bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2416: Reducing Door to Needle Time for Intravenous Alteplase in Community Hospital Based Primary Stroke Centers
Authors: Guisado Raul , de la Cuesta Karen , Catalli Linda
Published: March 2022

Intravenous alteplase (i.v. t-PA) for ischemic stroke is most effective when given early after stroke onset. The current national treatment initiative, Target:Stroke aims to administer i.v. t-PA within 60 minutes of patient’s arrival to the ED. This goal is challenging for community based primary stroke centers that do not have 24 hours in-house neurologists or radiologists and who are not able to mix alteplase in the ED. In 2010, we conducted a focused review of Stroke Alert Timelines in two community based Primary Stroke Centers in Santa Clara, California. This review led to the
hypothesis
that door-to-needle times for i.v. alteplase in ischemic stroke could be reduced by improving communication between key responders and by expediting the delivery of i.v. alteplase from pharmacy to the ED.

METHODS:
In January 2011 we implemented a new Emergency Room protocol for management of patients with acute ischemic stroke (
Fig
) and compared its performance with recent historical data in two community hospital based PSCs. This protocol emphasizes prompt communication between ED physician, on-call neurologist and radiology and expedites the delivery of i.v. alteplase to the ED.

FINDINGS:
The average door to needle time for patients treated between January 2009 and December 2010 was 89.5 ± 35.7 min (median 77 min). During this period, two patients (3.1%) received the drug within 60 minutes of arrival to the ED. The average door to needle time for patients treated between January 2011 and July 2011, was 70.7 ± 28.9 min, (median 60 min, p < 0.02). During this period, fourteen patients (58.3%) received i.v. t-PA within 60 minutes of arrival to the ED.

CONCLUSION:
an improved management protocol that optimizes communication between ED physician, neurologist, radiologist and pharmacy and makes alteplase promptly available at bedside, can significantly improve the door to needle time for i.v. alteplase in community hospital based primary stroke centers.
Abstract 2431: Angiographic Distinctions Of Radiation-induced Carotid Vasculopathy: A Case-controlled Study
Authors: Zou Xin ying , Yu Simon C.H. , Wong Edward H.C. , Soo Yannie O.Y. , Lam Wynnie W.M. , Siu Deyond Y.W. , Abrigo Jill , Cheung Tom C.Y. , Lee Kwok Tung , Lee Tom W.K. , Wong Ka Sing , Leung Thomas W.
Published: March 2022

Background:
Radiation-induced vasculopathy (RIV) predisposes survivors of head-and-neck cancers to refractory ischemic strokes. We aimed to investigate the angiographic extent and morphological attributes of symptomatic RIV.

Methods:
The study was approved by the Institutional Review Board and each participant provided an informed consent. One hundred thirty patients with ischemic strokes attributed to high-grade carotid stenoses (>60%) were recruited for digital subtraction angiograms (DSA). Among the enrolled patients, 65 had prior curative intent radiotherapy for head-and-neck cancers. The remaining 65 control patients who had no radiotherapy were presumed to have atherosclerotic vasculopathy. DSA revealed both carotid and vertebro-basilar circulations from the level of aortic arch up to intracranial branches. A radiologist blind to the group assignment recorded the distribution and characteristics of both stenotic and non-stenotic lesions. Fetal variant or incompetence of the circle of Willis, if any, was also documented.

Results:
The baseline characteristics of RIV and control patients were comparable except a lower prevalence of hypertension and diabetes mellitus in RIV group (p<0.01). Among a total of 279 stenoses, 176 were radiation-induced and 103

were atherosclerotic. Atherosclerotic stenoses were predominantly focal, involving the internal carotid artery adjacent to the bifurcation (93/103, 90.29%). RIV stenoses, in contrast, harbored more frequently at common carotid artery (96/176, 54.55%) and was associated with more tandem lesions (29.23% vs 10.77%, p<0.001), bilateral disease involvement (63.1% vs 36.9%, p<0.01) and concomitant vertebro-basilar steno-occlusions (53.85% vs 21.54%, p<0.001). Fetal variant or incompetence of the circle of Willis, non-stenotic ulcers and dissections were also found more commonly in RIV patients (all p<0.05).

Conclusion:
Radiation-induced carotid disease was frequently bilateral and associated with concurrent tandem and vertebra-basilar steno-occlusions. Fetal variant or incompetence of the Circle of Willis may potentiate further the hemodynamic insufficiency.
Abstract 2434: Maintenance Hemodialysis In Patients With Acute Intracerebral Hemorrhage Is Associated With Early Stroke Death.
Authors: Shimoyama Takashi , Shibazaki Kensaku , Yamashita Shinji , Matsumoto Noriko , Watanabe Masao , Inoue Takeshi , Iguchi Yasuyuki , Kimura Kazumi
Published: March 2022

Background:
Patients with end-stage renal disease (ESRD) are associated with markedly higher risk of stroke and poor outcome. However, few studies have reported the detailed clinical features including patient outcome of acute intracerebral hemorrhage (ICH) in patients with maintenance hemodialysis (HD).

Methods:
From April 2004 to June 2011, we enrolled consecutive patients with acute ICH within 7 days onset. All patients had detailed clinical characteristics including patient outcome, blood tests, and CT scan. ICH volume was measured on admission CT and follow-up CT (<24hr after admission) scan. Hematoma enlargement was defined as a hematoma that increased more than 33% of its initial volume. We divided all patients into HD group and non-HD group, and compared clinical characteristics between the two groups. Next, the factors associated with early stroke death within 14 days of onset were investigated by multivariate logistic regression analysis.

Results:
507 consecutive patients (320 males, 68.6±12.9 years old) were enrolled in the present study. 36 patients (7.2%) were receiving maintenance HD. HD group was younger (60.7±13.4 years vs. 69.2±12.7 years, P<0.001) and more frequently had diabetes (52.8 % vs. 17.8 %, P<0.001) than non-HD group. Prior antithrombotic agents were more used in HD group than non-HD group (41.7% vs. 21.9%, P=0.012). There was no significant difference in NIHSS score (16.3±11.6 vs. 13.1±9.0, P=0.114) and ICH volume on admission (24.4±34.1 ml vs. 17.8±32.1 ml, P=0.347). However, ICH volume enlargement was more frequently seen in HD group than non-HD group (25.8 % vs. 10.2 %, P=0.015). With respect to the hematoma location, brainstem (30.6% vs. 11.3%, P=0.003) and lobar (19.4% vs. 6.6%, P=0.013) were more frequently found in HD group than non-HD group. Early stroke death was more frequently observed in HD group than non-HD group (33.3% vs. 9.3%, P<0.001). On multivariate logistic regression analysis, NIHSS score ≥22 (OR 43.95; 95% CI, 13.46-143.50, P<0.001), ICH volume≥18ml (OR 4.55; 95% CI, 1.80-11.50, P=0.001), prior antithrombotic agents (OR 4.61; 95% CI, 1.70-12.56, P=0.003), HD (OR 6.95; 95% CI, 1.61-30.07, P=0.010),and plasma glucose level≥160 mg/dl (OR 2.56; 95%CI, 1.02-6.43, P=0.046) were independent factors associated with early stroke death.

Conclusion:
ICH patients on maintenance HD were independently associated with early stroke death.
Abstract 2458: Admission Hyperglycemia Causes Infarct Volume Expansion In Patients With ICA And MCA Occlusion: Association Of Collateral Grade On Cerebral Angiography.
Authors: Shimoyama Takashi , Shibazaki Kensaku , Uemura Jyunichi , Shiromoto Takashi , Watanabe Masao , Inoue Takeshi , Iguchi Yasuyuki , Kimura Kazumi
Published: March 2022

Background:
The collateral circulation sustains the ischemic penumbra to limit growth of infarct volume. Recent study showed hyperglycemia was associated with infarct volume expansion in acute ischemic stroke patients. The aim of present study is to investigate whether admission hyperglycemia is related with enlargement of infarct volume and poor outcome based on the collateral circulation grade.

Methods:
From April 2004 to July 2011, acute ischemic stroke patients with ICA and MCA occlusion on cerebral angiography within 24 h of onset were retrospectively studied. We excluded the patients treated with iv t-PA or endovascular therapy. Hyperglycemia was defined as admitting blood glucose value>140mg/dl. Angiographic collateral was evaluated with the ASITN/SIR collateral flow grading system. Grade 0 to 1 was designated as poor collateral and grade 2 to 4 as good collateral. Infarct volume was measured on admission and follow-up (<7days after admission) diffusion weighted imaging on MRI. We compared Δinfarct volume (follow-up-baseline) and patient outcome between hyperglycemic (HG) group and non-HG group according to each collateral grade.

Results:
93 patients (65 males, 67.7±13.3 years old, ICA occlusion in 52 and MCA in 41 patients) were enrolled in the present study. Collateral grade was poor in 34 patients (36.6%) and good in 59 patients (63.4%).In poor collateral grade (16 patients in HG group and 18 patients in non-HG group) , there was no significant difference in baseline infarct volume (66.2±93.7 mL vs. 61.8±81.5 mL, P=0.746). However, Δinfarct volume was markedly larger in HG group than non-HG group (106.0±101.4 mL vs. 22.7±54.9 mL, P=0.002). Poor outcome (mRS 5 to 6) at discharge was more frequent in HG group than non-HG group, but the differences were not significantly (56.3% vs. 27.8%, P=0.163). In good collateral grade (34 patients in HG group and 25 patients in non-HG group), the baseline infarct volume did not differ between HG group and non-HD group (17.1±39.2 mL vs. 17.9±37.2 mL, P=0.569). However, Δinfarct volume was more larger in HG group than non-HG group (53.3±74.1 mL vs. 10.9±24.3 mL, P=0.047). Moreover, poor outcome at discharge was frequently observed in HG group than non-HG group (38.2% vs. 12.0%, P=0.038).

Conclusion:
In patients with ICA and MCA occlusion, admission hyperglycemia should affect infarct volume expansion in poor as well as good collateral circulation.
Abstract 2463: Hydrogen Sulifde, A Novel Gasotransmitter, And Ischemic Stroke: Its Protective Role In Cerebral Ischemic - Reperfusion Injury Model
Authors: Ryu Wi-Sun , Kim Chi Kyung , Kim Beom Joon , Lee Seung-Hoon , Yoon Byung-Woo
Published: March 2022

Backgoround:
Hydrogen sulfide (H2S) has recently been highligted as the third gasotransmitter following its two counterparts, nitric oxide and carbon monoxide. Several lines of evidence have demonstrated that H2S is a potent vasodilator and has a protective role in ischeic-reperfusion injury of several organs, including heart, liver and kidney. In the present study, we examined the protective effect of H2S in rodent cerebral ischemia-reperfusion injury model.

Methods:
Ischemia-reperfusion injury model wsa induced by intraluminal middle cerebral artery occlusion (MCAo) for 120 min followed by reperfusion in Male Sprague Dawley rats. Sodium hydrosulfide (NaHS, 1mg/kg and 5mg/kg), the donor of H2S, and normal saline (1mL) was infused via tail vein, immediately after reperfusion. To confirm the protective effect of H2S, we used propargylglycine (PAG)(50mg/kg, intraperitoneal for 7 days befor MCAo). We used Nissl stain to measure infarct sizes, ELISA to determine the levels of IL-1b, IL-6 and TNF-a in the brain, and Western blot to assess the expression of ERK 1/2, STAT 3, phosphorylated STAT3, and Nrf 2. In addition, GSH/GSSG ratio and lipid peroxidase were measured to assess the levels of oxidative stress.

Results:
Injection of H2S significantly reduced infarct size (5mg/kg: 43 ± 10%; 1mg/kg: 48 ± 12% vs. Control: 58 ± 11%, p < 0.05, n= 9-11). Furthermore, intraperitoneal injection of PAG worsened the infarct size (n=5, p<0.01). Administration of NaHS (5mg/Kg) significantly increased STAT3 phosphorylation at 24 hour after ischemia (n=4, p<0.01). Furthermore, Nrf2, an important molecular in anti-oxidative response, expression signicantly increased in experiment group at 24 and 48 horus after ischemic compared with control (n=4, p<0.01). ELISA showed that the levels of IL-6 increased in experiement gorup (2.5 ± 0.5 ng/mL, n = 4) at 24 and 48 hours after ischemia compared with control gorup (1.9 ± 0.2 ng/mL, n = 4). The levels of IL-1b increased in H2S gorup (0.7 ± 0.1 ng/mL, n = 4) at 48 hours after ischemia but not at 24 hours compred with control (0.4 ± 0.1mg/mL, n = 4). However, TNF-a levels were not different. The levels of GSH/GSSG ratio and lipid perixidase were significantly lower in H2S treated gorup compared with control (p < 0.05, n = 4).

Conclusion:
In the present study, we showed that administration of NaHS, the donor of H2S, protects brain from ischemia-reperfusion injury. This effect may be driven from anti-oxidative and anti-inflammatory effects of H2S.
Abstract 2476: Hip Hop Stroke: Long-Term Retention of Stroke Knowledge Among Sixth Graders Living in a Low-Income Neighborhood.
Authors: Williams Olajide A , DeSorbo Alexandra L , Noble James
Published: March 2022

Objectives:
To evaluate the effect Hip Hop Stroke TM, a novel multi-media and musical school-based stroke literacy (knowledge of stroke symptoms, appropriate action, and prevention measures) intervention targeting children aged 8-12, on long-term retention of stroke knowledge.

Methods:
We enrolled 107 sixth grade children from one school in Harlem into a single dose of our Hip Hop Stroke intervention - three, one-hour classroom sessions, delivered over three consecutive days. Stroke knowledge surveys to evaluate stroke symptoms, appropriate response when presented with hypothetical stroke scenarios (calling ‘911’) and stroke localization (where a stroke occurs in the body) were conducted at baseline, immediately following the intervention, and 15-months following the intervention. A composite score was created from five stroke symptoms, which included blurry vision/loss of vision, sudden headache, facial weakness, clumsiness/incoordination, slurred/confused speech, and a distracter (chest pain). Data was analyzed using SAS 9.2.

Results:
A total of 105 students complete both pretests (PT) and immediate post tests (IP), and 85 students completed all three tests, which included a 15-month delayed post test (DP) [79.4% retention rate]. At PT, 36.2% correctly identified stroke localization, and 55.2% appropriately identified calling 911. The stroke knowledge composite score at baseline was 3.21. At IP, stroke knowledge increased significantly across all items: stroke localization (90.5%, p<.05), calling 911 (84.8%, p<.05), and composite score (5.25, p<.05). At 15 months, all items except headache were significantly retained by children, with a composite score of 4.73 (p<.05, PT vs. DP). Knowledge of stroke localization (80%, p<.05, PT vs. DP) and calling 911 (72.8%, p<.05, PT vs. DP) were also retained significantly.

Conclusion:
Three one-hour Hip Hop Stroke sessions significantly improved knowledge of stroke symptoms and response of sixth grade children, living in a high stroke risk neighborhood. This knowledge was significantly retained up to 15 months post-intervention.
Abstract 2478: Hip Hop Stroke: The Standalone Effect of Musical Cartoons on Stroke Knowledge of Fourth Grade Children Living in a Low-Income Neighborhood
Authors: Williams Olajide A , DeSorbo Alexandra L , Noble James
Published: March 2022

Objectives:
To evaluate the effect of two novel three and half minute-long musical cartoons on stroke knowledge of fourth grade children.

Methods:
We recruited 72 fourth grade children from a single elementary school in Harlem to view musical cartoons designed to increase stroke literacy (knowledge of stroke symptoms, appropriate action, and prevention measures). Baseline testing to evaluate knowledge of stroke symptoms and response was performed immediately prior to viewing the cartoons. Each cartoon was viewed a total of three times over two consecutive days. No additional stroke education was provided. Posttests were conducted immediately following completion of viewing. A composite score was created from five stroke symptoms, which included blurry vision/loss of vision, sudden headache, unilateral facial weakness, clumsiness/incoordination, slurred/confused speech, and a distracter (chest pain). Knowledge of stroke localization (where a stroke occurs in the body) and appropriate action when presented with hypothetical stroke scenarios (calling 911) were also evaluated. Data was analyzed using SAS 9.2.

Results:
A total of 64 students completed both pretests (PT) and immediate posttests (IP) [89% retention rate]. At PT, 12.5% were able to identify stroke localization, and 47.2% were able to identify calling 911 for suspected stroke. The stroke symptom composite score at baseline was 2.62. Immediately following viewing, children’s stroke knowledge increased significantly with regards to stroke localization (71.9%, P<.05) and calling 911 (87.5%, p<.05). Knowledge of stroke symptoms also improved significantly across three out of five items (with the exception of blurry vision and sudden headache), and the composite score was 4.2 (p<.05).

Conclusions:
Viewing two novel three and half minute musical cartoons, three times, significantly improved knowledge of stroke symptoms and response among fourth grade public school children, living in a high stroke risk neighborhood.
Abstract 2480: Does Stroke Bridge Clinic Reduce Hospital Readmission Rates in Patients Who Have Suffered a Stroke?
Authors: Hooker Allison F , Evans Hope
Published: March 2022

Does Stroke Bridge Clinic Reduce Hospital Readmission Rates in Patients Who Have Suffered a Stroke?

Introduction:
Approximately 795,000 people suffer a stroke every year. The complex health needs following a stroke requires a highly coordinated transition of care to the community. This transition often falls short, requiring re-hospitalization within 30 days. Re-hospitalization can result in significant lack of progress for the patient and loss of reimbursement for the hospital.

Purpose:
The purpose of this study was to determine the effectiveness of a Stroke Bridge Clinic in preventing hospital readmissions following an acute hospitalization with a stroke.

Methods:
A retrospective quasi-experimental design was employed to examine the re-admission rates of patients attending the Stroke Bridge Clinic with those that did not. The clinic “bridges” the patient’s inpatient care to the primary care physician. One week following discharge from acute care or from rehabilitation, the patient comes to the Bridge Clinic to be evaluated by a Stoke Interdisciplinary Team. The team consists of a nurse practitioner, nurse stroke navigator and a pharmacist. The team focuses on the individualized treatment plan, education of risk factors, stroke prevention and medication reconciliation and education. The visit findings are then communicated with the primary care physician and the patient to improve continuity of care. The team also schedules follow up appointments and arranges community resources as needed.

Results:
Since opening the Bridge Clinic in October 2010 readmission rates have declined by 12.3%. The patients without Bridge Clinic visits had a readmission rate of 14.5%. Patients with Bridge Clinic visits had a readmission rate of 2.2%.

Conclusions:
The initiation of the Stroke Bridge Clinic has resulted in a significant decline in readmissions for the patients that attend. We believe that by maintaining our connection to the patient post discharge, we can address every patient’s needs individually. The decline in hospital readmissions for this special patient population may be due to the increased education, support and preparation for their continued recovery addressed by our interdisciplinary approach.
Abstract 2493: Enrollment In Early Brain Stimulation Arm Motor Recovery Studies Is Limited Primarily By Stimulation-unrelated Exclusions Including Ethnic And Racial Characteristics
Authors: Hodics Timea , Cohen Leonardo , Upreti Bhim , Alex Arun , Kowalske Karen , Hart John , Dromerick Alexander
Published: March 2022

Introduction:
The high incidence of disability related to upper extremity (UE) motor impairments in stroke has led to an increasing number of clinical trials of UE motor interventions. These now include transcranial magnetic stimulation (TMS) and direct current stimulation (TDCS). Trial enrollment criteria typically depend on isolated unilateral motor impairments, a single acute stroke, with limited co-morbidities, and criteria specific to the intervention.

Objectives:
To determine the frequency of stimulation trial candidates in an acute stroke population, evaluate the impact of stimulation-specific exclusion criteria in trial recruitment, and examine how potential participants differ from the broader stroke population.

Methods:
1701 patients evaluated at an urban academic acute stroke service over a 3 year-period were screened for a TDCS trial. Demographics, stroke characteristics were recorded prospectively.

Results:
This was a young (mean 58.8 +14.8 yr), predominantly male (60.6%), and racially and ethnically mixed population (non-Hispanic white 38.1%, Hispanic 21.4%, AA 32.8%, Asian 2.6%, others 5.0%). Only 29 subjects met eligibility criteria (1.7%). The five most common causes for exclusion were in descending order: 1) UE motor impairment normal or complete, 2) old strokes causing weakness, 3) stroke mimics, 4) hemorrhagic strokes, 5) severe medical conditions. African American (AA) patients trended towards less likelihood of eligibility for participation (1.09%) then the other ethnic/racial groups (p=0.2). AA patients were more likely to have had old strokes causing weakness than other patients (p < 0.001), and this was the most common cause of their exclusion. 2.88% were excluded for stimulation related reasons. 8 individuals refused participation (1 non-hispanic white, 2 females). Minority men were more likely to refuse participation than minority women and non-Hispanic white patients (p=0.008). Demographics of the 21 enrolled participants were not significantly different (age 62.0+12.0 yr, 57.1% women, non-Hispanic white 52.4%, Hispanic 23.8%, AA 14.3%, Asian 9.5%).

Conclusion:
In this urban multiracial sample, potential participants for brain stimulation trials are rare, and the main reasons for exclusion are suitable motor impairments and stroke lesion characteristics. Exclusions specific to the stimulation intervention were few. African Americans had old strokes causing hemiparesis limiting their eligibility. Techniques to recruit minority men to stroke recovery studies require improvement. When recruiting for highly refined study populations, racial and ethnic differences in stroke characteristics and research participation are important.
Abstract 2500: Paroxysmal Atrial Fibrillation Detected By Prolonged Ambulatory Cardiac Monitoring In Patients With Cryptogenic Stroke: A Case-Control Study
Authors: Rabinstein Alejandro A , Fugate Jennifer , Mandrekar Jay , Burns Joseph , Seet Raymond C , Asirvatham Samuel , Friedman Paul A
Published: March 2022

Background:
Whether a significant proportion of cryptogenic stroke (CS) is caused by under-detected paroxysmal atrial fibrillation (PAF) is not known. Prolonged ambulatory cardiac monitoring may detect episodes of PAF in patients with stroke of unknown cause (cryptogenic stroke, CS). However, it is unclear whether PAF is more common in patients wtih CS compared with patients with stroke of known cause (SKC). We performed a case control study to compare the rates of detection of PAF in CS vs SKC using prolonged ambulatory cardiac rhythm monitoring.

Methods and Results:
We prospectively enrolled 132 patients within 3 months of a stroke (66 with CS and 66 with SKC) to undergo 3-week ambulatory cardiac rhythm monitoring using the CardioNet MCOT system. Stroke group was assigned by consensus between two vascular neurologists upon enrollment based on the Causative Classification of Stroke system. Primary endpoint was detection of PAF of any duration independently confirmed by two cardiologists blinded to the stroke group. The groups were well balanced except that patients with CS tended to be older and to have less hypertension and diabetes. Four patients (2 in each group) were excluded because of insufficient stroke evaluation or early discontinuation of monitoring. Episodes of PAF were detected in 16/64 (25%) patients with CS and 9/64 (14%) patients with SKC (p=0.12). Only 5 patients had episodes of PAF lasting > 30 seconds (3 with CS and 2 with SKC). Six of the 9 patients from the SKC group with PAF had small subcortical infarctions; the other 3 had cortical strokes ascribed to artery-to-artery embolism (2 with complex aortic plaques, 1 with severe vertebrobasilar stenosis). In patients under age 65, episodes of PAF were more common in the CS group (22% vs 3; p=0.07) while in patients age 65 or older the rates of detection were very similar (29% in CS vs 28% in SKC; p=0.9).

Conclusions:
Very short episodes of PAF are relatively common in patients with CS and with SKC, and their pathogenic significance is unclear. However, considering only patients under 65, a greater proportion of cryptogenic stroke patients had PAF, suggesting it might be pathogenic.
Abstract 2514: Role of NADPH oxidase 4 in Brain Endothelial Cells after Ischemic Stroke
Authors: Arimura Koichi , Ago Tetsuro , Kuroda Junya , Ishitsuka Koji , Nishimura Ataru , Sugimori HIroshi , Kamouchi Masahiro , Sasaki Tomio , Kitazono Takanari
Published: March 2022

NADPH oxidase (Nox) family proteins are membrane-bound enzymes, which are a major source of reactive oxygen species (ROS) and play various important roles in immune systems, arteriosclerosis, angiogenesis and aging. Nox4, a member of the Nox family, is abundantly expressed in the cardiovascular system. We have previously reported that it is a major ROS producing enzyme in endothelial cells; however, its roles in endothelial cells are not fully understood. In the present study, we investigated roles of Nox4 in acute brain ischemia using mice with endothelial cell-specific Nox4 overexpression (Tg-EC-Nox4) and cultured human brain microvascular endothelial cells (HBMEC). Nox4 was abundantly expressed in HBMEC and was significantly upregulated in response to hypoxia at O2 1% (2.0-fold increase, p < 0.001). In order to investigate the effects of upregulated Nox4 on endothelial functions during ischemia, we overexpressed Nox4 by adenovirus in HBMEC. Immunoblot analyses showed that phosphorylation of Akt at Ser-473 (47 %, p < 0.001) and endothelial nitric oxide synthase (eNOS) at Ser-1177 (43 %, p < 0.01) was significantly attenuated by Nox4. We next subjected Tg-EC-Nox4 to a permanent middle cerebral artery occlusion (MCAO) stroke model. Triphenyltetrazolium chloride (TTC) staining at 1 day after MCAO demonstrated that infarct volume was significantly greater in Tg-EC-Nox4 than wild-type mice (120 % vs wild-type, p < 0.05). Since it has been established that infarct volume is increased in eNOS-deficient mice, the enlargement of infarct volume in Tg-EC-Nox4 may be attributable in part to suppression of eNOS by Nox4. In conclusion, Nox4 may be an important regulator of endothelial functions. In ischemic stroke, Nox4 may increase infarct volume by suppressing eNOS activity.
Abstract 2554: Long-term Neuropsychological Outcomes after Childhood Arterial Ischemic Stroke (AIS)
Authors: Jack Jessica , Boada Richard , Goldenberg Neil A , Manco-Johnson Marilyn , Bernard Timothy J
Published: March 2022

Background:
Childhood AIS affects 2-6/100,000 children per year and is associated with significant morbidity and mortality. Although previous reports have demonstrated lower IQ’s in children following AIS as compared to healthy children, understanding of cognitive function more broadly in childhood AIS remains limited.

Methods:
In order to address this gap in knowledge, we collected data on demographics, stroke type, stroke size, stroke location, and long-term neuropsychological outcome, (defined as testing that occurred at least 10 months after stroke diagnosis). Patients were enrolled in an institution-based prospective cohort study of childhood AIS, comprising 63 children diagnosed with AIS from March 2006-August 2011. Neuropsychological assessment employed age-appropriate measures. In addition to IQ, other cognitive domains were tested, including academics, visual-motor skills, memory, and language. Single-tailed one-sample t-tests were performed to compare the childhood AIS group to the normative mean for neuropsychological exams. Furthermore, ANOVA analyses were used to compare neuropsychological outcome among subgroups of interest.

Results:
42 patients in our cohort had neuropsychological testing available at least 10 months after stroke diagnosis: 21 males and 21 females, with a mean age of 7 years at time of stroke (SD= +/-5.43). Mean neuropsychological testing was at 36 months after AIS (SD= +/- 30.72). Mean IQ for childhood AIS patients was 93.8 (SD= +/-17.75) and was significantly lower than the population mean (p < .05). Cognitive profile testing revealed significantly decreased functioning in the visual-motor (mean standard score = 84.1 [SD = +/-17.32], p <.001) and language domains (mean standard score = 82.9 [SD= +/-25.15], p = .002). By contrast, academic and memory profiles were not significantly reduced (standard score means of 95.1 and 97.0, respectively). In sensitivity analyses that excluded patients known to have pre-morbid (i.e., pre-AIS) neuropsychological abnormalities, visual-motor and language domains remained significantly reduced as compared to the population mean (p < 0.001, and p= 0.04, respectively). Stroke type, stroke size, stroke location and arteriopathy were not significant predictors of long-term neuropsychological outcome.

Conclusions:
Long-term neuropsychological outcome in this cohort confirms that childhood AIS patients have lower IQ’s than healthy children; in addition, results indicate that specific visual-motor and language skills are even more significantly affected. We recommend that children with AIS be comprehensively evaluated for the need for targeted interventions to improve visual-motor and language skills, and that the effectiveness of these interventions be evaluated in future studies.
Abstract 2561: Blood Pressure Variation Associated with Emergent Intubation and During Endovascular Treatment in Acute Stroke Patients
Authors: Devlin Thomas , Fesmire Francis , Smith Wade , Shapiro Jeffrey , Jones Justin , Baxter Blaise
Published: March 2022

Maintenance of airway stability is an essential part of critical care management of patients undergoing endovascular treatment for acute stroke. While some patients may undergo endovascular treatment utilizing conscious sedation alone, many patients require deeper sedation and emergent mechanical ventilation due to need to control patient movement, stabilize the airway, and facilitate patient comfort during prolonged procedures (average duration 1.9 hrs). Nine patients undergoing emergent intubation prior to endovascular treatment for acute stroke underwent observational study. Following completion of IRB-approved consent for study participation, patients received arterial line placement and vital signs were collected before, during, and after intubation and throughout endovascular treatment. Intubation was performed by experienced ED physicians using a variety of medications. An immediate and dramatic rise in mean arterial pressure (MAP) was associated with intubation (increased by 172% over baseline) followed by a decrease in the MAP (12% below baseline) in the ED prior to patient transfer to angiography. No consist trend was noted in PaCO2 levels drawn immediately after intubation but prior to initiation of mechanical ventilation. Average MAP in the angiogram suite during endovascular therapy was almost identical to pre-intubation baseline MAP (101% of baseline) despite utilization by interventionalists of a number of sedative medications. Transient decreases in the MAP to a nadir of 75 - 80 were seen during endovascular therapy in 3 patients; more significant drops did not occur. Mean duration of intubation, ICU stay, and total hospitalization was 3 days, 8 days, and 12 days respectively. In conclusion, real-world emergent intubation by ED physicians of acute stroke patients just prior to endovascular treatment is associated with significant fluctuations in MAP. Such fluctuations in either direction may further jeopardize tissue at risk. Recent reports from the national MERCI Registry Database indicate worse outcomes in intubated patients for unclear reasons; this could be due to fluctuations in MAP but might also be due to the effect of anesthesia itself. Assuming that these hemodynamic changes are causal in reducing clinical outcomes, ED intubation and angiographic sedation protocols should be designed to minimize fluctuations in MAP. Further investigations documenting improved MAP control utilizing standardized protocols are needed.
Abstract 2578: Methods of Recruitment into Familial Intracranial Aneurysm Study
Authors: Sauerbeck Laura , Moomaw Charles J , Hancher Jonathan , Hornung Richard , Brown Robert , Broderick Joseph P ,   The FIA Study Group
Published: March 2022

Background
Meeting Recruitment goals in a research study can be challenging. Recruitment for pedigree-based research, in which data and DNA are collected from genetically important family members, is especially difficult. The Familial Intracranial Aneurysm (FIA) study is a multicenter international study whose goal is to identify genetic and other risk factors for the formation and rupture of intracranial aneurysms (IAs). The chosen sites for the study are major referral centers for the diagnosis and treatment of IAs. In this analysis, we sought to determine what factors caused a recruited family to be incomplete, and what impact the methods used in identifying families had on the successful completion of family enrollment.

Methods
Three recruitment strategies were utilized to identify and enroll families: prospective monitoring of every new case of IA, subarachnoid hemorrhage, or intracranial hemorrhage; retrospective review of IA cases; and advertisement on the Internet, in scientific journals, and at professional meetings. An unexpected additional source of recruitment was exposure to the study through the news media. To help with public accessibility to the study, a web site and toll free number were established. Families were eligible for the study if they fit one of 4 patterns: [1] ≥2 living siblings affected with IA; [2] ≥2 affected siblings, 1 living and 1 genotype reconstructed from living spouse and children; [3] ≥3 affected members, 2 living and 1 reconstructed; [4] ≥ 3 affected members, 1 living, ≥1 reconstructed, and ≥1 living connecting relative. Exclusion criteria included fusiform-shaped IA; IA part of an AVM; family history of polycystic kidney disease; Ehlers-Danlos, Marfan, or moyamoya syndrome; fibromuscular dysplasia; or failure to obtain informed consent.

Results
Between 8/2002 and 10/2007, 3771 IA patients were screened for family history, and 681 potential families were identified, of which 441 successfully completed enrollment. There were 240 families which did not complete enrollment, due to refusal to participate (97), inability to locate needed relatives (87), exclusion criteria (50), no reason documented (5), and duplication (1 recruited at two sites). Completion of study enrollment was not significantly different by recruitment category (p=.17): 191 of 311 prospectively-recruited (61%), 66 of 89 retrospective (74%), 95 of 145 advertisement (66%), and 89 of 136 methods not documented (65%) families successfully completed enrollment.

Conclusion
In our study, the major reason for family exclusion was the inability to enroll needed family members, through refusal or failure to locate. All three methods used to identify potential families were successful in completing eligible families. The combination of recruitment strategies can be effectively implemented in future studies.
Abstract 2593: Pulse and Mean Arterial Pressure as Predictors of Stroke in the REGARDS Study
Authors: Halberg Daniel L , Sands Charlie , Le Anh , Howard Virginia J , Safford Monika , Glasser Stephen P , Muntner Paul , Howard George
Published: March 2022

Background:
The definition of hypertension (HTN) is based on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Recently, however, increased attention has been given to pulse pressure (PP) and mean arterial pressure (MAP) as potential risk factors of cardiovascular disease including stroke. We examined the relationship between 4 different blood pressure indices (SBP, DBP, PP, and MAP) and incident stroke.

Methods:
Data were derived from the REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study of 30,239 black and white participants aged ≥45, enrolled between 2003 and 2007 from the continental United States. A computer-assisted telephone interview obtained demographics, medical history, health behaviors and health status. At 3-4 weeks post interview, an in-home visit was conducted by a trained technician who collected blood pressure, biometrics, and blood and urine samples following standard protocols. SBP and DBP were defined as the average of two measurements obtained after a 5 minute seated rest. PP and MAP were calculated (PP=SBP-DBP and MAP=1/3SBP+2/3DBP). Follow-up by telephone occurred every six months for self or proxy-reported suspected stroke and events were confirmed using expert adjudication. Cox-proportional hazards models examined the association of incident stroke with the different BP measurements with multivariable adjustment for socio-demographic and clinical risk factors including hypertensive medication use.

Results:
This analysis included 27,680 men and women ages ≥ 45 (mean age=64.7±9.4 years, 40.4% black, 44.6% male) without prevalent stroke at baseline. A total of 609 strokes over 135,247 person-years of follow-up revealed graded associations between each blood pressure measure (SBP, DBP, PP and MAP) and incident stroke. The hazard ratio (HR) for stroke associated with one standard deviation higher SBP (16.5 mmHg) was 1.21 (95% CI 1.13 - 1.31), DBP (9.7 mmHg) was 1.16 (95% CI 1.07 - 1.24), PP (13.3 mmHg) was 1.15 (95% CI 1.07 - 1.24) and MAP (10.7 mmHg) was 1.21 (95% CI 1.12 - 1.31). Higher levels of SBP remained associated with an increased HR for stroke after additional adjustment for DBP (1.19, 95% CI: 1.09 - 1.30), PP (1.27, 95% CI: 1.11 - 1.46), and MAP (1.15, 95% CI: 0.99 - 1.30). After adjustment for SBP, the other BP indices were not associated with incident stroke.

Conclusions:
Although these data show that PP and MAP are positively associated with stroke, only SBP was independently associated with incident stroke after multivariable adjustment including other indices of blood pressure. PP, DBP, and MAP were not associated with incident stroke after adjustment for SBP.
Abstract 26: Role of Cytochrome c Oxidase Subunit 4- Isoform 2 in Neuronal Susceptibility to Lethal Ischemia/Reperfusion-Induced Injury
Authors: Sanderson Thomas H , Lee Icksoo , Kumar Rita , Przyklenk Karin , Grossman Lawrence I , Huttemann Maik
Published: March 2022

Brain ischemia-reperfusion injury (I/R) caused by stroke or cardiac arrest-resuscitation is associated with a high incidence of mortality and, in survivors, often results in profound neurological deficits. Specific regions of the brain (in particular, neurons in the CA1 hippocampus) are especially vulnerable to I/R injury, possibly due to exacerbated production of reactive oxygen species (ROS) and the resultant oxidative damage. However, the molecular mechanisms underlying excessive ROS generation in vulnerable neurons is unknown.

Hypothesis:
We propose that the

hyper-susceptibility of the CA1 hippocampus to I/R injury is due in part to the localized expression of mitochondrial cytochrome
c
oxidase subunit 4-isoform 2 (
COX4-2
)

- i.e., a specific hyperactive isoform of COX. COX is the rate-limiting enzyme of oxidative phosphorylation and its activity indirectly controls mitochondrial ROS production by regulating mitochondrial membrane potential. Therefore expression of a hyperactive COX isoform (COX4-2) would result in excessive ROS production and promote cell death.

Methods and Results:
We performed COX activity measurements of isolated COX complexes containing COX4-2 compared to COX without COX4-2 and found COX4-2 expression causes a two-fold increase in activity. Next, we generated COX4-2 knock-out mice to determine the role of COX4-2 in selective vulnerability of neurons. Wild-type mice (WT: with documented COX4-2 expression in the CA1) and COX4-2 knock-out mice (KO) underwent 12 min of global brain ischemia (bilateral carotid occlusion with hypotension) or no intervention (time-matched shams). At 3 days post-reperfusion, the number of viable neurons in the CA1 hippocampus was quantified by cresyl violet staining. As expected: (i) shams displayed 100% neuronal viability; while (ii), in wild-type mice, only 14±2.3% of neurons in the CA1 remained viable following I/R. In contrast, COX4-2 KO mice were characterized by a significant, ∼5-fold increase in the proportion of surviving neurons (68±1.1% viability; p<0.05
vs
WT I/R, n = 3).

Conclusion:
These data provide novel evidence that the absence of COX4-2 confers protection to the CA1 and suggest that expression of the hyperactive COX4-2 isoform in the CA1 hippocampus contributes to the vulnerability of these neurons to lethal I/R injury.
Abstract 2602: Changing Ethnic Disparity in Ischemic Stroke Mortality in US Children after the STOP Trial
Authors: Lehman Laura L , Fullerton Heather J
Published: March 2022

Objective:
A prior report showed higher stroke mortality in U.S. black children compared to white children (1979-1998), a disparity likely due in part to sickle cell disease. We hypothesized that this disparity has diminished since the publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP) trial in 1998 demonstrating the efficacy of chronic blood transfusions for primary stroke prevention. Because most childhood strokes in the setting of sickle cell disease are ischemic, we would expect a greater impact on ethnic disparities in ischemic than hemorrhagic stroke.

Methods:
We evaluated the demographics and secular trends in mortality from ischemic and hemorrhagic stroke in U.S. children <20 years of age, using death certificate data from the National Center of Health Statistics (NCHS) from 1988 to 2007.

Results:
A total of 1,555,045,537 person-years were included in the study. There were 4,425 deaths attributed to childhood stroke (as primary cause of death) within this cohort, yielding an average of 221 deaths per year. Ischemic strokes accounted for 20% of deaths; hemorrhagic strokes accounted for 67% (12% were unspecified). The relative risk of ischemic stroke mortality for black versus white children from 1988 to 1998 was 1.74 (95% CI 1.42-2.13, p<0.001) while the relative risk from 1999 to 2007 was 1.27 (95%CI 0.99-1.64, p= 0.063). While ischemic stroke mortality rates in black versus white children appear to be converging, the ethnic disparity in hemorrhagic stroke mortality has remained relatively stable (
Figure 1
).

Conclusion:
The excess risk of death from ischemic, but not hemorrhagic, stroke in U.S. black children has decreased over the past decade. This may be related to the implementation of an effective primary stroke prevention strategy for children with sickle cell disease.
Abstract 2604: Will “Real Time” Access to Electronic Medical Records Improve Telemedicine Stroke Consults?
Authors: Adams Robert J , Debenham Ellen , Chalela Julio , Chimowitz Marc , Hays Angela , Holmstedt Christine , Jauch Edward , Lazaridis Christos , Peterson Jessica , Turan Tanya N , Lackland Daniel T , Patterson David , Sanderson Iain
Published: March 2022

Objectives:
The Neuroscience stroke telemedicine program of the Medical University of South Carolina (REACH MUSC) is a robust network of 15 sites served by an academic hub in Charleston. South Carolina’s Health Information Exchange (SCHIEx) collects and displays data from all hospital discharges and emergency room visits. At present, our REACH MUSC stroke consults, like most, are not connected to a central electronic medical record or Health Information Exchange (HIE) like SCHIEx. We used our first 250 REACH MUSC consults to estimate the value to a stroke telemedicine consult of a hypothetical “real time” connection to an HIE.

Methods:
After IRB approval, names and identifying information of the first 250 consecutive REACH MUSC stroke consults were provided to the SC Office of Research and Statistics for analysis, along with 10 prespecified questions of interest based on their presumed value in the stroke setting (e.g. “can a history of atrial fibrillation be found?”). A retrospective search of 10 years from the date of the consult was performed using data available also available via SCHIEx. The REACH MUSC consult itself was examined using the same template and the two compared to see if relevant information would have been found in SCHIEx that was not obtained during the actual REACH MUSC consult.

Results:
249 unique patients were represented in the 250 REACH MUSC consults and, of these, 234 could be located in SCHIEx (others were probably tourists). Much information found on the 234 in SCHIEx was in the form of comorbidities and would not have been of crucial value to the REACH MUSC stroke consult. However, 4 patients in SCHIEx had a history of intra-cerebral hemorrhage and only one of these was noted in the REACH MUSC consult. 24 patients in SCHIEx had a history of “atrial fibrillation” but this history was recorded in only half of the REACH MUSC consults. SCHIEx does not yet have medication data so information on warfarin use was not available.

Conclusion:
This study suggests that real time linkage to an HIE or other sources of historical medical data might indeed improve the quality of stroke telemedicine consultations, at least from a safety perspective.