bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Stroke Patients Don’t Receive T-PA? An Analysis of Patient Eligibility: Implications for Improving Clinical Impact by Increasing Future Treatment Numbers
Authors: Barber Philip A , Zhang Jinijin , Demchuk Andrew M , Hill Michael D , Cole-Haskayne Andrea , Newcommon Nancy , Virji Humeira , Buchan Alastair M
Published: July 2021

P183

Background
T-PA is an effective treatment of acute ischemic stroke within 3 hours. However, the success of t-PA on reducing disability is dependent on it being accessible to more patients. We identified the reasons why patients with ischemic stroke did not receive intravenous t-PA and assessed the community impact of the therapy in a large North American city.
Methods
Consecutive patients with acute ischemic stroke were identified in a prospective stroke registry at a teaching hospital between October 1996 and December 1999. Additional patients with ischemic stroke admitted to one of three other hospitals during the study period were identified. The Oxford Community Stroke Program Classification was used to record stroke type.
Results
Of 2165 stroke patients presenting to the emergency department 1179 (54.5%) were diagnosed with ischemic stroke, 31.7% with intracranial hemorrhage, and 13.8 % with transient ischemic attack. 84/339 (29%) patients were admitted within 3 hours of stroke received intravenous t-PA. The major reasons for exclusion for stroke patients presenting within 3 hours were mild stroke (20%), clinical improvement (18.6%), and specific protocol exclusions (11.5%). Delay in presentation to emergency department excluded 840/1179 (71%). 1817 ischemic stroke patients were admitted to Calgary hospitals during the study period of which 4.6% received intravenous t-PA. Generalization of the Calgary experience to other Canadian communities suggests the benefit from t-PA for ischemic stroke may be substantial with an additional 460 independent survivors per annum.
Conclusion
The effectiveness of t-PA can be improved by understanding why patients are excluded from its use. The eligibility of patients for t-PA must increase by promoting health education programs and by developing organized acute stroke care infrastructure within the community.
Have Randomized Controlled Trials of Neuroprotective Drugs Been Underpowered?: An Illustration of Three Statistical Principles
Authors: Samsa Gregory P , Matchar David B
Published: July 2021

P185

Background and Purpose
— The results of phase III trials of neuroprotective drugs for acute ischemic stroke have been disappointing. We examine the question of whether these trials may have been underpowered.
Methods
— Computer simulations were based upon the binomial distribution.
Results
— We illustrated that even small overestimates of the efficacy of an intervention can lead to a serious reduction in statistical power, that use of data from phase II studies tends to lead to such overestimation, and that a minimum clinically important difference derived using cost-effectiveness modeling techniques is considerably smaller than might be suggested by intuition.
Conclusions
— We recommend placing more emphasis on minimum clinically important differences when planning stroke trials, with these differences being derived from an assessment of public health impact obtained in conjunction with the use of epidemiologic and cost-effectiveness models. Even small benefits, when averaged over a sufficiently large number of cases, will, in total, accrue to a large positive impact on the public health.
The impact of establishing a stroke center at a community hospital on the use of thrombolytic therapy: the NINDS-Suburban Hospital Stroke Center experience
Authors: Rodriguez Susan Unipan , DeGraba Thomas , Hamm Theresa , Nyquist Paul , Hallenbeck John , Warach Steven
Published: July 2021

P192

Background:
One strategy that has been advocated to increase the percentage of stroke patients treated with thrombolytic therapy is the establishment of primary stroke centers in community hospitals.
Methods:
A stroke center was established at a 397-bed private community hospital in Bethesda, Maryland consistent with published recommendations (M. Alberts, et al, JAMA. 2000;283:3102). Following a 4 month pilot phase during which the stroke critical care pathway was introduced into hospital practice, around the clock coverage by the on-call stroke team was initiated on January 3, 2000. According to the pathway, the team was to be paged for any patient identified with a suspected new stroke and persistent deficits of less than 6 hours in duration (initial screening criteria). Observations of patient characteristics and times of key points in acute management are reported through July, 2000.
Results:
Sixty-four patients met the initial screening criteria (58 of these patients arrived at the hospital within 3 hours of onset of symptoms). Time in minutes to action (patient arrival at hospital to paging of neurologist, to arrival of neurologist, to scan) decreased over the first 7 months of stroke coverage (24 to 12, 28 to 16, 52 to 32, respectively, per 2-month average). Of 143 patients hospitalized with ischemic stroke during this period, 15 patients (10%) were treated with t-PA (10 IV, 5 IA). For the IV-treated patients, the median time to treat was 130 minutes and median door to needle time was 83 minutes, in line with benchmark values. During the same 7-month period of the year prior to the center initiation, only 3 patients were treated with t-PA at this hospital.
Conclusions:
A 5-fold increase in t-PA usage was observed in the first 7 months following the establishment of the stroke center (3-fold increase for IV t-PA use only). Establishment of a stroke center at a community hospital is feasible. Our experience to date suggests that a substantial increase in the frequency of patients receiving t-PA therapy for ischemic stroke may be achievable shortly after initiation of a community hospital stroke center.
How are TIAs managed in a managed care setting? Resource use and costs.
Authors: Shireman Theresa , Pancioli Arthur M , Miller Elaine L , Spilker Judith A , Kissela Brett M
Published: July 2021

P193

This pilot study performed by members of the Greater Cincinnati / Northern Kentucky Stroke Team describes the retrospective examination of administrative claims data involving TIA survivors from a locally based managed care program. New TIA cases were identified between November 1997 and July 1998 and defined by an absence of a primary ICD9 code for a TIA or ischemic stroke during preceding 10–12 months. The managed care organization provided all inpatient hospital, outpatient hospital, ambulatory care and prescription claims for 12 months prior to and after the new case. Cases (n = 51) averaged 54.5 years of age and 56.9% were males. Predominant comorbidities included: hypertension (45.1%), and hypercholesterolemia (47.1%). Eight (15.7%) were hospitalized for their TIA. Total health care costs increased by only $568 from the period prior to the TIA. This limited increase in costs led us to question how these cases were evaluated and treated. We then compared the resources utilized to the AHA Stroke Council’s 1999 Supplement to Guidelines for the Management of Transient Ischemic Attacks and the 1997 AHA Practice Guidelines for Use of Imaging. This comparison was made to determine if these managed care enrollees received the recommended diagnostic evaluation and follow-up care directed towards the prevention of subsequent major cerebrovascular events. An analysis of the specific components of the managed care evaluation will be provided.
Resource use and costs of Ischemic Stroke in a Managed Care Setting
Authors: Shireman Theresa , Pancioli Arthur M , Miller Elaine L , Spilker Judith A , Kissela Brett M
Published: July 2021

P200

Members of the Greater Cincinnati/Northern Kentucky Stroke Team retrospectively examined administrative claims data for a pilot study of 12-month survivors of acute ischemic stroke from a locally based managed care program. New ischemic stroke cases were identified between November 1997-July 1998 and defined by an absence of a primary ICD9 code for a TIA or ischemic stroke during the preceding 10–12 months. The managed care organization provided all inpatient hospital, outpatient hospital, ambulatory care and prescription claims for 12 months prior to and after the new case. Cases (n=54) averaged 56.1 years of age, 61.1% males and all survived the 1st year past stroke. Predominant comorbidities included: hypertension (50%), diabetes (24.1%), hypercholesterolemia (33.3%), ischemic heart disease (24.1%), and chronic respiratory illness (20.4%). Total health care costs increased by 244% from the period prior to the stroke. Stroke-related costs increased over 6-fold while non-stroke costs increased by 46%. We compared the resources utilized in the period after the ischemic stroke event to the AHA Stroke Council’s 1994 Guidelines for the Management of Acute Ischemic Stroke and 1997 AHA Practice Guidelines for Use of Imaging. This comparison was made to determine if the managed care enrollees received evaluations, treatments and services directed towards preventing recurrent strokes and maximizing patient outcome. An analysis of specific components of care delivered will be provided.
Antithrombotic Prescription at Discharge in Medicare Patients with Ischemic Stroke/Transient Ischemic Attack: Results from the National Stroke Project
Authors: Kresowik Timothy F , Nilasena David S , Piskac Anton F , Hemann Rebecca A , Brenton Marian A , Wilwert June M , Hendel Marc E , Nevins Lynnette E
Published: July 2021

P205

Background:
Antiplatelet agents have been shown to be effective for secondary stroke prevention in patients with ischemic stroke (IS) or transient ischemic attack (TIA). As part of HCFA’s National Stroke Project, we examined patterns of use of antithrombotic agents for inpatients with IS or TIA.
Methods:
Findings were based on abstracted data from a sample of Medicare inpatient medical records (discharge dates 4/98 - 3/99). All U.S. states, the District of Columbia and Puerto Rico were sampled using a systematic random approach. Each record had a principal diagnosis of one of the following ICD-9-CM codes: 362.34, 433.xx, 434.xx, 435.0, 435.1, 435.3, 435.8, 435.9 or 436. The main outcome measure was the frequency of eligible patients with a prescription or a plan for antithrombotic therapy at discharge. Antithrombotics were aspirin, clopidogrel, dipyridamole, ticlopidine and warfarin.
Results:
Of the 36,650 cases reviewed, 25,659 met the criteria for inclusion in the indicator. A large percentage of excluded cases (53.1%) were removed due to a history or current finding of hemorrhage. Nationwide, 20,947 (unadjusted rate 81.6%) patients were prescribed an antithrombotic at discharge or had a plan for starting an antithrombotic after discharge. The state-specific rates ranged from 72.0% to 90.1%. Univariate analyses showed this therapy was prescribed less frequently (p<0.001) for adults 85 years and over (rate=77.8%, OR=0.74, 95% CI=0.69–0.80), women (rate=80.4%, OR=0.83, 95% CI=0.78–0.89) and African-Americans (rate=77.6%, OR=0.76, 95% CI=0.68–0.85). Asians were found to have been prescribed this therapy more frequently than other races (p<0.02, rate=87.2%, OR=1.54 95% CI=1.10–2.16). Among those IS/TIA patients who also had atrial fibrillation (AF), 57.1% received warfarin.
Conclusions:
Antithrombotic agents are not prescribed for almost one-fifth of eligible Medicare inpatients with IS/TIA. For those with IS/TIA and AF, a large proportion are not treated with warfarin. These results show important opportunities for improvement in secondary stroke prevention for Medicare patients.
Cerebral embolism and complex aortic plaques: Secondary prevention
Authors: Wetterholm Robert , Blomstrand Christian , Aspenlid Elisabeth , Bech-Hansen Odd , Caidahl Kenneth
Published: July 2021

P212

Background:
After a cerebral embolic event, complex plaques in the proximal aorta constitute an important finding by transesophageal echocardiography (TEE). Yet, there is no consensus regarding its optimal treatment, and we studied the short-term outcome in this group of patients.
Method:
Between August 1995 and August 1998, 424 patients were examined with TEE after a suspected cerebral embolic event. We re-evaluated the 94 examinations with any plaques noticed in the proximal aorta and reviewed the medical charts for previous embolic events, diabetes, hypertension, ischemic heart disease, ECG, laboratory findings, antithrombotic treatment and outcome (mean follow-up time 19 months).
Results:
Of 94 patients with any plaques in the proximal aorta, 75 were complex (protruded more than 4 mm or had a mobile component), and 55 of these were finally diagnosed as having suffered cerebral embolism. After exclusion of 8 patients with atrial fibrillation, 47 patients constituted the study group. As secondary prevention, 32 and 15 patients were on antiplatelets and oral anticoagulation, respectively, at event or end of follow-up. In the antiplatelet group (A), 8 of 32 patients (25%) suffered a new cerebral embolic episode vs. none in the anticoagulant group (B) (p=0.03). Mean time to recurrent embolism was 10 months. No hemorrhagic stroke or other important bleeding occurred during follow-up. Leukocyte count was slightly higher in group A (8.7±2.4 vs. 7.2 ± 1.9× 10
9
/L, p=0.04), no other significant difference was found between groups A and B regarding mean age (64 vs. 67 years), systolic blood pressure (171±32 vs. 166±23mmHg, p=0.60), left atrial size (17.9±4.0 vs. 19.0±5.0 cm
2
, p=0.42), hemoglobin conc. (143±15 vs. 140±14 g/L, p=0.53), S-cholesterol (5.9±1.5 vs. 6.5±1.2 mmol/L, p=0.23), S-triglycerides (1.9±1.0 vs. 2.0±1.1 mmol/L, p=0.70), history of diabetes, ischemic heart disease, hypertension or smoking.
Conclusion:
Complex plaques in the proximal aorta are frequently found in patients with cerebral embolism. Our study indicates that these patients benefit from oral anticoagulation, while treatment with antiplatelets is associated with a high incidence of recurrent embolism.
Risk of Recurrent Ischemic Events in Patients with Symptomatic Vertebro-Basilar Stenosis
Authors: Uzun Guven , Qureshi Adnan , Mohammad Yousef M , Zaidat Osama , Suarez Jose , Suri M Fareed K , Ali Zulfiqar , Lieb Amanda G , Martin Tina M , Yahia Abutaher M , Thaler David E , Guterman Lee R , Hopkins L N
Published: July 2021

P216

Background and Purpose:
The long-term outcome in patients with symptomatic vertebro-basilar stenosis is not well defined. We performed this study to determine the long-term risk of stroke or death in a large series of patients with vertebro-basilar stenosis.
Methods:
We identified patients admitted between January 1995 and December 1997 with ischemic stroke or transient ischemic attack related to stenosis in either the vertebral or basilar artery at 4 university hospitals. The stenosis was identified either by magnetic resonance angiography or conventional angiography. New ischemic events or death was identified during the follow-up period through clinic visits or telephone interviews.
Results:
A total of 77 patients (mean age 62.4 ±13.1 years; 43 were men) were identified with stenosis of either vertebral artery (n=28), basilar artery (n=26) or both (n=22). Of the 77 patients, 18 presented with transient ischemic attack and 59 with ischemic stroke. Eight patients died during hospitalization. Of the surviving 69 patients, 24 patients were treated with aspirin, 8 with ticlopidine or clopidogrel, 36 with warfarin and one patient received no treatment. The patients were followed for 47.4 ±35.8 months after the initial event. A total of 14 recurrent ischemic events were observed. The first year risk of new ischemic events for vertebro-basilar stenosis was 9%. The first year rate of ischemic events was similar between antiplatelet agents (9%) and warfarin (8%).
Conclusions:
A high rate of recurrent ischemic events was observed in patients with vertebro-basilar stenosis despite treatment with antiplatelet agents or anticoagulants.
Characteristics of Academic Medical Centers Associated with Ischemic Stroke Outcome
Authors: Johnston S. Claiborne , Gillum Leslie A
Published: July 2021

P235

Background:
Data supporting the efficacy of stroke center characteristics are limited.
Methods:

A questionnaire detailing stroke treatment practices was sent to 42 academic medical centers in the University Health Systems Consortium participating in a quality improvement project. In-hospital mortality of all emergency-department admissions for ischemic stroke at these institutions was evaluated in a large administrative database from 1997 through 1999. We used a multivariable method called generalized estimating equations, which broadens confidence intervals to adjust for clustering of variables at institutions. Using this technique, institutional characteristics were evaluated as predictors of in-hospital mortality after adjusting for age, gender, race, hospital treatment volume of ischemic stroke, and admission status (emergent, urgent, elective).
Results:
Thirty-two institutions completed the questionnaire and 29 of these were included in the administrative database. In-hospital deaths occurred in 758 (7.0%) of the 10,880 ischemic strokes admitted through the emergency department. In-hospital deaths were less frequent at hospitals with a vascular neurologist (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.36–0.74, p<0.001), and at those with guidelines stating that only neurologists could administer tPA (OR 0.65, 95% CI 0.49–0.88, p=0.004). There was a trend toward fewer deaths at hospitals with a dedicated stroke team available by pager (OR 0.76, 95% CI 0.56–1.04, p=0.09). The presence of a dedicated neurological intensive care unit, stroke unit, and written clinical pathway for stroke were not significantly associated with in-hospital death.
Conclusions:
Academic medical centers with a vascular neurologist and those with written guidelines limiting tPA administration to neurologists had lower rates of in-hospital mortality for ischemic stroke patients.
Supplemental Oxygen Use in Ischemic Stroke Patients, Does Utilization Correspond to Need for Oxygen Therapy?
Authors: Pancioli Arthur M , Bullard Mark J , Grulee Mary E , Jauch Edward C , Perkis David F
Published: July 2021

P236

Background:
In 1994, the American Heart Association Stroke Council stated that there is no data to support routine use of supplemental oxygen in stroke patients. The purpose of this study was to determine the degree of supplemental oxygen use in ischemic stroke and whether patients receiving oxygen met criteria for therapy.
Methods:
An extensive literature search was performed to generate a comprehensive list of explicit criteria for supplemental oxygen use. When the literature disagreed, criteria were included in the list to overestimate rather than underestimate the justification for oxygen use. A retrospective chart review of 169 consecutive, non-intubated, ischemic stroke patients admitted to a university hospital during calendar year 1998 was performed. Two patients were excluded due to missing data yielding a sample of 167 patients. Data included demographic and co-morbidity information as well as a check of each inpatient day for documentation of any of the explicit criteria for supplemental oxygen use.
Results:
A total of 167 patient charts were reviewed yielding a total of 600 inpatient days abstracted. Of the 167 patients, 102 (61.1%) received oxygen accounting for 322 patient days. Of the 322 inpatient days that patients received oxygen, 147 (45.6%) met at least one criteria for oxygen utilization. Of the 278 inpatient days that patients did not receive oxygen 69 (24.8%) would have met at least one of the criteria for oxygen use. For the entire population, statistically significant factors associated with patients receiving oxygen included: presence of at least one justifying criteria, increasing age, white race, male gender, history of atrial fibrillation, and a history of hypertension.
Conclusion:
We developed a comprehensive, literature-based list of criteria for supplemental oxygen therapy that was designed to overestimate rather than underestimate the justification of oxygen utilization. Using this explicit list, only 45.6% of days of oxygen therapy were justified in our ischemic stroke population. This study demonstrates that oxygen therapy is commonly given to ischemic stroke victims without clear indication.
Concomitant use of antiplatelet agents with tissue plasminogen activator during stroke thrombolysis.
Authors: Wong Edward H , Demaerschalk Bart , Merino Jose G , Silver Brian , Tamayo Arturo , Devasenapathy Ashok , O’Callaghan Christina , Kertesz Andrew , Young G Bryan , Spence J David , Hachinski Vladimir
Published: July 2021

P237

Background:
In the setting of acute myocardial infarction, aspirin has a significant benefit on mortality when combined with a thrombolytic. The NINDS guidelines recommend witholding antiplatelet agents (APA) for 24 hours after tPA administration for acute stroke.
Post hoc
analysis of the NINDS tPA study did not show worse outcomes in patients using APA prior to treatment, even though APA have a long platelet-inhibitory effect (the life of the platelet).
Objective:
To determine whether concomitant APA and tPA use was associated with worse outcomes.
Method:
We compared demographics, vascular risk factors, hemorrhagic complications, and 3 month outcomes of patients on APA at the time of their stroke with those patients not taking APA, in our prospective registry of tPA-treated patients.
Results:
Between 1 December 1998 and 24 July 2000, 64 patients were treated with tPA; 3 month follow-up data are available on 47 (73%). At the time of their stroke, 24 (38%) were taking APA, 40 (62%) were not. Patients taking APA were more likely to have a history of coronary heart disease, previous stroke and previous TIA, and they had higher baseline modified Rankin Scores (mRS). There was a trend for them to be older (75.3 years [APA] vs. 70.2 years [no APA],
p
=0.06). There was no increase in major intracranial or systemic hemorrhages at 36 hours (0% [APA] vs. 5% [no APA],
p
=0.54), or in mortality at 3 months (13% [APA] vs. 15% [no APA],
p
=1.00). More patients taking an APA had a NIH Stroke Scale score (NIHSSS) of 0–1, but this did not reach statistical significance (40% [APA] vs. 29% [no APA],
p
=0.42). There was a non-significant trend for fewer patients on an APA to have a 3 month mRS of 0–1 (20% [APA] vs. 41% [no APA],
p
=0.17). However, given their higher baseline mRS, we also looked at the percentage who returned to their baseline mRS, this favored the APA group but again it did not reach statistically significance (40% [APA] vs. 28% [no APA],
p
=0.38).
Conclusion:
Concomitant APA and tPA use appears safe and may be associated with an improved outcome. The potential beneficial effect of the combination merits further study.
Abstract 104: APOE Genotype Is Associated With CT Angiography Spot Sign In Lobar Intracerebral Hemorrhage
Authors: Brouwers H. B , Biffi Alessandro , McNamara Kristen A , Ayres Alison M , Valant Valerie , Simmons Andrew R , Delgado Almandoz Josser E , Schwab Kristin , Cortellini Lynelle , Romero Javier M , Viswanathan Anand , Greenberg Steven M , Rosand Jonathan , Goldstein Joshua N
Published: July 2021

Purpose:
The presence of active contrast extravasation following CT angiography (CTA), the spot sign, predicts the development of hematoma expansion and poor clinical outcome in patients with primary intracerebral hemorrhage (ICH). The biological underpinnings of the spot sign remain poorly understood, and there are no established risk factors for its presence. We conducted a prospective cohort study to identify determinants of the CTA spot sign.

Materials and Methods:
We performed a prospective cohort study of consecutive patients presenting to a single center with primary ICH over an 11-year period. Patients were included in this analysis if they underwent CT and CTA at presentation and consented to participation in genetic studies. CTAs were reviewed by two experienced readers, blinded to clinical data, according to previously published validated criteria. Due to its established association with lobar ICH volume, APOE genotype, as well as common clinical covariates, were analyzed for association with spot sign presence. Analyses were stratified by deep, lobar and probable / definite cerebral amyloid angiopathy (CAA) related ICH (by Boston criteria).

Results:
Of 372 patients, 151 had deep, 198 had lobar and 23 had mixed ICH. We identified at least 1 spot sign in 96 of 372 patients (25.8%). In multivariate analysis, patients on warfarin were more likely to have a spot sign regardless of ICH location: OR 3.85 (95% CI 1.33-11.13, p-value 0.013) in deep ICH, OR 2.86 (95% CI 1.33-6.13, p-value 0.007) in lobar ICH and OR 6.65 (95% CI 1.34-32.99, p-value 0.020) in the subset meeting criteria for CAA-related ICH. APOE ε2, but not ε4, was associated with spot sign in lobar ICH (OR 2.09 [95% CI 1.05-4.19], p = 0.036) and CAA-related ICH (OR 2.07 [95% CI 1.24-3.46], p-value 0.005). There was no effect for ε2 or ε4 in deep ICH. (

Table 1

)

Conclusion:
Patients on warfarin at the time of ICH are more likely to have a spot sign at presentation, regardless of the location of the ICH. Among patients with lobar ICH, those who possess the APOE ε2 allele are more likely to have a spot sign. Given the established relationship between APOE ε2 and vasculopathic changes in CAA, our findings suggest that both hemostatic factors and vessel pathology influence spot sign presence and risk of prolonged bleeding in ICH.
Abstract 13: A Locus on Chromosome 6p21 is Associated with Large Artery Atherosclerotic Ischemic Stroke
Authors: Holliday Elizabeth G , Maguire Jane M , Evans Tiffany-Jane , Golledge Jonathan , Biros Erik , Lewis Martin D , Koblar Simon , Jannes Jim , Hankey Graeme J , Baker Ross , Parsons Mark W , Sturm Jonathan W , Lincz Lisa F , McEvoy Mark , Peel Roseanne , Moscato Pablo , Scott Rodney J , Levi Christopher , Attia John
Published: July 2021

Introduction
Genetic influences upon ischemic stroke risk are supported by the trait’s familial aggregation, higher concordance among monozygotic than dizygotic twins, and the high heritability of intermediate phenotypes such as carotid intima-media thickness. In spite of this evidence, genome-wide association studies (GWAS) have detected few replicable genetic risk factors for ischemic stroke, potentially due to aetiological heterogeneity of this trait.

Hypothesis
We first assessed the hypothesis that common ischemic stroke subtypes differ in their heritability, defined as the proportion of observed phenotypic variation attributable to genetic variation. The second hypothesis was that GWAS may detect stronger and more replicable genetic associations for distinct stroke subtypes with high heritability, rather than the broad ischemic stroke diagnosis.

Methods
An Australian, European-ancestry sample of 1230 ischemic stroke cases and 1280 population controls was genotyped for a genome wide association study using the Illumina 610-Quad array. Ischemic stroke subtypes were assigned using TOAST criteria. The proportion of case-control variation attributable to genome wide genetic variation was estimated using a published approach based on linear mixed models. Genome wide association analyses incorporating approximately 2.5 million genotyped and imputed SNPs were subsequently performed using a one-degree of freedom trend test assuming an additive effect of allele dosage.

Results
Significant evidence for a genetic contribution to ischemic stroke risk was detected (

h
2

=0.39, SE=0.15, p-value = 0.0009), but this was higher and more significant for the large artery atherosclerosis (LAA) subtype (

h
2

=0.66, SE=0.21, p-value = 0.0001). The genetic contributions to small vessel disease and cardioembolic stroke were less significant than for overall ischemic stroke. Genome wide association analyses including 421 LAA cases and 1244 controls detected a novel LAA susceptibility locus on chromosome 6p21.1 (two SNPs with
P
<5×10
-8
). The 6p21.1 locus showed markedly diminished association with the broader ischemic stroke phenotype.

Conclusions
In conclusion, this study detected higher heritability of large artery atherosclerotic stroke than cardioembolic stroke, small vessel disease or broad ischemic stroke. It suggests a genetic risk locus for large artery atherosclerosis on chromosome 6p21.1 and supports the analysis of aetiological subtypes to better identify genetic risk alleles for ischemic stroke.
Abstract 133: Protocol Deviations During and After IV Thrombolysis in Community Hospitals
Authors: Adelman Eric E , Meurer William J , Skolarus Lesli E , Kade Allison M , Frederiksen Shirley M , Kalbfleisch Jack D , Scott Phillip A
Published: July 2021

Background and purpose
Protocol deviations (PDs) before and immediately after IV thrombolysis for acute ischemic stroke are common. Patient and hospital factors associated with PDs are not well described. We aimed to determine which patient or hospital factors were associated with pre- and post-treatment PDs in a cohort of community treated thrombolysis patients.

Methods
The INSTINCT (Increasing Stroke Treatment through Interventional Behavior Change Tactics) study was a multicenter, cluster-randomized controlled trial in 24 Michigan community hospitals evaluating the efficacy of a barrier assessment and educational intervention to increase appropriate tPA use. PDs were defined based on 2007 AHA guidelines with the addition of the 3-4.5 hour treatment window, for which the ECASS III criteria were applied. PDs were categorized as pre-treatment (Pre-PDs), post-treatment (Post-PDs) or both. Multi-level logistic regression models were fitted to determine whether patient and hospital variables were associated with Pre-PDs or Post-PDs. The models included all variables specified a priori to be potentially clinically relevant; Pre-PD was included as a covariate in the model for Post-PD.

Results
During the study, 557 patients (mean age 70; 52% male; median NIHSS 12) were treated with IV tPA. PDs occurred in 233 (42%) patients: 26% had only Post-PDs, 7% had only Pre-PDs, and 9% had both. The most common PDs included failure to treat post-treatment hypertension (131, 24%), antiplatelet agent within 24 hours of treatment (61, 11%), pre-treatment blood pressure over 185/110 (39, 7%), anticoagulant agent within 24 hours of treatment (31, 6%), and treatment outside the time window (29, 5%). Symptomatic intracranial hemorrhage (SICH) was observed in 7.3% of patients with PDs and 6.5% of patients without any PD. In-hospital case fatality was 12% with and 10% without a PD. The differences in SICH and case fatality were not statistically significant. In the fully adjusted model, older age was significantly associated with Pre-PDs (
Table
). When Post-PDs were evaluated with adjustment for Pre-PDs, age was not associated with PDs; however, Pre-PDs were associated with Post-PDs.

Conclusion
Older age was associated with increased odds of Pre-PDs in Michigan community hospitals. Pre-PDs were associated with Post-PDs. SICH and in-hospital case fatality were not associated with PDs; however, the low number of such events limited our ability to detect a difference. Stroke severity and hospital factors were not associated with PDs.
Abstract 137: Endovascular Intervention versus Standard Medical Therapy for Patients Presenting with Large Acute Ischemic Strokes - A Large Single Center Experience
Authors: Mokin Maxim , Kan Peter , Abla Adib , Dumont Travis , Jahshan Shady , Eller Jorge , Kass-Hout Tareq , Kass-Hout Omar , Ho Mei-jen , Snyder Kenneth , Siddiqui Adnan , Hopkins Nelson , Levy Elad
Published: July 2021

Objective.
Endovascular interventions for acute ischemic stroke have been widely adopted on the basis of single-arm registries that reported high recanalization rates with limited complications. We conducted a retrospective cohort study to compare the clinical outcomes in acute ischemic stroke patients who underwent endovascular treatment with patients who were treated with standard medical therapy alone at our institution.

Methods.
The study group consisted of two cohorts of patients with acute ischemic stroke over a 4-year period: 260 patients underwent endovascular treatment and 597 patients were treated with best medical therapy alone. All patients from the medical group presented with a NIHSS score of >8 and were ineligible for IV tPA. Clinical outcomes at discharge and at 3 months were compared.

Results.
Compared with the medical group, the endovascular group had a significantly greater proportion of patients who were discharged home (21.2% vs 8.7%, p<0.001) and who could ambulate independently at discharge (32.1% vs 16.8%, p<0.001). Of the patients with follow-up, the proportion of patients with a good outcome (mRS score of <=2) at 3 months was also significantly higher in the endovascular group (51.9% vs 35.7%, p<0.05). Conversely, the endovascular group had a significantly smaller proportion of patients who was discharged to nursing home (11.9% vs 24.1%, p<0.01) and hospice (6.9% vs 14.1%, p=0.003). Mortality rate at discharge was not different (21.2% vs 18.9%, p=0.451). The rate of symptomatic ICH was 9.2% in the intervention group.

Conclusion.
In our study, endovascular therapy provides a better functional outcome compared with standard medical therapy in select patients. Ultimately, determination of efficacy of endovascular therapy for acute ischemic stroke compared with best medical therapy will depend on results of randomized trials.
Abstract 149: Evaluating the Risk of Cerebrovascular Events Among Those Seeking Information on Transient Ischemic Attack Symptoms on the Internet
Authors: Kim Anthony S , Poisson Sharon N , Easton J. Donald , Johnston S. Claiborne
Published: July 2021

Background:
Despite the high risk of stroke after transient ischemic attack (TIA), many people do not seek urgent medical attention because symptoms may be mild or have already resolved or be incorrectly attributed to a benign mimic. Since the Internet has become an increasingly important source of medical information, we sought to reach these people by developing and testing an instrument to identify cerebrovascular events among those seeking information about TIA online.

Methods:
We developed an instrument to evaluate possible TIA symptoms (
http://tia.ucsf.edu/
) using items from the ABCD2 score excluding blood pressure since it may not be readily available by self-report. Using targeted Internet text advertisements for terms such as “transient ischemic attack symptoms” or “mini-stroke symptoms” we invited subjects to complete a 20-item demographic, medical history, and symptom inventory online. Neurologists that were blinded to these responses then contacted subjects by telephone to assess the likelihood that a true TIA or stroke had occurred. Logistic regression was used to assess univariate and multivariable associations and ROC curves were generated to assess model discrimination.

Results:
The study website received 26,602 hits over 122 days of study enrollment. A total of 289 visitors started the enrollment and eligibility screening process, 253 provided consent and recorded responses for the instrument, and 173 completed the follow-up telephone assessment. The mean age was 58.7 years (range 23-88) and 63% were women. A total of 36 (21%) subjects had had symptoms within 24 hours and 60 (37%) had not yet sought medical advice for their symptoms. The follow-up telephone assessment process determined that 43 (24.9%) had a TIA, and 67 (38.7%) had either a TIA or a stroke. The ABCD2 score (excluding blood pressure) demonstrated moderate discrimination overall (c-statistic 0.69, 95% CI 0.61-0.76), but 1 (8.3%) of 12 subjects with a score of 0 had a cerebrovascular event (isolated diplopia). Those who reported multiple prior episodes of similar symptoms in the past year were less likely to have had a cerebrovascular event (OR 0.18, 95% CI 0.10-0.37) and incorporating this predictor and the presence of diplopia into the model significantly improved discrimination (c-statistic 0.78, 95% CI 0.71-0.85, p=0.03) with no events among the 7 patients who had a score of 0.

Conclusion:
Patients with possible TIA symptoms turn to the Internet for medical information and prior to any attempt to seek formal medical advice. Although applying self-reported elements of the ABCD2 score was inadequate to rule-out cerebrovascular disease, a modified score with additional elements may provide an efficient, immediate, and individualized mechanism to reach patients with TIA who might not otherwise seek medical attention.
Abstract 154: A Comparison of Carotid Artery Stent Placement Performed Within and Outside Clinical Trials in the United States
Authors: Hussein Haitham M , Chaudhry Saqib A , Majidi Shahram , Khatri Rakesh , Rodriguez Gustavo J , Suri M. F , Qureshi Adnan I
Published: July 2021

Background:
A discrepancy between characteristics of patients treated with carotid angioplasty and stent placement (CAS) within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may lead to reduction in anticipated benefit. Objective: To identify differences in demographic and clinical characteristics and outcomes related to CAS in patients treated within clinical trials and those treated outside clinical trials in a large national cohort.

Methods:
We determined the frequency of CAS performed within and outside clinical trials and associated in-hospital outcomes using data from the Nationwide Inpatient Survey (NIS) data files from 2005 to 2008. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis.

Results:
Of the 47,899 patients who underwent CAS, 16,078 (1%) underwent the procedure as part of a clinical trial. The mean age of the patients was significantly lower in patients treated with CAS as part of a clinical trial than those treated with CAS outside a clinical trial. The proportion of women and non-whites was lower among patients treated with CAS as part of a clinical trial. The in-hospital mortality was two folds higher among patients treated with CAS outside clinical trial (1.12% versus 0.53%, p=0.0.0005). The rate of composite end-point of stroke, cardiac events, and death was significantly higher among patients treated with CAS outside clinical trials (p=0.02). After adjusting for age, gender, presence of hypertension, diabetes mellitus, renal failure, congestive heart failure, and hospital teaching status, CAS performed as part of clinical trial was associated with lower rates of in-hospital mortality (OR 0.349, 95% CI 0.219-0.555)(p<0.0001) and composite end point of stroke, cardiac events, and death (OR 0.349, 95% CI 0.219-0.555)(p<0.0001) .

Conclusions:
Our results suggests that CAS performed as part of clinical trial was associated with lower rates of in-hospital mortality and composite end point of stroke, cardiac events, and death in United States. These findings highlight the need for strategies that ensure appropriate adoption of CAS to ensure that the benefits observed in clinical trials can be replicated in general practice.
Abstract 163: Discovery of Asymptomatic Moyamoya Arteriopathy in Pediatric Syndromic Populations: Radiographic and Clinical Progression
Authors: Lin Ning , Baird Lissa , Scott R. Michael , Smith Edward R
Published: July 2021

Introduction:
Limited data exists to guide management of incidentally discovered pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in which the unaffected side is monitored, this phenomenon also occurs in populations undergoing routine surveillance of the cerebral vasculature for other conditions, such as sickle cell disease (SCD) or neurofibromatosis type I (NF1). Here we present our experience with specific syndromic moyamoya populations to better characterize the natural history of radiographic and clinical progression in asymptomatic moyamoya.

Methods:
Retrospective review of a consecutive series of 418 patients who underwent surgical revascularization for moyamoya disease at a single institution from 1988-2010.

Results:
Of 418 patients, 83 were asymptomatic at the time of radiographic diagnosis of moyamoya, while also having either unilateral moyamoya or moyamoya in association with either SCD or NF1. Average age at presentation was 9.1 years (range 1-21), with 47 females (60%) and 31 males (40%). Mean follow-up was 5.4 years (SD +/-3.8), with 45 patients (54%) demonstrating radiographic progression and 37 patients (44.6%) becoming symptomatic within this period. The time interval between radiographic progression from the diagnosis of syndromic disease, to evidence of arteriopathy, to signs of slow cortical blood flow, and to stroke was 5.8 years (SD +/-4.7), 0.7 years (SD +/-1.1), and 0.3 years (SD +/-0.5), respectively. SCD patients had the highest incidence of both radiographic (n=15, 75%) and clinical (n=13, 65%) progression, followed by NF1 (n=20, 59% radiographic, n=15, 44% clinical) and unilateral patients (n=10, 34.5% radiographic, n=9, 31%). Transient ischemic attacks were the most frequent symptoms during follow-up (29 patients, 35%), and 10 patients (12%) developed clinical stroke. Overall 49 patients (59%) underwent surgical treatment, and the time between arteriopathy to surgery was 1.1 years (SD +/-1.2).

Conclusion:
Radiographic progression occurred in the majority of asymptomatic patients and generally heralded subsequent clinical symptoms. SCD or NF patients with asymptomatic moyamoya are more likely to progress and require treatment than unilateral moyamoya patients without a syndromic disease. These data demonstrate that moyamoya is a progressive disorder, even in asymptomatic populations, and supports the rationale of early surgical intervention to minimize morbidity from stroke.
Abstract 166: Indirect Revascularization for Symptomatic Intracranial Arterial Stenoses: Clinical and Angiographic Outcomes
Authors: Dusick Joshua R , Liebeskind David S , Saver Jeffrey L , Martin Neil A , Gonzalez Nestor
Published: July 2021

Objective:
Symptomatic intracranial arterial stenoses have a high rate of recurrent stroke despite medical and endovascular treatments. We present clinical and angiographic quantitative outcomes of indirect revascularization for patients with symptomatic intracranial stenosis.

Methods:
Patients treated for symptomatic intracranial arterial stenosis by indirect revascularization were included. Patients had failed maximal medical management and were unsuitable for or had failed endovascular therapy. Patients underwent encephaloduroarteriosynangiosis (EDAS) with or without burr holes. Preoperative and postoperative angiograms were evaluated for change in caliber of extracranial blood vessels (superficial temporal artery and middle meningeal artery) and for evidence of neovascularity.

Results:
Thirteen patients underwent EDAS. Ischemic symptoms ceased within 3 weeks of surgery in 92.3% of patients and in all patients by 3 months. During the follow-up period (median follow-up 4.5 years) 85% of patients remained symptom-free, returning in a delayed fashion in only 2 (one at 1 year and one at 4 years). No patients treated with EDAS developed strokes or died. All donor blood vessels increased in size relative to preoperatively (average increase of 52% for proximal STA, p=0.01, 74% for midpoint of STA, p=0.01, and 84% for the MMA, p=0.02). In addition, 8 of 11 (73%) patients demonstrated direct spontaneous anastamoses from extracranial to MCA branches and all patients demonstrated angiographic evidence of vascular blush and/or new branches from the STA and/or MMA.

Conclusions:
Indirect revascularization appears to be a safe and effective method to reduce TIAs, stroke and death in patients with symptomatic intracranial arterial stenosis. Neovascularity and enlargement of the external carotid branches were observed in all patients and correlated with improvement in ischemic symptoms. Indirect revascularization is an option for patients who have failed medical therapy.
Abstract 200: CD40 Signaling Mediates Postischemic Inflammation, Oxidative Stress, And Tissue Injury Following Focal Cerebral Ischemia
Authors: Jin Rong , Song Zifang , Yu Shiyong , Daunis Daniel J , Hopkins Brittany S , Nanda Anil , Granger D Neil , Li Guohong
Published: July 2021

Rationale:
Although CD40/CD40 ligand (CD40L) signaling has been implicated in clinical and experimental ischemic strokes, the underlying mechanisms are largely unclear.

Objective:
We investigated how CD40 participates in the cellular and molecular events underlying the postischemic inflammation and oxidative stress that may contribute to the tissue damage during cerebral ischemia.

Methods and Results:
Wild-type (WT, n=164) and CD40 knockout mice (n=132) were subjected to middle cerebral artery occlusion (MCAO, 60 minutes) followed by reperfusion. We found that ischemia/reperfusion induced CD40 expression in the brain in a time-dependent manner, primarily localized to the microvascular endothelial cells in the early phase (6h) and then to the activated microglia in the later time (24h). The adhesion and infiltration of neutrophils as well as the activation and expansion of microglia induced by ischemia/reperfusion were inhibited in CD40-/- mice, which were time-dependently correlated with suppressing nuclear factor-kB activation and proinflammatory cytokines (IL-1β, TNFα) and adhesion molecules (E- and P-selectin, ICAM-1,MCP-1). Infarct volumes and mortality were reduced in CD40-/- mice at 72h after ischemia/reperfusion. Treatment with an inhibitor of either NADPH oxidase or COX-2, the known enzymes that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD40-/- mice. In contrast, treatment with an inhibitor of inducible nitric oxide synthase (iNOS) further reduced tissue injury in CD40-/- mice. Consistently, ischemia/reperfusion-induced upregulation of NADPH oxidase (Nox2, and Nox4) and COX-2, but not iNOS, were attenuated in CD40-/- mice.

Conclusions:
The findings unveil an essential role for CD40 in the regulation of early molecular and cellular events leading to postischemic inflammation. Inhibition of CD40 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.