bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP64: In-Field Paramedic Validation of the Ambulance Clinical Triage for Acute Stroke Treatment (ACT-FAST) Algorithm for Endovascular Thrombectomy
Authors: Zhao Henry , Smith Karen , Bernard Stephen , Stephenson Michael , Parsons Mark , Yassi Nawaf , Davis Stephen M , Campbell Bruce C
Published: January 2019

Background:
Clinical triage for endovascular thrombectomy (EVT) is the most easily deployable solution to reduce unequal geographical access to comprehensive stroke centers, but current tools have limited prehospital validation. We present results of the ongoing paramedic validation study of Ambulance Clinical Triage For Acute Stroke Treatment (ACT-FAST), a published algorithmic severity-based triage tool utilizing only 2 examination steps designed for specificity and practicality.

Methods:
From July 2017, Ambulance Victoria paramedics assessed ACT-FAST (arm drift followed by speech if right arm weak, or shoulder tap for inattention if left arm weak plus screening eligibility questions) in suspected stroke patients pre-hospital in Melbourne, Australia, and in the Royal Melbourne Hospital Emergency Department. Algorithm results were validated against in-hospital CT imaging.

Results:
Data were available from n=196 assessments (ED n=76, pre-hospital n=120). Figure 1 shows correlation with CT imaging. Overall, ACT-FAST had 92% sensitivity for ICA/M1 occlusions with NIHSS≥6 (AHA Class 1 indication for EVT). Specificity purely for large vessel occlusion was 83% (positive predictive value 57%). Only a small proportion of distal occlusions (6/46, 13%) or patients with normal imaging (4/67, 6%) were falsely identified. When considering all patients requiring comprehensive stroke center care including neurosurgery (large vessel occlusion, hemorrhage and tumor) generated a positive predictive value for ACT-FAST of 83.3%.

Discussion:
Current results of the real-world ACT-FAST paramedic field validation study show high accuracy for clinical recognition of patients likely to require EVT or comprehensive stroke center care. The overall benefits of expedited thrombectomy for the majority of patients with large vessel occlusion is likely to outweigh the theoretical harms of delayed thrombolysis for a small minority of patients not requiring EVT.
Abstract TMP70: Hospital Factors Associated With Interhospital Stroke Transfer Destination in the Northeast United States
Authors: Zachrison Kori S , Onnela Jukka-Pekka , Reeves Mathew J , Hernandez Adrian , Camargo Carlos A , Zhao Xin , Matsouaka Roland , Metlay Joshua P , Goldstein Joshua N , Schwamm Lee H
Published: January 2019

Background:
The role of hospital factors in the decision to transfer acute ischemic stroke (AIS) patients is not clear.

Objective:
To determine whether hospital quality is associated with the transfer of stroke patients between 2 hospitals.

Methods:
Medicare claims data were used to identify AIS patients transferred between hospitals in the Northeast US from 2007-2011. We categorized hospitals as transferring hospitals (TH), retaining hospitals (RH), and accepting hospitals (AH) based on the largest proportion of AIS patient encounters that were transferred, retained, or accepted. All AHs participated in Get With The Guideline (GWTG)-Stroke, enabling the use of registry data to determine hospital performance by tPA use, composite quality measure score and door-to-needle (DTN) time for tPA. We identified connected TH-AH dyads as those with
>
5 patients transferred annually and used logistic regression to identify hospital characteristics associated with the establishment of a given TH-AH connection. We fitted separate models for each measure of performance (rate of tPA use, GWTG composite quality measure and median DTN time); we also adjusted for driving distance between hospitals, AH stroke volume, and the number of hospitals in the AH’s referral region.

Results:
Of 394 Northeast hospitals, there were 136 THs, 241 RHs, and 17 AHs. The odds of an establishing an AH-TH connected dyad were influenced by many factors and increased when quality measure performance increased at the AH or decreased at the TH (Table).

Conclusion:
Among Northeast U.S. hospitals, we found that interfacility transfer destinations of choice were sensitive to differences in AH quality, with higher AH performance associated with increased likelihood of being a transfer destination. Further research is needed to better understand AIS transfer patterns in order to optimize the transfer system for maximal patient benefit in the future.
Abstract TMP72: Detection of a Novel Signal of Large Vessel Occlusion Stroke Using Cranial Accelerometry- The Headpulse
Authors: Smith Wade S , Keenan Kevin J , Lovoi Paul
Published: January 2019

Introduction:
Cranial accelerometry is used to detect cerebral vasospasm and concussion. We explored this technique in a cohort of code stroke patients to see if a signature could be identified to aid in the diagnosis of large vessel occlusion (LVO) stroke.

Methods:
A military-grade 3-axis accelerometer was affixed to a headset. Accelerometer output and ECG was digitized at 1.6Khz. The resulting digitized signals we call the “Headpulse”. Three-minute recordings were performed immediately after CTA and/or immediately before and after attempted mechanical thrombectomy. The resulting waveforms were inspected by eye then subjected to supervised machine learning (MATLAB Classification Learner R2018a) to train a model using 5-fold cross validation.

Results:
Of 42 code stroke subjects with recordings, 18 (43%) had LVO and 24 (57%) had normal CTAs. In patients without LVO, ECG-triggered waveforms followed a tightly similar time-course revealing that the Headpulse is highly coupled to the cardiac contraction (Figure A - small vessel stroke; Figure B - stroke mimic migraine). However, in LVO patients many recordings showed little correlation with the ECG (Figure 1 C). This abnormality we term “chaos” and parameterized it with 176 measures of trace-by-trace variation from the ECG-signal-averaged mean for machine learning model training. Selecting the best model, using biometric data only, we properly classified 15/18 LVOs and 18/24 non-LVO patients (p=0.0002, Fisher’s exact test). Headpulse waveforms following thrombectomy showed return of cardiac contraction correlation (Figures C and D).

Conclusions:
Headpulse recordings reveal a unique signature in LVO patients during acute stroke. This lack of correlation of the Headpulse with cardiac contraction and later return of correlation likely reflects changes of cerebral blood flow and may provide a useful technique to triage stroke patients using a non-invasive device.
Abstract TMP75: Gender Disparities in International Stroke Conference Leadership
Authors: Guzik Amy K , Kapral Moira K , Bishop Laura E , Barghouthi Tamara T , Vu Quang D , El Husseini Nada , Reynolds Patrick S , Tegeler Charles H , Bushnell Cheryl D
Published: January 2019

Background:
Increasing data demonstrate a gender gap in career progression in neurology including underrepresentation of women in high impact neurology journal authorship and American Academy of Neurology recognition awards. We examined gender differences in leadership roles at the International Stroke Conference (ISC) from 2014-2018.

Methods:
As a retrospective analysis of conference data, this study was exempt from review by the institutional review board. Names of program committee members, early career development leaders, award recipients, invited speakers, and moderators for those sessions were taken from the Final Program from the 2014-2018 ISC. Conference leader gender was determined by name inspection and internet search. In a few instances of ambiguity, common gender association of the name was used. Self-reported ISC attendance demographics were obtained through the American Heart Association (AHA). Chi square test or Fisher exact test was used to compare demographics of invited leadership with attendance.

Results:
Between 29.9% and 44.7% of conference attendees were women. Attendees who did not disclose gender increased from 7.38% to 33.02%. Female membership on the program committee increased from 14.3% in 2014 to 48.2% in 2018. Women represented a minority of invited speakers, moderators and award recipients across all years, however, there were increases in female representation over time (see table).

Conclusions:
Women are less likely than men to hold leadership positions at the ISC. This is significant as such opportunities can play a valuable role in networking and career progression. It is reassuring that this gender gap has been decreasing over time, however, the AHA and program committee may wish to consider additional strategies to narrow this gap.
Abstract TMP77: Nurse-driven Bedside Swallow Screen Facilitates Identification of Dysphagia in Stroke Patients and Reduces Aspiration Pneumonia
Authors: Meletis Stephanie , Bloom Lisa , Pierce Nicole L , McKoy Cedric , Brorson James
Published: January 2019

Introduction:
Dysphagia occurs in over half of patients who have sustained acute stroke, and can lead to aspiration, subsequent pneumonia, increased length of hospital stay and death. Identification of dysphagia is vital to reduce these risks prior to oral intake or administration of oral medications. Swallow screening is an effective tool to identify at-risk patients. However, the swallow screen is often informal or omitted, resulting in premature oral intake. Nurses are highly skilled healthcare team members that are at the bedside with the patients and can be effectively trained as the first line of defense in identification of dysphagia.

Methods:
We implemented a nurse-driven swallow screen using the Iowa Model for Evidence-Based Practice. An interprofessional task force consisting of neurologists, nurse practitioners, speech pathologists, bedside nurses, nursing leadership, and nursing education selected a reliable swallow screening tool, which has been validated on the stroke population. Bedside nursing staff was trained and validated on the swallow screening tool. Subjects included all patients with ischemic or hemorrhagic stroke admitted to our institution in 2015 (n=220 spanning 12,607 patient days) pre-intervention, and in 2017 (n=263 spanning 12,691 patient days) post-intervention. We evaluated swallow screen completion rate and pneumonia rates on the neurology units.

Results:
The nurse-driven swallow screen initiative increased the percentage of patients with stroke screened from 73.3% in 2015 to 93.5% in 2017 (p<.001). Pneumonia rates on the neurology unit also decreased following this initiative, with aspiration pneumonia rates decreasing from 9.5 per 10,000 patient days to 4.7 per 10,000 patient days and all pneumonia rates decreasing from 28.6 per 10,000 patient days to 18.9 per 10,000 patient days.

Conclusions:
Empowering bedside nurses in the swallow screen process significantly improves dysphagia screening rates and decreases pneumonia rates in patients with stroke. In conclusion, implementation of nurse-driven swallow screen at bedside is an effective way to increase dysphagia identification in stroke patients and thereby improve patient care outcomes.
Abstract TMP78: Healthcare Costs Before and After Stroke in Non-Valvular Atrial Fibrillation (NVAF) Patients Who Initiated Treatment With Rivaroxaban or Warfarin
Authors: Milentijevic Dejan , Lin Jennifer H , Wang Kun , Bisht Deepti , Kogan Emily , Twyman Kathryn , Alberts Mark
Published: January 2019

Objective:
To compare total cost of care in pre- and post-stroke periods between rivaroxaban- and warfarin-treated NVAF patients.

Methods:
De-identified Optum Clinformatics® Database (OptumInsight, 2011-17) was used in this study of patients initiating rivaroxaban or warfarin within 30 days after a 1
st
observed NVAF diagnosis. Patients had ≥6 months continuous health plan enrollment, CHA2DS2-VASc score ≥2 and no history of stroke or anticoagulation. Inpatient stroke diagnosis was identified by ICD-9/-10 code, and severity status was defined by National Institutes of Health Stroke Scale (NIHSS) score, imputed by a random forest method. For all patients who developed stroke, total per-patient per-month (PPPM) cost of care was estimated before (from treatment initiation to time of stroke) and after (from stroke until the earliest of either death or end of enrollment) stroke occurrence. Generalized linear models adjusted for confounders were used to compare PPPM cost between the 2 groups in the 2 periods, with gamma distribution, log link and weighted by follow up.

Results:
During a mean follow up of 27 months, 2.6% of rivaroxaban and 3.9% of warfarin patients developed stroke and were included in the analysis. During pre-stroke period, total cost of care was similar for both treatment groups (~$3400 PPPM), which increased 3-fold in the post-stroke period (Table 1). During post stroke period, total cost of care was 21% lower for rivaroxaban patients vs. warfarin. Of those with less severe stroke (NIHSS<16) total cost was 40% lower for rivaroxaban patients vs. warfarin.

Conclusions:
Total cost of care for stroke prevention was similar in rivaroxaban and warfarin treated patients, but post-stroke cost was lower in rivaroxaban patients. These findings suggest favorable long-term cost benefit with rivaroxaban, driven by significant savings in less severe stroke.
Abstract TMP8: High Flow Normobaric Oxygen (NBO) Therapy Provides Effective Neuroprotection After Endovascular Recanalization in Acute Ischemic Stroke
Authors: Geng Xiaokun , Cheng Zhe , Dornbos David , Du Huishan , Ding Yuchuan
Published: January 2019

Introduction:
Recent advancements in endovascular thrombectomy for large vessel acute ischemic stroke (AIS) have achieved longer intervention time windows (16-24 h) and higher rates of revascularization (71%). Despite improvements, 40% of patients still have severe disability [modified Rankin scale (mRS): 3-5] with 15% mortality. Thus, adjuncts to improve clinical outcomes after endovascular recanalization need to be explored. NBO has long been recognized as a potential adjuvant therapy in AIS. Previous clinical trials have failed to demonstrate efficacy, while vessel recanalization was not assessed in the trials. The present study was performed to determine whether administration of NBO after endovascular recanalization conveys a clinical benefit.

Methods:
In this single-center prospective study (ChiCTR-INR-17013685), all AIS patients with large vessel occlusion who underwent endovascular recanalization (TICI≥1) were recruited between January 2016 to June 2018. Patients received NBO therapy by Venturi mask (FiO2 50%, 15 L/min) or routine low-dose oxygen supplementation (3 L/min) for 6 h, immediately after vessel recanalization. Clinical outcome measures, including NIIHSS scores, mRS scores, and mortality, as well as the incidence of symptomatic intracerebral hemorrhage (ICH) were recorded.

Results:
138 AIS subjects (69 randomized to NBO) were analyzed. Average NIHSS score at stroke onset were similar (17.7±5.1 in NBO;17.8±5.1 with control, p=0.89). There were no significant differences in other baseline characteristics either. Mild disability (mRS 0-3) in patients in the NBO group (78%) was significantly higher (p=0.04) than in control (61%) at 90 days. Severe disability (mRS 3-5) was equal in both groups (30 v. 26%, p=0.706), while mortality in the NBO group (9%) was largely decreased (p=0.016) compared to control (25%). Additionally, 61% (n=42) of patients in the NBO group were functionally independent (mRS 0-2) compared to 49% (n=34) in control, although this difference did not reach a significant level (p=0.231). ICH was low in both groups (3 vs 7%, p=0.44).

Conclusion:
The utilization of NBO following endovascular revascularization appears to be safe and may enhance the therapeutic effect of endovascular thrombectomy in AIS.
Abstract TMP85: Optimizing Mean Arterial Pressure in Acutely Comatose Patients Using Cerebral Autoregulation Multimodal Monitoring With Near-Infrared Spectroscopy
Authors: Rivera Lara Lucia , Geocadin Romergryko , Zorrilla-Vaca Andres , Healy Ryan J , Palmisano Caitlin , RadziK Batya , Mirski Marek , Anderson White Mirinda , Suarez Jose , Brown Charles , Hogue Charles W , Ziai Wendy
Published: January 2019

Introduction:
The cerebral oximetry index (COx) is a validated marker of cerebral autoregulation derived from near-infrared spectroscopy (NIRS) in comatose patients with acute neurological injury. The utility of this non-invasive technique to determine the optimal arterial blood pressure (MAP
OPT
) at the bedside in this population is not known. This study investigated whether comatose patients with greater duration and magnitude of clinically observed MAP outside MAP
OPT
have worse functional outcomes and increase mortality than those with MAP closer to MAP
OPT
calculated by bedside multimodal monitoring using NIRS.

Methods:
In this prospective observational study COx was continuously monitored with NIRS for up to three days in acutely comatose patients secondary to brain injury admitted to a neurocritical care unit. MAP
OPT
was defined as that MAP at the lowest COx (nadir index) for each 24 hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of MAP outside MAP
OPT
and the absolute difference between clinically observed MAP and MAP
OPT
(
Abstract TMP86: Improved Outcomes After Mechanical Thrombectomy for In-Hospital Strokes
Authors: Ehab Jasmina , Beltagy Abdelrahman , Hilker Nicholas , Slye Nicole , Chen Henian , Burgin William S , Rose David Z , Renati Swetha
Published: January 2019

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 TMP87: Beat-to-beat Blood Pressure Accurately Predicts Subsequent Arm Cuff Blood Pressure Variability in Acute Ischemic Stroke Patients
Authors: Wong Ka-Ho , Aitken Kinga , Neate Crystal , de Havenon Adam
Published: January 2019

Introduction:
Higher blood pressure variability (BPV) is associated with worse outcome after stroke. Accurate quantification of BPV requires frequent measurements, which is not practical with arm cuff sphygmomanometry.

Hypothesis:
15 minutes of beat-to-beat BPV (bBPV) will accurately predict arm cuff BPV (aBPV) for acute ischemic stroke patients' entire hospitalization.

Methods:
To measure aBPV, we used all arm cuff blood pressures during hospitalization. We measured bBPV with a finger photo-plethysmographer (Figure 1) for 15 minutes. We report Pearson’s correlation coefficient for 5 different statistical estimations of variability.

Results:
We enrolled 30 patients with acute ischemic stroke. Mean age was 60.9 years, NIHSS was 5.4, and 19/30 were male. The mean days from stroke onset to bBPV measurement was 2, and the mean length of hospitalization was 5 days. The mean number of arm cuff and beat-to-beat blood pressure measurements was 62 and 1,830. Correlation between aBPV and bBPV was moderate to excellent (Table 1 and Figure 2).

Conclusion:
This pilot study demonstrates the feasibility of predicting long-term BPV with 15 minutes of finger photo-plethysmography. As opposed to deriving BPV from arm cuff measurements, which takes days, our approach allows early and rapid identification of patients who will subsequently have high BPV and may benefit from therapeutic intervention.
Abstract TMP9: Procedural and Functional Outcomes of ADAPT Thrombectomy for Stroke Involving Anatomical Divisions of the M2 Segment
Authors: Kellogg Ryan T , Alawieh Ali , Spiotta Alejandro M
Published: January 2019

Introduction:
Endovascular thrombectomy (ET) is the current standard of care for acute ischemic stroke (AIS) for large vessel occlusion. Recently, there has been interest and an effort to extend thrombectomy to patients with M2 occlusions. Here, we evaluate the difference in presentation, and procedural and clinical outcomes of patients undergoing ADAPT thrombectomy between superior or inferior divisions of M2 and M1.

Methods:
We retrospectively reviewed a database of patients undergoing ADAPT for AIS between 06/2013 and 04/2018. Patients with M1 or M2 segment AIS were included. M2 occlusions were classified to superior and inferior divisions. Procedural outcomes were obtained from procedural notes, and functional outcomes were collected at the 90-day visit to neurologist.

Results:
A total of 205 patients with M1, 65 with M2 superior division (M2S), and 57 patients with inferior division (M2I) AIS were included. As shown in Table 1, M1 and M2S patients had comparable NIHSS at presentation and were both significantly higher than M2I group (p< 0.01). M2 occlusions had significantly longer procedure times and higher number of aspiration attempts (p<0.05). M2S occlusions had significantly lower recanalization rates and higher rates of stent retriever use. The rates of good outcome (mRS 0-2) were 46% in M1, 34% in M2S, and 44% in M2I patients. On multivariate analysis controlling for presenting deficits and ASPECTs, an M2S occlusion was associated with longer procedure times (p<0.01), lower odds of good outcomes (OR=0.4, p<0.05), and lower odds of TICI 2C/3 recanalization (OR=0.36, p<0.05) compared to M1 occlusions. No difference in post-procedural hemorrhage was observed.

Conclusions:
ADAPT is safe and effective in M2 occlusions, but the procedural success and efficacy of ADAPT in M2 stroke is influenced by the anatomic division.
Abstract TMP96: Carotid Plaque Characteristics Correlated to Baseline Vascular Risk Factors in a Large Randomized Trial: Results from CREST-2
Authors: Lal Brajesh K , Chrencik Matthew , Khan Amir , Jones Michael , Huston John , Sternbergh Charles , Rapp Joseph , Mukherjee Dipankar , Henke Peter , Yokemick John , Moore Wesley , Sikdar Siddhartha , Voeks Jenifer , Howard George , Meschia James F , Brott Thomas G
Published: January 2019

Objectives:
Assessment of carotid disease is most commonly performed with duplex ultrasonography (DUS). Measures of plaque area and tissue composition from DUS images may identify patients at risk for future neurologic events, and may assess the effects of vascular risk-factor modification (by measuring change in plaque area and/or tissue constituents). We quantified plaque area and tissue constituents from DUS images of CREST-2 participants at baseline and correlated them with their baseline vascular risk factors.

Methods:
CREST-2 consists of two multicenter, randomized trials in patients with asymptomatic ≥70% carotid stenosis comparing intensive medical management (IMM) plus endarterectomy or stenting vs IMM alone. Baseline B-mode DUS images from 500 patients underwent manual plaque outlining and automatic pixel brightness assessment. Plaque area, grayscale median (GSM), Gray-Weale score for heterogeneity, and areas for intraplaque hemorrhage and lipid were the output parameters. We computed the parameter estimates (95% confidence intervals) for baseline patient characteristics (age, sex, race, diabetes, smoking, BMI, blood pressure and LDL levels) versus plaque characteristics.

Results:
High-risk plaque features (larger plaque area, lower GSM , lower Gray-Weale scores, or larger areas of hemorrhage and lipid) were present in older patients, males, and those with elevated diastolic blood pressure and LDL levels (Table).

Conclusions:
In a randomized trial of asymptomatic patients with high-grade carotid stenosis, DUS-based computation of plaque geometry and tissue composition is feasible. Elevated diastolic blood pressure and LDL levels at baseline are associated with high-risk plaque characteristics. These novel findings identify potentially modifiable targets for aggressive treatment to reduce stroke-risk in patients with carotid stenosis.
Abstract TMP98: A New Class of Precision Oral Anticoagulants (proacs) That Mostly Preserves Platelet Activity in vitro and in vivo
Authors: Sivaraja Mohanram , Clemens Daniel , Sizikov Sivan , Xu Chengpei , Yang Bo , Igoudin Lev , Chattopadhyay Madhuri , Kirtadze Tamari , Chang Stephanie , Estiarte Angels , Short Kevin , Shiau Timothy , Williams David , Datta Anirban , Kita David
Published: January 2019

Introduction:
Anticoagulants, while an effective prophylactic for ischemic stroke increase a patient’s risk of major bleeding. There is currently an unmet need for new anticoagulants with the ideal combination of efficacy and low bleeding risk. Here we describe the in vitro and in vivo pharmacology of two development candidates VE-01902 and VE-02851, expected to enter phase I clinical trials in 2018 and 2019 respectively. These compounds belong to a new class of anti-coagulants, the PRecision Oral AntiCoagulants (PROACs), which inhibit fibrinogen cleavage at potencies comparable to the known Direct Thrombin Inhibitors (DTIs) while only weakly inhibiting thrombin induced platelet activation in plasma and whole blood.

Methods:
Enzyme activity assays by optical methods. Platelet status by expression of CD62P by flow cytometry. In vitro coagulation by Thrombin Generation Assay (TGA). In vivo efficacy and bleeding risk evaluated by rodent models of thrombosis and bleeding time tests.

Results and Conclusions:
The PROACs are a class of compounds that share a unique mechanism of action: reversible covalent inhibitors of thrombin with slow enzyme kinetics. We examined Thrombin Generation in platelet Poor Plasma (PPP) and Platelet Rich Plasma (PRP) of VE-01902 and VE-02851 and compared it to the known DTIs argatroban and dabigatran. In both plasma samples the PROACs potently inhibit the propagation phase (Endogenous Thrombin Potential (ETP)) while, unlike the known DTIs, only weakly affect the initiation phase of thrombin generation (10 to 20-fold weaker). In the PRP samples the PROACs do not significantly affect platelet activation even while suppressing ETP. To better understand the unique in vitro properties of the PROACs we studied the activity of multiple key factors of the coagulation cascade. Like argatroban and dabigatran, the PROACs protect mice from the effects of thrombin-induced pulmonary embolism and inhibit clot formation in the arteriovenous shunt rat model. However unlike these DTIs, they do not significantly inhibit platelet activation in either of these rodent models. Despite its strong anticoagulant properties, the PROACs show significantly lower bleeding than comparators.
Abstract TP103: The Use of Tissue Plasminogen Activator for Treatment of Acute Ischemic Stroke in Patients With Various Vascular Malformations Appears to be Safe
Authors: Stone David K , Viswanathan Vyas , Ballur Narayna Reddy Varalakshmi , Almeida Leonarndo , Khanna Anna
Published: January 2019

Introduction:
The number of acute ischemic stroke patients who receive IV r-tPA have been shown to be lower than those estimated to be eligible for acute thrombolysis. One potential reason providers may be hesitant to give r-tPA is fear of hemorrhagic conversion in patients with underlying vascular abnormalities. Recent guidelines changed to suggest that r-tPA administration is reasonable for unruptured, unsecured aneurysms (< 10 mm). However, the reports on which this was based involved small sample sizes, warranting further study. Also, there is incomplete information regarding the risk of hemorrhagic transformation and outcomes after r-tPA use in those with other preexisting vascular abnormalities.

Methods:
We performed a retrospective chart review at our academic institution of 438 patients treated with r-tPA for stroke and found 56 total patients with preexisting vascular malformations at the time of treatment. We describe the vascular conditions, and used logistic regression to predict outcomes in this population.

Results:
The vascular anomalies included 13 intracranial aneurysms, 14 dissections, 4 cavernomas, 10 infundibula, 3 dural venous anomalies, 1 sinus venous thrombosis, 1 cortical venous varix, 1 pseudoaneurysm, 1 vertebral intimal web, 1 fenestration, 1 basilar ectasia, 1 extracranial aneurysm, 2 dolichoectasias, 2 aortic aneurysms, and 2 aortic ectasias. Mean size of aneurysms was 4.18 mm and maximal size was 8 mm. Importantly, there was no significant association with ICH or poor outcome after r-tPA. There were no cases of hemorrhagic transformation in the population who had a cerebral aneurysm(s); this included one patient with a previously coiled basilar aneurysm. Only one patient in the entire cohort had hemorrhagic transformation following r-tPA, but the patient’s blood pressure was not well controlled following balloon angioplasty and mechanical thrombectomy after tPA administration during a time of difficult intubation which likely contributed to the ICH.

Conclusions:
These data support the safety of IV-tPA in those with preexisting vascular malformations, and adds to the body of literature for these relatively rare conditions.
Abstract TP104: Theophylline as an Add-On to Thrombolytic Therapy in Acute Ischemic Stroke: Results of the Randomized Controlled PhaseII TEA-Stroke Trial
Authors: Modrau Boris , Andersen Grethe , Mouridsen Kim , Mikkelsen Irene K , Oestergaard Leif , Bach Flemming W , Hjort Niels
Published: January 2019

Introduction:
In acute ischemic stroke, delayed revascularisation increases the risk of enlargement of the ischemic core associated with poor clinical outcome. Neuroprotective agents may immediately protect the penumbra and by that extend the time window for tissue-saving reperfusion. The vasoactive agent theophylline has been shown to reduce brain tissue edema, brain damage and mortality in animal stroke models. However, results from the animal studies, clinical case series and previous randomized clinical trials with theophylline in stroke patients were controversial. In this prospective trial, the primary study objective was to evaluate whether theophylline is safe and efficient in acute ischemic stroke patients as an add-on to thrombolytic therapy.

Hypothesis:
We hypothesized that treatment with theophylline can improve capillary flow in acute ischemic brain tissue and thus facilitate reperfusion leading to reduced volume of infarct growth and clinical improvement.

Methods:
The TEA-Stroke Trial is a two-center, proof of concept phase II clinical study with a randomized, double-blinded, placebo-controlled design. Patients with acute ischemic stroke verified by magnetic resonance imaging (MRI) and a National Institute of Health Stroke Scale ≥4 were randomized 1:1 to either theophylline or placebo as an add-on to standard thrombolytic therapy. The dual primary outcome measures included infarct growth assessed by MRI and clinical improvement assessed by the National Institute of Health Stroke scale at the 24-hour follow-up. A sample size of 120 subjects was estimated to detect a 22% difference between the treatment groups (80% power, alpha = 0.05) based on the MRI surrogate marker.

Results:
The study was stopped early after randomization of 64 patients for futility reasons because of slow recruitment. There were no safety concerns. Detailed blinded data analysis is ongoing and the main results will be presented.

Conclusion:
The TEA-Stroke Trial is the first study to evaluate whether the addition of theophylline to thrombolytic therapy is safe and efficient in patients with acute ischemic stroke. The main trial results will be discussed. Trial Registration: EudraCT number 2013-001989-42
Abstract TP106: Cerebral Microhemorrhages and the Risk of Symptomatic Intracerebral Hemorrhage After Intravenous Thrombolysis
Authors: Mac Grory Brian , Yaghi Shadi , Cutting Shawna , Burton Tina , Sacchetti Daniel , Dakay Katarina , Reznik Michael , Wendell Linda , Thompson Brad , Jayaraman Mahesh , McTaggart Ryan , Mahta Ali , Furie Karen , Schrag Matthew
Published: January 2019

Introduction and Background:
Cerebral microhemorrhages/microbleeds (CMBs) are proposed to increase the risk of thrombolysis-related hemorrhage. This may be because A) they are a marker of cerebral small vessel disease (a known risk factor for hemorrhagic transformation) and B) they are a feature of cerebral amyloid angiopathy (CAA). We sought to understand the relationship between CMB burden and risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in our institution.

Methods:
We undertook a retrospective observational study of patients who had received intravenous thrombolysis for presumed acute ischemic stroke. Patient information was gathered including demographics, past medical history, treatment and ischemic stroke subtype. T2*/GRE imaging was inspected and the presence or absence, number and distribution of definite CMBs (according to Microbleed Anatomic Rating Scale (MARS) criteria) was documented for each patient.

Results:
Four hundred and twenty five patients were identified who had received IV tPA during our study period of whom 90 (21.2%) had evidence of CMBs on T2*/GRE imaging. Three patients (3.3%) with CMBs had symptomatic intracranial hemorrhage compared with 7 (2%) of those without CMBs (p=0.49). The mean number of CMBs in those with tPA-related hemorrhage was 0.30 while in those without sICH was 0.84. 12 patients had greater than 5 microhemorrhages and in that group 0 patients had tPA-related hemorrhage. Three of the 12 cases with >5 microhemorrhages met modified Boston criteria for probable CAA.

Discussion:
In contrast to other reports, we found no association between either presence or number of CMBs and sICH. The subgroup of patients with >5CMBs also did not demonstrate an increased risk. Our study was limited by the low numbers of sICH observed. The presence of CMBs may correlate with other variables that decreased the likelihood of tPA being administered such as presence of prior intracerebral hemorrhage or CAA.
Abstract TP107: Acute Anticoagulation After Stroke in Patients With Left Ventricular Assist Devices
Authors: Ibeh Chinwe , Creutzfeldt Claire , Mahr Claudius , Tirschwell David
Published: January 2019

Background:
Despite reductions in major adverse events with the latest generation of left ventricular assist devices (LVADs), the incidence of thromboembolic complications remains high. Optimal anticoagulation (AC) strategies immediately after an ischemic stroke remain controversial. We aim to explore practices of anticoagulation management following acute ischemic stroke in LVAD patients at our institution and to identify the optimal strategies.

Methods:
We performed a retrospective analysis of our institutional LVAD database between 11/2012 and 5/2018. Patients were categorized into 3 groups based on the timing of AC post-stroke: (1) AC immediately continued, (2) AC held for 1-4 days, (3) AC held > 4 days. Primary outcome events included recurrent ischemic stroke or TIA, pump thrombosis, systemic thrombosis, hemorrhagic conversion or other intracranial or extracranial bleeding, and death. Other variables collected included age, sex, and year of LVAD placement. Descriptive and nonparametric survival analysis was performed.

Results:
A total of 39 adult patients met our criteria. Median age was 60 years (IQR 51-68), 18% were women, and 23% non-white. One half (56%) of procedures occurred after 2014 and ischemic stroke occurred a median of 11 days (1-260) after LVAD implantation. We found a total of 48 outcome events among 28 patients including 30 first events (2 ischemic strokes/TIAs, 4 pump thromboses, 7 systemic thrombotic events, 8 intracranial hemorrhages, 1 systemic hemorrhage, and 8 deaths). Kaplan-Meier survival free of a primary outcome was 64%, 49% and 41% at 7, 14 and 30 days post ischemic stroke, respectively. There was no association between survival and timing of anticoagulation, age > 60, sex, or LVAD placement before vs after 2014.

Conclusions:
We found a high rate of early outcomes after ischemic stroke in LVAD patients, with no evidence of increased risk with continued anticoagulation. Accepting the limitations of a retrospective study, these data suggest that anticoagulation may not need to be held acutely to prevent hemorrhagic conversion. Risk factors for these post ischemic stroke outcomes however were not identified. Further research is needed to identify approaches to decrease these secondary complications.
Abstract TP110: Preischemic Neuroprotective Effect of Minocycline and Sodium Ozagrelon Transient Cerebral Ischemic Rat Model
Authors: Park Sang Kyu , Nam Yun Jung
Published: January 2019

Background:
We investigated the neuroprotective properties of single doses of minocycline and ozagrel when administered prior to stroke.

Methods:
Male Sprague-Dawley rats were assigned randomly to one of the following groups: (1) control (Con) group (n=10), (2) minocycline (Mino) group (n=10), (3) sodium ozagrel (SO) group (n=10). Rats were treated with a single dose of minocycline or ozagrel at 30 minutes before stroke. A middle cerebral artery occlusion (MCAO) was made at 30 minutes after drug administration and reperfusion was done. The rats were subjected to a neurobehavioral test at days 1, 3 and 7 after MCAO. The cerebral ischemic volume was quantified by MetaMorph imaging software after TTC staining. The neuronal cell survival and astrocytes expansion were assessed by the NeuN and GFAP immunohistofluorescence staining. Apoptosis was detected by the TUNEL assay. We statistically analyzed and compared the results with each other.

Results:
Mino and SO groups had neuroprotective effect and showed a better behavioral performance of adhesive removal and treadmill test at 7 days after stroke. Mino and SO groups also showed a smaller infarct volume than control group at 7 days after stroke. Immunohistofluorescence staining showed a higher number of NeuN positive cells, lower activated astrocytes in GFAP and a lower apoptosis in TUNEL staining.

Conclusion:
This study showed that single doses of minocycline and ozagrel prior to stroke had neuroprotective effects. These agents will be useful not only in post-stroke therapy but also in stroke prevention in several cerebrovascular procedures like carotid endarterectomy, bypass procedure, endovascular angioplasty, thromboembolectomy or thrombolysis
Abstract TP111: Outcomes After thrombolysis of Acute Ischemic Stroke Patients With M2 Occlusion
Authors: Salam Smeer , Lakhani Sushil , Lee Vivien
Published: January 2019

Introduction:
The American Heart Association Stroke Guidelines recommend intra-arterial therapy (IAT) for acute ischemic stroke with large vessel occlusions involving the internal carotid and proximal middle cerebral artery, but the role of IAT for M2 occlusions is unclear. We sought to report the outcomes of acute ischemic stroke patients with M2 occlusions who received intravenous tissue plasminogen activator (IVtPA).

Methods:
Among 322 acute ischemic stroke patients who received IVtPA from July 1, 2016 to July 1, 2017, we identified 23 patients (7%) with imaging-confirmed M2 occlusions. Two patients with M2 occlusions who underwent IAT were excluded. Data was abstracted on demographics, time of Last Known Normal (LKN), National Institutes of Health Stroke Scale (NIHSS), neuroimaging, clinical presentation, and 90-day modified Rankin Scale (mRS). Good outcome was defined as 90-day mRS of
<
2.

Results:
Among the 21 ischemic stroke patients who received IVtPA for M2 occlusions, the mean age was 64.3 years (range, 21 to 88) and 10 (48%) were male. IVtPA was administered from LKN at a mean 2.5 hours (range, 0.8 to 5.1). Most patients (90%) were transferred from outside facilities. Initial NIHSS prior to IVtPA was a mean of 11.2 (range, 3 to 29). All patients had CT angiogram which was done at a mean of 4.0 hours from LKN (range, 1.2 to 7) and showed 10 (48%) right-sided and 11 (52%) left-sided M2 occlusions. Most (20/21) had CT perfusion, which was done at a mean of 4.1 hours from LKN (range, 1.2 to 7.3) and all showed mismatch in the corresponding territory of the arterial occlusion. MRI brain was performed in 19/21 patients at a mean of 21 hours from LKN (range, 3 to 53) and restricted diffusion in the corresponding arterial territory was seen in 17 (89%). Discharge NIHSS was a mean of 8.1 (range, 0 to 24). Among 20 patients with 90-day mRS data available, good clinical outcome was seen in 7 (35%).

Conclusions:
Among acute ischemic stroke patients with M2 occlusions, good clinical outcome was seen in only 35%, despite receiving IVtPA. Further studies are warranted to investigate the potential role of IAT in improving the natural history of medically treated acute ischemic stroke with M2 occlusions.
Abstract TP112: Achieving 30 Minute Median Door to Needle Time at an Urban Center Using Telemedicine
Authors: Chase Melissa , Jensen Judd , Wagner Jeffrey
Published: January 2019

Introduction:
We constantly strive to improve outcomes for stroke patients. Current ASA Guidelines recommend a door to needle (DTN) time of 60 minutes or less, with a secondary goal DTN time of 45 minutes or less. Our goal was to decrease IV Alteplase (tPA) DTN times to 30 minutes or less using primarily Telemedicine.

Methods:
In February of 2017, significant changes were made to our stroke alert process:Solidified process for direct neurology beam into the Telemedicine camera (rather than phoning first)Pharmacy responds to stroke alerts in person, and pre-mixes (if the neurologist deems appropriate) tPA at the bedsideThe Teleneurologist remains on the camera, which accompanies the patient to CAT Scan (CT). Through the camera, the neurologist reads the head CT in real timeIf no hemorrhage is confirmed on the CT scan, a verbal order to administer tPA is given while in the CT suite
Challenges:
Staff concern for patient safety, staff matrices, time constraints to implement these changes, our stroke committee collaborated with all affected departments. Resources were created including checklists and a Stroke Kit that contains tPA mixing guidelines, dosing charts, and blood pressure medications. The staff and physicians were educated on the new process via multiple venues including mock stroke alerts

Summary:
From 2016 to 2017, there was a significant increase in the percentage of stroke patients who received tPA within 45 minutes or less, and within 30 minutes or less. There were no symptomatic hemorrhages post tPA administration in either 2016 or 2017.Our median DTN time decreased by 11 minutes 8 months after the implementations discussed (from 41 minutes in 2016 to 30 minutes in 2017). Many individual DTN times were under 30 minutes.Because of our success, these process changes were adapted by sister facilities within our division.Our stroke alert process is an excellent example of staff interdisciplinary collaboration, open mindedness, flexibility, enthusiasm and knowledge.
Abstract TP113: Advanced Imaging is Associated With Longer Door to Needle Time in Candidates for Thrombolytic Treatment With No Benefit Regarding Clinical Decisions
Authors: Calleja Juan , Cervantes Roberto , Gomez Enrique , Sanchez Diego , Gonzalez Gina
Published: January 2019

Introduction:
Growing availability of advanced imaging studies (AdIS) has resulted in increasing use of studies other than non-contrast CT (NCCT) in the evaluation of acute ischemic stroke (AIS) patients. The diagnosis of AIS is mainly clinical, and thrombolysis in patients with stroke mimics is generally considered to be safe. However, the need for diagnostic certainty and timely detection of large vessel occlusion (LVO) may incline physicians to perform more AdIS.

Hypothesis:
Performing pre-treatment AdIS in all patients with AIS will prolong DNT without conferring clear benefits regarding treatment decisions.

Methods:
We reviewed a prospective registry of AIS patients arriving at the Neurologic Emergency Department. We obtained additional information from the patients’ clinical records, and all pertinent imaging studies were reviewed to confirm diagnosis and site of arterial occlusion.

Results:
We analyzed 128 AIS patients treated with IV thrombolysis. Mean Door to-Needle-Time (DNT) was 83 min. Only 46% of patients were thrombolysed in the first 60 minutes after arrival. AdIS were performed in 60 patients (48%) They were equally performed among patients with NIHSS scores below and above 10 points, a possible cutoff for the presence of LVO. They also were performed equally in patients with clinically mild, and severe strokes, when the clinical diagnosis of AIS was not in doubt. On bivariate analysis, factors associated with DNT<60 minutes were: female sex, posterior circulation stroke and whether only NCCT was performed. Exclusive use of NCCT was associated with a higher percentage of DNT<60 minutes (59 vs 34%, p=0.005). On multivariable analysis, NCCT use was independently associated with DNT<60 min (OR= 2.92, p<0.007) Regarding different imaging studies, DNT means were as follows: NCCT: 69 min, CTA:79 min, CTP: 125 min, MRI 108 min (Difference between groups p=0.007). No patients were excluded from thrombolytic treatment based on AdIS results.

Conclusions:
The pre-thrombolysis performance of AdIS carries the risk of prolonging DNT and lowering the possibility of benefit for AIS patients. Selection of patients for specific studies and deferring AdIS until after initiating alteplase should be pursued.