bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3464: Incidence of Cerebral Ischemia After Discontinuation Of Clopidogrel (Plavix) In Patients With Cerebral Aneurysms Treated Using Stent-Assisted Technique
Authors: Rossen James D , Thomas Jacob , Kung David K , Smietana Janel , Hasan David M
Published: March 2022

Background:
The optimal antiplatelet medication protocol for prevention of thrombotic complications after stent-assisted coil embolization of cerebral aneurysms is unknown. Premature cessation of antiplatelet medication has been associated with increased risk of thrombosis. The current analysis is undertaken to assess the incidence of stroke or transient ischemic attack after discontinuation of 6 weeks of prescribed clopidogrel (Plavix) in patients with cerebral aneurysms treated by stent-assisted technique.

Method:
275 patients with cerebral aneurysms treated at the University of Iowa Hospitals and Clinics by a single surgeon (DH) during a period of 24 months were retrospectively analyzed for aneurysms treated by stent-assisted coiling or stent-in-stent flow diversion and who also received follow-up at our center. Our antiplatelet protocol was aspirin 81 mg PO and plavix 75 mg PO daily for 6 weeks, followed by aspirin 325 mg PO daily indefinitely. Patients were assessed for incidence of stroke or transient ischemic attack as diagnosed by a neurologist or neurosurgeon by reviewing their medical record during the period of three months following discontinuation of plavix.

Results:
154/275 (56%) patients underwent stent-assisted coil embolization during this interval. Documentation of neurologic follow-up after discontinuation of six-weeks of palvix treatment was available in 121/154 (78.6%) patients. Seven patients suffered an ischemic event after cessation of plavix (5.7%) with stroke in 6 patients (5.0%) and transient ischemic attack in 1 patient (0.8%). These events developed over a wide range of intervals from time of plavix discontinuation (1-12 weeks), with only one event within 2 weeks.

Conclusion:
The three-month incidence of cerebral ischemic events in patients treated with stent-assisted technique is low following cessation of six-week treatment of plavix. Events within two weeks of discontinuation were rare, suggesting etiologies other than stent thrombosis may have been operative in our patients.
Abstract 3475: A Plasminogen Activator Inhibitor-based Therapy of Infection-Sensitized Hypoxia-Ischemia Injury in Newborn Rodent Brains
Authors: Yang Dianer , Sun Yu-Yo , Lawrence Daniel , Lindquist Diana M , Kuan Chia-Yi
Published: March 2022

Introduction:
The combination of intrauterine infection and hypoxia-ischemia (HI) is a severe threat to immature brains. Further, infection may alter the response to HI in immature brains, but key steps of the switch are unclear. Better understanding these differential responses may suggest new therapeutic targets in neonatal care. This is particular urgent for premature infants who have a high incidence of chorioamnionitis and HI insults, but are unfit for hypothermia therapy.

Hypothesis:
(1) Infection pre-exposure significantly amplifies the nuclear factor-kappa B (NF-κB) signaling activity following HI in a tissue-plasminogen activator (tPA)-dependant manner. (2) CPAI, a stable-mutant form of plasminogen activator inhibitor-1 (PAI-1) that resists pure HI, also confers significant protection against infection-sensitized HI brain injury in newborns.

Methods:
Seven-day-old Wistar rat pups were injected with a low-dose lipopolysaccharide (LPS, 0.3 mg/kg, IP) 4 h before imposing cerebral HI using the Rice-Vannucci model, followed by post-hypoxia injection of CPAI or saline into cerebral ventricles. The brains were collected between 4-24 h recovery for biochemical and histological analyses, at 7 d to measure damage, or at 2 months of age for behavioral testing and diffusion tensor imaging of the white-matter (WM).

Results:
LPS mitigated HI-induced parenchymal tPA activity, but intensified NF-kB signaling, microglia activation, synthesis of chemoattractive cytokines, damage to blood-brain-barrier, and brain tissue loss, which were all significantly ameliorated by the CPAI treatment. The therapeutic window of CPAI was at least 4 h after the LPS/HI insult. CPAI-treated pups also developed near-normal motor and WM functions at 2 months of age.

Conclusions:
Infection alters the immature brain response to HI by activating tPA-dependent NF-_B signaling but diminishing the tPA proteolytic activity. Because CPAI effectively inhibits both proteolytic and pro-inflammatory functions of tPA, it may be a promising therapeutic of infection-sensitized neonatal HI brain injury.
Abstract 3506: Acupuncture in Managing of Spasticity of Post Stroke Survivor: A Systematic Review
Authors: Lee Sui Hei , Wong Yeuk Oi , CHU Ming Kei , CHE Chun Tao
Published: March 2022

Background
Stroke is the second leading cause of death in the world. Spasticity is one of the most commonly found sequelae of stroke. No systematic review of trials of acupuncture mainly focusing on spasticity management in post stroke patient have been searched.

Objective
The objective of this review was to evaluate the efficacy of acupuncture in managing of spasticity for patients with acute, subacute and chronic stroke.

Search strategy
We searched the MEDLINE (Ovid), EMBASE, AMED, CINAHL Plus, Cochrane Controlled Trials Register (CCTR), CBM and CMCC, from inception to March 2010. Reference lists of retrieved articles were also searched.

Selection criteria
Randomized controlled clinical trials and crossover studies in stroke patients with spasticity syndrome in any phase were included in this review.

Data collection and analysis
Two review authors independently extracted data and assessed the quality of the papers. The Cochrane Review Manager software RevMan 4.2 was used for meta-analyses. For dichotomous outcomes, the results were expressed as odds ratio (OR) with 95% confidence intervals (CI), for continuous data, the weighted mean difference (WMD) was used.

Main results
There were 4 relevant trials in the review including one trial with adequate quality and three trials with low quality, involving 176 participants. Conflicting results were found among the trials for the change of the spasticity level of the affected extremities and the change of the activities of daily life. Only one trial reported the change of upper extremity motor function, grip strength of affected upper extremity, range of motion of affected upper and/or lower extremity and health-related quality of life. No statistically significant differences in all mentioned outcomes between active and sham acupuncture groups were found by Intention to treat analysis. No data was available to analyze ambulation function. There was insufficient available data to be pooled in meta-analysis. Limited safety information was reported.

Reviewers’ conclusion
This review does not provide evidence to support the routine use of acupuncture in management of spasticity for patients with acute, subacute and chronic stroke. Large, methodologically sound randomized controlled trials are needed.
Abstract 3517: Rate of Post-procedural Stroke and Death in SAMMPRIS Trial Eligible Patients Treated with Intracranial Angioplasty and/or Stent Placement in Practice
Authors: Siddiq Farhan , Chaudhry Saqib A , Khatri Rakesh , Rodriguez Gustavo J , Tummala Ramachandra , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Object:
To study the 30 day stroke and death rate in intracranial angioplasty and stent treated patients meeting Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial eligibility criteria.

Background:
SAMMPRIS trial, comparing aggressive medical versus stent treatment in patients with symptomatic intracranial stenosis, was halted after a 14% stroke and death rate observed in the stent treated group. Material and

Methods:
A retrospective analysis of 96 patients treated with intracranial angioplasty and stent placement at two University affiliated institutions was performed. Patients were divided into SAMMPRIS eligible and ineligible groups based on inclusion and exclusion criteria for SAMMPRIS trial.

Results:
Sixty-nine patients were determined to be SAMMPRIS eligible and 27 patients were ineligible. SAMMPRIS eligible group was divided into angioplasty and stent treated subgroups (30 and 39 patients, respectively). The overall 1 month post-procedure stroke and death rate was 7.2% (95%CI 2.3%-15.4%) in SAMMPRIS eligible group and 7.4% in SAMMPRIS ineligible group (p=0.97). The 1 month post-procedure stroke and death rate was 3.3% in the SAMMPRIS eligible angioplasty treated subgroup and 10.2% in the SAMMPRIS eligible stent treated subgroup (p=0.27). The SAMMPRIS eligible stent treated subgroup comprised of relatively younger patients compared to angioplasty treated subgroup (mean age of 58 versus 63 years, p=0.041). Lesion length was 6.4 ± 2.5 mm in SAMMPRIS eligible angioplasty and stent treated subgroups and 8.2 ± 3.7 in SAMMPRIS ineligible group (p=0.041).

Conclusion:
The overall 30 day post-procedure stroke and death rate in our study was lower in both SAMMPRIS eligible and ineligible than the reported 14% stroke and death in SAMMPRIS trial. We hypothesize that a more judicious use of primary angioplasty may be responsible for better post-procedural outcomes and should be considered as an acceptable treatment in future trials.
Abstract 3539: Can Stop Trial Velocity Criteria Be Applied To Iranian Children With Sickle Cell Disease?
Authors: Shahripour Reza B , Keikhaei Bijan , Azarpakhooh Mahmoodreza , Sajedi Seyed A , Oghbaee Moteza , Chaudhary Asad A , Kolieskova Stanislava , Kepplinger Jessica , Barlinn Kristian , Albright Karen C , Alexandrov Andrei V
Published: March 2022

Background&Purpose:
Although sickle cell disease (SCD) is strongly linked to stroke across all haplotypes in the pediatric population, Iranian children with Saudi-Asian haplotype are less affected by this complication. TCD is known to identify the highest risk group in African-Americans who need to receive and stay on blood transfusions, but it is unclear if the same flow velocity cut-offs can be applied to the Iranian population. We therefore aimed first to evaluate baseline TCD findings in Iranian children with SCD and no prior strokes.

Subjects&Methods:
Children with genetically confirmed SCD (Arabian haplotype, homozygote) and without SCD (controls) aged 3 to 16 years were prospectively recruited from pediatric outpatient clinic over a period of 9 months. All children had no previous stroke or any neurologic deficit. No transfusion was given within one month prior to TCD examination and patients were not on any medication that may affect cerebral hemodynamics. We performed TCD examinations in both groups to determine flow velocities in the middle cerebral (MCA) and terminal internal carotid arteries (TICA). Mann-Whitney U test was used to compare TCD variables between the two groups.

Results:
Of 74 screened children, 60 met the inclusion/exclusion criteria (62% female; mean age 10±4 years). Baseline characteristics did not differ between the cases and controls, except hemoglobin (Hb) which was significantly lower in the SCD group (mean 8.83±1.43 g/dL vs. 10.3±1.03 g/dL, p<0.001). In children with SCD, the highest MCA MFV (92 cm/s vs. 67 cm/s, p<0.001) and the highest TICA MFV (62 cm/s vs. 45 cm/s, p<0.001) were significantly higher than in controls. Among asymptomatic Iranian children with SCD only 1/30 (3%) had conditional >170 cm/s MFV.

Conclusions:
Among Iranian children with asymptomatic SCD and without receiving recent transfusion TCD velocities could be much lower than those observed in STOP studies, and some of the high risk group may be identified with velocities lower than 170 cm/s. A prospective validation of ethnicity-specific diagnostic criteria is warranted.
Abstract 3561: Associations of Carotid Plaque Composition with Prior Coronary and Peripheral Artery Events
Authors: Sun Jie , Hippe Daniel , Yamada Kiyofumi , Yuan Chun , Hatsukami Thomas
Published: March 2022

Background:
Patients with prior coronary (CAD) or peripheral artery (PAD) events have increased plaque burden in the carotid artery, which is subsequently found to indicate future risks in prospective studies. Carotid MRI is capable of measuring both plaque burden and components (calcification [CA], lipid rich necrotic core [LRNC], intraplaque hemorrhage [IPH]). We sought to determine if certain plaque components detected by MRI are associated with prior CAD and PAD events independently of traditional risk factors and plaque burden.

Methods:
Subjects with asymptomatic carotid stenosis by ultrasound were referred for a standardized multi-contrast carotid MRI. Plaque area and areas of CA, LRNC and IPH were traced on each cross-sectional slice, which were aggregated to determine plaque volume, presence and percent volumes of components for each subject. Prior CAD events were defined as prior acute coronary syndrome and/or coronary revascularization. Prior PAD events were defined as ABI<0.90 and/or prior peripheral artery revascularization. Logistic regression analysis was used to evaluate the independent associations between plaque compositional variables and prior CAD or PAD events after adjustment for clinical variables and plaque volume.

Results:
A total of 159 subjects were scanned, of which 36 (22.6%) had prior CAD events, 34 (21.4%) had prior PAD events and 30 (18.9%) had both. The rest 59 (37.1%) subjects, free of both CAD and PAD events, were used as a reference group. All compositional variables were significantly associated with plaque volume. Subjects with prior CAD events (n=66) demonstrated a higher prevalence of IPH (31.8% vs. 13.6%, adjusted OR: 5.16, p=0.006) and larger percent volume of IPH (3.5% vs. 0.8%, adjusted OR: 1.21 per 1% change, p=0.017) compared to the reference group after adjustment for clinical variables and plaque volume. No independent associations were found between prior PAD events and carotid plaque components compared to the reference group.

Conclusions:
Subjects with prior CAD events appeared to have a higher prevalence of IPH and larger percent volume of IPH given a comparable plaque burden with those without prior events. Prospective studies are needed to evaluate if the composition of asymptomatic carotid plaques provides additional information for CAD risk stratification.
Abstract 3569: The Effect of Minocycline on the HARM MRI Marker of Blood-CSF Barrier Opening After Transient MCAO in SHR Rats
Authors: Warach Steven , Henning Erica C , Leoni Renata F , Arai Allison L , Latour Lawrence L , Silva Afonso C
Published: March 2022

Introduction.
Early blood-CSF barrier opening imaged as gadolinium enhancement of CSF on FLAIR MRI, the Hyperintense Acute Reperfusion Marker (HARM), has been associated with increased plasma MMP-9 in both clinical and experimental stroke [
1
-
2
]. In patients, both elevated MMP-9 and HARM have been associated with tPA treatment and hemorrhagic transformation [
3
-
4
]. Minocycline is an MMP-9 inhibitor under investigation as an acute stroke therapy [
5
]. We hypothesized that minocycline would reduce the early HARM signal in SHR rats undergoing 45 minutes of transient right middle cerebral artery occlusion (MCAO) via the intraluminal suture model.

Methods.
Twenty-two consecutive male SHR rats with confirmed non-hemorrhagic stroke on 7T/30cm MRI were randomly assigned to receive minocycline (3mg/kg @ 1mg/mL) or saline control intravenously, injected at the time of reperfusion. Gadolinium was injected at 60 minutes post-reperfusion. Outcome FLAIR images were acquired pre-contrast and at 10 minutes post-contrast. Image analysis, performed blinded to treatment assignment, assessed pre-post FLAIR changes for (1) signal intensity of gadolinium enhancement in the ventricles (2) appearance of HARM in the ipsilateral ventricle (3) appearance of parenchymal enhancement within the infarct.

Results.
Ipsilateral ventricular HARM was visible in 9 of 11 animals in each group. Parenchymal enhancement was seen in 6 of 11 in each group. Increase in gadolinium enhancement in the ventricle (either total or ipsilateral only) did not significantly differ between the two groups.

Conclusions.
We found no evidence that minocycline reduced blood-CSF or blood-brain barrier opening in this model of 45 minutes transient MCAO in SHR rats. Potential effects of minocycline on blood-CSF or blood-brain barrier at later times after minocycline, on MMP-9 levels or in the presence of tPA in this model requires further study.
Abstract 3593: Challenges to Recruiting Stroke Patients Into Cell Therapy Clinical Trials
Authors: sahota Preeti , Vahidy Farhaan , Hovis James P , Hicks William J , Wu Tzu-Ching , Lal Aditya P , Chen Zhongxue , Hossein Rahbar M , Grotta James C , Savitz Sean I
Published: March 2022

Objective:
Stringent selection criteria pose challenges to recruiting patients into clinical trials testing potential novel therapies for stroke. We conducted a pilot study, Safety of Intravenous Mononuclear Cells for Acute Stroke (SIMVAS) trial involving autologous bone marrow cell administration in patients with middle cerebral artery (MCA) territory stroke within 72 hours of symptom onset. Given the stringent selection criteria for initial cell therapy clinical trials in stroke, we analyzed reasons for patient ineligibility into the SIVMAS trial to assess feasibility of recruitment.

Methods:
We retrospectively collected ischemic stroke patients from our stroke registry admitted from March 2009 to June 2010, the recruitment period of SIVMAS, and identified which of the selection criteria the patients did not meet.

Results:
Of a total of 534 MCA territory stroke patients, 25 met all the selection criteria. Ten patients were enrolled as planned over the 15 month period, 3 declined enrollment, 2 were excluded due to pending DSMB review on previously enrolled patients, and the rest did not have an adequate time window between bone marrow aspiration and dosing. A total of 1,943 exclusions were recorded; major reasons were NIHSS (15.3%) and infarct sizes above or below the selection criteria (12.4%). The
table
summarizes the patient exclusion frequency based on selection criteria. Among ineligible patients (n=509), 47 (9.2%) had a single exclusion, 81 (15.9%) had two exclusions and 108 (21.2%) had three exclusions. The
figure
presents a CONSORT flow diagram of the entire recruitment.

Conclusion:
This is the first study to assess recruitment of patients with acute ischemic stroke into a pilot cell therapy clinical trial. Among eligible patients, there was a low refusal rate. Among excluded patients, stroke severity and infarct size were major reasons for exclusion from SIVMAS. It is hoped that the data from this study may help facilitate the design of future clinical trials testing new cell-based therapies for ischemic stroke. We encourage investigators to choose selection criteria that will provide scientifically meaningful data but are not overly rigid in selecting potential research candidates.
Abstract 3599: Cyclosporine A Treatment Abrogates Ischemia-Induced Neuronal Cell Death By Preserving Mitochondrial Function By Upregulating The Parkinson's Disease Protein DJ-1
Authors: Tajiri Naoki , Kaneko Yuji , Borlongan Cesar V
Published: March 2022

Background:
Stroke is characterized by neural tissue death after deprivation of oxygen, glucose, and other nutrients due to a reduction in blood flow to the brain. Disease manifestations of stroke involve primarily an infarcted core, and subsequently the formation of an ischemic penumbra which over a sub-acute period remains as salvageable neural tissue, thereby amenable to therapeutic intervention. Secondary cell death processes, including oxidative stress-induced mitochondrial dysfunction, can endanger the penumbra thereby limiting neuroprotection. Exploring the direct effects of drugs, such as Cyclosporine A (CsA), acting on neuronal mitochondria may reveal novel mitochondria-based cell death signaling therapeutic targets for stroke.

Objective:
Under hypoxic ischemia condition, the mitochondrial membrane potential (Δψ
m
), respiratory-related enzymes, and mitochondrial DNA deteriorate resulting in the aberrant accumulation of free radicals and reactive oxygen species. CsA, traditionally considered a robust immunosuppressant drug, has been shown as a potent neuroprotectant against neuronal cell death. However, the molecular mechanism by which CsA interacts with mitochondrial membrane-associated proteins remains not fully understood. Using the
in vitro
stroke model of oxygen glucose deprivation (OGD), we examined here this interaction between CsA and the Parkinson’s disease protein DJ-1, which has been recently implicated in the regulation of mitochondrial function.

Methods:
Primary rat astrocytes/neurons (6/4) were exposed to the OGD and processed for immunocytochemistry and ELISA to reveal the role of DJ-1 in CsA modulation of mitochondrial function. In addition, ATP content, hexokinase activity (accumulation of intracellular glucose 6-phosphate), and mitochondrial DNA (mtDNA) stability were measured by a bioluminescence assay kit.

Results:
Administration of CsA before stroke onset (24 hrs pre-OGD), but not after stroke (2 hrs post-OGD), afforded significant neuroprotective effects compared to OGD-treated cells without CsA, characterized by the following cellular and molecular events: (1) CsA prevented the mitochondria-dependent cell death signaling pathway involved in cytochrome c induced apoptosis; (2) CsA protected cellular ATP decline (two-fold higher) without altering the hexokinase activity and the Δψ
m
; (3) blocked mtDNA degradation, and, interestingly; (4) enhanced secretion of DJ-1into neighboring cells. This neuroprotection was achieved with the effective dose range of 500 nM - 10 μ M of CsA.

Conclusion:
These novel observations indicate that CsA- and DJ-1-neuroprotection amplify the maintenance of mitochondrial function, and that mitochondria-based treatments targeting the early phase of disease progression may prove beneficial in stroke.
Abstract 3635: Mentoring a Stroke Program Coordinator: A Planned, Staged Approach
Authors: Nolten Donna , Clarkson Katherine
Published: March 2022

Background and Issues:
Transitions between stroke coordinators can have a deleterious effect upon stroke program development and operations. Typically, a one-month notice of resignation is given. This allows insufficient time to advertise, interview, hire and train or orient new staff. Complicating the issue, the number of experienced stroke coordinators has not kept pace with demand. Hence, extensive training may be required for the replacement if one with experience is not available.

Purpose:
The purpose of our project was to prepare for a seamless transition between a retiring stroke coordinator and her replacement while maintaining quality and adding neurovascular intervention to the program.

Methods:
Our facility provides a phased-retirement program that allows gradual transition between full time employment and retirement. In July 2009, a eighty percent stroke coordinator position was split between a coordinator mentee and the experienced coordinator mentor. Over an eighteen-month period, responsibilities were gradually shifted to the replacement with ongoing education, guidance and support from the previous coordinator. For the first six months, orientation and coaching took place on an almost daily basis. Over the following year, progressive periods were planned for independent program management with available backup and support

Results:
A cerebrovascular intervention program was successfully implemented during the period. Primary Stroke Center Certification was maintained. Compliance with stroke performance measures did not decrease. The Get with the Guidelines Gold Plus Award was received for 2009, 2010 and 2011. Acute stroke treatment rates increased due to program enhancements and improvements during the period.

Conclusions:
This planned, progressive approach to program leadership transition allowed sufficient training for the replacement coordinator. At the conclusion of the process, the mentee stepped into the full-time position. This seamless transition provided for successful program operations and development.
Abstract 3647: Institution of a Telemedicine for Acute Stroke Protocol in a Major Metropolitan Setting to Decrease iv-tPA Administration Times
Authors: Fanale Chris , Ruiz Lisa , McDonald Megan , Whaley Michelle , Salottolo Kristin
Published: March 2022

Introduction:
Telemedicine for Acute Stroke Evaluation and Treatment has been widely used for providing expert stroke neurology advice for patients presenting to rural hospitals. Iv-TPA administration rates in these experiences are high (20-25%). However, national iv-tPA administration rates still are below this level. In addition, less than 30% of patients are receiving iv-tPA in less than 60 minutes. We describe a novel telemedicine network that augments existing on-call neurological support to decrease door to needle times for iv-tPA administration.

Methods:
Data from 6 metropolitan hospitals in the Denver area were collected to assess rapidity of iv-tPA administration for Acute Ischemic Stroke. All hospitals had existing acute stroke protocols, on-call board certified neurologists, board certified Emergency Room Physicians (EDP) available on a 24/7 basis. Stroke Program leaders including Emergency Room Physicians, Neurologists, and administrators from these hospitals were invited to participate in an initiative to decrease door to needle times. Through this committee, consensus was reached that the arrival of a neurologist be less than 15 minutes from arrival of the patient to the Emergency Room. At times and places where this could not be achieved by physical presence, telemedicine technology was employed. This Telemedicine Intiative (TI) was instituted on May 1st, 2011. Time data regarding patient arrival, time to CT scan, time in CT scan, arrival of neurologist, first Emergency Room physician evaluation, tPA administration will be tracked.

Results:
Prior to institution of the Telemedicine Initiative, average door to needle times for the six hospital network was 86 minutes. In the first month of institution of TI, average door to needle times decreased to 67 minutes across the network. 102 telemedicine consultations have been performed to date. All telemedicine consultations were instituted within 10 minutes of arrival of the patients to the emergency room.

Conclusions:
Employing Telemedicine in a metropolitan hospital setting with exisiting neurological coverage, acute stroke protocols and board certified ED Physicians may decrease the time needed to administer iv-TPA in acute ischemic stroke patients.
Abstract 3650: Community Poverty and Pre-Hospital Delay in Acute Ischemic Stroke
Authors: Farrell Danny , Sucharew Heidi , Moomaw Charles , Alwell Kathleen , Khatri Pooja , Adeoye Opeolu , Flaherty Matthew , Woo Daniel , Kissela Brett , Kleindorfer Dawn
Published: March 2022

Introduction
Many factors contribute to pre-hospital delays for ischemic stroke patients, including knowledge of stroke warning signs and risk factors. However, the direct association of community poverty with pre-hospital delay is unknown. We present data regarding the association of community socioeconomic status (C-SES) with pre-hospital delay after acute ischemic stroke in 2005 within a large, biracial, economically diverse population.

Methods
Hospitalized cases of AIS were ascertained as part of the Greater Cincinnati / Northern Kentucky Stroke Study; cases were only included if they lived at home, had their stroke at home, and presented to an ED. C-SES was defined as the proportion of residents within the patients' census tract of residence who fell below the federal poverty line (2000 US Census). Pre-hospital delay time (DT) was calculated using ED arrival time and time of symptom onset, categorized into <3hrs, 3-12 hrs, 12-24 hrs, and >24 hrs. Patients were grouped into quartiles according to their C-SES (less than 5%, 5% to 10%, 10 to 25%, and greater than 25%). Estimated travel time was calculated using Arcview software.

Results
There were 2196 hospitalized cases of acute ischemic stroke recorded in 2005, 1453 of which occurred at home, 1377 of which reported to local ED's. Of these, 434 reported an exact time of symptom onset, but an estimated time of onset was available for 915 cases. C-SES was not significantly associated with DT. The proportion arriving in less than three hours, which was >25% poverty: 17%, 10%-25% poverty: 22%, 5%-10% poverty: 22%, <5% poverty 21%, was also not associated with C-SES. See
table
for odds ratios for earlier arrival to the ED. EMS use was strongly associated with earlier arrival time (p < .01).

Discussion
Greater community poverty was not associated with the percentage of patients arriving within the rt-PA eligibility window. EMS was strongly associated with shorter delay times. Further study is needed to inform educational efforts toward improving pre-hospital delays.
Abstract 3680: Hemostatic Genes Variant Predictivity Of Intracerebral Hematoma Growth
Authors: Appelboom Geoffrey , Piazza Matthew , Han James , Bruce Samuel S , Hwang Richard Y , Monahan Aimee , Badjatia Neeraj , Mayer Stephan , Connolly E.Sander
Published: March 2022

BACKGROUND AND PURPOSE:
Hematoma expansion (HE), the leading cause of neurological deterioration after intracerebral hemorrhage (ICH). In the present study, we explored whether common genetic variants in within the hemostasis pathway were related to hematoma expansion during the acute period after ICH.

METHODS:
Patients with spontaneous ICH admitted to the instutional Neuro-ICU from 2009 to 2011 were enrolled in the study (Table 1) and clinical data were collected prospectively. Hematoma size was measured volumetrically for CT scans obtained on or before post-bleed day 2. Baseline models for hematoma growth were construted using backwards-stepwise logistic regression. Genotyping of single nucleotide polymorphisms for 15 genes (Table2) involved in hemostasis was performed and the results were individually included in the above baseline models to test for independent association with hematoma expansion.

RESULTS:
During the study period, eighty-two patients were enrolled in the study and had complete data. Mean age was 65.9±14.9 and 38% were female. Only von willebrand factor (vWF) was associated with absolute and relative hematoma growth in univariate analysis (p<0.001 and p=0.007, respectively); vWF genotype was independently predictive of relative hematoma growth but only approached significance for absolute hematoma growth (p=0.006 and p=0.097, respectively).

CONCLUSIONS:
Our genomic analysis of various hemostatic factors identified vWF as a potential predictor of HE in patients with ICH. The identification of vWF SNPs may allow us to better identify patients who are at risk for hematoma enlargement and will benefit the most from treatment. The relationship of vWF with regards to hematoma enlargement in a larger population warrants further study.
Abstract 3684: Post-Stroke Fatigue: A Systematic Evidence-Based Critique
Authors: Lee Vincent , Balucani Clotilde , DeLuca John , Lederman Yitzchok S , Arnedo Vanessa , Lushbough Catherine A , Levine Steven R
Published: March 2022

Background:
Post-stroke fatigue (PSF) is common and manifests as both a physical and mental lack of energy not ameliorated by rest. Studies suggest fatigue has a significant impact on patients’ functioning and dependency, interfering with rehabilitation.

Objectives:
to identify (a) gaps in PSF understanding and (b) areas of consensus and recommendations.

Methods:
A repetitive search study in PubMed and EMBASE using pre-specified medical subjects heading (MeSH) terms, Boolean logic, and Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. All identified publications were screened for inclusion using the following criteria: 1) all relevant randomized controlled trials (RCTs), prospective, retrospective, cross-sectional, cohort and case-control studies; 2) studies providing a pre-specified definition of PSF; and 3) a sample size of at least 10 patients. Additional references were identified from bibliographies of pertinent articles. All languages were included. Uncontrolled case-series were excluded.

Results:
414 publications were retrieved, 221 were duplicates, and 14 related references through bibliographies. A total of 207 abstracts were reviewed by at least 2 independent reviewers for relevance; 63 publications met inclusion criteria and were included. Twenty-four different fatigue scales were used to measure PSF. Only 13 (21%) studies used validated scales and 16 (25%) studies used the non-validated Fatigue Severity Scale (FSS). The prevalence of PSF ranged from 10% to 74%, depending on the fatigue scale used and study population. Independent predictors of PSF included: acute striatal infarct (n=1 study), motor control (n=1), falls efficacy (n=1), peak oxygen uptake (n=1), higher geriatric depression scale score (n=1), depression (n=2), younger age (n=1), infratentorial stroke (n=1), female sex (n=1), and declined mobility (n=1). PSF was an independent predictor of mortality (n=2), long-term morbidity (n=1), reduced health-related quality of life (n=1), institutional placement (n=1), dependency on activities of daily living (n=1), and post-stroke depression (n=1). PSF was associated with the biomarkers C-reactive protein (n=1), and IL-1β, IL1-ra, and IL-9 (n=1). Suggested PSF therapeutic strategies included exercising, assistive technologies, and cognitive behavioral therapy. A RCT found a small benefit from modanifil treatment.

Conclusion:
Current research on the predictors of PSF is difficult to interpret because relatively few studies used validated scales combined with a large heterogeneity of PSF definitions. Treating PSF remains a clinical challenge without valid evidence from RCTs. The interplay between PSF and other associated factors as well as specific treatment approaches require further study.
Abstract 3691: High Resolution Imaging of Brain Vessels at 7 Tesla
Authors: sein julien , Chaudry Saqib , Tariq Nauman , Majidi Sharham , Adriany Gregor , Auerbach Eddie , Suri Muhammad F , Urgubil Kamil , Van de Moortele Pierre-Francois
Published: March 2022

Introduction:
Brain vessel wall MRI has the potentiality to visualize abnormal thickness and/or structure in intracranial vessel wall and could provide critical biomarkers to diagnose atherosclerosis.This, however, is a challenging task with MR images, given the small size of the vessels, variability in directions and their localization deep in the brain. A human 7T system was chosen to benefit from expected gains in Signal to Noise Ratio (SNR) and tissue contrast. Brain vessel wall MRI at 7T has been demonstrated, but the spatial resolution utilized so far (0.8mm isotropic) makes it difficult to assess the size of the brain vessel walls.

Methods:
We describe the preliminary results of a multi modality approach that investigates both ex-vivo and in-vivo achievable cerebral vessel MR limits at 7 Tesla. Samples are imaged with the same sequence and on the same system used for in-vivo studies, facilitating sequence and parameter transfer. Both ex vivo and in vivo studies are conducted on a human 7T MR scanner, facilitating sequences and parameters transfer. Samples of circle of Willis (CW), excised from human cadaver brains were immersed in a perfluoropolyether fluid (no signal in proton MRI) and imaged with a 3D turbo spin echo sequence with TR/TE= 1500/13 ms, an acquisition time of 1h 30 min and 0.16 mm isotropic resolution. In vivo, healthy subjects were scanned with TR/TE/TI= 3000/22/1100 ms, acquisition time of 13min and a 0.64 mm isotropic resolution.

Results:
Ex-vivo MR images of CW at high-resolution allow for clear distinction of vessel boundaries. The same sequence was used to acquire in vivo images at high resolution, imaging the brain vessel walls with the additional difficulty to suppress the CSF signal surrounding the brain vessels.

Conclusion:
Preliminary results show the potentiality of this multi modality study to image brain vessel walls at 7T. Our goal is to ultimately provide rationales to optimize contrast and spatial resolution tradeoff in clinical protocols aiming at imaging intracerebral arteries within limits of scanning time acceptable for neurological patients. The next step will be to directly compare histopathology with ex-vivo MR images to accurately measure the wall thickness.
Abstract 3694: Competing Risk for Long-Term Mortality in Patients with Unruptured Intracranial Aneurysm
Authors: Torner James C , Jones Michael , Xie Diqiong , Piepgras David , Huston John , Meissner Irene , Zhang Jie , Brown Robert ,   ISUIA Investigators
Published: March 2022

Introduction:
Mortality in patients with unruptured intracranial aneurysm (UIA) is significantly higher than the general population. However a minority of the deaths are due to subarachnoid hemorrhage.

Hypothesis:
There are differential characteristics of patients that might predict specific causes of death that would be informative in counseling patients about aneurysm risk.

Methods:
4059 patients with UIA who were enrolled prospectively between 1991 and 1998 were followed by 61 medical centers in North America, Canada, and Europe. Patients have at least one UIA, which may or may not be symptomatic. Patients were Rankin grade 1 or 2 at enrollment. Patients were followed annually from enrollment to 2007. For patients who died a death certificate search was done and information was requested from local physicians and other contacts. A National Death Index search in 2008 determined cases who died and cause of death. Foreign centers also did a national search where possible. Patients who died before 30 days post treatment or lost to follow up before 30 days post enrollment were excluded.

Results:
Twenty-five percent of patients died during follow-up. The life expectancy was significantly less than age-, sex-, and country-matched expected estimates. Among the total of 4004 patients with UIA who survived 30 days after enrollment, 2331 were treated and 1673 were not. There were 965 deaths after 30 days after treatment, of which 320 died from vascular disease (252 died from non-SAH vascular disease), 114 died from respiratory tract disease, 255 died from cancer, and the rest died of other or unknown reasons. Predictors of SAH death were aneurysm size, site, age and convulsive disorders at enrollment. Factors related to vascular death were UIA treatment, age, gender, race, hypertension, Rankin at discharge and diminishing influence of aneurysm characteristics over time. Respiratory deaths were related to treatment, race, smoking, age, initial Rankin and presentation with convulsive disorder. Cancer deaths were related to gender, race, smoking and age.

Conclusions:
In patients with UIA, an assessment of risk for death underscores the importance of age, race and gender and several modifiable risk factors. Patient management should include not only aneurysm rupture prevention but also modification of smoking and hypertension.
Abstract 3698: Ischemic Stroke Etiology in a Population Based Study: Temporal Trends in Ischemic Stroke Subtyping Over Time
Authors: Kissela Brett M , Khoury Jane , Alwell Kathleen , Moomaw Charles , Woo Daniel , Flaherty Matthew , Khatri Pooja , Adeoye Opeolu , Ferioli Simona , Broderick Joseph , Kleindorfer Dawn
Published: March 2022

Introduction:
Ischemic stroke subtyping is important for genetic research phenotyping, selection into some clinical trials, and for public health purposes regarding optimal stroke prevention. Population-based studies have high rates of unknown etiology due to insufficient testing to allow definitive subtyping. We sought to investigate temporal trends in testing after ischemic stroke and etiologic subtype determination over three periods.

Methods:
Our study ascertained all strokes for residents of a 5-county region during three one-year study periods, 7/93- 6/94, 1999 and 2005, by screening ICD-9 codes 430-436. An abstract of hospital records for every potential case was done by a study nurse and then adjudicated by a study physician. Testing performed during ER encounters and hospitalization was recorded, and copies of relevant test results were provided. Our etiologic subtype definitions are based upon the Classification of Cerebrovascular Diseases III and previous work from our center. We calculated the proportion of subjects who had "complete testing" for documenting stroke subtypes, i.e., the minimum required for recently proposed classification systems. For first-ever cases of ischemic stroke ≥20 years of age at onset, we compared the proportions for each possible etiology over time, as well as the proportions of subjects with multiple identified causes.

Results:
The proportions of ischemic stroke patients who received relevant testing in each study period and subtype determinations are shown in the
table
. Notably, significant increases were seen over time in the number of MRIs, MRAs, and echocardiograms. The proportion of patients who received "complete testing" significantly increased over time, but only 57% of patients received complete testing in the most recent study period. .The major difference over time in ischemic stroke subtypes was an increase in “other” causes with a corresponding decline in “unknown” subtype. There was a significant trend towards determining single or multiple etiologies, compared with “unknown” (p = 0.01).

Conclusions:
Despite the representative nature and statistical power of a large population based study, many ischemic stroke patients would not have a defined etiologic subtype utilizing recently proposed subtyping methods due to insufficient testing and would be classified as "unknown". Further study of subtyping methods is warranted, as requiring “complete” testing for every stroke patient is not feasible in current community practice and because it is possible to assign a most likely phenotype in some patients who have incomplete testing.
Abstract 3708: Safety and Efficacy of Antiplatelet Monotherapy (clopidogrel) in Stent Assisted Elective Coil Embolization of Cerebral Aneurysms
Authors: Sharma Jitendra , Kulhari Ashish , Sehgal Siddharth , Jung Richard S , Blackham Kristine A
Published: March 2022

BACKGROUND AND PURPOSE:
Thromboembolic events are the most common complication seen in elective coil embolization of cerebral aneurysms. Previous studies have shown that administration of oral clopidogrel and/or aspirin may lower the thromboembolic complication rate but little data exists regarding clinical outcome with the use of antiplatelet monotherapy in stent assisted elective aneurysm coil embolization.

Objectives:
To assess the safety and efficacy of antiplatelet monotherapy (clopidogrel) in elective stent assisted coil embolization of cerebral aneurysms

MATERIALS AND METHODS:
Retrospective chart review was performed in 94 consecutive patients who underwent endovascular treatments for elective coil embolization of cerebral aneurysms between 2008-2010. Thirty patients were included in this study who met the inclusion criteria of stent assisted coil embolization. All these patients received 75mg clopidogrel for one week prior to the procedure. Clopidogrel was continued post procedure for six to eight weeks. Primary outcome measure was peri-procedure and post-procedure symptomatic thromboembolic complications.

RESULTS
The study included 23 females and 7 males with mean age 52.6 years.Twenty (66.7%) patients had anterior circulation aneurysms and 10 (33.3%) patients had posterior circulation aneurysms. Twenty (66.7%) patients were treated with Neuroform, 9 (30%) patients with Enterprise stent and 1 (3.3%) patient was treated with both Neuroform and Enterprise stent assisted coil embolization. One (3.3%) patient had an iatrogenic flow limiting vertebral artery dissection during embolization of vertebrobasilar artery aneurysm with no clinical deficit. The patient’s vertebral artery dissection was treated with 2 Wingspan stents and 1 Medtronic driver stents. Symptomatic thromboembolic complication was seen in 1 patient (3.3%) at discharge. The patient had a giant basilar tip aneurysm which was treated with stent assisted coil embolization. Postprocedure the patient had a right facial palsy with gaze deviation. The MRI was consistent with acute posterior circulation stroke. The patient was discharged home with a modified Rankin Scale <2. Follow up at six to eight weeks post procedure clinical data was available for 21 patients (73.3%). No delayed thromboembolic complication was observed in these patients at follow up visit.

CONCLUSION:
Oral clopidogrel is safe and efficacious as an antiplatelet monotherapy during elective stent assisted coil embolization. Further multicenter prospective trials are warranted to evaluate safety and efficacy of clopidogrel as a monotherapy for elective stent assisted coil embolization.
Abstract 3709: Acute Stroke opens Neuronal Pannexin1 Channels
Authors: Foreman-Mackey Annie , Peterson Nicole , Andrew David , Kaur Jaspreet , Singh Supriya , Jin Albert Y
Published: March 2022

Introduction:
Oxygen-glucose deprivation induces neuronal uptake of the sulforhodamine-based dye SR101 via pannexin1 channels in cultured neurons and brain slices. We assessed the hypothesis that pannexin1 channels are opened during acute stroke.

Methods:
Focal cerebral ischemia was induced in male C57BL/6 mice (20 to 25g, n=5) by middle cerebral artery occlusion (MCAO) for 30 minutes using the intraluminal suture occlusion method. Brain slices (2mm thickness) were taken immediately after stroke and incubated at room temperature in oxygenated sucrose-modified artificial cerebral spinal fluid for 60 minutes in 3 μ M Texas Red hydrazide (TRH), a structurally similar SR101 analog selectively taken up by astrocytes under non-ischemic conditions. Five brain slices co-incubated with 1 mM probenecid (a specific pannexin1 channel blocker) and seven brain slices without were assessed for pannexin1 channel-mediated dye uptake. Following cryosectioning and NeuN immunofluorescent labelling, the proportion of neurons showing TRH uptake (mean percentage ± S.E.M.) was determined in both hemispheres by fluorescence microscopy from 114 regions within the dorsomedial and lateral cortex, and 54 regions within the striatum. In a separate mouse, 2-photon laser scanning microscopy was used to assess in vivo neuronal uptake of sulforhodamine B (an SR101 analog) during acute stroke. Detailed neuronal morphology following 30 minutes of MCAO was assessed in a separate group of transgenic mice (n=3, C57 background) expressing yellow fluorescent protein in a subpopulation of neocortical pyramidal neurons.

Results:
Neuron morphology was unaltered after 30 minutes MCAO in the ipsilateral and contralateral hemisphere. TRH uptake was dramatically increased in the ischemic hemisphere in the lateral neocortex (ipsilateral vs contralateral 28% ± 1.8% vs 14% ± 1.6%, p < 0.0001) and striatum (ipsilateral vs contralateral 55% ± 3.0% vs 38% ± 3.1%, p = 0.005). The pannexin1-specific blocker probenecid reduced ipsilateral dye uptake to the same level seen contralaterally: (ipsilateral vs contralateral) lateral cortex 14% ± 2.5% vs 16% ± 2.6% (p = 0.58), dorsomedial cortex 13% ± 2.0% vs 16% ± 2.1% (p=0.31), and striatum 40% ± 3.2% vs 36% ± 2.2% (p=0.31). In vivo uptake of sulforhodamine B was demonstrated in neocortical and striatal neurons only in the ipsilateral hemisphere by 2-photon laser scanning microscopy.

Conclusion:
The opening of neuronal pannexin1 channels is widespread specifically in ischemic tissue within 30 minutes of MCAO onset. Pannexin1 channel opening appears to precede and possibly contribute to early neuronal membrane breakdown during acute stroke.