bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3027: Report of Stroke Symptoms in the Absence of Stroke Predicts Incident Cognitive Impairment
Authors: Kelley Brendan J , McClure Leslie A , Letter Abe , Unverzagt Frederick W , Wadley Virginia G , Kissela Brett M , Kleindorfer Dawn O , Howard George
Published: March 2022

Introduction:
Stroke and vascular risk factors are recognized as important markers of increased risk of cognitive impairment. Experience of stroke-like symptoms and/or transient ischemic attack (SS/TIA) are suspected to represent another independent marker of risk for cognitive impairment.

Methods:
We assessed these relationships in REGARDS, a national longitudinal cohort study following over 30,000 black and white participants aged 45 and older from the 48 contiguous states. Cognitive function is assessed by several scales, including the Six-Item Screener (SIS), conducted by telephone at baseline and annually during follow-up. After excluding those who were impaired at first assessment, 23,830 participants (mean baseline age 64.2) were stroke free at baseline and had at least two cognitive function assessments (11,096 with two to four, and 12,734 with more than four). Observation time was censored after a suspected stroke during follow-up (censoring 1439 assessments in 515 participants). SS/TIA were assessed using the Questionnaire for Verifying Stroke-Free Status. The association between report of SS/TIA and subsequent impairment was assessed using logistic regression, both univariately and after adjustment for a variety of risk factors. In addition, the role of the Framingham Stroke Risk (FSR) in these relationships was examined. Incident impairment was characterized as a score of 4 or fewer on the most recently assessed SIS. Models were fitted separately for white and black subjects to evaluate race-specific effects.

Results:
Among blacks, the presence of any incident SS/TIA was associated with 1.66 (95% CI: 1.45, 1.89) times the likelihood of impairment in an unadjusted model, compared to those with no SS/TIA, which was slightly attenuated to 1.41 (95% CI: 1.23, 1.62) in a model incorporating gender, income, region and education. Among whites, the unadjusted OR was 2.08 (95% CI: 1.81, 2.39), with an adjusted OR of 1.85 (95% CI: 1.61, 2.13). The association between SS/TIA differed by FSRF, with a stronger association between SS/TIA and impairment among those with lower FSR, both for blacks and whites.

Discussion:
In an initially stroke-free cohort and with censoring of incident stroke cases in the follow-up, report of SS/TIA was strongly related to increased risk of cognitive impairment. The stronger association between self-report of SS/TIA and incident cognitive impairment among those with lower FSR score suggests these symptoms may reflect risk factors for cognitive impairment not captured in the FSR. This effect was larger in whites, suggesting differential sensitivity or exposure to this risk.
Abstract 3035: Thrombectomy In Acute Ischemic Stroke: A Single-Comprehensive Stroke Center Experience.
Authors: Cardona Pedro , Quesada Helena , De Miquel Maria Angeles , Aja Lucia , Mora Paloma , Cano Luis , Rubio Francisco
Published: March 2022

BACKGROUND
In acute thromboembolic stroke, mechanical recanalization with stents may result in immediate flow restoration. In this single-center experience, we analiyze safety and efficacy data on the application of the thrombectomy devices. All cases of acute ischemic stroke in which a self-expandable fully retrievable intracranial stent was deployed as acute endovascular intervention were included in the analysis. Criteria for intervention were the onset of neurological symptoms a National Institute of Health Stroke Scale score ≥9 at presentation, large vessel occlusion stroke demonstrated by angio-CT, and failure of intravenous thrombolysis or exclusion criteria.

MATERIALS AND METHODS:
We performed an analysis of 72 consecutive patients with acute ischemic stroke treated with thrombectomy from April of 2010 to June of 2011. Forty patients were treated with the device (Solitaire, Trevo): 66 with anterior circulation stroke and 6 with posterior circulation stroke. Thirty two (44 %) patients received previously rtPA. Six patients had an occlusion of the basilar artery, forty had a middle cerebral artery occlusion, twenty had terminal carotid artery occlusions and six extracranial carotid occlusion. Successful recanalization results were assessed by follow-up angiography immediately after the procedure (TIMI II-III). We divided them in two groups, good (90 days mRankin score ≤3) or bad neurological outcome and find out variables associated with it.

RESULTS:
The mean age was 66.5 years (range, 32-86 years; 53% men). The median NIHSS score at presentation was 18 (range, 6-26). Recanalization (TIMI 2-3) was achieved in (67%). Symptomatic hemorrhage occurred in 8%. Procedural complications occurred in 2 patients, vessel perforation without clinical consequences. Ninety-day mortality was 23%; good 90-day functional outcome (mRS, ≤ 2) was achieved by 39%. Good neurologic outcomes (mRankin ≤3 at 90 days) were more frequent (83% versus 18%), and mortality rates were lower (5 % versus 18 %) with successful compared with unsuccessful recanalization . Besides good or bad prognosis of patients aren’t associated with severe carotid stenosis or occlusion (carotid T or tandem occlusion) . Neither sex nor other epidemiologic datas were indicator of bad prognosis.

CONCLUSIONS:
Efficacy and safety of thrombectomy and translation to improved patient outcome is sufficiently established. New thrombectomy devices might be used in case of unsuccessful recanalization as failure of complete recanalization is associated with poor outcome.
Abstract 3041: Activated Thrombin Increase after Ischemic Stroke
Authors: Lei I-Farn , Van Winkle Jessica , Chen Bo , Lyden Patrick D
Published: March 2022

Background and Purpose-
The role of thrombin in mediating cytotoxicity after intracerebral hemorrhage is well known. Recently, we demonstrated activated thrombin co-localizing with neurons after ischemia using immunohistochemistry (IHC). We sought to quantify activated thrombin protein levels in ischemic brain using protein extraction and Western blots.

Methods-
Focal ischemia was induced by middle cerebral artery occlusion (MCAo) with a suture for 4 hours in adult Sprague Dawley rats (n=4). Brain regions with severe neurovascular disruption were identified using 2MD dextran linked to fluorescein isothiocyanate (FITC) injected intravenously during surgery. After 30 minutes reperfusion, brains were divided_using FITC whole-brain fluorescence_into ischemic, non-ischemic ipsilateral, and non-ischemic contralateral sections. Protein was extracted from homogenates and thrombin and prothrombin were quantified using Western immunoblots. Integrated density values (IDV) were normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) bands.

Results-
In ischemic brains, we detected severe vascular damage after 4 hours MCAo as significant FITC leakage. Thrombin was elevated (p<0.05 Newman-Keuls) in ischemic core (0.1908 ± 0.05) compared to non-ischemic region contralateral (0.05 ± 0.005) to the MCAo. In addition, non-ischemic tissue was devoid of FITC, but trace amounts of thrombin were detected on Westerns. Using IHC on sections for ischemic regions, prothrombin was detected within damaged blood vessels only, and activated thrombin co-localized with neurons and less so with vessels, astrocytes, or microglia.

Conclusion-
Elevation of thrombin was found in both ischemic and non-ischemic regions after MCAo. While prothrombin appeared to localize in vessels, activated thrombin was clearly localized to neurons. These findings suggest that after ischemia, prothrombin enters brain via disrupted BBB where it undergoes activation to thrombin then aggregates on neurons. Future experiments are needed to confirm this hypothesis and determine the effect of thrombin on neurons.
Abstract 3062: Chronic Kidney Disease is an Independent Predictor of Cerebral Microbleeds in Black Patients with Intracerebral Hemorrhage
Authors: Ovbiagele Bruce , Wing Jeffrey J , Menon Ravi S , Burgess Richard E , Gibbons M C , Sobotka Ian , German Laura , Shara Nawar M , Fernandez Stephen , Jayam-Trouth Annapurni , Edwards Dorothy , Kidwell Chelsea S
Published: March 2022

Background:
Among patients with ischemic stroke, a link between chronic kidney disease (CKD) and presence of MRI-defined cerebral microbleeds (CMB), a harbinger of future hemorrhagic stroke, has been reported. However, the association of CKD with CMB among patients with intracerebral hemorrhage (ICH) has not been systematically investigated. The objective of this analysis was to evaluate the relationship between CKD and CMB in a biracial cohort of patients with ICH.

Methods:
Using data from subjects with a recent ICH enrolled in a NIH-sponsored observational study between September 2007, and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate (GFR) <60 ml/min per 1.73 m
2
) and CMB. The number and location of CMBs were identified on gradient-echo T2*-weighted magnetic resonance imaging. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB after adjusting for confounders (age, sex, systolic BP, history of hypertension, antihypertensive drug use, and diabetes).

Results:
Of 162 subjects with complete data, mean age was 59 years, 44% were female, 74% were Black, 97 (60%) had 1 or more CMBs and 47 (29%) had CKD. In univariate analyses, subjects with CKD differed from those without CKD (p<0.1): history of hypertension (100% vs. 81%), history of diabetes (34% vs. 21%), on antihypertensive drug (74% vs. 51%), on renin-angiotensin system [RAS] modulator (44% vs. 26%), higher systolic BP (186 vs. 173 mmHg), presence of CMB (75% vs. 54%), number of deep located CMB (62% vs. 44%), number of deep located CMB (median, IQR: 2 {0, 3} vs. 0 {0, 2}), and size of index ICH (median, IQR: 7.5 {2.3, 29.7} vs. 13.8 {5.2, 34.2}). Overall, CKD was independently associated with presence of CMB (adjusted OR 2.29, 95% CI: 1.00-5.22, p=0.049) and number of CMB (adjusted RR 1.91, 95% CI: 1.08-3.38, p=0.027). There was also a borderline interaction between RAS drug use and CKD for number (i.e. fewer CMB) but not presence of CMB (p=0.09). In Black subjects CKD was associated with CMB presence (adjusted OR 3.11, 95% CI: 1.47-6.59) and number (adjusted RR 3.43, 95% CI:1.22-9.67), but not CMB presence (adjusted OR 2.00, 95% CI:0.37-10.92) or number (adjusted RR 1.56, 95% CI:0.25-9.78) in Non-Hispanic White subjects (interactions by race: p=0.84 and 0.74 respectively).

Conclusions:
CKD is associated with presence, number and location of CMB in ICH patients. These relationships are more pronounced in Black compared to Non-Hispanic White ICH patients. Low GFR may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB. Further investigation is required to see if RAS modulators may have a role to play in ameliorating CMB occurrence.
Abstract 3064: Validation of ABCD3-I Score: Predictive Value of Brain and Vascular Imaging in Transient Ischemic Attack Patients
Authors: Purroy Francisco , Jiménez-Caballero Pedro E , Girón J. , Torres Maria J , RamÍrez-Moreno J. M , Gorospe Arantza , de la Ossa Natalia P , Cánovas David , Arenillas Juan F , Álvarez-SabÍn José , MartÍnez-Sánchez Patricia , Delgado-Medeiros Raquel , RodrÍguez Anna , Montserrat Josep , Masjuán Jaime
Published: March 2022

Objective:
Diffusion-weighted magnetic resonance imaging (DWI) is not only a sensitive diagnostic tool for detecting acute ischaemic lesions in patients with transient ischaemic attacks (TIAs) but also a prognostic tool. Morever, large-artery aterosclerosis (LAA) is a marker of poor prognosis. Recently, brain and vascular imaging have been added to a new prognostic score: ABCD(3)-I score.

Methods:
We analyzed data from TIA patients of the PROMAPA study who underwent diffusion weighted imaging (DWI) within 7 days of symptom onset. Items that contribute to the ABCD(3)-I score (age, blood pressure, clinical weakness, duration, diabetes, LAA, recurrence events and DWI), other clinical variables and stroke recurrence at seven- and 90-day follow-up were recorded.

RESULTS:
462 TIA patients were included in the study. DWI abnormalities were identified in 117 (46.1%) patients. During follow-up, eight patients (1.7%) had a stroke within 7 days, and 14 (3.1%) had a stroke within 3 months. In cox proportional In the Cox logistic regression model, the combination of LAA and positive DWI remained as independent predictors of stroke recurrence at 90-day follow-up (HR 8.23, 95 CI 2.89-23.46, p<0.001). The area under the receiver operating characteristic curve was 0.79 (0.68-0.91, p=0.005) at 7 days and 0.67 (0.51-0.83, p=0.029) at 90 days.

Conclusion:
The combination of neuroimaging and vascular information improve prognostic accuracy in patients with TIA. ABCD3-I could select patients at high risk of very early recurrent stroke who need immediate evaluation and treatment.
Abstract 3085: Does Newly Diagnosed Sleep Apnea Favour Sleep-Related Ischemic Stroke?
Authors: Kepplinger Jessica , Barlinn Kristian , Boehme Amelia K , Pallesen Lars-Peder , Schrempf Wiebke , Albright Karen C , Alexandrov Andrei V , Bodechtel Ulf
Published: March 2022

Background&Purpose:
Sleep apnea (SA) is an increasingly recognized stroke risk factor. Little is known about the relationship between SA and sleep-related ischemic stroke (SIS). As part of our prospective study of early in-hospital overnight sleep studies in stroke patients, we aimed to evaluate the proportion and severity of SA in patients with SIS.

Subjects&Methods:
We prospectively (11/2009-05/2011) performed overnight sleep studies in consecutive patients with acute cerebral ischemia without known SA during their hospital stay (<5 days) to determine the presence of SA, defined as an apnea-hypopnea-index (AHI) ≥5/h. Demographics, clinical and sleep-related variables were collected at baseline. Sleep-related ischemic stroke was defined as the presence of stroke symptoms on awakening (wake-up stroke, WUS) or symptom-onset within 1 hour of awakening from nocturnal sleep. Functional outcome was assessed using the modified Rankin Scale at discharge and 180 days. Baseline demographics were analyzed using chi-square and Wilcoxon rank sum test. Correlations were used to examine the relationship between the outcome of interest and collected variables, and logistic regression was used to predict SIS or WUS.

Results:
Of 61 patients who met the inclusion criteria, 56 had analyzable sleep studies (18% TIA; 54% women; mean age 64±8 years; mean BMI 27.2±3.9; median baseline NIHSS score 1 point, range 0-15; median Epworth Sleepiness Scale score 5 points, range 0-13; mean AHI 23.6±19.3/h). SIS was found in 19 (34%) patients including 14 (25%) WUS. Nearly 91% (51/56) had SA; 32% (18/56) mild, 30% (17/56) moderate, and 29% (16/56) severe. There were no significant differences in baseline characteristics between SIS and non-SIS patients except for gender (males 26% vs. 57%, p=.03) and atrial fibrillation (32% vs. 5%, p=.008). Functional outcome at discharge (p=.24) and 6 months (p=.35) did not differ between SIS and non-SIS patients. When comparing SIS and non-SIS patients, no differences were found regarding the presence (95% vs. 89%, p=.49) or severity (e.g., severe SA: 32% vs. 27%, p=.69) of SA. Similarly, there were no differences in the presence (100% vs. 88%, p=.17) or severity (e.g., severe SA: 32% vs. 29%, p=.66) of SA when comparing WUS and non-WUS patients. AHI did not prove to be a significant independent predictor of SIS (p=.45) or WUS (p=.56).

Conclusions:
The similar proportions and severity of SA in our patients with sleep-related and non-sleep-related ischemic strokes may be due to the overall high prevalence of SA (91%) in the entire study population, which highlights the importance of early screening for SA in all ischemic stroke patients. As the majority of our patients had mild strokes, these findings warrant further investigation in a moderate-to-severe stroke population.
Abstract 3090: Transcranial Magnetic Stimulation (TMS) reveals Correlates of Response to Intensive Robotic Rehabilitation in Chronic Stroke
Authors: Pandya Jui , Lush Jaime , Jones-Lush Lauren M , Yang Suzy , Guarino Peter D , Richards Lorie G , Conroy Susan S , Bever Christopher T , Wittenberg George F
Published: March 2022

Introduction:
Intensive task practice assisted by robots is a promising treatment for hemiparesis after stroke. However, not all respond to the treatment, so a better patient selection method is needed. Previous studies have shown that motor cortical responsiveness to transcranial magnetic stimulation (TMS) may predict gains from practice and may change with those gains.

Hypotheses:
In the first study, we hypothesized that more intact motor cortical pathways would predict better response to treatment, and that motor cortical excitability would increase when motor function improved. In the second study we had the same hypotheses, and: Motor cortical excitability would increase during a single session of intensive therapy, and that this increase would itself predict gains in motor function.

Methods:
Study 1:
participants in trials of upper extremity robotic rehabilitation in chronic stroke were recruited to have TMS measures for extensor digitorum communis (EDC) and biceps muscles before and after the therapeutic intervention, which consisted of 6-12 wks. of intensive rehabilitation for 3 hr. each wk., using either robotics or more conventional methods. TMS measures included motor maps, threshold, recruitment curves, and ipsilateral silent period.
Study 2:
all participants received 12 wks. of a newly optimized robotic training, with or without functional task practice. In addition to TMS measures before and after the intervention, participants had the same measures before and after one of the first sessions of therapy using a particular robot.

Results:
Study 1:
(N=13) TMS thresholds in the EDC was lowered in 6/8 and recruitment curve threshold increased in 5 /8 with measurable responses after treatment, particularly in one participant with an 18 point increase in upper extremity Fugl-Meyer (FM) score. MEP presence showed a non-significant trend towards prediction of functional response (3.3 higher FM gain) even when baseline FM was included in the analysis.
Study 2:
While this is an ongoing study and outcome data are not available, motor threshold fell in the EDC after 1 hr. of robotic therapy for one participant and an MEP was present only after a therapy session for another.

Conclusion:
TMS measures in multiple muscles in moderately impaired stroke patients are feasible for rehabilitation trials and may be valuable both for prediction of response to therapy as well as demonstrating mechanisms of motor function improvement.
Abstract 3096: Poor Neurocognitive Outcomes in a Longitudinal Study of Primary Intracerebral Hemorrhage
Authors: Edwards Dorothy F , Smith Keisha , Menon Ravi S , Tiffany Deirdra , Gibbons M. C , Fernandez Stephen , Shara Nawar M , German Laura , Wing Jeffrey J , Sobotka Ian , Jayram-Trouth Annapuri , Kidwell Chelsea S
Published: March 2022

Background:
Performance on neurocognitive outcomes in patients with primary intracerebral hemorrhage (ICH) has not been well described, particularly in black populations. We sought to characterize neurocognitive performance at 30 days and 1 year in ICH patients enrolled in the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) Project.

Methods:
Inclusion criteria were: primary ICH, age ≥ 18. Neurocognitive outcomes were assessed at 30 days, and 1 year. Domains assessed were: memory, executive function, verbal fluency, depression, and functional outcome. African American norms were used to establish cut-points. Independent t-tests were used to examine differences by race; paired t-tests were used to compare changes in performance between 30 days and 1 year, and p values were corrected for multiple comparisons.

Results:
Of 162 subjects enrolled, mean age was 59±13 years, 44% were female, 75% were black. Mean admission NIH Stroke Scale score was 9 (median 6). Neurocognitive outcomes were available for 142 subjects at 30 days and 100 subjects at 1 year. Significant impairment was observed for all domains at each interval: memory (30 days 88%, 1 year 84%); verbal fluency (30 days 84%, 1 year 84%); attention (30 days 51%, 1 year 49%), and executive function (30 days 52%, 1 year 51%). Depression was observed in 44% at 30 days and 38% at 1 year. Functional impairment (mRS > 2) was found in 46% at 30 days and 40% at 1 year. Twenty one percent screened positive for dementia at 30 days and 13% at 1 year. Blacks had significantly lower scores at 30 days for memory (p<0.04), verbal fluency (p<0.05), and attention (p<0.02), while whites had higher depression scores (p<0.03). No racial differences were observed at year 1. While the average scores improved for all neurocognitive measures between 30 days and 1 year for the 87 subjects with longitudinal data, improvements were greatest for attention (p<0.001) and executive function (p<0.01).

Conclusions:
Significant impairments in all neurocognitive domains were observed at both 30 days and 1 year in this population of ICH subjects. Blacks had greater cognitive impairment and less depression at 30 days, however, these differences were no longer present at 1 year. While performance improved over time, significant impairment in memory, attention, fluency, and executive function persisted at 1 year.
Abstract 3101: Post-ischemic Development and Resolution of Infarct and Behavioral Deficits Induced by Permanent Middle Cerebral Artery Occlusion in Middle-aged Rats: A Progesterone Dose-response Study
Authors: Wali Bushra , Sayeed Iqbal , Ishrat Tauheed , Yousuf Seema , Stein Donald G
Published: March 2022

BACKGROUND:
There is currently no safe, effective, widely applicable post-stroke treatment for ischemic stroke, especially when treatment is delayed beyond a few hours. Our group and others have shown progesterone (PROG) to be beneficial after brain injury in several injury models. A systematic pre-clinical PROG dose-response study in ischemic stroke models is lacking. Since focal pMCAO models better simulate the typical human stroke injury without reperfusion, our study sought to determine PROG's dose-response effects on behavioral performance after pMCAO. We used a clinically relevant, middle-aged rat model and long-term sensory, motor, and cognitive outcome measures.

METHODS:
Male Sprague-Dawley rats (12 months old) underwent pMCAO by electrocoagulation or sham operation. At 1h post-pMCAO, the animals were given an intraperitoneal injection of one of three doses of PROG (8, 16, or 32 mg/kg), followed by subcutaneous injections 6h post-injury and then once every 24h for the next 7 days. The dose was tapered over the final 2 treatments. Behavioral recovery was evaluated at repeated intervals for locomotor activity, grip strength, rotarod performance, sensory neglect, gait impairment and spatial navigation learning and memory. Rats were killed at 22 days post-stroke and brains perfused for evaluation of infarct volume.

RESULTS:
Repeated measures ANOVA showed significant group (
F
(4,88)
= 17.15,
p
<0.001) effects in grip strength, significant group (
F
(4,41)
= 3.5,
p
< 0.05) and time (
F
(4,164)
= 2.6,
p
< 0.05) effects on rotarod, significant group (
F
(4,41)
= 2.94,
p
< 0.05) effects on latency to remove sticky paper from the affected contralateral forepaw, and significant group (
F
(4,41)
= 14.63,
p
< 0.0001) effects on total distance traveled. The best recovery in grip strength, rotarod and sensory neglect was seen in the 8mg/kg PROG group. In spatial learning memory, percent time spent in the platform quadrant of the MWM showed that progesterone improved performance (
F
(4, 40)
=2.7,
p
<0.05). Automated, computer-assisted, gait assessment showed that PROG significantly improved gait deficits in the affected limb. Significant decreases in stride length, print area and swing speed were observed. Both 8mg/kg ansd 16mg/kg of PROG treatment produced significant attenuation in infarct volume compared to the vehicle-alone group (
F
(3, 19)
= 4.38,
p
< 0.05).

CONCLUSION:
All doses of PROG improved functional deficits in a clinically relevant model of stroke. The 8mg/kg dose was optimal in improving motor, sensory and memory function. PROG shows pre-clinical promise as a potential therapeutic agent and should be examined for safety and efficacy in a clinical trial for ischemic stroke.
Abstract 3118: Star: Solitaire Fr Thrombectomy For Acute Revascularisation, International Clinical Evaluation Of The Solitaire™ Fr Used In The Treatment Of Patients With Acute Ischemic Stroke
Authors: Pereira Vitor M , Bonafé Alain , Castano Carlos , Chapot Rene , Gil A , Besselman M , Gralla Jan
Published: March 2022

Objective:
The aim of the study is to evaluate mechanical thrombectomy with the Solitaire FR when used according to hospitals’ stroke protocols (direct intra-arterial, bridging IV/IA and endovascular after failed or contraindicated IV lysis).

Design:
Single arm, observational, multi-center, prospective study with consecutive inclusion.

Sample size:
The target number of patients is 200 in 20 centers with a maximum of 30 patients per center.

Centers:
2 centers in Switzerland, 9 centers in Germany, 1 in Austria, 4 centers in Spain, 1 in Canada, 1 in Australia, 1 in Portugal, 1 in France.

Study population:
Patients presenting with acute ischemic stroke in anterior circulation, aged 18-85 years. Baseline NIH stroke scale between 8 and 30. Pre-stroke mRS ≤2. Treatment initiated within 8 hours of symptom onset. Meet specific imaging criteria based on ASPECT score.

Interventions:
Patients will be treated with the Solitaire FR Revascularization Device used as 1st intention device in routine practice.

Endpoints:
Primary endpoint will be recanalization of the occluded vessel, core lab reviewed, using TICI score with TICI 2b and 3 defined as successful recanalization. Correspondent TIMI scores will be determined for comparison with other studies.

Safety endpoint:
Adverse events related to the device or the procedure. All adverse events will be reviewed by an independent clinical event committee.

Secondary endpoints:
Time to revascularization, NIHSS at 90 days, mRS at 90 days, incidence of symptomatic intracranial hemorrhage, immediate flow reperfusion.

Trial status:
Enrollment is ongoing. There are currently 7 enrolling centers with a total of 37 patients.

Registers:
ClinicalTrials.gov
NCT01327989
Abstract 3140: Genetic Variants Within the Oxidative Phosphorylation Pathway Influence Risk of Ischemic Stroke
Authors: Anderson Christopher D , Biffi Alessandro , Nalls Michael A , Ross Owen A , Cortellini Lynelle , Rost Natalia S , Saxena Richa , Furie Karen L , Meschia James F , Rosand Jonathan
Published: March 2022

Background:
Prior studies have shown an association between mutations within the oxidative phosphorylation (OXPHOS) pathway and familial ischemic stroke syndromes. We investigated whether common autosomal and mitochondrial genetic variants within OXPHOS genes were associated with sporadic ischemic stroke in case-control.

Methods:
This multicenter association study was performed using a discovery cohort of 1643 individuals and a validation cohort of 2432 individuals from sites participating in the International Stroke Genetics Consortium. We employed a gene-set enrichment analysis (GSEA) using all 95 genes structurally involved in OXPHOS to determine the probability that the OXPHOS gene-set harbored more variants associated with stroke than predicted by chance. We then constructed a genetic score consisting of common variants within these genes. This genetic score was developed in the discovery cohort, and then tested for association with ischemic stroke in the validation cohort.

Results:
GSEA identified an aggregate association between the OXPHOS gene-set and ischemic stroke (p = 0.012). Based on this result, we constructed and validated a genetic score which demonstrated an association between OXPHOS genetic variation and ischemic stroke (odds ratio (OR) = 1.17, p = 0.008). In order to further distill the association between OXPHOS and stroke, we developed and tested additional scores for each of the five OXPHOS respiratory complexes. This sub-analysis revealed an independent association between OXPHOS Complex I and ischemic stroke (OR = 1.06, p = 0.050).

Conclusions:
This pathway-based study, informed by GSEA, employing independent discovery and validation cohorts, establishes an association between common genetic variants within OXPHOS genes and ischemic stroke. Analysis of variants within each OXHPOS Complex suggests that Complex I mediates this effect. Further studies are needed to identify the individual variants which influence ischemic stroke risk. Such discoveries offer the promise of new therapeutic targets for the prevention and treatment of stroke.
Abstract 3145: Nationwide Trends in Inpatient Admission for Transient Ischemic Attack from 2005 to 2009
Authors: Cutting Shawna , Ouyang Bichun , Prabhakaran Shyam
Published: March 2022

Objective:
To characterize admission trends, length of stay, and hospital costs for transient ischemic attacks (TIAs) in the United States over a five year period.

Introduction:
Transient ischemic attacks are relatively common, affecting an estimated 200,000 to 500,000 Americans annually. Rates of admission and characteristics of hospitalized patients with suspected or diagnosed TIA are unknown.

Design/Methods:
We searched the Nationwide Inpatient Sample (NIS) for adults discharged with a diagnosis of TIA (diagnosis related group 524) between January 1, 2005 and December 31, 2009; this database represents approximately 20% of all inpatient admissions in the United States. Data reviewed included patient demographics, hospital and regional characteristics, length of stay, and costs associated with admission.

Results:
Over the five year period, the number of patients hospitalized for TIA did not vary significantly by year or demographics (38,451 per year; mean age 70.5 years; 59.1% female) though the proportions with hypertension (68.8% to 76.2%) and who were admitted to teaching hospitals (30.1% to 38.4%) increased significantly. Elective admissions also decreased over time from 5.0% to 3.4% (P < 0.001). While the proportion of weekend admissions did not vary, it was slightly less than predicted (25.4% vs. predicted 28.6%). The median length of stay declined slightly per year (2005: 2.89 to 2009: 2.53 days) while hospital total charges increased from $14,341 in 2005 to $18,806 in 2009 (average annual increase: 6.2%). Length of stay was not lower at teaching hospitals compared to non-teaching hospitals (2.73 vs. 2.71 days) while costs were higher ($17,753 vs. $15,945, P < 0.001).

Conclusions:
Based on these data, we estimate that over 190,000 TIA patients are hospitalized each year in the United States. Despite the common rationale that TIA evaluation is expedited, average length of stay exceeds 2 days and costs exceeded $18,000 per patient in 2009. Teaching hospitals account for an increasing proportion of TIA admissions and are associated with higher costs. Further study is needed on cost-effective strategies (including expedited outpatient evaluation) for TIA patients.
Abstract 3168: “Drip-and-Ship” Thrombolysis Combined with Intra-Arterial Therapy for Acute Ischemic Stroke: a Single Center Experience
Authors: Conners James J , Lee Vivien H , Prabhakaran Shyam
Published: March 2022

Introduction:
A subset of patients with acute ischemic stroke (AIS) who are treated with intravenous tissue plasminogen activator (IV tPA) may benefit from further intra-arterial (IA) treatment but are initially treated at hospitals without endovascular resources. This necessitates emergent transfer (“drip-and-ship” strategy) to a facility with IA capabilities. The safety and utility of this method has not been sufficiently evaluated.

Hypothesis:
We assessed the hypothesis that the “drip-and-ship” strategy can be safely combined with IA therapy and leads to improved outcomes following acute ischemic stroke.

Methods:
We retrospectively reviewed consecutive AIS patients from July 2007 to May 2011 who were treated with IV tPA at community hospitals and then emergently transferred to our comprehensive stroke center. Demographic, clinical, and radiographic data were retrieved from an electronic registry. National Institutes of Health Stroke Scale scores were abstracted from the medical records prior to tPA administration and at hospital discharge (amongst survivors). Protocol violations and treatment-related complications were abstracted from the medical record.

Results:
Among 65 “drip-and-ship” IV tPA patients (mean age 62 years, 57% male) admitted to our stroke center, the median NIHSS score was 16 and median onset-to-treatment time was 160 (IQR 125-193) minutes; 72% were treated in the 3-hour window. There were 8 (12.3%) protocol violations: 1 treated > 4.5 hours from onset, 1 treated with cardiac dose of tPA, 1 treated in 3-4.5hr window despite NIHSS score > 25, 2 despite prior stroke and diabetes history, and 3 despite age > 80 years. Twenty-five patients (38%) underwent subsequent IA therapy. Overall, there were 12 (18.5%) intracranial hemorrhages (IV-9.8%, IV + IA-33.3%, p=0.024), of which 3 (4.6%) were sICH (IV-2.4%, IV + IA-8.3%; p=0.274). In-hospital mortality was higher among IV-IA patients (16.7 vs. 4.9%, p=0.183) than IV tPA alone. Among survivors (n=59), the median NIHSS improved from admission to discharge for IV tPA alone (13 to 6, p < 0.001) and following IV-IA treatment (20 to 13, p < 0.001).

Conclusions:
“Drip-and-ship” thrombolysis appears safe despite an increase in protocol violations. A combined approach with IA treatment leads to improvements in the NIHSS score at discharge and has a safety profile comparable to previous studies. A combined “drip-and-ship” model for acute ischemic stroke may be a safe and effective strategy to increase access to IA therapy among eligible patients presenting to community hospitals with large artery occlusion.
Abstract 3169: Reduced PDGFR-beta Expression After Regional Alk1 Deletion and VEGF Stimulation in the Brain is Associated with Reduced Mural Cell Coverage
Authors: Chen Wanqiu , Guo Yi , Bollen Andrew W. , Su Hua , Young William L.
Published: March 2022

Background and Purpose:
About 2% of brain arteriovenous malformations (bAVM) are attributable to Hereditary Hemorrhagic Telangectasia (HHT). Previously we created a bAVM model in the adult mouse using regional Alk1 (the causal gene in HHT2) deletion and VEGF stimulation, and reported that the dysplastic vessels in this model have less smooth muscle cell coverage than the normal cerebrovasculature. We hypothesized that VEGF stimulation in the setting of Alk1 loss-of-function leads to impaired mural cell coverage through reduction of platelet-derived growth factor receptor (PDGFR) signaling, and is associated with impaired cerebrovascular integrity.

Methods:
Brain AVM formation was induced by injection of 2X107 PFU adenoviral vector expressing cre-recombinase (AdCre) and 2X109 genome copies of adeno-associated viral vector (AAV) expressing VEGF (AAV-VEGF) into the basal ganglia of Alk1-floxed mice (loxP sites flanking Exons 4-6). The brain samples were collected 8 weeks after vector injection. Intra-parenchymal hemorrhage, microglial/macrophage counts, Alk1 and PDGFR/PDGFB protein expression were evaluated using Prussian blue staining, Iba1 staining and Western blot.

Results:
We found a 66±27% reduction in Alk1 protein expression around the injection site of the AdCre and AAV-VEGF-treated group compared with the control vector treated group (p=0.002, ANOVA). Fresh red blood cells (RBCs) were detected in the extravascular space in the Alk1-deficient brain parenchyma (Ad-Cre-treated Alk1-floxed mice), with ≈10-fold increase of Prussian blue coverage area compared to the brain with intact Alk1 gene (Ad-GFP-treated Alk1-floxed mice; p=0.016, rank sum test; or AdCre-treated wild-type mice, p=0.010, rank sum test) after VEGF stimulation. The area of Prussian blue coverage was positively correlated with the number of Iba1+ cells (R2=0.39, p<0.05). Alk1 deletion resulted in a 26±10% reduction of PDGFR-beta expression compared to controls (p<0.001; ANOVA) after VEGF stimulation. However, Alk1 deletion did not affect the level of one of the PDGFR-beta ligands, PDGF-B.

Conclusions:
These results indicate an important role for Alk1 in maintaining cerebrovascular integrity as shown by its effect on pericyte function through interaction with PDGFR-beta signaling. Alk1 deletion plus VEGF stimulation reduced vessel wall integrity that was associated with an inflammatory response. Altered pericyte-endothelial cell interaction may play a causal role in the pathogenesis of human bAVM, possibly involving a local inflammatory response associated with RBC extravasation.
Abstract 3180: Hypotensive Events at Stroke Onset in the absence of Severe Carotid Disease
Authors: Ryan Daniel J , Kenny Rose A , Meaney James F , Rice Ciarra P , Harbison Joseph A
Published: March 2022

Hypotensive strokes frequently occur in the context of severe carotid disease. Aside from this cohort, evidence is lacking for the role of hypotension in stroke. The aim of this study was to investigate the presence of hypotensive behavior at stroke onset in those who do not have severe carotid disease. Prospective screening was conducted on all acute stroke patients for hypotensive symptoms at stroke onset. Suitable patients were referred to a syncope unit for assessment. There they underwent head-up tilt and rhythm assessment at least 8 weeks post stroke. All underwent 1.5T MRI in the acute stroke period. Where borderzone infarction was suspected repeat 3T MRI took place with perfusion imaging software to confirm this diagnosis. In total, 318 acute stroke patients presented to St. James Hospital, Dublin during a 14 month period. Of these, 20 patients exhibited hypotensive symptoms at stroke onset and did not have severe carotid disease (6.3%). In 12 patients TILT assessment induced symptom reproduction, thus confirming hypotensive behavior,in 2 this occurred during active stand, in 4 expert opinion established a diagnosis of vasovagal syncope while in 1 patient bradyarrythmia and in 1 autonomic failure was attributed. Median carotid stenosis was 20-30% bilaterally (range 10-70%). Ten of 20 patients underwent MRA. No intracranial stenosis was detected. Mean age was 74 years and 70% were female (n=14). Using phasic blood pressure (BP) assessment during active stand the mean BP drop in these patients was 47/26mmhg. Nadir BP drop occurred within 15 seconds in 17 patients (85%) and thus may have gone undetected by a sphygmomanometer. 19 patients reported a prior history of presyncope(95%). The mean duration of symptoms was 4.9 years (0.1-30 years), mean frequency 6 episodes per month. In 13 patients the neurological deficit resolved within 24 hours. An acute infarct was detected in 3 of 13, all borderzone infarction. In 7 patients the deficit persisted beyond 24 hours. An acute infarct was detected in 4 of 7, all borderzone infarction. Both cortical and internal borderone infarcts were detected. Mean 24 hour blood pressure was 143/77. Neither mean BP, nor BP variability statistically differed from 40 age and gender matched stroke controls. Hypotensive symptoms do occur at the time of stroke onset. Patients are often female, describe a prior history of hypotensive symptoms, have hypotensive disorders and exhibit a strong tendency for borderzone infarction. Caution is advised regarding the use of aggressive anti-hypertensive therapy in these patients.
Abstract 3187: Inflammatory Cell Infiltration Correlates with Hemosiderin Deposition (Intra-lesion Hemorrhage) in Surgical Excised Unruptured Human Brain Arteriovenous Malformations
Authors: Guo Yi , Su Hua , Kim Helen , Lawton Michael T. , Bollen Andrew W. , Young William L.
Published: March 2022

Background and Purpose:
Human brain arteriovenous malformations (bAVM) are common cause of hemorrhagic stroke in young adults. Evidence of inflammation in bAVM pathogenesis includes neutrophil and macrophage infiltration, and increased expression of various inflammatory signals, such as matrix metalloproteinase-9, interleukin-6, myeloperoxidase and adhesion molecules. Hemosiderin deposition in unruptured bAVM has been detected by magnetic resonance imaging (MRI), consistent with episodes of clinically silent micro-hemorrhage. We hypothesized that the inflammatory cell (macrophage and lymphocyte) burden is positively correlated with the degree of hemosiderin deposition in the lesion.

Methods:
A total of 19 unruptured, non-embolized surgically-excised bAVM specimens were examined. Macrophages (CD68+), T-lymphocytes (CD3+), and B-lymphocytes (CD20+) were detected by immunohistochemical staining using specific antibodies and quantified using stereological microscopy. Hemosiderin deposition were detected on H&E stained sections and confirmed by Prussian blue staining. Prussian blue positive cells were quantified by NIH image J software. Three superficial temporal arteries (STA) were used as controls.

Results:
Both CD68+ cells (5-75×103/cm2) and CD3+ cells (0-34×103/cm2) were detected in bAVM samples. Few CD20+ cells were detected. The CD3+ cells were clustered on the lumen surface of endothelial cells, in the vascular wall and, in some cases, in the perivascular regions. In contrast, CD68 and hemosiderin staining was observed in a more diffuse pattern.. No CD68+, CD3+ and CD20+ cells were detected in STA. Hemosiderin deposition (Prussian blue positive) was present in 8/19 (42%) patients and was co-localized with CD68+ cells.

Conclusions:
In addition to CD68+ cells, the finding that T lymphocytes were prominently present in bAVM lesion raises the question of the relationship of cell-mediated immunological mechanisms to bAVM pathogenesis and/or clinical course. The causal link between cellular infiltration and extravasated blood remains indeterminate, the co-localization of CD68+ cells and micro-hemorrhage_cellular infiltration may represent novel risk factors for clinical AVM rupture risk.
Abstract 3196: Effect Of Marital Status On Health-seeking Behavior Following Onset Of Acute Stroke Symptoms
Authors: Lee-Iannotti Joyce K , Ingall Timothy J. , Aguilar Maria I. , Capampangan Dan J. , Dodick David W. , Kiernan Terri J. , Vargas Bert B. , Demaerschalk Bart M.
Published: March 2022

Background:
Each year, nearly 700,000 Americans suffer from strokes, resulting in 150,000 deaths and significant disability among survivors. Despite advances in therapeutic options for acute stroke within a critical time window, patient delay in seeking medical attention remains a significant barrier to improving outcomes. In a recent study of the effect of marital status on the timing of presentation for medical care in patients with chest pain, married men presented earlier than married women. In this study, we hypothesize that marital status is a predictor of earlier health-seeking behavior following the onset of stroke symptoms.

Methods:
We conducted a retrospective review of 100 patients with acute stroke symptoms in our stroke alert quality initiative database who were brought by Emergency Medical Services (EMS) to the Mayo Clinic Hospital, Arizona between December 1, 2010 and June 30, 2011. Nine patients were excluded due to lack of data. The database contains the following information for each patient: age, gender, marital status, the time of symptom awareness, and the time of EMS dispatch. Using both an independent samples t-Test and ANOVA, we compared the time from symptom awareness to EMS dispatch both between married and single patients, and between men and women, (married and single).

Results:
The mean age of the 91 patients studied was 76 years (SD = 12.5 years) and 52% were women. Forty-five patients (49.5%) were married, and 46 (50.5%) were single. The mean time from symptom awareness to EMS activation was 52 minutes (median 21.0, SD 87.3, range 2-519 minutes.) Categorized by marital status, married patients activated EMS earlier that single patients, but this difference was not significant (43 versus 60 minutes, p=0.35.). Analyzing the data separately for gender, we found that married men activated EMS significantly earlier than married women (26 versus 72 minutes, p=0.04.). Single men activated EMS earlier than single women, but this difference was not significant (50 versus 66 minutes, p=0.60.)

Conclusions:
Among persons with acute stroke symptoms, earlier medical-seeking behavior was seen in married compared to single persons, and particularly in married men. We plan to analyze a larger sample of patients, and if these preliminary findings are confirmed, we will conduct a prospective study evaluating reasons why married men with stroke symptoms seek medical attention earlier.
Abstract 3201: Impact of a Stroke "Quick Look" Assessment on meeting Brain Attack Coalition Guidelines
Authors: Lee Richard E
Published: March 2022

Background and Issues:
Emergency Departments (ED) are challenged to meet Brain Attack Coalition Guidelines (BACG) for treatment of patients with acute stroke symptoms. BACG recommends that patients with acute stroke symptoms be assessed by a physician within 10 minutes of arrival to the ED, have a Computed Tomography (CT) scan within 25 minutes, receive results of the CT scan within 45 minutes, and receive intravenous TPA within 6o minutes if appropriate.

Purpose:
The purpose of our study was to radically change our delivery system for stroke patients and exceed BACG guidelines to improve patient outcomes for an emergency department servicing greater than 100,000 visits annually.

Methods:
The innovation that was vital in streamlining our process was a “Quick Look” neuro assessment by a physician for patients presenting with acute stroke symptoms. At-risk patients progress immediately to radiology, bypassing the traditional serial process of going straight to an ED room and waiting for the stroke team. Implementation of this “Quick Look” process included activation of the Neurologist and Rapid Response Team member.

Results:
A retrospective review of 479 charts between December 2009 and December 2010 was conducted to determine process outcomes. Implementation of a “Quick Look” assessment decreased “Door to Doctor” time from 10 minutes to 2.75 minutes (73% decrease); “Door to CT” time from 41 minutes to 18 minutes (56% decrease); door-to-administration-of-IV-TPA time from 82 minutes to 62 minutes (24% decrease); “Door to CT Results” time from 53 minutes to 27 minutes (49% decrease); and “Door to IV-TPA” time from 82 minutes to 62 minutes (24% decrease). Current 2011 year to date results through June 2011 meet the BACG door-to-needle time of less than 60 minutes.

Conclusions:
The implementation of the “Quick Look” process has sustained these positive outcomes throughout 2011, meeting BACG the first two quarters of 2011, and meeting the American Heart Association/American Stroke Association’s Target: Stroke Honor Roll. Although the success of this process improvement was driven by the stroke council; the amazing results are due to the efforts and collaboration of a highly functioning interdisciplinary Emergency, Rapid Response and Neurosciences team.