bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 186: A New Risk Model to Predict Stroke in Atrial Fibrillation
Authors: Singer Daniel E , Chang Yuchiao , Borowsky Leila H , Fang Margaret C , Pomernacki Niela K , Udaltsova Natalia , Reynolds Kristi , Go Alan S
Published: March 2022

Objective:
Evaluating stroke risk in patients with atrial fibrillation (AF) is central to the anticoagulation decision. Our goal was to develop and internally validate a more accurate model to predict stroke in AF.

Methods:
We analyzed all person-time off warfarin from our large ATRIA community cohort of patients with AF treated in Kaiser Permanente Northern California. Patient demographics, clinical features, and thromboembolism outcomes (TE, 92% ischemic stroke) were obtained from health plan databases. Outcomes were adjudicated by medical record review and assigned a Rankin severity score. Utilizing a split-sample approach to permit internal validation, we used Cox proportional hazards models with time-varying covariates and bootstrap sampling to minimize overconfidence in selecting among candidate variables for the new model. Points were assigned proportional to regression coefficients. The score’s 0-15 point range was collapsed into low risk (TE rate <1%/yr), moderate risk (TE rate 1- 2%/yr), and high risk (TE rate ≥2%/yr) categories. We compared our ATRIA score to the CHADS
2
and CHA
2
DS
2
-VASc scores in our cohort by c-index measure of discrimination and by net reclassification improvement (NRI).

Results:
10,927 patients accumulated 32,609 person-years off warfarin during follow-up, with 685 TE events. Age was the dominant univariate risk factor among those without prior stroke but all patients with prior stroke were at high risk. Eight variables,
age, prior stroke, age*prior stroke interaction, female sex, diabetes, congestive heart failure, hypertension, proteinuria, and eGFR<45
were included in the final ATRIA model (
Table
). For the entire cohort, the c-statistic for the ATRIA score was 0.73 (95% CI 0.71-0.75) versus 0.69 (95% CI 0.67-0.71) for the CHADS
2
score and 0.70 (95% CI 0.68-0.72) for the CHA
2
DS
2
-VASc score. The c-statistic for the ATRIA score improved to 0.76 (95% CI 0.74-0.79) when the model was tested on Rankin 3+ (severe stroke) events. The ATRIA score led to an NRI of 20% compared to CHADS
2
and 9% compared to CHA
2
DS
2
-VASc, using cut-points for the latter scores optimized to fit ATRIA data. Using the scores’ original published cut-points, NRI increased to 26.4% for CHADS
2
and 27.0% for CHA
2
DS
2
-VASc.

Conclusion:
Our new stroke risk score with 8 easily available clinical features showed improved performance in categorizing stroke risk in AF patients as compared to existing stroke risk scores. Its performance was even better for predicting severe strokes. The ATRIA score merits external validation.
Abstract 188: Total And Frontal Lobe White Matter Hyperintensity Volume And Impaired Mobility Among Older Adults
Authors: Willey Joshua Z , Scarmeas Nikolaos , Provenzano Frank , Luchsinger Jose A , Mayeux Richard P , Brickman Adam
Published: March 2022

Introduction:
Gait speed is associated with multiple adverse outcomes of aging. White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been associated with gait speed, though few studies have examined changes in gait speed over time, regional localization of WMH, or enrolled participants community-based studies and in ethnic/racial minorities. We examined the association between a decline in gait speed and total and regional WMH volumes in a community-based study of aging.

Methods:
Participants were enrolled in the Washington Heights Inwood Columbia Aging Project (WHICAP), a cohort of Medicare recipients residing in Northern Manhattan. At enrollment participants underwent a comprehensive medical evaluation, as well as neuropsychological testing and assessment of gait speed via a 4 meter walk test. An MRI sub-study was started in 2004, at which time participants underwent a second gait speed measurement (mean 4.7 [SD=0.5] years apart). Odds ratios (OR) and 95% confidence intervals (CI) were calculated to examine the associations of large (defined as one standard deviation above the age-expected mean) WMH volume and regional WMH volumes (as a continuous measure) with the primary outcome (transition from normal to abnormal gait speed, defined as < 0.4 meters/second) using logistic regression. Analyses were adjusted for socio-demographic factors, clinical history of stroke, hypertension, diabetes, body mass index, the presence of mild cognitive impairment or dementia, the length of time between the two physical performance measures, and the initial gait speed measure.

Results:
A total of 758 participants in WHICAP underwent MRI and two measures of gait speed. At the time of MRI the mean age was 80.3 (SD=5.6) and 114 (14.4%) had a large WMH volume. Large WMH volume was associated with a transition to an abnormal gait speed between the two visits (adjusted OR 3.09, 95% CI=1.21-7.93). Total frontal WMH volume (adjusted OR 1.06, 95%CI=0.93-1.20), or other regional volumes, were not associated with a transition to an abnormal gait speed between the two gait speed measurements.

Conclusion:
Total, but not regional, WMH are associated with slowing of gait over time. Modification of the known risk factors associated withWMH presents a potential strategy for the prevention of gait speed decline.
Abstract 190: Effect of Stroke Legislation on Emergency Medical Services (EMS) Pre-notification and Thrombolysis Rates for Stroke in Chicago
Authors: Prabhakaran Shyam , Stein-Spencer Leslee , Walter Jim , Alberts Mark J , O'Neill Kathleen
Published: March 2022

Background:
Many stroke patients are not treated with intravenous tissue plasminogen activator (IV TPA) due to hospital arrival beyond the treatment window. We evaluated the impact that a state law that mandated transportation of acute stroke patients to the nearest stroke center had on EMS pre-notification and thrombolysis.

Methods:
We assessed the period before and after the law was implemented (March 1, 2011) among a benchmark group of 10 Primary Stroke Centers and 1 hospital pending stroke certification. Using the Get With The Guidelines-Stroke (GWTG-S) registry, we analyzed data on demographics, onset-to-arrival times, diagnoses, and treatments from these stroke centers comparing March-June 2011 to the same period 1 year earlier. We used chi-square statistics to compare pre- and post-intervention rates of EMS pre-notification and IV TPA utilization and Mann-Whitney tests to compares times.

Results:
The number of stroke discharges was 768 (61.8% ischemic stroke) in March-June 2010 and 749 (63% ischemic stroke) in March-June 2011. Demographics including age and sex were not different between the two periods (mean age 65 years and 53% female). EMS mode of arrival increased from 32.4% in 2010 to 37.6% in 2011 (P=0.043). EMS pre-notification was used in 54.5% of patients in 2010 versus 75.2% in 2011 (P<0.001). Onset-to-arrival times decreased from median 200 minutes to 133 minutes (P=0.003). Eleven of 30 (36.7%) ischemic stroke patients arriving with 3 hours were treated with IV tPA for those 3 months in 2010 compared with 30/45 (66.7%)during the same period in 2011 (P=0.017). Door-to-needle (DTN) times were not significantly different (median 87 vs. 86 minutes; 10.0% vs. 11.1 % DTN < 60 minutes).

Conclusions:
Implementation of a law with preferential triage of stroke patients to the nearest stroke center in Chicago has shown significant improvements in EMS utilization, EMS pre-notification, a substantial decline in onset-to-arrival times, and a near doubling of IV TPA utilization. State legislation based stroke system organization can significantly improve health care delivery within a very short period of time.
Abstract 1900: Collateral Circulation and Hemodynamics of Severe Intracranial Atherosclerosis: Angiography and Clinical Correlates at Baseline in the SAMMPRIS Trial
Authors: Liebeskind David S , Cotsonis George A , Lynn Michael J , Turan Tanya N , Cloft Harry J , Fiorella David J , Derdeyn Colin P , Chimowitz Marc I
Published: March 2022

Background:
Severe intracranial atherosclerosis, in excess of 70% luminal stenosis, is an established cause of recurrent stroke. Collateral circulation and the hemodynamic effects of such stenoses, however, may further delineate such risk. We conducted angiographic analyses in the SAMMPRIS trial to correlate the degree of collaterals and hemodynamic effects of such stenoses with baseline clinical and imaging characteristics of enrolled subjects.

Methods:
Baseline angiography of SAMMPRIS subjects was submitted for blinded review to grade collaterals with the ASITN/SIR scale and antegrade flow across the lesion with TICI. Hemodynamic effect was defined as any flow reduction (a partial TICI score). The association of these angiographic scores (dichotomized as none/partial versus complete collaterals and partial versus complete TICI) and baseline demographic, clinical and imaging variables were evaluated using chi-square tests for percentages and independent group t-tests for means.

Results:
424/451 subjects enrolled in SAMMPRIS had baseline angiography available for review, with adequate information to score collaterals in 376 cases. Complete collaterals were noted in 117 (31%). Hemodynamic effects (partial TICI scores) were noted in only 188 (50%) of these lesions, which were all in excess of 70% luminal stenosis. Mean lesion length (n=184, from stenting arm) did not differ between the two categories of either collaterals or hemodynamic impairment. Mean percent stenosis was higher for patients with complete collaterals (none/partial, mean 73.7%; complete, 77.4%; p<0.001) and hemodynamic impairment was more common (p<0.001). More robust collaterals (complete versus none/partial) were associated with patients who at baseline were younger (mean age 58.0 versus 61.5 years; p=0.009), had higher serum HDL (40.0 versus 37.7 mg /dL, p=0.035), participated in moderate exercise (43.1 versus 27.9%, p=0.004) and did not smoke (79.5 versus 69.4%, p=0.042). Previously reported associations with collateral circulation (diabetes, statins, presence of infarction on CT or MRI) were inapparent. These relationships of collaterals with hemodynamic impairment and other baseline variables were established across all anatomical distributions of intracranial stenosis.

Conclusions:
Severe intracranial atherosclerotic lesions are not always associated with hemodynamic effects. Collateral circulation may also frequently compensate for severe stenosis, with more robust collaterals in younger and healthier individuals.
Abstract 191: Trends in Timely Arrival for Acute Ischemic Stroke Patients in the Paul Coverdell National Acute Stroke Registry 2005-2010
Authors: Tong Xin , George Mary G
Published: March 2022

Background:
Thrombolytic therapy (tPA) is administered infrequently due to the narrow therapeutic window limitation. This study assesses trends over time for hospital arrival, EMS use, and tPA use among acute ischemic stroke patients in the Paul Coverdell National Acute Stroke Registry (PCNASR), a quality improvement program for acute stroke implemented by state health departments.

Methods:
There were 114,420 PCNASR patients enrolled from January 2005-December 2010 with a clinical diagnosis of acute ischemic stroke. Cochran-Armitage tests were used to test for a trend on selected demographic or clinical characteristics over time. Logistic regression analysis was used to assess factors associated receipt of tPA within 3 hours of time last known to be well (LKW) among patients who arrived by EMS or private auto.

Results:
Among 114,420 acute ischemic stroke patients admitted between 2005 and 2010, documentation of LKW increased slightly (45.3% vs. 46.6%, p<0.001). Patients arriving within 2 hours of LKW decreased from 2005 to 2010 (40.0% vs. 35.2%, p<0.001). Overall, 39.1% patients with documented LKW arrived at the hospital more than 4.5 hours in 2005 as compared to 43.9% in 2010 (p<0.001). Use of EMS decreased slightly from 2005 to 2010 (49.9% vs. 49.1%, p<0.001). Overall use of any tPA (IV or IA) increased from 6.4% to 9.2% (p<0.001) within the PCNASR. Factors significantly associated with receipt of IV tPA were use of EMS (AOR 3.2, [2.8, 3.6]), minority status (AOR Black 1.22 [1.08-1.38], AOR other non-white 1.49 [1.19, 1.86]), age less than 65 (AOR 1.29, [1.12, 1.49]), and independent ambulation prior to stroke (AOR 2.12, [1.77, 2.55]).

Conclusion:
Little or no improvement in knowing LKW, use of EMS, and sooner arrival for acute stroke demonstrates the continued need for public education on signs, symptoms, and actions to take for acute stroke. Use of EMS had the largest association with the use of IV tPA, yet use of EMS has not improved over 6 years. Despite no improvement in timely arrival, overall use of tPA has increased over 6 years, suggesting benefit from the extended tPA time window, increased use of IA tPA, and/or increased willingness to provide IV tPA.
Abstract 2184: Role of Transesophageal Echocardiography in Patients with Ischemic Stroke of Undetermined Etiology
Authors: De Cock Dries , Budts Werner , Thijs Vincent
Published: March 2022

Background:
In one-third of patients with ischemic stroke, the etiology remains unknown after diagnostic evaluation. This study examined the diagnostic value and therapeutic impact of routine TEE in patients with stroke of otherwise undetermined etiology.

Methods:
Between April 2005 and March 2009, 989 stroke patients > 18 years of age with documented brain ischemia on CT and/or MRI received TEE. Without the TEE results, patients were retrospectively classified according to the Trial of Org 10172 in Acute stroke Treatment (TOAST) criteria, based on the results of routine diagnostics, including ECG, Holter-ECG, brain imaging (computed tomography and/or magnetic resonance imaging) and ultrasound or magnetic resonance arteriography of the brain supplying arteries. In 602 patients (63%), stroke etiology could be determined before the TEE results were available. In the remainig 348 patients (37%), the stroke etiology could not be determined after routine diagnostics. We reviewed the TEE examinations of these 348 patients for possible cardiovascular sources of embolism (CSE).

Results:
All patients (mean age 76 years (range 18 - 95 years) , 53% males) received TEE within a median of 5 days after the stroke event. TEE detected at least one possible source of cardiac embolism in 293 patients (84%). In 8 patients (2%), TEE revealed a high-risk source of embolism with indication for oral anticoagulation or cardiac surgery (
Table
). Seventy-seven patients in the study group were ≤ 55 years of age. In this subgroup, 61% had a positive TEE finding, compared to 91% in the older subgroup. There was no difference in the prevalence of PFO and/or ASA between patients ≤ 55 years and patients > 55 years (36% vs. 32%). In the patients with otherwise normal TEE (cryptogenic stroke patients), the prevalence of PFO and/or ASA was higher, although there was again no difference observed between patients ≤ 55 years > 55 years (45% vs. 42%) (

Table

). However, when an interatrial septum anomaly was detected in a patient ≤ 55 years, it was the only CSE in 89% of cases (versus 16% in the older group, p < 0.001).

Conclusion:
TEE identified a potential source of cardiac embolism in most patients with stroke of otherwise undetermined etiology. In a limited number of cases, TEE influenced the management of these patients directly. The prevalence of interatrial septum anomalies was high in cryptogenic stroke patients. In stroke patients < 55 years, a PFO was in most cases the only pathologic finding, suggesting its pathogenic character in this subgroup.
Abstract 2191: A Multidiciplinary Team Approach To Improving The Quality Of Care In The Setting Of Tissue Plasminogen Activator
Authors: Paletz Laurie , Nunez Nancy , Steiner Nili , Robertson Betty , Gutierrez Jenita , Wolber Nicole , Booth Phil , Guerra Sonia , Lamer Amanda , Palestarnt David
Published: March 2022

Background and Purpose:
Monitoring of vital signs and neurolgic status is imperative after thrombolytic therapy to prevent complications but can be difficult to document in real time. We sought to improve the documentation of vital signs and neurologic evaluations during and after t-PA.

Methods:
We retrospectively audited all acute ischemic strokes receiving t-PA March through June 2010. A total of 12 patients received t-PA. The average age was 68.4 years with 48% of this population being male. These patients did not have adequate and consistent vital sign and neurologic check documentation. Of the 12 patients receiving t-PA, only 27.5% of patients had proper documentation as defined by the NINDS. In June and July 2010, the stroke team held 7 meetings with the nursing staff, ED, Neuro ICU, pharmacy and physicians to gather ideas for methods to improve compliance. An aggressive education endeavor was developed with nursing, physicians and pharmacy staff. The stroke team reinforced and re-educated staff regarding the standard order sets, stroke competencies and stroke guidelines. The nursing staff developed signage to place above the patient’s bed when receiving t-PA, to remind the staff of the required time frames for documentation. The ED staff created a reminder ticket/ flyer that the pharmacist carries in the t-PA administration box to hand to the nurse when t-PA is about to be administered. We moved the vital sign frequency from the second page to the front page of the standard t-PA administration order set.

Result:
Between July 2010 and February 2011, we gave t-PA to 39 patients, of whom the average age was 61.0 years with 47.4% of this population being male. Utilizing all of the methods and extraordinary collaboration, 91% were fully compliant for neurologic checks and vitals signs during and following t-PA administration.

Conclusion:
We conclude that ongoing education and reinforement is effective for promoting change in adherence to documentation guidelines after thrombolytic therapy. When we have the occasional fallout, we reach out to that area immediately to talk with and educate the staff to determine the cause and most importantly what we can do to prevent this. Working together has greatly improved documentation compliance.
Abstract 2217: Magnetic Resonance Blood-Brain Barrier Permeability Measurements To Predict Hemorrhagic Transformation In A Rat Model Of Ischemic Stroke
Authors: Hoffmann Angelika , Bredno Jörg , Wendland Michael F , Derugin Nikita , Hom Jason , Su Hua , Ohara Peter T , Young William L , Wintermark Max
Published: March 2022

Objectives:
To evaluate the predictive value of blood-brain barrier permeability (BBBP) measurements extracted from perfusion-weighted MRI for hemorrhagic transformation (HT) in stroke.

Methods:
Spontaneously hypertensive rats and Wistar rats with unilateral, 2h filament occlusion of the right MCA underwent imaging during occlusion, post reperfusion at 4h and 24h. BBBP was imaged by perfusion-weighted MRI and quantified by Patlak analysis. Cresyl-violet staining was used to detect and characterize hemorrhage on histology in sacrified rats at 24 hours, immediately following the last imaging study. Permeability changes were evaluated at baseline, after reperfusion and at 24 hours, in animals with or without macroscopic hemorrhage. Receiver-operating characteristic curve (ROC) analysis was performed to determine the most accurate permeability threshold to predict HT.

Findings:
In animals that showed macroscopic hemorrhage at 24 hours, the 95th BBBP percentile values on the infarcted side were 0.323 [0.260, 0.387], 0.685 [0.385, 0.985], and 0.412 [0.210, 0.613] ml/min·100g (marginal mean [95%CI]) during occlusion, at 4h post reperfusion and at 24h post reperfusion, respectively. The 95th BBBP percentile values on the nonischemic, contralateral side were 0.280 [0.212, 0.348], 0.266 [0.065, 0.665], and 0.203 [0.080, 0.483] respectively. The BBBP values on the infarcted side and the contralateral side were significantly different at 4h post reperfusion (p=0.034) and at 24h post reperfusion (p=0.031). The predictive value of BBBP in terms of macroscopic hemorrhage was highest on imaging obtained 4 hours after reperfusion (ROC area under the curve = 0761). The negative predictive value of BBBP measurements was high, while the positive predictive value was limited. For instance, for a BBBP threshold of 0.35 ml/min·100ml positive and negative predictive values for imaging 4 hours post reperfusion were 7.2 % and 98.6%, respectively.

Conclusion:
Altered BBBP is a necessary but not sufficient condition to cause HT in rats with an infarct. Further research is needed to identify those additional risk factors that are required for HT to develop in the setting of an ischemic stroke.
Abstract 2220: Fast Versus Slow Recoverers Following Acute Ischemic Stroke
Authors: Minzer Brandon M , Dambkowski Carl L , Schweber Adam B , Lazar Ronald M , Marshall Randolph S
Published: March 2022

INTRODUCTION:
Prior work has identified that the majority of acute hemiparetic patients recover a very predictable (adjusted R2=0.85) 70% of their maximum potential recovery on the Fugl-Meyer Upper Extremity Motor exam (FM) at 3-months. We examined these data to investigate whether the early recovery trajectory was uniform among these patients at 3 months. Among first-time acute stroke patients who recover motor function at 3 months, we assessed the hypothesis that the rate of recovery will be variable at one week after stroke.

METHODS:
We examined 30 patients with first-ever unilateral hemiparetic stroke using the FM score (max score=66) at 24-72 hours (FMinit), 1 week (FM1wk), and 3-months (FM3mo). Initial impairment was defined as 66 - FMinit. Recovery was defined as the change in FM over 3 months (FM3mo - FMinit). A Pearson correlation coefficient was calculated for predicted vs. observed change to assess how well (0.70 x initial impairment) predicted 3-month recovery, as well as to identify the subgroup of non-recoverers. A histogram was plotted for the recoverers to examine the distribution of patients based on the proportion of the 3-month recovery that had been achieved by 1-week.

RESULTS:
A strong correlation (R2=0.96) was demonstrated of predicted vs. observed recoveries, with non-recoverers (n=4) removed. Among recoverers, there was a bimodal distribution of patients by the proportion of 3-month recovery achieved at 1-week-- those who achieved >50% of 3-month recovery (fast to recover-- FTR, N=14) vs. those who achieved <50% of 3-month recovery (slow to recover--STR, N=12). The difference in the proportions of recovery achieved at 1-week for FTR (0.93,95% CI, 0.75-1.11) vs. STR (-0.07,95% CI, -0.30-0.16) patients was highly significant (p<0.001).

CONCLUSION:
Patients who recover over the first 3 months follow distinct trajectories, either achieving approximately 90% of their total recovery by 1 week or making marginal recovery early, and only later achieving their total expected recovery (
Fig
). These findings have important implications for rehabilitation and predicting recovery after stroke. Future work must address the biological correlates of this dichotomy.
Abstract 2251: Signal-To-Noise Ratio and Acquisition Duration Explain Erroneous Mean Transit Times in Acute Stroke Computed Tomography Perfusion Imaging
Authors: Boutelier Timothé , Kudo Koshuke , Pautot Fabrice , Sasaki Makoto
Published: March 2022

Introduction:
Erroneous, decreased or even negative Mean Transit Time (MTT) estimated by Computed Tomography Perfusion (CTP) imaging in acute stroke hypoperfused areas have been reported. We use CTP simulation data to investigate this issue.

Hypothesis:
Two possible hypotheses to explain this phenomenon: voxel-wise CTP Signal-To-Noise Ratios (SNR) are too low and/or concentration-time curves (CTC) are truncated before relaxation to baseline.

Materials:
In silico data were prepared to match typical in vivo CTP acute stroke hypoperfused data previously described in the literature. To investigate the impact of truncation, acquisition duration was set to D=40, 50, 60, 70, 80 and 160s. To investigate the impact of SNR, SNR was set to 10, 20, 40, 80 and 160. Data were processed by singular values decomposition with oscillation index (oSVD) (POI=0.095) and a Bayesian reference method (BP).

Results:
For low Cerebral Blood Volumes CBV<=3%, simulations with in vivo parameters reproduce Cerebral Blood Flow (CBF) and MTT empirical distributions well: oSVD returns negative MTT while BP returns increased MTT most of the time, oSVD MTT are negatively correlated while BP MTT are positively correlated with true values (see
figure
). Increasing D degrades the estimates even more. Increasing SNR improves low MTT<=15s estimates if SNR>=40 for BP and SNR>=80 for oSVD. At D=50s, high MTT>=15s are always underestimated due to CTC truncation but positively correlated with BP and negatively correlated with oSVD. At high SNR, low CBF estimates are excellent with BP but have poor linearity with oSVD.

Conclusion:
CTP SNR are too low to reliably estimate CBF and MTT in acute stroke hypoperfused areas. Spatial downsampling, averaging or regularization is required to reach higher SNR. The Bayesian method is more robust against noise than oSVD. Short acquisition duration prevents reliable estimation of high MTT, which can potentially impact on stroke assessment in clinical practice.
Abstract 2259: Age-related Increases In Microvascular Phosphodiesterase 4d Expression And Perimicrovascular Space Following Transient Global Ischemia In Rats
Authors: Cui Li , He Zhen , Behrle Brian L , He Bei , C. Fejleh M. P , Paule Merle G , Greenfield John L
Published: March 2022

Background and purpose.
While a majority of clinical genomic studies indicate that the gene encoding phosphodiesterase 4D (PDE4D) increases risk of cerebral ischemia, the role of PDE4D in the actual pathogenic mechanisms of ischemia remains unclear. The present study attempts to define a role for PDE4D in the acute phase of cerebral ischemia by monitoring changes in microvascular PDE4D expression and changes in the inside bore of the microvasculature in young and aged rats.

Methods.
Male F344 rats aged 4- and 24-months were subjected to sham surgery (n=4/group): young control (YC) and aged control (AC) groups or transient global ischemia: young ischemia (YI, n=7) and aged ischemia (AI, n=8) groups. Histological assessments and measurements of PDE4D immunoreactivity in the hippocampus were performed 8 days following ischemia.

Results.
Perivascular tissue density (defined by an index of the intensity of weak positive per square micron) was significantly lower in the AC group than in the YC group (p<0.05,
Fig. 1
E). Transient global ischemia elicited a significant decrease in tissue density in the perimicrovascular space in both young and aged animals as compared to controls (
Fig. 1
E). In addition, internal bore circumference and cross-sectional area increased dramatically as a result of ischemia (
Fig. 1
F). Ischemia also caused a severe loss of hippocampal CA1 neurons (
Fig. 2
A,B,C) in association with significant increases in PDE4D immunoreactivities (
Fig. 2
D-F). Interestingly, hippocampal neuron loss following ischemia paralleled PDE4D expression in microvessels: cell loss was accompanied by much higher levels of perivascular PDE4D expression with this effect being greater in the younger animals.

In conclusion,
decreases in perivascular tissue density and enlargements in microvascular bore likely indicate an increase in brain-blood barrier (BBB) permeability following the onset of ischemia. This is associated with an increased expression of PDE4D. Increased PDE4D expression following cerebral ischemia may play a role in changing BBB permeability and, thus, secondarily affect ischemic outcome.
Abstract 2326: Timing of Clinical Grade Assessment and Poor Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage
Authors: Giraldo Elias A , Mandrekar Jay N , Rubin Mark N , Dupont Stefan A , Zhang Yi , Lanzino Giuseppe , Wijdicks Eelco F , Rabinstein Alejandro A
Published: March 2022

Introduction:
Timing of clinical grading has not been fully studied in patients with aneurysmal subarachnoid hemorrhage (aSAH). Our primary objective was to identify at which time point the clinical assessment using the World Federation of Neurological Surgeons Scale (WFNS) and the Glasgow Coma Scale (GCS) is most predictive of poor functional outcome.

Methods:
Retrospective cohort study on the association of clinical grading determined at presentation, nadir and post-resuscitation, and poor outcome. Poor functional outcome was defined as Glasgow Outcome Scale score of 1-3 at 6 months. The study was approved by our Institutional Review Board.

Results:
We identified 186 consecutive patients admitted to a teaching hospital between January 2002 and June 2008. Patients’ mean age was 56.9±13.7 years and 63% of the patients were women. Twenty-four percent had poor functional outcome (mortality was 17%). On univariable logistic regression analyses, GCS determined at presentation (OR=0.80; p<0.0001), nadir (OR=0.73; p<0.0001) and post-resuscitation (OR=0.53; p<0.0001), modified Fisher Scale (OR=2.21;p=0.0013), WFNS assessed at presentation (OR=1.92;p<0.0001), nadir (OR=3.51; <0.0001) and post-resuscitation (OR=3.91; <0.0001), intracerebral hematoma on initial CT (OR=4.55;p<0.0002), acute hydrocephalus (OR=2.29;p=0.0375), and cerebral infarction (OR=4.84; <0.0001) were associated with poor outcome. On multivariable logistic regression analysis, only cerebral infarction (OR=5.80; 0.0013) and WFNS grade post-resuscitation (OR=3.43;<0.0001) were associated with poor outcome. Receiving operating characteristics/area under the curve (AUC) analysis demonstrated that WFNS determined post-resuscitation had a stronger association with poor outcome (AUC=0.90) than WFNS assessed upon admission or at nadir.

Conclusions:
Timing of WFNS assessment affects its prognostic value. Outcome after aSAH is best predicted by rating WFNS after neurological resuscitation.
Abstract 2345: Do the 10 PSC Measures Improve Outcome in Stroke Patients
Authors: Meyer Dawn M , Raman Rema , Emond Jennifer , Faraday Eema , Hemmen Thomas , Meyer Brett
Published: March 2022

Background and Purpose-
While many healthcare systems are currently attempting to achieve Primary Stroke Center (PSC) certification, no study has evaluated the impact of the 10 PSC measures on long term outcome. The purpose of this study was to determine the compliance with and association between the 10 PSC measures and 90 day outcome in a certified PSC vs a non-certified center.

Methods-
A retrospective review of prospectively collected data was performed. Analysis included patients presenting between 01/01/2009 and 12/31/2010 as stroke codes to the University of California San Diego Medical Center (PSC) and Sharp Hospital (non-PSC, practicing under Brain Attack Coalition (BAC) guidelines). Both centers utilize the same acute ED stroke code team, though decisions to activate these codes and inpatient stroke code protocols are different. All patients or surrogates provided consent and had 90 day outcome data available. Analysis plan included the statistical association of each PSC measure with stroke outcome (90 day mRS) using Fisher's Exact. Data analysis plan also included comparing 90 day outcome for a PSC center to those of a non-PSC center using chi squared. Good outcome was defined as mRS 0-2 at 90 days.

Results-
138 patients were included in the analysis (UCSD=52; Sharp=86). 47.3% were female. There was no significant difference in good outcome (p>0.99) or mortality (p=0.309) between the sites. Significant differences existed for compliance with 1) “DVT prophylaxis” (p=0.004); 2) “antiplatelet on discharge” (p<0.001); 3) “thrombolytics administered” (p<0.001); 4)“stroke education” (p<0.001); 5) “rehab considered” (p=0.001) and 6) “lipid evaluation” (p=0.002), all in favour of the PSC. “Antiplatelet on discharge” (p=0.001), “thrombolytics administered” (p=0.011), and “lipid evaluation” (p=0.012) were the only PSC measures that were significant predictors of 90 day outcome.

Conclusions-
This study found that the PSC provided significantly more compliance with the 10 PSC measures. Only 3 of the PSC measures are independent predictors of outcome at 90 days. It is vital to re-examine the PSC requirements to ensure that guidelines are in place to significantly impact patient outcome.
Abstract 2381: Standardising The Approach To Evidence-based Physiotherapy For Upper Limb Rehabilitation Following Stroke
Authors: McDonnell Michelle N , Hillier Susan L , Esterman Adrian J
Published: March 2022

Objective:
Increasing the amount of practice performed by the upper limb is a critical element of stroke recovery and task-specific training is an effective method of achieving this. There is a need to standardise the application of task-specific training to individuals with differing levels of impairment and that allows for individual progress.

Design:
Secondary analysis of a standardised task-specific training protocol in a previously-reported randomised controlled trial.

Setting:
University, outpatient clinical trial.

Participants:
Referred sample of 0 participants in the sub-acute phase following stroke completed the study.

Interventions:
A clinical algorithm was devised based on the ICF framework. It involved assessment of 18 critical impairments of upper limb function and application of task-specific exercises appropriate to the level of impairment. These tasks were consistent with recent evidence-based guidelines and were constantly re-evaluated and task difficulty progressed.

Main Outcome Measures:
Action Research Arm Test, Fugl-Meyer Assessment, Motor Activity Log.

Results:
All participants attended the nine sessions of training over the three week intervention period (100% compliance). No adverse events were reported. There were significant improvements in functional ability and use of the affected arm (P < 0.001) and pinch strength and tapping speed (P < 0.01).

Conclusions:
This evidence-based upper limb clinical algorithm provides a framework for standardising task-specific physiotherapy following stroke based on the assessment of functioning of the individual following stroke in day-to-day life. This approach is appropriate for patients with different functional levels and may be used in rehabilitation to standardise groups of self-directed practice sessions or standardise the intervention and progressions in rehabilitation studies.
Abstract 2385: Investigation Of Aromatase Gene (CYP19A1) Variations In Stroke Patients
Authors: Southerland Andrew M , Dueker Nicole , Reiner Alexander P , Chen Fang , Cheng Yu-Ching , Bookman Ebony , Chen Wei-Min , Doheny Kimberly , Jackson Rebecca D , Mirel Daniel B , Udren Jenna I , Kooperberg Charles , Kittner Steven , Sale Michele , Worrall Bradford B , Mitchell Braxton D , Wang Liewei , Rexrode Kathyrn M
Published: March 2022

Introduction:
Estrogens have been associated with risk of stroke in both men and women. Estradiol and estrone are synthesized from testosterone via the aromatase enzyme in both men and postmenopausal women. Genetic variation affecting function of the aromatase gene (CYP19A1) has been linked to elevated estradiol levels. We tested the hypothesis that these variants, as well as a modifying gene, are associated with ischemic stroke in three cohorts: the Vitamin Intervention for Stroke Prevention trial (VISP), Women’s Health Initiative (WHI), and Genetic Susceptibility to Early-Onset Stroke study (GEOS).

Methods:
Genomic data for individuals of European descent with ischemic stroke was compared against an equal number of controls: VISP (1723 cases - 65% men), WHI (436 cases - all postmenopausal women), GEOS (557 cases - all men age <55). Genotyping was funded through the Genomics and Randomized Trials Network (GARNET) and Gene Environment Association Studies (GENEVA) consortia. All cohorts used the Illumina Omni1-Quad chip for genotyping with imputation as needed. Eight candidate single nucleotide polymorphisms (SNPs) in CYP19A1 on chromosome 15 and an additional regulatory SNP in a modifier locus on chromosome 8 were chosen for analysis due to coding status or previous association with estradiol levels. Analyses were adjusted for age, hormone therapy use (women), and the top three principal components. Association results were determined as odds ratios for individual SNPs (effect allele = minor), with significance level of p<0.05.

Results:
GWAS results are tabulated. There were no significant differences in allele frequency for four SNPs in CYP19A1 among stroke patients and controls. The additional four SNPs were monomorphic in all three populations. The modifier gene SNP (rs1864729) was less common among young men with prior stroke in GEOS, but not men in VISP or in women.

Conclusions:
Aromatase genetic variation was not associated with risk of stroke in these three cohorts. One SNP that modifies aromatase function was less common among young, but not older men with stroke. Replication in other studies is necessary.
Abstract 2442: Range of Post-operative Findings on CT Angiography For Patients Undergoing CEA
Authors: Gallati Christopher P , Jain Minal , Jain Anunaya , Kanthala Abhijit R , Jahromi Babak S
Published: March 2022

Introduction:
Carotid endarterectomy (CEA) is an established standard of care for patients with significant carotid stenosis today. Pre-op CTA is now frequently used to evaluate and plan for CEA, however no study to date has examined the findings of routine immediate post-CEA CTA.

Aim:
The aim of our study is to document the normal and abnormal findings on immediate post-op CTA and evaluate for possible clinical associations.

Methods:
Registry of all the subjects undergoing CEA, from 1
st
July 2008 with available post-CEA CTA. Their medical records were reviewed to record details of the procedure and post-op complications.

Results:
We found 50 patients with post-CEA CTA, of which 16% had CTA ordered because of postoperative neurological deficit. Nearly 88% of CEAs were performed for symptomatic carotid stenosis/occlusion. All CEAs were performed under general anesthesia, 7 involved shunting and an equal number had patch placement. Only 1 CEA involved an eversion procedure. The mean cross clamp time was 69 minutes (SD 23.7 minutes). On post-CEA CTAs, we found that 78% of subjects had 0-20% residual stenosis, 20% had 20-50% residual stenosis, while 1 subject had 50-69% residual stenosis. A total of 5 subjects had a postoperative stroke. Amongst these, 80% were shunted, 100% had placement of a patch and the mean cross clamp time was 10.8 minutes (SD 15.7 minutes). The most commonly noted abnormality on CTA was a transitional step-off at the most proximal site of endarterectomy in the common carotid artery (CCA) (60% - Panel B). No flap, thrombus, or postoperative stroke was associated with this finding. This finding was associated with longer cross clamp times (76.5 mins v/s 58 mins, p=0.011). A total of 16.3% subjects developed post-op hematoma which resolved without intervention. Postop CTA demonstrated flaps (Panel A) in the ECA in 18% of subjects, in the ICA in 6% of patients, and in the CCA in 10% of patients. All patients with an ICA flap and 66.7% patients with a CCA flap developed a thrombus. All patients with a CCA flap and thrombus developed a post-op stroke, and 66.7% of patients with an ICA flap and thrombus developed a post-op stroke.

Conclusion:
Common carotid artery step off was the most common finding noted on post-operative CTA, and was not associated with any post-operative stroke. ICA and CCA flaps, seen in a small percentage of patients, were associated with thrombus formation and post-op stroke. This association needs to be further verified in a larger cohort.
Abstract 2459: A Full-automatic Penumbra Segmentation Tool for Clinical Settings
Authors: Nagenthiraja Kartheeban , Ribe Lars , Østergaard Leif , Mouridsen Kim
Published: March 2022

Introduction:
Perfusion- and diffusion weighted MRI (PWI/DWI) is widely used to select patients who are likely to benefit from recanalization therapy. The visual identification of PWI-DWI-mismatch tissue depends strongly on the observer, prompting a need for software, which estimates potentially salavageable tissue, quickly and accurately. We present a fully Automated Penumbra Segmentation (APS) algorithm using PWI and DWI images. We compare automatically generated PWI-DWI mismatch mask to mask outlined manually by experts, in 168 patients.

Method:
The algorithm initially identifies PWI lesions by applying a connected component-labeling algorithm on thresholded Time-To-Peak maps (TTP > 4 seconds). Smooth PWI lesion borders are then identified by applying a level-set algorithm on the initial PWI lesion mask. The initial DWI lesion was located by thresholding Apparent Diffusion Coefficient (ADC) at 600•10-6 mm2/sec. Due to the nature of thresholding, the ADC mask overestimates the DWI lesion volume and consequently we initialized level-set algorithm on DWI image with ADC mask as prior knowledge. Combining the PWI and inverted DWI mask then yield the PWI-DWI mismatch mask. Four expert raters manually outlined the penumbra for each patient. To quantify the geometric and volumetric similarity between APS and manually outlined penumbra we used volumetric correlation and Dice coefficient (DC). The performance of classification was evaluated in terms of sensitivity and specificity.

Results:
Penumbra volumes determined by APS demonstrated excellent correlation with the manually outlined penumbra volumes R2 = 0.93, with a mean difference of 2.1 mL. A geometrical comparison of penumbra masks resulted in a median DC of 0.70 and the median sensitivity was 73 % and the median specificity was 97 %. The median penumbra mask processing time per patient was 21.4 seconds.

Conclusion:
Combining the automatically generated PWI and DWI lesion mask yields a fast, robust estimate of the PWI-DWI mismatch. The APS algorithm demonstrates exceptional agreement with manually outlined mismatch masks. Requiring no user intervention, this algorithm allows fast, reliable identification of tissue-at-risk, and we speculate this feature may aid clinical decision-making, thus reducing the critical door-to-needle time period.
Abstract 2503: Plasma Estradiol and Testosterone Levels and Risk of Ischemic Stroke in Postmenopausal Women
Authors: Lin Jennifer H , Jimenez Monik , Manson JoAnn E , Hankinson Susan E , Rexrode Kathryn M
Published: March 2022

Background:
Large randomized trials have shown that use of exogenous estrogens with or without progestin increase the risk of ischemic stroke among women. Current data on the association between endogenous sex hormones and ischemic stroke are very limited. Data are also lacking on the association with endogenous androgens, which, through aromatization, are the primary source of endogenous estrogen in postmenopausal women. Thus, we evaluated plasma estradiol and testosterone levels and risk for ischemic stroke among women in the Nurses’ Health Study (NHS).

Methods:
Among 32,826 participants in the NHS who provided blood samples in 1989-1990, 405 postmenopausal women (209 never/past users and 196 current users of hormone therapy) had a confirmed diagnosis of ischemic stroke through 2006. An equal number of controls who were free of stroke during follow-up were matched for age, use of postmenopausal hormones, and smoking status. Estradiol and testosterone levels were measured by mass spectroscopy. Conditional logistic regression was used to evaluate the association of log-transformed levels of estradiol and testosterone with stroke risk, within strata of hormone therapy use.

Results:
Circulating estradiol was not associated with stroke risk among never/past users; the relative risk (RR) (95% confidence interval) for highest to lowest estradiol quartiles was 1.27 (0.74-2.19), when adjusted for matching factors (p trend=0.75). However, there was a nonsignificantly increased risk of stroke among current users with higher estradiol levels; conditional on matching factors, the RRs were 2.28 (1.20-4.33), 1.55 (0.81-2.96), and 1.90 (0.96-3.79), for quartiles 2-4, respectively (p for trend=0.56). No association was observed between total testosterone levels and stroke risk in either group; the RRs for highest to lowest quartiles were 0.86 (0.50-1.49) and 1.06 (0.60-1.87) in never/past and current users, respectively (p for trends ≥0.39). The associations with free sex hormone levels were similar to those observed with total circulating levels. Additional adjustment for body mass index, aspirin use, alcohol consumption, and history of diabetes, elevated cholesterol, hypertension, or coronary heart disease, as well as levels of c-reactive protein (CRP) and the total/HDL cholesterol ratio did not materially change the associations. No association was observed between total and free testosterone levels and stroke risk in either never/past or current users (p for trends ≥0.39). These associations did not vary across levels of aspirin use smoking status, or CRP (p for interactions >0.05).

Conclusions:
Estradiol and testosterone levels were not associated with risk of ischemic stroke in this cohort of postmenopausal women.
Abstract 2523: Isolation And Characterization Of Neural Stem/progenitor Cells From Infarct Area In Neonatal Rat
Brains
Authors: kido jun , Iwai Masanori , Matsumoto Shirou , Tajiri Hiroko , Nakamura Kimitoshi , Mitsubuchi Hiroshi , Endo Fumio
Published: March 2022

Background and purpose
In adult brain, it has been reported newly generated neural stem / progenitor cells survived and differentiated to mature neurons in the severely damaged area after stroke. In neonatal brain, however, it was demonstrated that neurogenesis was stimulated after hypoxia ischemia (HI) and provided neuronal progenitors to the infarct area, but only few new neurons could survive under an unfavorable microenvironment and lack of appropriate trophic support. Recently, neural stem / progenitor cells were isolated from the infarct area in adult mouse brain and elucidated its character as a neural stem / progenitor cell. However, it is still unclear whether the infarct area in neonatal brain has neural stem / progenitor cells as same feature as adult brain. Therefore, the present study was conducted to investigate whether neural stem / progenitor cells could be isolated from infarct area in neonatal rat brain, and to clear its feature.

Methods
HI brain injury was induced in 7-days-old rat pups by the left common carotid artery occlusion followed by 120 minutes exposure to 8% oxygen. Three days after HI, the brain is removed and sliced at 2 mm thickness, and then six columns are punched out from various infarct areas for cell culture using neurosphere method. The cell clusters are analyzed by immunocytochemistry and mRNA expression for neuron, astrocyte and oligodendrocyte. Also, the cell clusters are investigated the ability of induction for neuron, astrocyte and oligodendrocyte.

Results
The numbers of neurospere-like cell clusters from infarct areas at 3 days after HI are dramatically increased compared with those from sham control animals. Four and 30 days incubation of the cell clusters provided various types of cells positive for BrdU, Nestin, NG2, β III tubulin, GFAP, O4, Vimentin or Iba1. These cell clusters expressed mRNA such as Nanog, Sox2, Oct3/4 and Rex1 as same as ES cell. Also these cell clusters could be differentiated into neurons, astrocytes or oligodendrocytes, and expressed mRNA such as Nestin, βIIItubulin, GFAP and MBP.

Conclusion
We have isolated injury-induced neural stem / progenitor cells form ischemic area after neonatal HI. This cell has a potential to use as a source for new neurons driving CNS repair after neonatal HI.