With Endovascular Therapy in Acute Ischemic Stroke Patients Presenting With Low National Institute of Health Stroke Scale Scores
- Nicholas D Osteraas,
- Daniel Schacter,
- James Conners,
- Alejandro Vargas,
- Laurel Cherian,
- Sarah Song and
- Rima M Dafer
Stroke Volume 50, Issue Suppl_1

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Background: Endovascular thrombectomy (ET) is indicated for select patients with anterior circulation large vessel occlusion (ACLVO) with NIHSS > 6. Safety and efficacy of ET in patients with NIHSS <6 and ACLVO is an area of clinical equipoise; we present our experience with this population.Methods: Internal ischemic stroke database was queried for patients with admission NIHSS <6 from 1/2015 to 6/2018. NIHSS on presentation, cortical signs, use of ET (on arrival or after clinical decline) and outcomes were retrospectively collected. Outcomes were compared between patients taken directly for ET and those observed using Mann Whitney U.Results: Of 173 admissions with NIHSS <6 upon arrival, 15 patients had ACLVO. Of those, all had cortical signs; 8 patients were admitted and monitored, 7 patients went directly to ET . Of the 8 monitored patients, 3 (38%) received IVtPA, 6 (75%) underwent rescue ET after clinical decline, all with favorable aspects . Arrival mean NIHSS was 3.3 (4.6), NIHSS at time of ET was 10.6 (7.4). Occlusions were located in the first branch of the middle cerebral artery (M1) in 3 cases, with one case each of M2, internal carotid artery (ICA) and tandem occlusion. A symptomatic intracerebral hemorrhage occurred in a patient with re-occlusion, stent placement and IV antiplatelet use. Five patients (63%) were discharged to an acute rehab facility, the remaining 27% were discharged to home, with NIHSS of 7.7 (7.2) on discharge and mRS of 1.75 (1.5) at 90-day follow-up. Of the 7 patients who proceeded directly to ET, arrival NIHSS was 2.3 (2.2), 43% received IVtPA, occlusions were present in the terminal ICA in all cases, with tandem occlusions additionally present in 3 (43%). One patient clinically worsened and was found to have vasospasm. This same patient was discharged to rehab, the remainder (85.8%) were discharged to home. Discharge stroke scale (mean 1.4, SD 2.2) approached significance (U=11, p=0.052) compared to the observation group, discharge location (chi 3.6, p=0.58) and discharge mRS did not (U=12, p=0.28).Discussion: Despite the low sample size, there was a trend toward significance in discharge NIHSS in favor of patients that were taken directly for ET. Further study regarding management of patients with low NIHSS and LVO is merited.
Abstract TP87: Gaze Deviation on Initial CT as Predictor of Large Vessel Occlusion
- Jeremy E Kulacz,
- Laurel J Cherian,
- James J Conners,
- Rima M Dafer,
- Nicholas D Osteraas,
- Sarah Y Song and
- Alejandro Vargas
Stroke Volume 50, Issue Suppl_1

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Introduction: Treatment of large vessel occlusion (LVO) stroke is traditionally preceded by imaging evaluation of vessels using computed tomographic angiography (CTA). However, CTA may not be feasible due to renal dysfunction or contrast allergy; in smaller hospitals, CTAs may not be easily obtainable. Given this, early LVO signs on initial non-contrast computed tomography (CT) could prove practical, such as the hyperdense vessel sign (HVS). We aimed to investigate the sensitivity of another potential indicator of LVO on CT, gaze deviation, and to compare it to HVS.Methods: We conducted a retrospective analysis of consecutive patients with anterior circulation LVO stroke admitted to a comprehensive stroke center from July 2015 to July 2018, who underwent endovascular therapy (ET). All patients had confirmed LVO on CTA prior to ET. Initial head CTs were reviewed for HVS and gaze deviation by two neurology-trained examiners and compared to official diagnostic radiology reports. Two analyses were performed: detection of HVS and gaze deviation by each examiner, diagnostic radiologist with sensitivity calculation; and interrater agreement for identification of HVS and gaze deviation using a Kappa Coefficient between the two primary examiners and between diagnostic radiologist.Results: A total of 121 patients were included. Sensitivity of HVS by examiner 1 was 46% (56/121) and 2 was 60% (72/121). Sensitivity of HVS by in-house radiology was 36% (42/116) and OSH radiology was 27% (24/90). Sensitivity of gaze deviation by examiner 1 was 65% (79/121) and 2 was 79% (95/121). Inter-rater reliability of HVS for examiners 1 and 2 had substantial agreement (K=0.64), and for in-house and OSH radiology had fair agreement (K=0.27). Inter-rater reliability of gaze deviation for examiners 1 and 2 had substantial agreement (K=0.69). No radiology report noted gaze deviation, despite 2 reports of unrelated ocular findings.Conclusions: Gaze deviation may be a more sensitive and more reliable indicator of LVO on initial non-contrast head CT than the hyperdense vessel sign. This is the largest sample size to examine and directly compare signs of LVO. More research should be invested in this and other indicators of LVO that can assist in the efficient triage and treatment of these severe strokes.
Abstract TP92: When Less is More: Do We Need Advanced Perfusion Neuroimaging Prior to Mechanical Thrombectomy?
- Sitara Koneru,
- Shazli Khan,
- Kimberly Cole,
- Mouhammad A Jumaa and
- Syed F Zaidi
Stroke Volume 50, Issue Suppl_1

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Objective: To assess whether the choice of pretreatment neuroimaging has an impact on clinical outcomes following mechanical thrombectomy (MT).Background: Most MT trials required advanced neuroimaging including either CT or MR based perfusion studies for patient selection prior to randomization. However, in practice, centers may offer MT based on favorable findings (ASPECT score > 6) on non-contrast head CT (HCT) ± CT angiogram (CTA). We compared outcomes between patients who underwent MT based on HCT ± CTA (HCT- group) versus additional including CT or MR perfusion scan (HCT+ group).Design/Methods: Case records of all patients who underwent MT at our center between Jun 2012 - Jun 2017 were reviewed. Patient demographics, risk factors, presentation, pretreatment scan findings, treatment times and clinical outcomes were compared. Favorable outcome is defined as mRS of 2 or less at 90-days.Results: A total of 528 patients were identified, of which 46.4% were male. There were 385 (72.9%) patients who underwent MT based on findings on HCT or CTA (HCT-); while the remaining 143 (27.1%) also underwent additional CTP (121/528; 22.9%) or MRI perfusion (22/528; 4.2%) prior to MT (HCT+). Median age (73 vs 72, p=0.1) and baseline ASPECT scores (8.4 vs. 8.3, p=0.5) were comparable. The HCT- patients had higher NIHSS (17.8 vs. 15.3, p<0.01) and presented earlier with faster onset-to-onsite arrival time (241 vs. 476 minutes, p<0.01). Also, rate of TICI 2b/3 recanalization was higher in the HCT- group (82.8 vs 71.5, p<0.01); however favorable outcome rates were comparable (44.6 vs 47.4, p=0.6).Conclusions: Our findings suggest that HCT ± CTA based MT selection may achieve similar outcomes as compared to more advanced perfusion based neuroimaging protocols. Further prospective studies are warranted.
Abstract WMP10: A Closer Look at Late Window Thrombectomy Selection
- Thabele M Leslie-Mazwi,
- Scott Hamilton,
- Michael Mlynash,
- Aman B Patel,
- Lee H Schwamm,
- Maarten G Lansberg,
- Michael P Marks,
- Joshua A Hirsch and
- Gregory W Albers
Stroke Volume 50, Issue Suppl_1

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Introduction: The DAWN and DEFUSE 3 studies established thrombectomy as standard care for patients with emergent large vessel occlusions (ELVO) presenting 6-24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3 we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN.Methods: Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 Non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large (CTL), NIHSS 6-9 and mRS 2. Subgroups were compared to the DEFUSE 3 Non-Dawn and entire DEFUSE 3 cohorts.Results: There were 71 DEFUSE 3 Non-DAWN patients; 31 patients with NIHSS 6-9, 33 with CTL, and 13 with pre-morbid mRS 2 (some patients met multiple criteria). For CTL patients, median 24-hour infarct volume was 119ml (IQR 74.6-180) versus 31.5ml (IQR 17.6-64.3) for Core Not Too Large (CNTL) patients, p= <0.001. Complications and functional outcomes were similar between the groups. Thrombectomy in CTL patients compared to the remaining DEFUSE 3 Non-Dawn patients conveyed benefit for functional outcome (OR 20.9, CI 1.3-337.8). Comparing the NIHSS 6-9 group with the NIHSS ≥10 patients, mRS 0-2 outcomes were achieved in 74% versus 22% (p=<0.001), with mortality in 6% versus 23% (p=0.024) respectively. For patients with NIHSS 6-9 compared to the remaining DEFUSE 3 Non-Dawn patients thrombectomy conveyed a better chance of functional outcome (OR 1.86, CI 0.36-9.529); results lacked statistical significant in this small subgroup.Conclusions: Patients with pretreatment core infarct volumes <70ml but too large for inclusion by DAWN criteria demonstrate robust benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. Despite a trend towards benefit of thrombectomy in patients with NIHSS 6-9 additional data regarding late window thrombectomy for these patients is needed.

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