bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 157: MicroRNA Expression Signature in Human Brain Arteriovenous Malformations and Brain Hemangioblastoma
Authors: Huang Jun , Zhu Wei , Song Jianping , An Qingzhu , Wang Yang , Zhang Song , Xu Tony , Tang Guanghui , Liu Yanqun , Li Yaning , Wang Yongting , Yang Guo-Yuan
Published: July 2021

Objectives:
Small noncoding microRNAs (miRNAs) play critical roles in many biological and pathological processes and are differentially expressed in normal tissue and diseased tissue. miRNAs expression and function in brain vascular diseases are unknown. In this study, we aim to investigate the miRNAs signature in human brain arteriovenous malformations (BAVM) and hemangioblastoma.

Methods:
Total miRNA from the surgical specimen of BAVM patients (n=6), hemangioblastoma patients (n=5), and healthy individuals (n =5) were assessed using qPCR and Exiqon Human Panel. 739 miRNAs were validated with qRT-PCR analysis to establish the miRNA expression signature. To predict potential miRNA targets and analyze their functions, the preliminary qRT-PCR data was analyzed by GenEx and Ingenuity Pathway Analysis software.

Results:
miRNAs were differentially expressed in BAVM and hemangioblastoma patients vs. healthy controls. The miRNA expression levels of 85 and 166 miRNAs were significantly different (
p
<0.05) in BAVM and in brain hemangioblastoma patients compared to healthy controls, respectively. 93 miRNAs expressed significantly differently (
p
<0.05 and passed Bonferroni correction) in the BAVM patients compared to hemangioblastoma patients; Principal component analysis demonstrated a distinction between BAVM and hemangioblastoma vs. healthy controls based on the miRNAs. Bioinformatic analysis indicated that the most of miRNAs were involved in notch signal pathway and angiogenesis.

Conclusions:
This study showed that there was a distinct miRNA expression signature in brain vascular diseases. Our findings provided a valuable clue on the identification of miRNAs’ function in cerebrovascular pathologic processes and the development of therapeutic targets.

1
Abstract 175: The Role of ER-α, ER-ß, and AR in the FCG Model of Ischemic Brain Injury
Authors: Bentivegna Kathryn C , Manwani Bharti , Benashski Sharon E , Doran Sarah , Pan Sarah , McCullough Louise D
Published: July 2021

Background:
Ischemic stroke is a sexually dimorphic disease. Females are protected from ischemic brain injury throughout most of the lifespan, but the contribution of hormones in this “ischemia resistant” phenotype remains unclear. The “four core genotype” (FCG) model is used to differentiate the effect of the chromosomal complement (XX vs. XY) from an animal’s gonadal (estrogen vs. testosterone producing) sex through examination of five genotypes XYMwt, XY-M, XXM, XXF, and XYF. XY-M FCG mice are made by the translocation of Sry from the Y chromosome to an autosome. Stroke sex differences have been largely attributed to the neuroprotective effects of estrogen. However, it remains unclear whether hormonal receptors can be influenced at the chromosomal level, which could further explain sexual dimorphism in stroke phenotypes. We hypothesize that the sex chromosome complement and transgene Sry (the testis determining gene found on the Y chromosome) contribute to the sexually dimorphic stroke phenotype.

Methods:
FCG animals were gonadectomized at 3 weeks of age. Animals were subjected to stroke at 8-12 weeks of age. Cytosolic samples were evaluated for androgen receptor (AR) and estrogen receptor (ER-α and ER-β) levels in sham and stroke samples. RT-PCR for Sry on the stroke hemisphere (delta-delta-CT) was performed on the FCG mice and wild type males.

Results:
Western blot analysis showed that XXM and XXF mice had significant stroke induced reduction in AR expression (p<0.01). No significant difference in the expression of ER-α was seen in sham and stroke mice among genotypes. ER-β expression increased significantly in XXM post stroke (p<0.05), but not in the other genotypes. RT-PCR analysis showed approximately 90-fold increase of mRNA expression of Sry in the phenotypes with the exogenous Sry (XYM and XXM) compared to WTM mice with endogenous Sry (p<0.05).

Conclusion:
XXM and XYM mice show an increase in Sry expression compared to WTM suggesting insertional and positional effects of Sry transgene. AR expression in XXM and XXF mice is influenced at the chromosomal level, suggesting effects of X chromosome dosage on AR expression. Stroke induced ER-β expression in XXM mice may be an effect of the interaction between transgene Sry and other hormonal axes.
Abstract 177: Oral Anticoagulation Related Intracerebral Hemorrhage Is Becoming More Common and Less Fatal. A Nationwide Study From Finland
Authors: Meretoja Atte , Malmivaara Antti , Roine Risto O , Hakkinen Unto , Kaste Markku
Published: July 2021

Background and Purpose:
Intracerebral hemorrhage (ICH) is a highly lethal stroke subtype, especially when associated with oral anticoagulation (OAC). We sought to explore the frequency and case-fatality of OAC-ICH in a nationwide consecutive database of all hospitalized incident cases in Finland, the country with the most rapidly aging population in Europe.

Methods:
The data from 1999 to 2010 were extracted from the PERFECT Stroke registry, a national database of all incident stroke patients hospitalized in Finland. OAC-ICH was defined as a first-in-a-lifetime ICH admission in a patient using warfarin, the only OAC available during the study period in Finland. Case-fatality was determined by linking to the national death registry using a unique identifier, which ensured 100% follow-up.

Results:
Over the 12 years, there were 17,185 cases of ICH registered out of which 2354 (13.7%) were on OAC at the time of their ICH. The annual number of OAC-ICH patients increased from 178 to 269 (+51%) with no increase in annual non-OAC-ICH (1271 to 1228; -3%). The median age increased from 76 to 79 in the OAC-ICH cases, staying at 71 in the non-OAC-ICH cases, while the national population older than 75 increased from 223,000 to 436,000 (+95%). After age and sex adjustment to the common year 1999, the national incidence of OAC-ICH remained at 3.5 to 3.7 per 100 000 population (non-significant change of +6%; 95% CI -8% to +22%), while non-OAC-ICH decreased from 24.1 to 18.9 per 100,000 (-22%; -17% to -26%). In OAC-ICH, case-fatality at 28 days decreased from 51.2% in 1999-2000 to 43.4% in 2009-2010 (annual trend -0.9%; 95% CI -0.3% to -1.4%;
P
=0.005). The decrease in 28-day case-fatality was smaller in non-OAC-ICH (30.2% to 25.9%; annual trend -0.3%; 95% CI -0.1% to -0.5%;
P
=0.002). Sensitivity analyses were done adjusting for age, sex, and comorbidities, with similar Results annual trend -0.9% (
P
=0.002) and -0.4% (
P
<0.001) for OAC and non-OAC ICH correspondingly.

Conclusion:
As the population ages, the proportion of ICH that is related to oral anticoagulation increases, in our series from 12% to 18% over 12 years. While the age and sex adjusted incidence of ICH in general is decreasing, that is not the case with OAC-ICH. Reassuringly, survival from OAC-ICH is improving.
Abstract 185: Risk-adjusted Comparison of Good Functional Outcome at 3 Months after Primary Endovascular Therapy or Intravenous Thrombolysis Alone. Results from an Observational, Population-based Study
Authors: Abilleira Sònia , Dávalos Antoni , Chamorro Ángel , Ribó Marc , Cardona Pere , Serena Joaquín , Krupinski Jerzy , Martí-Fàbregas Joan , Roquer Jaume , Martínez-Yélamos Antonio , Álvarez-Sabín José , Cánovas David , Ustrell Xavier , Purroy Francisco , Gómez-Choco Manuel , Garcés Moisés , de Miquel Maria Angels , Tomasello Alejandro , Macho Juan M , Ribera Aida , Gallofré Miquel ,   The Catalan Stroke Code and Reperfusion Consortium
Published: July 2021

Background:
Evidence clearly supports intravenous thrombolysis (IVT) as first-line therapy for AIS. Yet, endovascular treatment (EVT) might be an alternative for patients with IVT contraindications. Our aim was to study whether patients treated with primary EVT in daily practice did as well as those treated with IVT alone in terms of functional outcome.

Methods:
Observational, population-based study of consecutive AIS patients treated with either isolated EVT or IVT within 2011 and 2012 in Catalonia. Patients were prospectively included in a health-administration based registry with external monitoring of completeness. Inclusion criteria: EVT or IVT delivered under routine conditions. Exclusion criteria: combined IVT+EVT therapy, pre-stroke mRS >2, lacunar stroke subtype, unusual stroke etiology, baseline NIHSS >25 and onset-to-treatment (OTT) > 400 minutes. We determined the risk-adjusted probability [adjustment variables: age, NIHSS, OTT, pre-morbid mRS, hypertension, dyslipidemia, diabetes, AF, OCSP classification and etiology] of achieving functional independence at 3 months (mRS <=2) and performed subgroup analyses.

Results:
1149 patients underwent IVT and 129 (10.1%) EVT. Patients in the EVT arm were younger (71.2+/-11.5 vs. 74.3+/-11.9), had higher NIHSS scores (18 [12-20] vs. 11 [7-18]), were treated later (198 [150-270] vs. 140 [105-190]) and more frequently had concomitant AF (55% vs. 21.9%), heart failure (12.4% vs. 4.9%), and were on anticoagulants (49.6% vs. 5.4%). Dyslipidemia (45.4% vs. 36.4%) and antiplatelets (42.7% vs. 26.4%) were more frequent in the IVT arm. Overall, the risk-adjusted likelihood of good functional outcome was better for EVT (OR: 1.56; 95% CI: 0.97-2.52). Subgroup analyses showed that patients with NIHSS =>14 (OR: 1.92; 95% CI: 1.10-3.46) and those treated within 180-270 minutes post-stroke (OR: 3.44; 95% CI: 1.41-8.39) benefited more from EVT.

Conclusions:
In a population-based study of reperfusion therapies for AIS, patients undergoing isolated EVT were more likely to achieve functional independence at 3 months as compared to patients treated with IVT, particularly those with severe strokes or those treated within 3-4.5 hours post-stroke. These findings need to be confirmed in a RCT.
Abstract 197: The TeleStroke Mimic (TM) Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network
Authors: Ali Syed F , Singhal Aneesh B , Feske Steven K , Davis Lawrence W , Forducey Pamela G , Nystrom Karin , Schindler Joseph L , Schlegel Sherene , Likosky William H , Solenski Nina J , Southerland Andrew M , Schwamm Lee H
Published: July 2021

Intro:
Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). SMs are likely common in telestroke as well, and a model to help a priori identify these patients might be clinically useful.

Methods:
We used 829 consecutive patients from 01/04 to 04/13 in our internal New England based Partners TeleStroke Network for a derivation cohort and 332 cases for internal validation. External validation was performed on 226 cases from 01/08-08/12 in our Partners National TeleStroke Network. Performance of a prediction rule developed with stepwise logistic regression was characterized by ROC curve analysis.

Result:
There were 23% SM in the derivation, 24% in the internal and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (CVD), SM had lower mean age, fewer vascular risk factors, more often prior seizure and a different profile of presenting symptoms (Table 1). The TM-Score (Figure 1) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness and NIHSS >14. The TM-Score performed well on ROC curve analysis (derivation cohort AUC=0.753, internal validation AUC=0.710, external validation AUC=0.770).

Conclusion:
As telestroke consultation expands, increasing numbers of SM patients are being evaluated. These patients differ substantially from their ischemic CVD counterparts in their vascular risk profiles and other characteristics. Decision-support tools based on predictive models, like the one we propose, may help highlight these differences during complex, time-critical telestroke evaluations.
Abstract 37: Pediatric Brain Attacks: Differentiating Between Stroke and Mimics in the Emergency Room.
Authors: Mackay Mark T , Lee Michelle , Churilov Leonid , Yock-Corrales Adriana , Donnan Geoffrey , Monagle Paul , Babl Franz
Published: July 2021

Objective:
Timely recognition of stroke in the pediatric emergency room (ER) is critical to improving access to hyper-acute therapies. We aimed to identify key clinical features which discriminate between stroke and non-stroke brain attacks (mimics).

Methods:
Two-hundred and eighty consecutive children presenting to the ER with non-stroke brain attacks, prospectively recruited over 18 months in 2009-2010, were compared to 104 children with stroke, prospectively/retrospectively recruited from 2003-2010. Brain attack was defined as acute onset focal brain dysfunction with ongoing symptoms or signs on arrival to the ER. Exclusion criteria included known epilepsy, hydrocephalus, head trauma and isolated headache.

Results:
Stroke diagnoses included arterial ischemic stroke (AIS) (55), hemorrhagic stroke (HS) (37), TIA (10) and sinovenous thrombosis (2). The most common mimic diagnoses included migraine (87), first seizure (46), Bell’s palsy (29) and conversion disorder (18). Children with stroke were more likely to have sudden onset of symptoms (85% vs. 71%), arrive by ambulance (63% vs. 33%) and receive higher triage category (43% vs. 23%) than mimics (p<0.001 all variables). Symptoms with good discriminatory value (stroke vs. mimic) included focal weakness (58% vs. 34%), altered consciousness (31% vs. 19%) and speech disturbance (36% vs. 16%) (p<0.001 all variables). Signs with good discriminatory value included focal weakness of the face (45% vs. 14%), arm (47% vs. 13%) or leg (38% vs. 15%), dysarthria (22% vs. 5%), dysphasia (11% vs 3%) and altered consciousness (43% vs. 23%) (p<0.001 all variables). Absence of focal neurological signs (20% stroke vs 35% mimic) on examination predicted mimic (p=0.005).

Conclusions:
Focal weakness and speech disturbance predict stroke diagnosis in children with brain attack symptoms, findings which are similar to adults. These findings will inform the development of pediatric bedside stroke recognition tools to improve rapid recognition of stroke by emergency physicians.
Abstract 38: Herpes Viruses in Childhood Arterial Ischemic Stroke: Interim Results of the VIPS Study
Authors: Fullerton Heather J , Elkind Mitchell S , Glaser Carol A , Hills Nancy K , Luna Jorge , Sear Katherine , Wintermark Max , DeVeber Gabrielle A ,   on behalf of the VIPS Investigators
Published: July 2021

Background:
Varicella zoster virus (VZV) is a known cause of cerebral arteriopathy and arterial ischemic stroke (AIS) in children, and scant evidence suggests other herpes viruses may also play a role. An objective of the Vascular effects of Infection in Pediatric Stroke (VIPS) study was to determine whether recent infection with herpes viruses_as measured by serologies_is associated with childhood AIS.

Methods:
VIPS is an international prospective 35-center case-control study enrolling 350 children (28 days-18 years) with AIS and 120 unmatched trauma controls. Case confirmation and vascular imaging review are performed centrally. Acute blood samples are collected ≤3 weeks after stroke/trauma; convalescent samples 7-28 days after the acute draw in cases only. Samples were tested for IgG and IgM antibodies to herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), Epstein Barr virus (EBV), and VZV. An algorithm developed a priori by a pediatric infectious disease expert (C.A.G.) classified acute infection as a dichotomous variable.

Results:
Of 310 cases enrolled thus far, 141 cases with paired samples and 44 controls underwent serologic analysis. Median age (IQR) was 7.0 years (2.9, 14.3) for cases and 8.3 (3.3, 13.3) for controls (P=0.90). Evidence of an acute herpes infection was found in 41% of cases versus 9% of controls (P<0.0001; Table). The most commonly identified virus was HSV-1. After adjusting for age in a multivariable logistic regression analysis, herpes exposure remained a significant predictor of AIS (OR 9.0, 95% CI 3.1, 38.7; P=0.0004). Of the 58 cases positive for herpes, 36% had a definite arteriopathy, and 33% a possible arteriopathy, compared to 34% and 24%, respectively, of 83 negative cases.

Conclusions:
In this interim analysis, acute exposure to a herpes virus appears associated with childhood AIS, present in 41% of cases that were tested.
Abstract 56: Genome-wide Association Studies of Incident Stroke: The Charge Consortium
Authors: Debette Stephanie , Chauhan Ganesh , Chu Audrey , Fornage Myriam , Bis Josh C , de Stefano Anita , Verhaaren Benjamin , Smith Albert V , Teumer Alexander , Luting Xue , Nalls Mike , Trompet Stella , Liu Yongmei , Wolf Philip A , Schmidt Carsten O , Chasman Daniel I , Mosley Thomas H , Tzourio Christophe , Launer Lenore , Van Duijn Cornelia , Ikram MA , Kurth Tobias , Seshadri Sudha , Longstreth Will T ,   neuro-CHARGE working group
Published: July 2021

Background:
Despite a high heritability, only few stroke risk genes are known. Genetic association studies performed in a hospital-based setting may fail to detect genes modulating both stroke susceptibility and severity, given early deaths at the acute stage. This selection bias is avoided when studying incident stroke in a population-based setting.

Methods:
We conducted a meta-analysis of genome-wide association studies of incident stroke in 11 community-based longitudinal studies from the Cohorts of Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Genome-wide Cox regressions were performed adjusting for age, gender and population substructure, using 1000GpIv3 imputed genotypes. Results were combined using inverse variance weighted meta-analysis.

Results:
The study sample comprised 65,204 participants (71.5% women) of European ancestry, aged 66.2±8.0 years at DNA draw, followed up for 10.8±3.8 years. In 11 studies, 3,389 participants developed incident stroke, and in 8 studies, 2,223 developed incident ischemic stroke (IS): 531 cardioembolic [CE] and 1,576 atherothrombotic [AT]. The most significant association with incident stroke was for a novel variant on chr9p23 (MAF=0.35), HR=1.15 [95%CI:1.09[[Unable to Display Character: ‒]]1.21], p=8.5х10-8: p=2.54x10-5 for IS; 1.19x10-4, AT-IS; and 0.019, CE-IS. Associations were in the same direction for all participating studies, and 5 additional SNPs in this locus reached p<10-6. The most significant association with incident IS was for rs11833579 [NINJ2], HR=1.21[1.13[[Unable to Display Character: ‒]]1.30], p=2.1х10-7, but p-random-effects=9.54x10-3 (p-heterogeneity=0.02, I2=57.9%). We replicated published associations for CE-IS (rs6843082-G [PITX2], HR=1.30[1.13-1.49], p=1.95x10-4) and for large artery stroke with AT-IS (rs2107595-A [HDAC9], HR=1.13[1.03[[Unable to Display Character: ‒]]1.24], p=0.012)

Conclusion:
In the largest GWAS of incident stroke, we detected one novel association with all stroke, requiring confirmation in independent samples. Expansion of the discovery sample and replication of findings are planned in the coming months. Detecting genetic variants associated with incident stroke may provide important clues for understanding pathways involved in stroke susceptibility and tolerance to acute vascular brain injury.
Abstract 61: Safety and Feasibility of Acute Dabigatran Therapy in Minor Ischemic Stroke Patients Without Atrial Fibrillation.
Authors: Butcher Ken , Kate Mahesh , Gioia Laura , Jeerakathil Tom , Buck Brian , Emery Derek , Khan Khurshid , Saqqur Maher , Shuaib Ashfaq
Published: July 2021

Introduction:
Transient Ischemic Attack (TIA) and Minor ischemic stroke (MIS) patients are at high risk for recurrent events. Older anticoagulants are associated with a reduction in recurrent events, but also an increase in hemorrhagic transformation (HT). Dabigatran etexilate (DE), a novel oral anticoagulant that is associated with reduced risk of intracranial bleeding in atrial fibrillation (AF) patients, may be an effective therapy in this population. DE is not indicated within 14 days of ischemic stroke, due to an absence of data. We tested the feasibility and safety of initiating DE therapy within 24 h of TIA/MIS.

Methods:
We designed a 50 patient single arm open label treatment trial. The primary endpoint was symptomatic HT within 30 days of enrolment. All patients underwent MRI prior to treatment. TIA/MIS patients (NIHSS score ≤3) with a DWI lesion were prospectively treated with DE 150 mg BID (110 mg BID in patients ≥ 80 or if CrCl <40 ml/min). Treatment began within 24 h of onset and continued for 30 days. Patients with known atrial fibrillation (AF) were excluded. Patients were re-imaged at day 7 and 30, with clinical assessment to 90 days.

Results:
Forty-three of 50 patients have been enrolled to date (March 2012-August 2013). The mean age was 66±12 years and median (IQR) NIHSS was 1 (2). Median baseline DWI volume was 0.89(1.9) ml. The median time from onset to initial DE dose was 18.5 (12.2) h. Therapy was completed in 41 patients and discontinued in two (withdrawal of consent (1) and dysphagia (1)). Two patients died within the 90 day study period, both after completion of DE therapy. No patients experienced systemic bleeding or symptomatic intracranial hemorrhage. One patient had asymptomatic HT (ECASS grade, HI1) on day 7, which resolved by day 30 despite continuing DE. No patients experienced recurrent clinical stroke. New asymptomatic DWI lesions developed in 7 (16%) patients by day 30.

Conclusion:
These preliminary data suggest DE may be used safely in acute TIA/MIS patients and larger randomized trials are warranted. The low HT rate may make DE an ideal antithrombotic for use immediately after TIA/ischemic stroke.
Abstract 81: Recurrent Stroke Risk After Angioplasty and Stenting for Symptomatic Intracranial Stenosis: Data From the SAMMPRIS Trial
Authors: Derdeyn Colin , Fiorella David , Turan Tanya , Montgomery Jean , Lane Bethany , Janis Scott , Lynn Michael , Chimowitz Marc ,   for the SAMMPRIS Investigators
Published: July 2021

Purpose:
To investigate the incidence and clinical characteristics of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting for symptomatic intracranial stenosis.

Methods:
Primary endpoints in SAMMPRIS (Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke) after 30 days past enrollment were defined as ischemic stroke in the territory or any stroke or death within 30 days of a subsequent revascularization procedure. Endpoints were independently and blindly adjudicated. Study records and imaging studies of subjects randomized to the stent arm with post-30 day primary endpoints were reviewed. Instent restenosis (ISR) was categorized as severe (>70%), moderate (50-69%) or mild (< 50%) based on consensus of two reviewers. Findings were categorized as definite, probable, or indeterminate based on imaging modality and study quality.

Results:
224 subjects were randomized to the stent arm and 33 suffered a primary endpoint within 30 days of enrollment. Nineteen of the remaining 191 subjects (9.9%) suffered a primary endpoint during follow up (median follow up of 32.4 months). Eighteen had an ischemic stroke in the territory and one had a symptomatic intracranial hemorrhage after repeat angioplasty for in stent restenosis (ISR). In the 18 patients with ischemic stroke, the vascular imaging findings were: complete stent occlusion in 2 (1 of these was acutely revascularized and severe underlying ISR was identified), severe ISR by catheter angiography in 5, severe ISR or occlusion by computed tomographic angiography (CTA) in 1, probable ISR by CTA or magnetic resonance angiography (MRA) in 3, moderate stenosis on angiography in 2 (1 with ISR and 1 with a residual stenosis), indeterminate in 2, normal in 2, and not done in 1. Lesion locations included: distal internal carotid (6), petrous carotid (1), basilar (5), middle cerebral (6), and vertebral (1) arteries. Median time to recurrent stroke was 7.7 months from enrollment (2.2 to 28.2 months).

Conclusions:
The incidence of recurrent stroke beyond 30 days after uncomplicated angioplasty and stenting in the SAMMPRIS trial was nearly 10% over a mean follow-up of almost 3 years. In stent restenosis was associated with the majority of recurrent strokes.
Abstract 84: Low Risk of Stroke or Death Among Patients With Recently Symptomatic Carotid Stenosis Awaiting Revascularisation - A Pooled Analysis of Randomised Trials
Authors: Bonati Leo H , von Felten Stefanie , Roubin Gary S , Mali Willem P , Jansen Olav , Howard George , Fraedrich Gustav , Chatellier Gilles , Becquemin Jean-Pierre , Algra Ale , Ringleb Peter A , Mas Jean-Louis , Brown Martin M , Brott Thomas G ,   Carotid Stenosis Trialists Collaboration
Published: July 2021

Background:
Historical data suggest that patients with recently symptomatic carotid stenosis are at high risk of early recurrent stroke. Guidelines therefore recommend revascularization within 2 weeks of symptoms. We assessed the risk of stroke or death occurring before revascularization in modern trials of symptomatic carotid stenosis.

Methods:
We pooled data of all individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in the EVA-3S, SPACE, ICSS and CREST trials. The outcome event (OE) was death or any stroke occurring between randomization and treatment by CAS or CEA, or up to 120 days after randomization among patients not undergoing treatment in this period.

Results:
4707 patients were included in the analysis. Median time from qualifying event until randomization was 18 (interquartile range 7-50) days. Median time from randomization until treatment was 6 (2-11) days in the CAS group, and 7 (3-12) days in the CEA group (p<0.001). 31% of patients in the CAS group and 27% in the CEA group underwent revascularization within 14 days of the qualifying event. The OE occurred in 21 patients (CAS: 8, CEA: 13), all within 31 days of randomization (Kaplan Meier estimate: 2.4%, standard error 0.7%; fig.), including 18 non-fatal strokes, 1 fatal stroke, and 2 non-stroke related deaths. In 2 of the patients, the date of the qualifying event was unknown, in 8 patients the OE occurred within 14 days of the qualifying event and in 11 patients >14 days after the qualifying event. All patients with the OE had severe (70-99% degree) stenosis. No other baseline variables predicted the OE.

Discussion: Despite the fact that less than a third of patients underwent revascularization within 14 days of the qualifying event, only 2.4% of patients had a recurrent stroke or died before treatment. The risk is lower than expected from historical data, which may reflect advances in medical therapy. Patients at risk are those with severe degree of stenosis.
Abstract 89: Instituting a 24/7 Enrollment Plan for Acute Ischemic Stroke Clinical Trials: Feasibility, Implementation and Potential Impact
Authors: Shen Loren F , Indupuru Hari , Jacobs Amber , Guerrero Waldo R , Rahbar Mohammad H , Gonzales Nicole R , Pandurengan Renga , Grotta James C , Barreto Andrew D
Published: July 2021

Background and objectives:
Enrollment into acute stroke trials is usually limited to weekday working hours. As a result, a large portion of eligible patients do not receive the opportunity to participate in these trials, hence enrollment rate suffers. We share our experience regarding the feasibility and implementation of a 24/7 enrollment plan for two acute ischemic stroke (AIS) trials. We also compare differences in patients’ characteristics enrolled during working hours (
WH
) vs. after hours+weekend (
AH
).

Methods:
Data used for this study is from a single-center that actively enrolls AIS patients into 2 time-sensitive, tPA-adjunctive clinical trials (CLOTBUST-HF & ARTSS-2). This center implemented a 24/7 on-call system for research coordinators to respond after-hours (5:01pm-6.59am) and on weekends. Approach for AH comprises a coordinated effort that includes: prompt call to on-call coordinator if in-house physician identifies a potential eligible patient; on-call physician delivers IV-tPA and introduces the study; study PI accesses the electronic medical record from home and if applicable the randomization website to screen and prepare for enrollment. The coordinator arrives at ED to assist in-house physician with study procedures. We conducted descriptive analyses that explore differences between
WH
(Mon-Fri: 7am-5pm) vs.
AH
(Mon-Thurs: 5.01pm-6.59am and Fri-Mon: 5.01pm-6.59am).

Results:
During 01/2010 - 05/2013, a total of 34 patients were eligible for the 2 trials of whom 33 were enrolled. 17/33 (52%) patients were enrolled AH and had lower NIHSS scores and longer onset-to-tPA times. Table includes data comparing the groups.

Conclusion:
24/7 research enrollment for AIS patients is feasible and increased recruitment by 106% with no delays in randomization or initiation of investigational treatments. Reproducibility in other centers should be explored. Efforts to provide 24/7 coverage should be evaluated as a way to improve recruitment rates.
Abstract 90: Nursing Education: A Critical Need in the Delivery of High Quality Stroke Care
Authors: Daggett Virginia , Williams Linda , Burrus Nicholas , Myers Jennifer , Plue Laura , Robinson Joshua , Miech Edward , Woodward-Hagg Heather , Damush Teresa
Published: July 2021

Objectives:
High quality stroke care is complex, and requires strong multidisciplinary teams, including nurses, to ensure care processes are timely and appropriate. The purpose of this study was to identify training needs of nurses who deliver care to patients who present with acute stroke and are admitted to inpatient units.

Methodology:
Using semi-structured interviews, we conducted a qualitative study for a formative evaluation in 12 Department of Veterans Affairs Medical Centers (VAMCs) that had ≥ 50 acute ischemic stroke admissions a year and were diverse in the structure of stroke care. The interviews focused on current context and structure of stroke care, including educational practices and training needs. Secondary analyses were conducted, targeting frontline nurse and physician respondents (N = 113) in emergency, acute care and rehabilitation units.

Results:
Respondents across the sites reported insufficient nurse education and training for acute stroke care as an overarching theme. Moreover, themes related to the acute stroke care quality indicators emerged as areas of competencies that nurses needed training on a continuum: a) timely recognition of acute stroke and transient ischemic attacks, b) NIH Stroke Scale and neurological exams, c) dysphagia screening, d) administration of tissue plasminogen activator and management post treatment, and e) deep vein thrombosis prophylaxis. Themes that were related to structure of stroke care and/or context also emerged and attributed to training challenges across the sites, listed in order of prevalence: a) centralized care versus decentralized care, b) low volume of acute strokes, c) nurse engagement, d) structured acute stroke care education, and e) release time.

Conclusions:
VA stroke care providers identify educational needs around specific stroke quality indicators, but also describe key barriers including lower volume, time for training and engagement of nursing staff in acute stroke care. Future programs to improve VA stroke care need to address these barriers to optimally support high quality multidisciplinary stroke care.
Abstract 99: Geographic Access to Acute Stroke Care in the United States
Authors: Adeoye Opeolu , Carr Brendan G , Albright Karen C , Wolff Catherine , Mullen Michael , Abruzzo Todd , Ringer Andrew , Khatri Pooja , Branas Charles , Kleindorfer Dawn
Published: July 2021

Background:
Only 5% of ischemic stroke (IS) patients receive IV tPA and less than 1% receive endovascular therapy (ET). Prior work has described access to Primary Stroke Centers (PSC). We describe access of the US population to all facilities that provide IV tPA or ET for IS.

Methods:
We used US demographic data and IV tPA and ET rates in the 2011 Medicare Provider and Analysis Review (MEDPAR), a claims-based dataset that contains fee-for-service Medicare-eligible inpatient hospital discharges in the US. ICD-9 codes 433.xx, 434.xx and 436 identified IS cases. ICD-9 code 99.10 defined IV tPA treatment. Among IS cases, hospitals that gave any IV tPA were considered IV capable. ET was defined by ICD-9 code 39.74. Hospitals that performed any ET in IS cases were considered endovascular capable. PSCs were defined as hospitals certified as such by the Joint Commission in 2010. We estimated ambulance response times using arc-GIS’s network analyst and helicopter transport times using validated models. Population access to care was determined by summing the population contained within travelsheds that could reach capable hospitals within 60minutes.

Results:
Of 370351 IS primary diagnosis discharges, 14926 (4%) received IV tPA and 1889 (0.5%) had ET. By ground, 81% percent of the US population had access to IV capable hospitals within 60minutes, 66% had access to PSCs and 56% had access to ET capable hospitals. By air, 97% percent had access to IV capable hospitals within 60minutes, 91% had access to PSCs and 85% had access to ET hospitals. The Figure shows 60 (yellow) and 120 minute (green) access to IV rt-PA capable hospitals.

Conclusion:
Most of the US population has geographic access to acute stroke care, but treatment rates remain extremely low. Given our definitions of capability, actual access may be less than described. To optimize US stroke care systems and increase the use of acute therapies, pre- and inhospital interventions to overcome barriers in access to acute stroke care are needed.
Abstract NS7: Measurement of Acute Stroke Nursing Knowledge: Opportunities for Improvement in Stroke Nursing Education
Authors: Alexandrov Anne W , DiBiase Stephen E , Walker Artney P , Wojner Alexis J , Brewer Barbara B , Swatzell Victoria
Published: July 2021

Background:
Nurses caring for acute stroke patients require significant knowledge and skills to deliver expert evidence-based care. However, stroke nurse knowledge has not been captured with standardized methods until recently. We sought to measure knowledge in nurses participating in the NET SMART Junior program.

Methods:
NET SMART Junior is a novel on-line acute stroke learning system with more than 2500 users worldwide. The program provides both didactic and optional clinical skills exercises, with topics covering all aspects of prehospital and acute hospital management. We analyzed an international sample of test scores from NET SMART Junior, among users that completed the clinical competency portion of the program. Data were auto-assembled in Moodle and analyzed in SPSS.

Results:
216 scores were analyzed; the sample consisted of 8 MSN nurses and 208 (96%) basic nurses. Overall program entry knowledge scores were 37%+/-14%, median 39% correct; significantly lower scores of 36%+/-14%, median 38% correct were found among staff nurses, as compared to 50%+/-15%, median 49% correct (mean diff 13.8; 95% CI 3.8-23.8; p=0.007) among MSN nurses. The lowest knowledge scores were found for reperfusion therapy, neurocritical care and complication avoidance (Table). No differences were found in users indicating completion of unit-based stroke educational programs or other for-profit on-line educational programs. Post-test scores were similar between groups with MSN nurses scoring 94%+/-5% (median 90%) and staff nurses scoring 95%+/-5% (median 100%; p=ns) on completed modules. Among 29 (13%) users indicating completion of a stroke certification examination (SCRN or NVRN), 100% pass rates were reported.

Conclusions:
Staff nurses have a variety of learning needs tied to acute stroke management. Comprehensive acute stroke education programs should include more expert level content and be supported by clinical application methods to ensure content mastery.
Abstract T MP105: Relationship Between Compliance With the Lifestyle Modification Program and Risk Factor Control in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial
Authors: Turan Tanya N , Nizam Azhar , Lynn Michael J , Montgomery Jean , Derdeyn Colin P , Fiorella David , Lane Bethany F , Janis Scott , Chimowitz Marc I ,   SAMMPRIS Investigators
Published: July 2021

Background and Purpose:
SAMMPRIS was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to subjects to enhance risk factor control. We sought to determine the relationship between compliance with the lifestyle modification program and risk factor control in SAMMPRIS.

Methods:
SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n=451) during their participation in the study. Subjects with < 3 expected lifestyle coaching calls were excluded from these analyses. Subjects with ≥ 78.5% of calls (median % of completed/expected calls) were considered Compliant (n=201). Subjects with < 78.5% and those who refused to participate were considered Noncompliant (n=200). Mean risk factor values or % in-target for each risk factor were compared between Compliant vs. Noncompliant subjects, using t-tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences between the groups.

Results:
As shown in the figure, Compliant subjects had better risk factor control throughout follow-up for LDL, SBP, HgA1c, non-HDL, non-smoking, and exercise than Noncompliant subjects, but there was no difference for BMI. Compliant subjects also had better control of LDL, non-HDL, and HgA1c at baseline. Both groups had some improvement in risk factors throughout the study (except for BMI), but after adjusting for baseline differences between the groups, Compliant subjects had a greater change from baseline than Noncompliant subjects for SBP at 24 months and HgA1c at 6 months.

Conclusions:
SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors.
Abstract T MP113: Symptoms During Carotid Sinus Massage, but Not the Magnitude of Haemodynamic Change, are Associated with White Matter Lesions in Later Life
Authors: McDonald Claire , Firbank Michael , Lewis Ieuan , Pearce Mark , Kerr Simon , Blamire Andrew , Newton Julia
Published: July 2021

Introduction:
White matter hyperintensities (WMH) on MRI are common in older people and are associated with cognitive impairment, falls and depression. They are believed to represent cerebrovascular small vessel disease but as frank infarction is not always seen it is suggested that WMH represent damage resulting from hypoperfusion. Carotid sinus hypersensitivity (CSH) is an exaggerated fall in blood pressure (BP) or heart rate (HR) in response to stimulation of the carotid sinus. It is defined as a ≥50 mmHg drop in systolic BP & / or ≥3 second asystole in response to carotid sinus massage (CSM). CSH, is often associated with syncope & presyncope, thought to indicate cerebral hypoperfusion.

Aim:
To examine, over a ten year follow-up, if CSH is associated with WMH volume.

Method:
In 2002, 274 people age ≥65 underwent CSM. BP & HR response were recorded using beat to beat monitoring. Symptoms suggestive of cerebral hypoperfusion e.g. syncope or presyncope were recorded. In 2012, 53 of these participants underwent MRI. Volume of WMH was calculated using a validated quantitative method.

Results:
Of the 53 participants who underwent MRI, 17 had CSH. Presence of CSH was not associated with WMH volume. Mean BP response was 46.5 mmHg (SD 20.4) and mean HR response was 2.5s (SD 1.9). Change in BP or HR were not associated with WMH volume.

Eight of the 53 participants had syncope or presyncope during CSM. These symptoms were significantly associated with greater total WMH volume (P=0.004) & greater periventricular WMH volumes (P=0.001). Findings remained significant after adjusting for age, sex & history of hypertension, [total WMH R
2
0.29 (p=0.006) & periventricular WMH R
2
0.34 (P=0.002)].

Conclusion:
Presyncope or syncope during CSM, rather than hemodynamic response, predict volume of WMH. These findings suggest clinical symptoms of cerebral hypoperfusion rather than hemodynamic changes are a better indicator of patients at risk of WMH.
Abstract T MP118: Microinfarct Disruption of Cerebral White Matter: A Longitudinal Diffusion Tractography Analysis
Authors: Auriel Eitan , Reijmar Yael , Edlow Brian , Fotiadis Panagiotis , Martinez-Ramirez Sergi , Jun Ni , Reed Anne , Vashkevich Anastasia , Schwab Kristin , Viswanathan Anand , Gurol Mahmut Edip , Greenberg Steven M
Published: July 2021

Introduction:
Cerebral microinfarcts (CMI) are associated with cognitive decline in clinico-pathological studies. Acute CMI can be detected by diffusion-weighted imaging (DWI). We prospectively evaluated the effect of incidental CMI on white matter (WM) ultrastructure using longitudinal diffusion tensor imaging (DTI)-based tractography.

Methods:
Nine incidental DWI lesions were identified in six subjects (all males, age 67±9 years, mean pre-to-post lesional scan interval 19±4 months). All patients were diagnosed with probable cerebral amyloid angiopathy and underwent at least three MRIs as part of a prospective study. Silent DWI lesions were observed on the middle scan, enabling longitudinal analysis. Control regions-of-interest (ROIs) were generated in the contralateral hemisphere using semi-automated coregistration, and the lesion/control ROIs were coregistered to the pre- and post-lesional scans. DTI parameters [fractional anisotropy (FA); mean diffusivity (MD)] were measured within each ROI, along a short-segment of WM fiber tracts (within 6mm of the ROI), and along the entire tract. For the lesional scan, we compared DTI parameters between lesion and control ROIs. For the longitudinal analysis, we compared the ratio of lesion-to-control FA and MD at the pre-lesional and post-lesional scans.

Results:
On the lesional scan, FA within the lesion ROI was significantly lower than in the control ROI (0.28±0.13 vs. 0.40±0.20, p=0.04) and MD was non-significantly reduced in the lesion ROI versus the control ROI (p=0.09). A significant decline within lesion ROI in FA ratio (1.22±0.45 vs. 0.91±0.439, p=0.04) and an increase in MD ratio (0.96±0.14 vs. 1.25±0.37, p=0.02) were observed between the pre-lesional and post-lesional scans. There was no difference in FA ratio or MD ratio for the short segment or entire tracts at the time of the lesion and in the longitudinal analysis.

Conclusion:
We demonstrate persistent microstructural alterations of WM caused by incidental DWI lesions. Although these alterations do not extend outside the lesional ROI to associated fiber tracts, their accumulation over time may explain their association with cognitive decline.
Abstract T MP21: Effect of IV rtPA in Mild Strokes in the Third International Stroke Trial (IST3): A Post Hoc Analysis
Authors: Khatri Pooja , Tayama Darren , Cohen Geoff , Lindley Richard I , Wardlaw Joanna M , Yeatts Sharon D , Broderick Joseph P , Sandercock Peter ,   on behalf of the PRISMS and IST-3 Investigators
Published: July 2021

BACKGROUND:
A relatively small number of patients with mild ischemic stroke (NIHSS 0-5) had been included in randomized trials of IV tPA up to 2012, and debate continues about the balance of risk and benefit from thrombolysis in this group. In the recent IST3 trial, among patients with NIHSS 0-5, 221/304 (72.7%) tPA vs. 232/308 (75.3%) control subjects were alive and independent (OHS 0-2) at 6 months, a nonsignificantly adverse effect. To determine whether a further trial in mild stroke patients was justified, we examined the effect of tPA in a more restricted subset of IST3 patients with NIHSS 0-5 who met NINDS tPA Study criteria.

METHODS:
The IST3 trial was a pragmatic, international, randomized-controlled, open-treatment trial with broad entry criteria comparing IV tPA with control within 6 hours of onset in 3035 subjects conducted in 12 countries outside the USA. We restricted analysis to subjects with NIHSS 0-5 who were treated within three hours, had pretreatment BP<185/110, and met all other NINDS tPA Study criteria. No age restriction was applied. The primary outcome was the proportion alive and independent (OHS 0-2) at 6 months; key secondary analyses were an ordinal analysis of OHS and the proportion alive and with ‘favorable outcome’ (OHS 0-1). (Details at www.ist3.com).

RESULTS:
612 of 3035 (20.2%) subjects enrolled in the IST3 trial had an NIHSS of 0-5. 106 of 612 (17.6%) were recruited within 3 hours, had pretreatment BP<185/110, and met all NINDS tPA Study criteria. In this subset, tPA was associated with a significant increase in the proportion alive and independent, and a favorable shift in distribution of OHS grades. There was no significant effect on ‘favorable outcome’. See Table.

CONCLUSIONS:
This post-hoc analysis in a highly selected sample of the IST3 trial supports the rationale of the PRISMS trial, a randomised placebo-controlled Phase III, 950-subject, 75-center, North American study to evaluate the efficacy and safety of IV tPA in mild ischemic strokes.
Abstract T MP39: Mirror Therapy in Unilateral Neglect after Stroke: Systematic Review and Meta Analysis
Authors: Arora Rani
Published: July 2021

Specific Aims:
To carry out a systematic review and meta-analysis of randomized controlled trials (RCTs) in the treatment of unilateral neglect after stroke using mirror therapy (MT).

Approach:
Inclusion criteria: We used the following criteria: RCTs of MT in the treatment of hemi-neglect and stroke, use of standardized tools to document neglect, clearly defined intervention including duration of treatment and blinded outcome assessment. We conducted a literature search on stroke and hemi neglect limited to the following databases: Cochrane Library, PubMed/Medline, PeDRO, Cinahl and EIRA. There were 15034 hits between 1990 to 2013 with the key words cerebrovascular accident (MeSH) and rehabilitation; there were 1578 hits with hemispatial neglect and rehabilitation. There were 16 RCTs trials where MT was used to study motor recovery. Out of 16 trials, only in 3 RCTs MT was evaluated in hemineglect patients.

Innovation:
The 3 trials had used different screening tools and outcome measures. Star cancellation score was the common outcome measure used in 2 RCT’s and in the 3rd study they used self-defined neglect score. There were total 75 patients. Using change in the star cancellation score from the baseline, we found that MT had significant effect on improving visuospatial neglect at the end of intervention: Standard mean deviation (SMD) 2.61: 95% confidence interval (CI) 1.85 to 3.36; P<0.00001. A single trial had done follow up at 6 months and showed significant positive effect: SMD 3.67; 95% CI 2.70 to 4.65; P<0.00001. Third study used self-defined five point neglect score based on the Behavioral Inattention Test (BIT) and the Test of Attentional Performance (TAP) and showed significant improvement in the treatment group (SMD 1.22; 95% CI 0.24 to 2.19; P=0.01)

Conclusion:
MT had significant effect on visuospatial neglect at the end of intervention and at 6 months follow up. However there is no large scale RCT available in the use of MT in the treatment of unilateral neglect.