bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 96: CTP-Mismatch Maps Improve Interobserver Agreement
Authors: Tai Waimei A , Purushotham Archana , Straka Matus , Sugg Rebecca M , Akhtar Naveed , Rymer Marilyn , Mlynash Michael , Albers Gregory W , Bammer Roland , Lansberg Maarten G
Published: July 2021

Introduction:
The use of mismatch between the ischemic core and penumbra to select patients who are likely to benefit from acute stroke therapy has gained popularity. Interpretation of the ischemic core and penumbra on standard CT-perfusion (CTP) maps is subjective. This may lead to variability among physicians in the decision if a patient is a good candidate for acute stroke therapy. A CTP-Mismatch map with outlines of the ischemic core and penumbra could limit this variability. The goal of this study was to determine if inter-observer agreement regarding a patient’s suitability for acute stroke therapy improves with the use of a CTP-Mismatch map. The
figure
shows a typical CTP-Mismatch map.

Methods:
Ninety-six consecutive patients evaluated with CTP prior to intra-arterial therapy at St. Lukes Hospital in 2008-09 were included. 79 patients had adequate quality CTP for this analysis. Standard CTP maps (CBV, CBF, MTT, and Tmax) and a CTP-Mismatch map were generated with a fully automated program for processing of CTP source images (RAPID). RAPID assessed the ischemic core using a CBF threshold <30% of the contralateral hemisphere (rCBF<30%). The ischemic penumbra was defined by a Tmax threshold of >6 sec (Tmax>6s). The standard CTP maps and the CTP-Mismatch map were independently analyzed by two vascular neurologists in a blinded fashion. The raters assessed a patient's suitability for intra-arterial therapy based on the following mismatch criteria: (1) a ratio between (Tmax>6s) and (rCBF<30%) volumes >1.8 and (2) an absolute difference between (Tmax>6s) and (CBF<30%) volumes >15ml. Interobserver reliability was assessed with Cohen’s kappa.

Results:
When assessment of suitability for intra-arterial therapy was based on interpretation of standard CTP maps, the two raters agreed in 58 of 79 patients (kappa=0.46; 95% CI=0.24-0.60). The agreement between observers improved when suitability was determined using CTP-Mismatch maps (agreement in 76 of 79 cases; kappa=0.92; 95% CI=0.75-0.92; p<0.001 for difference between kappa values). The 3 cases with inter-observer disagreement had artifact on the CTP-Mismatch map. Following concensus adjudication of these 3 cases, 40 of the 79 patients (51%) were deemed suitable candidates for acute stroke therapy.

Conclusion:
CTP-Mismatch maps with estimates of ischemic core and penumbra volumes markedly improve inter-observer agreement regarding assessment of suitability for acute stroke therapy. Such maps, which can be generated automatically, may help standardize decision making algorithms for evaluation of potential intra-arterial therapy candidates.
Abstract NS 2: Antiphospholipid Associated Hypercoagulability and Subclinical White Matter Lesions in Patent Foramen Ovale Related Stroke - Searching for Footprints of Paradoxical Embolism
Authors: Buonanno Ferdinando S , Meng Ran , Thayer Molly , Feeney Kathleen , Cao Jing , Lo Eng H , Ning MingMing
Published: July 2021

Background:
Patent foramen ovale (PFO) related stroke has been reported to have higher frequency of hypercoagulable state and “non-specific” subclinical white matter lesions on MRI. While it is interesting to hypothesize that paradoxical embolic events may trigger subclinical infarcts in the setting of prothrombotic state, the associations are unclear. We examined antiphospholipid antibody status, one of the hypercoagulable conditions, with respect to white matter lesions (WMLs) in PFO related stroke to better understand this relationship.

Methods:
79 consecutive prospectively recruited non-migrainous PFO-related stroke patients (adjudicated by two vascular neurologists) underwent FLAIR sequence MRI and anticardiolipin antibody IgG, IgM and lupus anticoagulant measurement. Subclinical (or clinically “silent”) white matter lesions (WMLs) were inspected by investigators blind to clinical information using two scales (Fazekas and Scheltens) to insure inter-rater reliability and accuracy.

Results:
Patients with elevated anticardiolipin titer (n=6; 7.6%; 50% men) had similar age (mean = 53 vs 48) to those with normal titers (n= 73; 92.4%). Of the patients with positive anticardiolipin antibody, mean IgG was 27 GPL (range 21.4-38.6; normal range 0-15); mean IgM was 32.7 MPL (range 22.2-36.6; normal range 0-15), and none had lupus anticoagulant. WMLs were found in both periventricular regions (PV-WML) and in deep white matter (D-WML). Overall, global WML burden is statistically significantly increased in PFO stroke patients with positive anticardiolipin antibody compared to those with negative titers (Fazekas scale - 2.333 vs 1.35 , p < 0.01, Scheltens scale - 2.5 vs 1.54, p < 0.01). This difference remains statistically significant after adjusting for major confounders associated with WML such as diabetes, hypertension, and smoking status.

Conclusions:
In non-migraineur PFO-related stroke patients with antiphospholipid-associated hypercoagulability, there is greater global WMLs burden than those without any hypercoagulable states. Antiphospholipid antibody positivity may contribute to global burden of WMLs in patients with PFO related stroke, independent of conventional risk factors for WML. WMLs found on MRI FLAIR maybe “footprints” of subclinical embolic events which can potentially be used to follow disease progression and triage more aggressive stroke prevention strategy in this patient population. Further study with a larger disease cohort and other hypercoagulable states are needed to validate these preliminary findings.
Abstract NS 6: Community Hospital Nurse-Led Stroke Team Improves IVtPA Treatment Rates
Authors: Handler Diane L , Wehr Michelle R , Kane Catherine A , Alexandrov Anne W
Published: July 2021

Background:
Our 350-bed community hospital in the rural Midwest has been designated as a Primary Stroke Center (PSC) since 2005. Under general neurologist leadership, our 2007-2008 intravenous (IV) tPA treatment rate was 9% with no sICHs and an average 65 minute Emergency Department (ED) door to bolus time. We sought to understand the effect of post-graduate acute neurovascular fellowship advanced practice nurse (APN) education/training and nurse-led Stroke Team leadership on our PSC IVtPA treatment rates.

Methods:
Our APN Stroke Coordinator enrolled in the NET SMART-AP program in September 2008 and graduated in 2009 becoming one of the first acute neurovascular post-graduate educated/trained APNs in the world. The APN led development of nurse-led Stroke Team consisting of a Stroke Coordinator and 2 stroke data abstractors. A report card system was created to provide continuous feedback on process and outcome measures to staff nurses, ED physicians, EMS, and general neurologists. Individual “case” feedback was relayed within 24 hours to all stakeholders and aggregated quarterly into a benchmark report card to stimulate competition/improvement within the pre-hospital and hospital settings. The nurse-led Team responded to Stroke Alerts and provided rapid communication to general neurologists about suspected vascular territory by clinical localization, CT results, suspected pathogenic mechanism, and made recommendations for IVtPA treatment. Numerous improvements were implemented including, ongoing interdisciplinary hospital, EMS and community education, and an Acute Stroke Emergency Toolkit. IVtPA treatment rates and sICH rates were tracked alongside stroke admission numbers for the duration of the project.

Results:
In 2009, a total of 165 acute stroke patients were admitted; of these, 148 were ischemic strokes and 15% (n=19) were treated with IVtPA (sICH rate=0). In 2010, a total of 173 acute strokes were admitted; of these, 152 were ischemic strokes and 21% (n=32; p<0.08) were treated with IVtPA (sICH rate of 0). ED door to bolus time decreased from 65 minutes on average in 2007-2008, to 60 minutes in 2009 and 54 minutes in 2010 (p=ns). Satisfaction with the nurse-led Stroke Team is uniformly high among physicians, nursing staff, and administrators, with general neurologists voicing confidence in Team performance and decision making.

Conclusion:
Acute neurovascular fellowship education/training supports development of nurse-led Stroke Teams, safely improving IVtPA treatment rates for acute ischemic stroke, and providing a convenient mechanism for community general neurologists to respond to stroke call.
Abstract NS 9: An Educational Intervention to Enhance Acute Stroke Symptom Recognition Skills Among Nursing Home Nursing Assistants
Authors: Schaab Emily , Newland Jamesetta A , Tuhrim Stanley
Published: July 2021

Background:
Treatment of stroke requires a coordinated effort by clinicians educated to identify and transfer presumed acute stroke patients to hospital Emergency Departments (EDs) for expedited evaluation. With the aging of the population and the increasing demand for nursing home (NH) services, the community of clinicians educated to identify acute symptoms of stroke needs to be inclusive of Nursing Assistants (CNAs) in NH settings, who provide 70 to 80% of direct-care hours to NH residents. Approximately 25% of NH residents are referred to EDs for emergency care each year. Poorly executed transitions between EDs and NHs have the potential to delay assessment and intervention in a context in which “time is brain.”

Purpose:
The goal of this educational intervention was to integrate evidence-based messages for acute stroke symptom recognition into NH CNA practice and to assess knowledge change by comparing stroke-related knowledge at baseline to knowledge acquired immediately post-intervention.

Methods:
An educational module on acute stroke symptom recognition based on the Massachusetts Department of Public Health’s “Stroke Heroes Act FAST Education Guide” was delivered live by an advanced practice nurse to a convenience sample of 39 CNAs from 4 of an urban NH’s skilled nursing units. Pre- and post-test surveys, based on the “Hip Hop Stroke” survey questions, were administered to participants and results were analyzed using descriptive statistics.

Results:
Mean age of participants was 43.2 years (SD = 8.1), 82.1% were female, and 74.4% were Black. Mean years of clinical experience were 12.6 (SD = 8.2). Most (94.7%) described stroke as involving the brain on the pre-test, but only 22.2% of CNAs could select all 4 signs of stroke from the eight options offered on the pre-test. Post-intervention, 100% indicated that a stroke involves the brain and 33.3% correctly selected all 4 signs of stroke. In addition, 78.6% accurately described the meaning of all 4 “FAST” letters on the post-test.

Conclusions:
This educational intervention improved NH CNA knowledge of stroke symptoms. While this intervention could be replicated in other NH settings, the effect of early stroke symptom recognition on the quality of the emergency care provided to NH residents, and the impact of that emergency care on stroke-related morbidity and mortality among NH residents, warrant further study. It is notable that most participants were Black, as it is well documented that racial-ethnic minorities are less likely to be aware of acute stroke symptoms and the need for urgent treatment. Further research is needed to determine the optimal design of educational interventions in at-risk populations.
Abstract 101: Prehospital Study Enrollment Enables Initiation of Neuroprotective Agent for Acute Stroke in Hyperacute Time Windows
Authors: Modir Royya F , Rao Neal , Starkman Sidney , Sanossian Nerses , David Liebeskind , Ali Latisha , Restrepo Lucas , Valdes-Sueiras Miguel , Kim May , Stratton Sam , Eckstein Marc , Pratt Frank , Conwit Robin , Hamilton Scott , Saver Jeffrey
Published: July 2021

Background:
As “time lost is brain lost” in acute ischemic stroke, earlier start of therapy will maximize access of promising drugs to salvageable brain tissue. We hypothesized that prehospital treatment initiation would accelerate treatment delivery of neuroprotective agent in a prehospital randomized clinical trial.

Methods:
We analyzed research treatment initiation times in consecutive patients enrolled in the NIH Field Administration of Stroke Therapy – Magnesium (FAST-MAG) Phase 3 clinical trial. In FAST-MAG, patients with suspected acute stroke within 2 hours of onset are randomized to paramedic initiation of magnesium sulfate or placebo in 358 participating ambulances and 59 receiving hospitals.

Results:
Among 1486 patients, mean age was 69 (SD13.7), 42% were female, median pretreatment Los Angeles Motor Scale score was 4, and final diagnosis was acute cerebral ischemia in 71.9%, intracranial hemorrhage in 24.4%, and stroke mimic in 3.7%. Figure 1 shows the distribution of values for time from onset (last known well) to treatment (OTT). Clustering of experimental treatment start times at the maximum permitted time window, common in in-hospital stroke trials, was not seen in this cohort with prehospital care mandated early transports. Across all patients, the median OTT was 49.0 minutes. 73.5% of patients were treated within the first 60 minutes of onset (the “golden hour”) and 10.8% within the first 30 minutes of onset. Mean time from paramedic arrival on scene to start of treatment was 23.0 (SD 7.6) minutes, and 4.3% of patients were treated within 10 minutes of medic arrival (the “platinum ten minutes”).

Conclusions:
Prehospital initiation enables start of experimental neuroprotective therapy in times previously not achievable in acute stroke treatment trials. Nearly three-quarters of patients can be treated within the golden hour and more than one in ten within the first 30 minutes of onset.
Abstract 111: Comparison of Long-term Outcomes Associated with Endovascular Treatment Versus Surgical Treatment Among Medicare Beneficiaries with Unruptured Intracranial Aneurysms
Authors: Qureshi Adnan I , Chaudhry Saqib A , Tekle Wondwossen G , Suri M Fareed K
Published: July 2021

Objective:
To determine the 5 year risk of new intracranial hemorrhage, second procedure, and all-cause mortality in elderly patients with unruptured intracranial aneurysms who underwent either surgical or endovascular treatment.

Methods:
The study included a representative sample of fee-for-service Medicare beneficiaries aged 65 years or older who underwent endovascular or surgical treatment for unruptured intracranial aneurysms between 1999 through 2010. The Medicare Provider Analysis and Review files were linked to the Center for Medicaid and Medicare Services denominator files for 2000-2010 to ascertain any new admission or mortality. Cox proportional hazards and Kaplan Meir survival analyses were used to assess the relative risk of all-cause mortality, new intracranial hemorrhage, or second procedure for patients treated with endovascular treatment compared with those treated with surgical treatment after adjusting for potential confounders.

Results:
A total of 1005 patients with unruptured intracranial aneurysms were treated with either endovascular (n=569) or surgical treatment (n=436) with post-procedure follow-up available for 4.64 (±2.98) years. The rate of immediate post-procedural neurological complications (8.7% vs. 3.2%, p<0.0001) and requirement for intraventricular catheter (2.8% vs. 0.7%, p=0.019) was higher among patients treated with surgery compared with those treated with endovascular treatment. The estimated 5 year survival was 93.6% and 95.8% in patients treated with surgical and endovascular treatments, respectively. After adjusting for age, gender, and race/ethnicity, relative risks of all-cause mortality (RR 0.5, 95% CI 0.3-0.9) and new intracranial hemorrhage (RR 0.4, 95% CI 0.2-0.8) were significantly lower with endovascular treatment.

Conclusions:
In elderly patients with unruptured intracranial aneurysms, endovascular treatment was associated with lower rates of acute adverse events, long-term all-cause mortality and new intracranial hemorrhages.
Abstract 16: EARLY: EMS Prenotification Augments Stroke Code Timepoints But Rigorous Training is Needed for Larger Yield in stroke.
Authors: Guzik Amy K , Raman Rema , Ernstrom Karin , Meyer Dawn M , Hemmen Thomas , Meyer Brett C
Published: July 2021

Background:
rtPA for AIS is time sensitive, requiring efficient and coordinated acute care. We evaluated time to evaluation, stroke diagnosis, treatment rate, and 90 day outcome in patients with stroke team prenotification by EMS and those identified after arrival.

Methods:
The UCSD SPOTRIAS prospectively collected database was analyzed for patients with stroke team prenotification by EMS and other patients seen in stroke code, excluding inpatient codes. Multivariable regression models used outcome of interest as independent variable. Models were adjusted for pre-specified covariates: pre-stroke mRS, age, gender, smoking, baseline NIHSS and glucose. Time differences between groups were analyzed using Wilcoxon Rank Sum Tests.

Results:
We assessed 2867 patients, with EMS prenotification in 643 (22.4%). Assessment at 90 days was obtained in 216 with prenotification and 807 others. Those with prenotification were older (mean 68 vs 66, p=0.0498), with higher pre-stroke mRS (p=0.0243), NIHSS (10.9 vs 8.5, p< 0.0001) and glucose (139 vs 135, p=0.0013). Prenotification led to shorter time to imaging, decision, and IV rtPA treatment (all p<0.0001). No difference was seen in IV rtPA treatment rate (18% EMS prenotifications vs 16% others). When controlling for baseline characteristics, stroke was diagnosed more frequently in patients without EMS prenotification (OR 1.31, 95% CI 1.08-1.58, p=0.0057). Poor outcome (mRS 3-6) was seen more frequently in prenotification patients (45.83% vs 35.32%, p=0.006, NS after adjusting for baseline covariates).

Conclusions:
In the UCSD experience, EMS prenotification leads to faster evaluation critical in stroke. Prenotification occurred in patients at a medically worse baseline, but did not result in higher rates of final stroke diagnosis or IV rtPA. With improved education, accurate identification of AIS patients may improve, further expediting care and improving treatment and outcomes.
Abstract 164: Outcome Prediction After Endovascular Reperfusion Therapy For Acute Ischemic Stroke: The SNARL Score
Authors: Prabhakaran Shyam , Sheth Kevin N , Terry John B , Nogueira Raul G , Horev Anat , Nguyen Thanh N , Gandhi Dheeraj , Wisco Dolora , Glenn Brenda A , Tayal Ashis H , Ludwig Bryan , Hussain Muhammad S , Jovin Tudor G , Clemmons Paul F , Cronin Carolyn , Tian Melissa , Gupta Rishi
Published: July 2021

Background:
Tools to predict outcome after endovascular reperfusion therapy (ERT) for acute ischemic stroke (AIS) have previously included only pre-treatment variables. We sought to derive and validate an outcome prediction score based on readily available pre-treatment and treatment factors.

Methods:
The derivation cohort consisted of 516 patients with anterior circulation AIS from 9 centers from September 2009-July 2011. The validation cohort consisted of 110 patients with anterior circulation AIS from the Penumbra Pivotal Trial. Multivariable logistic regression identified predictors of good outcome, defined as a modified Rankin Score (mRS) of < 2, in the derivation sample; model beta coefficients were used to assign point scores. Discrimination was tested using C-statistics. We then validated the score in the Penumbra cohort and performed calibration (predicted versus observed good outcome) in both cohorts.

Results:
Good outcome at 3 months was noted in 189 (36.8%) patients in the derivation cohort. The independent predictors of good outcome were
A
ge (2 pts: <60; 1 pt: 60-79; 0 pts: >79),
N
IHSS score (4 pts: 0-10; 2 pts: 11-20; 0 pts: > 20),
L
ocation of clot (2 pts: M2; 1 pt: M1; 0 pts: ICA),
R
ecanalization (5 pts: TICI 2 or 3), and
S
ymptomatic hemorrhage (2 pts: none, HT1-2, or PH1; 0 pts: PH2). The outcome (SNARL) score demonstrated good discrimination in the derivation cohort (C-statistic 0.78, 95% CI 0.72-0.78) and validation cohort (C-statistic 0.74, 95% CI 0.64-0.84). There was excellent calibration in each cohort (Figure).

Conclusions:
The SNARL score is a validated tool to determine the probability of functional recovery among AIS treated with endovascular reperfusion strategies. Unlike previous scores that did not include treatment factors such as successful recanalization or hemorrhagic complications, our score can be applied to patients after treatment and may provide guidance to physicians, patients, and families about expected functional outcome.
Abstract 173: Effect Of B-Vitamins On Cognition In Patients With Prior Stroke
Authors: Hankey Graeme J ,   VITATOPS Trial Study Group
Published: July 2021

High serum total homocysteine (tHcy) and stroke are associated with increased risks of cognitive decline and cognitive impairment. This study aimed to determine whether B-vitamin treatment would reduce the risk of cognitive decline and cognitive impairment among individuals with recent stroke or transient ischemic attack (TIA) of the brain.

Methods:
8,164 patients with recent stroke or TIA (< 7 months) were randomly allocated to double-blind treatment with one tablet daily of placebo or B-vitamins (folic acid 2 mg, vitamin B
6
25 mg, vitamin B
12
500 μg) and followed for a median of 3.4 years for the occurrence of stroke, myocardial infarction or death due to vascular causes in the VITAmins TO Prevent Stroke (VITATOPS) trial. The Mini-Mental State Examination (MMSE) score was undertaken at least 6 months after the qualifying stroke (baseline) and every 6 months thereafter for the duration of follow-up. The primary outcome for this pre-specified secondary analysis was the composite of a decline of 3 or more points in the MMSE score compared with the baseline score at > 6 months after the qualifying stroke (cognitive decline) or a new MMSE score < 24 (cognitive impairment).

Results:
Among the 2214 participants who undertook the MMSE at least 6 months after the qualifying stroke event, and who were not cognitively impaired (MMSE > 24), and who underwent repeat MMSE assessments over a median of 2.8 years, there was no significant difference in the incidence of cognitive decline or cognitive impairment among participants assigned B-vitamins compared with placebo (24.6% vs 21.7%; risk ratio [RR]: 1.13, 95% confidence interval [CI]: 0.97 to 1.32 ; p=0.1113) and no difference in cognitive decline alone (22.7% vs 20.7%; RR: 1.10, 95% CI: 0.94 to 1.19; p=0.2417). These results were consistent among clinical subgroups. From baseline (at 6 months post-stroke), the MMSE score decreased by a mean of 0.22 (SD 1.82) among participants assigned B-vitamins vs 0.25 (SD 2.08) among participants assigned placebo (p=0.7258).

Conclusion:
Daily administration of folic acid, vitamin B
6
and vitamin B
12
to non-demented patients with previous stroke or TIA for a median of 2.8 years had no significant effect, compared with placebo, on the rate of cognitive decline or incidence of cognitive impairment.
Abstract 182: Early Perfusion Instability Profoundly Impacts Tissue Outcome In Acute Ischemic Stroke Patients
Authors: An Hongyu , Ford Andria L , Chen Yasheng , Vo Katie D , Powers William J , Lee Jin-Moo , Lin Weili
Published: July 2021

Background:
During the first hours after stroke onset, tissue perfusion in stroke patients may undergo a highly dynamic phase of instability. We examined the characteristics of this perfusion instability (improvement and deterioration) and its impact on tissue outcome.

Methods:
Mean transit time (MTT) and FLAIR maps were obtained in 45 acute stroke patients (mean NIHSS: 14; 73% received IV tPA) at 3.0 hrs (tp1), 6.4 hrs (tp2), and 1 month after onset. MTT prolongation (pMTT) was calculated as: MTT - (median MTT of the non-ischemic hemisphere). Tissue was classified into three subtypes: stable (

Methods:
Mean transit time (MTT) and FLAIR maps were obtained in 45 acute stroke patients (mean NIHSS: 14; 73% received IV tPA) at 3.0 hrs (tp1), 6.4 hrs (tp2), and 1 month after onset. MTT prolongation (pMTT) was calculated as: MTT - (median MTT of the non-ischemic hemisphere). Tissue was classified into three subtypes: stable (|pMTT tp2-tp1| ≤ 2 sec), improving (pMTT tp2-tp1< -2 sec), and deteriorating (pMTT tp2-tp1>2 sec) perfusion. Percent volume was computed as: (the # of voxels of a tissue subtype/total # of voxels at a specific tp1 pMTT) for each subtype and their infarct probabilities (IP) were graphed (Fig A and B). To further evaluate perfusion change and the corresponding impact on IP, a 3D plot of IP (color axis, Fig. C) as a function of pMTT tp1 and tp2 was generated, pooling voxels from all patients.

Results:
Early perfusion instability (within 6.5 hrs) was observed in 70-85% of total volume at a specific tp1 pMTT (50-60% improving and 20-30% deteriorating perfusion) for a range of tp1 pMTT of 3-21 sec (Fig. A). Differences in IP were observed among the three tissue subtypes for pMTT 3-17 sec, while IPs were similar at small pMTT (< 3 sec) and large pMTT (>17 sec), (Fig. B). For pMTT of 3-17 sec, IP was highly dependent on perfusion changes at tp2 (Fig. C). For example, IP for voxels starting with pMTT of 12sec at tp1 ranged from 35-95% depending on perfusion change at tp2 (Fig. C, vertical blue line).

Conclusions:
Early perfusion changes profoundly impact tissue viability, especially with initial pMTT ranging from 3-17 sec (likely representing penumbral range). Acute stroke therapies may be effective not only by promoting reperfusion, but also by preventing deteriorating perfusion.
Abstract 185: New Predictive Scoring Scale for Prospective Symptomatic Hemorrhage of Cavernous Malformation in Adults
Authors: Kim Jeong Eun , Jeon Jin Sue , Ahn Jun Hyong , Bang Jae Seung , Son Young-Je , Sheen Seung Hun , Kang Hyun-Seung , Han Moon Hee , Oh Chang Wan
Published: July 2021

Purpose:
The purpose of this study was to assess the risk factors of prospective symptomatic hemorrhage in a large adult CM population. We also proposed a new predictive scoring scale for estimating the hemorrhage-free survival in patients with multiple risk factors.

Materials and Methods:
A total of 326 adult patients (over 18 years) with 410 CM were retrospectively evaluated during the mean follow-up of 31.4 months. Prospective symptomatic CM hemorrhage was defined as following: 1) a new clinical symptoms, and 2) radiographical hemorrhage including intra-or extralesional signal change or size increase>20%. A new CM classification was suggested: type I, typical mulberry appearance; type IIa, uniloculated CM in the hemisphere; type IIb, deep-seated uniloculated CM. Other risk factors, such as previous hemorrhage, the size and the location of CM, multiplicity and combined venous anomaly, were also evaluated using univariate and multivariate statistical analyses. Kaplan-Meier analysis was performed to assess the cumulative survival rate without symptomatic hemorrhage.

Results:
Prior symptomatic hemorrhage (p<0.001), multiplicity (p=0.04) and CM type (p<0.001) were associated with prospective hemorrhage. A multivariate analysis disclosed prior symptomatic hemorrhage (HR, 4.46; p<0.001) and type IIb (HR, 1.95; p=0.04) were significant factors. The cumulative survival rate without symptomatic hemorrhage at five years reached the significance (p<0.001): prior hemorrhage, 52.84% vs. without hemorrhage, 85.61%; type I, 74.50% vs. type IIa, 84.76% vs. type IIb, 53.17%. According to these results, new predictive scoring scale for symptomatic hemorrhage was proposed, which was the sum of both scores from that previous symptomatic hemorrhage was scored 1, and without hemorrhage was scored 0, and from that type I and type IIa were scored 0 and type IIb was scored 1. The cumulative survival rate without symptomatic hemorrhage at five years was 89.01% at 0 point, 60.74% at 1 point, and 37.58% at 2 point.

Conclusion:
New predictive scoring system, including prior history of symptomatic hemorrhage and deep-seated CM without mulberry appearance, may be feasible for measuring the hemorrhage-free survival in adult CM patients with multiple risk factors.
Abstract 187: Constitutively Active Notch4 Elicits Brain Arteriovenous Malformations through Capillary Enlargement
Authors: Kim Tyson N , Murphy Patrick A , Huang Lawrence , Schaffer Chris B , Wang Rong A
Published: July 2021

Brain arteriovenous (AV) malformation (BAVM) is characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries to veins. BAVMs can rupture and cause life-threatening stroke. The origin of BAVM is currently unknown. We have developed a transgenic mouse model of BAVM via endothelial expression of constitutively-active Notch4 (Notch4*). Here, using two-photon excited fluorescence microscopy through chronically-implanted cranial windows, we obtained 4D data on the formation of BAVMs in live animals. We found that BAVMs arose from enlargement of pre-existing capillaries - judged as vessels with capillary diameter and blood flow as well as the absence of smooth muscle coverage. Capillary enlargement began promptly following the start of Notch4* expression and often occurred before increases in blood flow. Supporting the capillary origin of BAVMs, alterations in Notch signaling in endothelial cells of capillaries and veins, but not arteries, affected BAVM formation. Although the initiation of capillary enlargement was widespread, more proximal, lower resistance, AV connections grew into AVMs at the expense of more distal AV connections, by increasing in diameter and blood flow velocity through a positive feedback effect. Our data uncovers a mechanism underlying the focal BAVM formation elicited by a perturbation in gene expression throughout the endothelium.
Abstract 190: Repeated Doses of Dodecafluoropentane Emulsion Provide Neuroprotection Up to 24 Hours Following Cerebral Artery Occlusion in Rabbits
Authors: Woods Sean D , Skinner Robert D , Brown Aliza T , Ricca Aaron M , Johnson Jennifer L , Unger Evan C , Borrelli Michael J , Lowery John D , Culp William C
Published: July 2021

Introduction:
Neuroprotective strategies in ischemic stroke include oxygen delivery to sustain penumbra and prevent hypoxic cell death. Hyperbaric oxygen, blood substitutes, and liquid fluorocarbon-based oxygen carriers have often failed in treatment of stroke and other ischemic disorders. Dodecafluoropentane emulsion (DDFPe, boiling point 29°C) shifts to quasi-gas phase at body temperature, which allows absorption and transportation of very high levels of oxygen. Exceptionally small particle size, 250-300 nm, may allow oxygen delivery even through occluded vessels, by diffusion into hypoxic tissue unreachable by whole blood. In a preliminary stroke study in rabbits, DDFPe reduced infarct volumes in all experimental groups by 80% or more.

Hypothesis:
Repeated doses of DDFPe can reduce infarct volume for up to 24 hours after permanent cerebral artery occlusion in rabbits.

Methods:
New Zealand White rabbits (N=55) received cerebral angiography from a femoral artery approach. Embolic microspheres (diameter=700-900 μm) were injected into the internal carotid artery, permanently occluding the middle cerebral and/or anterior cerebral arteries. Rabbits were randomly assigned to treatment groups and sacrifice times as in Table 1. In all treated groups, intravenous DDFPe dosing with a 2% w/v emulsion began at 1 hour post-embolization and was repeated every 90 minutes until sacrifice at either 7 or 24 hours post-embolization. Following sacrifice, infarcts were measured as a percent of brain volume using vital stains on brain sections.

Results:
Percent infarct volume means significantly decreased for all DDFPe treated groups compared with controls (Table 1).

Conclusion:
Intravenous DDFPe begun 1 hour after stroke onset protects the brain from ischemic injury in the rabbit model of permanent embolic stroke. Decreased infarct volumes represent salvaged brain tissue. This effect can be observed for 24 hours with repeated doses.
Abstract 200: Adherence to Guidelines: Are Ischemic Stroke Patients Receiving Guideline-Concordant Cardiac Stress Testing?
Authors: Sico Jason , Myers Laura J , Williams Linda S , Bravata Dawn M
Published: July 2021

Introduction:
Current guidelines recommend screening for coronary heart disease (CHD) using cardiac stress testing for ischemic stroke patients at ‘high risk’ of future cardiac events. However, it is unknown whether high risk stroke patients routinely receive guideline concordant cardiac stress testing.

Methods:
Medical records were abstracted for a sample of 3965 Veterans from 131 Veterans Health Administration (VHA) facilities who were admitted for a confirmed diagnosis of ischemic stroke (fiscal year 2007). Patients with a history of CHD, receipt of cardiac stress testing within 18-months prior to stroke event, and patients who died during the index hospitalization were excluded (n=1628). Framingham Risk Scores (FRS) were calculated on the basis of: age, gender, systolic blood pressure, blood pressure treatment (yes/no), smoking status (smoker/non-smoker), diabetes, total cholesterol, and high-density lipoprotein cholesterol. FRS ≥20 was used to define patients at “high-risk” of CHD. Administrative data were used to determine whether or not cardiac stress testing was performed within 6-months following discharge from the index stroke hospitalization. Logistic regression was used to assess whether cardiac stress testing was performed more frequently among high risk stroke patients.

Results:
Among 2337 stroke patients, 28% (n=664) had FRS≥20, and a total of 6% (n=140) had cardiac stress testing within 6-months of discharge. Cardiac stress testing was not more frequently performed among those with ‘high risk’ (5.6%) than those with ‘low risk’ (6.2%) FRS. High risk patients (FRS ≥20) were as likely to have received cardiac stress testing as those with low FRS (OR = 0.90; CI95: 0.61-1.32).

Conclusions:
Guideline concordant cardiac screening is underutilized among ischemic stroke patients without evidence of previous cardiac stress testing. Patients at the highest risk of future cardiac events were not more likely to receive cardiac stress testing than patients with lower risk. Additional research is required to identify potential barriers to CHD screening, and to determine whether outcomes are improved among patients who received CHD screening.
Abstract 37: Inducible Nitric Oxide Synthase In Infiltrating Neutrophils Mediates Neurotoxicity After Ischemic Brain Injury In Mice
Authors: Garcia-Bonilla Lidia , Anrather Josef , Moore Jamie , Racchumi Gianfranco , Iadecola Costantino
Published: July 2021

Nitric oxide produced by inducible nitric oxide synthase (iNOS) contributes to brain damage after cerebral ischemia and iNOS-deficient mice have smaller infarcts after middle cerebral artery occlusion (MCAO) (J Neurosci, 17:9157, 1997). However, the cell type(s) expressing iNOS and mediating tissue damage remain to be defined. We tested the hypothesis that iNOS expressed in neutrophils infiltrating the ischemic brain contributes to tissue injury. To this end, we examined the outcome of cerebral ischemia in iNOS
-/-
mice reconstituted with iNOS+/+ leukocytes. Lethally irradiated iNOS
-/-
mice were transplanted with iNOS+/+ bone marrow (BM) to produce chimeric mice expressing iNOS in peripheral leukocytes. Control chimeras were also obtained by transplanting iNOS+/+ or
-/-
BM in iNOS+/+ or
-/-
mice, respectively. Five weeks later, mice underwent transient MCAO (n=10/group) and injury volume was assessed after 3 days in cresyl violet-stained brain sections. Chimerism was 89%, indicating successful BM engraftment. iNOS
-/-
mice transplanted with iNOS+/+ BM had larger infarcts (40±3 mm3; Mean±SE) than iNOS
-/-
mice receiving iNOS
-/-
BM (25±3 mm3; p<0.05; ANOVA), and not different from those of iNOS+/+ mice transplanted with iNOS+/+ BM (36±5 mm3; p>0.05). Cell sorting demonstrated iNOS expression in neutrophils infiltrating the infarct of iNOS
-/-
mice transplanted with iNOS+/+ BM. To confirm that iNOS in neutrophils contributes to tissue damage, adoptive transfer experiments were performed. Neutrophils (Ly6G positive) from iNOS+/+ or
-/-
mice were isolated by negative selection and 5x105 cells were administered i.v. to iNOS+/+ or
-/-
mice 24h after MCAO (n=10/group). Consistent with the result in chimeric mice, transfer of iNOS+/+ neutrophils into iNOS
-/-
mice increased the infarct 3 days after MCAO (vehicle: 35±6; iNOS+/+ neutrophils: 47±6 mm3; p>0.05 from iNOS+/+ mice receiving vehicle), but not when iNOS
-/-
neutrophils were transferred (38±8 mm3; p>0.05 from iNOS
-/-
mice). The findings identify iNOS in infiltrating leukocytes, particularly neutrophils, as a mediator of neurotoxicity in the post-ischemic brain and establish iNOS in circulating leukocytes as a therapeutic target for ischemic brain injury. Supported by NIH grant NS34179
Abstract 40: Xenon-Loaded Liposomes in Combination with IV tPA Extends the Time Window for Treatment of Thrombotic Stroke
Authors: Peng Tao , Miao Yifeng , Britton George L , Klegerman Melvin E , Laing Susan T , McPherson David D , Huang Shao-Ling
Published: July 2021

BACKGROUND:
Xenon (Xe) provides great promise for stroke treatment due to its unique neuroprotective effect. Building on previous work for Xe-loaded liposomes (Xe-ELIP) to effectively deliver Xe into the brain, this study investigates the effect of Xe-ELIP in combination with intravenously (IV) administered tissue plasminogen activator (tPA) to extend the time window of treatment for embolic stroke.

METHODS:
Thrombotic strokes were induced in rats by injecting a standardized blood clot into the middle cerebral artery. In the treatment groups, Xe-ELIP (20mg/kg) and tPA (10mg/kg) were administrated IV at 2 and 4 hours, respectively, after the stroke onset. Continuous wave ultrasound (1 MHz, 50% duty cycle, 1 W/cm
2
) was applied over the common carotid artery during Xe-ELIP administration to trigger Xe release. Behavioral tests were conducted three days after stroke. Following sacrifice, brain sections were evaluated with triphenyltetrazolium chloride (TTC) and Tunel staining. Infarct size was presented as normalized infarct volume (%).

RESULTS:
Thrombotic stroke without treatment exhibited the largest infarct size (18.98±2%); tPA treatment reduced the infarct size to 6.1±1% (p<0.001
vs.
no treatment). Xe-ELIP in combination with tPA treatment further reduced the infarct size to 1.8±0.4% (p=0.032 vs. tPA treatment; Fig 1a) with lower hemorrhagic adverse effects, improved neurological function and reduced apoptosis (Fig 1b).

CONCLUSIONS:
This study demonstrates that Xe-ELIP in combination with IV tPA provides improved therapeutic efficacy with reduced neuronal cell death and tPA-associated hemorrhagic side effects. These results have important implications for extending the time window of treatment of thrombotic stroke.
Abstract 45: Thrombolytic Treatment for In-Hospital Ischemic Strokes in United States
Authors: Emiru Tenbit , Adil Malik M , Qureshi Adnan I
Published: July 2021

BACKGROUND:
Despite the recent emphasis on protocols for emergent triage and treatment of in-hospital acute ischemic stroke, there is little data on rates and outcomes of patients receiving thrombolytics for in-hospital ischemic strokes.

OBJECTIVE:
To determine the rates of in-hospital ischemic stroke treated with thrombolytics and to compare outcomes with patients treated with thrombolytics on admission.

DESIGN/METHODS:
We analyzed a seven-year data (2002-2009) from the National Inpatient Survey (NIS), a nationally representative inpatient database in the United States. We identified patients who had in-hospital ischemic strokes (defined by thrombolytic treatment after one day of hospitalization) and those who received thrombolytics on the admission day. We compared demographics, baseline clinical characteristics, in hospital complications, length of stay, hospitalization charges, and discharge disposition, between the two patient groups.

RESULT:
A total of 18036 (21.5%) and 65912 (78.5%) patients received thrombolytics for in-hospital and on admission acute ischemic stroke, respectively. In hospital complications such as pneumonia (5.0% vs. 3.4%, p=0.0006), deep venous thrombosis (1.9% vs. 0.6%, p<0.0001) and pulmonary embolism (0.8% vs. 0.4%, p=0.01) were significantly higher in the in-hospital group compared to on admission thrombolytic treated group. Hospital length of stay and mean hospital charges were not different between the two groups. Patients who had in-hospital strokes had had higher rates of in hospital mortality (12.1% vs. 10.6%, p=0.02). In a multivariate analysis, in-hospital thrombolytic treated group had higher in-hospital mortality after adjustment for age, gender and baseline clinical characteristics (odds ratio 0.84, 95% confidence interval 0.74-0.95, p=0.008).

CONCLUSION/RELEVANCE:
In current practice, one out of every five acute ischemic stroke patients treated with thrombolytics is receiving treatment for in-hospital strokes. The higher mortality and complicated hospitalization in such patients needs to be recognized.
Abstract 63: Correlation of AOL Recanalization, TIMI Reperfusion and TICI Reperfusion with Infarct Growth and Clinical Outcome in the DEFUSE 2 Trial
Authors: Marks Michael P , Lansberg Maarten G , Mlynash Michael , Straka Matus , Kemp Stephanie , Inoue Manabu , Tipirneni Aaryani , McTaggart Ryan , Zaharchuk Greg , Bammer Roland , Albers Gregory W ,   DEFUSE 2 Investigators
Published: July 2021

Objective:
To understand how three commonly utilized angiographic outcome measures of endovascular therapy correlate with clinical outcome and infarct growth in acute stroke patients.

Methods:
Prospectively enrolled patients with anterior circulation strokes underwent baseline MRI and started endovascular therapy within 12 hours of stroke onset. The final angiogram was given a recanalization score of the primary arterial occlusive lesion- AOL (0-3), a Thrombolysis in Myocardial Infarct (TIMI) Score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) Score (0-3) using previously described definitions. TICI 2 scores were divided into partial reperfusion < 50% (TICI 2a) and > 50% (TICI 2b). Scores were dichotomized into poor recanalization or reperfusion (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified as Target Mismatch (TMM) if: PWI (Tmax>6s) / DWI >1.8, (Tmax>6)-DWI>15ml, DWI <70mL, and PWI (Tmax>10s)

<100mL. Good functional outcome (GFO) was a 90 day mRS of 0-2.

Results:
There were 99 patients with endovascular treatment and adequate baseline MR data. Following therapy, 46% were TICI 2b-3, 76% TIMI 2-3 and 59% had an AOL score of 3. TICI scores correlated with GFO (p=0.009). In TMM patients, 63% with TICI 2b-3 reperfusion had GFO, versus 28% of TICI 0-2a (p=0.003). Patients with TICI 2a had only a 36% rate of GFO. Overall TIMI scores also correlated with GFO at 90 days, p=0.036. In TMM patients, 54% with TIMI 2-3 had GFO, versus 16% of TIMI 0-1 patients (p=0.007). AOL recanalization scores did not correlate with GFO, nor did the dichotomized scores in TMM patients. Median lesion growth was 23 ml (IQR, 6-69) for TICI 2b-3 patients versus 80 ml (39-159) for TICI 0-2a, p<0.001. Considered separately, TICI 2a patients had more growth, 86 ml (21-178), than TICI 2b-3 patients (p=0.003). Median lesion growth was 41 ml (IQR, 8-93) for TIMI 2-3 patients versus 68 (45-127) for TIMI 0-1 patients, p=0.024.

Conclusion:
TIMI and TICI reperfusion scores identified Target Mismatch patients with good functional outcome. The AOL recanalization score did not. The TICI 2a patients had poorer outcome and more lesion growth than TICI 2b-3 patients.
Abstract 66: Predictors of Vascular Events or Death within One Year of Carotid Artery Stenting: Investigation on Devices and Anti-platelet Therapy for Carotid Artery Stenting (IDEALCAST)
Authors: Yamagami Hiroshi , Sakai Nobuyuki , Matsubara Yoshihiro , Okada Yasushi , Yokoi Hiroyoshi , Ezura Masayuki , Matsumaru Yuji , Miyachi Shigeru , Terada Tomoaki , Hyodo Akio ,   IDEALCAST Investigators
Published: July 2021

Background and Purpose:
Carotid artery stenting (CAS) using distal filter protection device has been approved in April 2008 in Japan. However, factors affecting the development of vascular events and deaths after CAS have not been clarified in our country. The present study was conducted to identify the predictive factors for the development of vascular events or death after CAS.

Methods:
CAS was indicated for patients with at least one risk factor for carotid endarterectomy and with > 50 % stenosis in symptomatic or > 80% stenosis in asymptomatic carotid arteries. Between June 2008 and June 2010, we enrolled 949 patients who were planning to undergo elective CAS in 43 Japanese centers. Patients were followed at 30days and 12 months after stenting. The primary endpoint was the composite of death, any stroke, transient ischemic attack, myocardial infarction, and serious systemic bleeding.

Results:
Of the 934 patients (818 men, 72 ± 7 years old) followed for 1 year after stenting, primary endpoint was observed in 109 (11.7%) patients, including 18 (1.9%) deaths, 52 (5.6%) ischemic strokes, 7 (0.8%) hemorrhagic strokes, 16 (1.7%) transient ischemic attacks, 4 (0.4%) myocardial infarctions, and 11 (1.2%) serious systemic bleeding. In a multivariate proportional hazard model, older age (hazard ratio [HR], 1.24 per 5 years; 95% confidence interval [CI], 1.07 to 1.44; P=0.005), history of ischemic stroke (HR, 1.68; 95% CI, 1.10 to 2.62; P=0.015), combination of pre-procedural antiplatelet drugs (P=0.03), usage of diabetes drugs (HR, 1.93; 95% CI, 1.29 to 2.88, P=0.002), femoral artery puncture (HR,0.36; 95% CI 0.18 to 0.80; =0.015), use of guiding catheter system (HR, 1.69; 95% CI 1.08 to 2.71, P=0.021) and use of Angioguard XP in the procedure (HR, 1.92; 95% CI, 1.16 to 3.40, P=0.011) were associated with the development of vascular events or death.

Conclusions:
In addition to older age and medical history, selection of pre-procedural antiplatelet drugs and procedural devices can predict vascular events or death after CAS.