bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 98: Direct Transfer to Angio-suite to Reduce Times to Intra-arterial Treatment and Improve Outcomes in Large Vessel Occlusion Strokes: A Multicenter Matched Analysis
Authors: Bouslama Mehdi , Ribo Marc , Psychogios Marios , Sargento-Freitas João , Haussen Diogo , Requena Manuel , Brehm Alex , Sousa João André , Al-Bayati Alhamza , Cruz Luís , Martins Leonor , Frankel Michael , Nogueira Raul
Published: June 2021

Background and Purpose:
Bypassing the emergency department (ED) and the CT suite by directly transporting to the neuroangiography suite for imaging assessment and treatment may shorten reperfusion times while maintaining proper patient selection.

Methods:
Patients from prospectively collected databases of 4 international comprehensive stroke centers with large vessel occlusion strokes transferred for endovascular therapy (ET) were identified and divided into 2 groups:(1) Direct to angio-suite (DTAS) and (2) standard protocol including CT+/-CTA/CTP. Only patient with anterior circulation strokes, pre-mRS 0-2 and baseline NIHSS The groups were matched for age and baseline NIHSS ≥6 were included. Baseline characteristics, time metrics and outcomes were compared.

Results:
548 patients (274 pairs) were included in the analysis. Baseline characteristics were well-balanced. DTAS patients had shorter median picture-to-puncture (14 [8-20] vs 37 [25-50] minutes, p<0.001)and door-to-reperfusion (68 [57-91.5] vs 100.5 [74-140] minutes,p<0.001)times. In terms of outcomes, DTAS patients had higher rates of successful reperfusion (mTICI 2b-3, 87.2% vs 73.3%, p<0.001) and full reperfusion (mTICI 2c-3, 51.3% vs 38.3%, p=0.004), and lower rates of parenchymal hematomas (14% vs 27%, p<0.001). There were no differences between groups in rates of good outcome (90-day mRS-0-2, 39.2% vs 38.5%, p=0.87) and 90-day mortality (24.2% vs 24.9%, p=0.87).

Conclusions:
DTAS is safe, feasible and an effective strategy to reduce treatment times. The clinical benefit of this approach should be assessed in a prospective randomized trial.
Abstract 99: Mobile Stroke Unit CTA and Direct Notification of Interventional Team Shortens Door-to-Puncture Time by One Hour
Authors: Czap Alexandra L , Singh Noopur , Bowry Ritvij , Jagolino-Cole Amanda , Parker Stephanie A , Bratina Patti , Gutierrez Nicole , Phan Kenny , Wang Mengxi , Sheth Sunil A , Rajan Suja S , Yamal Jose-Miguel , Grotta James C
Published: June 2021

Introduction:
Endovascular thrombectomy (ET) is an effective but time sensitive treatment of acute ischemic stroke. Time from Emergency Department (ED) arrival to start of ET (door-to-puncture time, DTPT) is a modifiable metric. One of the most time consuming steps in prolonging DTPT is identification of large vessel occlusion (LVO) by CT angiography (CTA). BEST-MSU is a prospective multicenter comparative effectiveness study of tPA-eligible patients managed on a mobile stroke unit (MSU) vs Emergency Medical Services (Standard Management, SM). After discovering that DTPT was greater than 60 minutes in both groups at three BEST-MSU centers in 2018, we began to routinely obtain CTA on the MSU and directly alert the ET team at receiving hospitals if a LVO was identified. We hypothesized this would shorten DTPT by over 30 minutes.

Methods:
In this single center experience, we compared the median (interquartile range, IQR) DTPT and MSU on-scene time for MSU patients having on-board CTA and then ET from 9/2018 to 7/2019 to corresponding MSU ET patients (excluding any that had on-board CTA) from 8/2014 to 8/2018. All CTAs were completed after tPA bolus and during tPA infusion on a Ceretom 8 slice scanner with OptiStat hand injector. All imaging occurred on-scene with the MSU stationary. Consent was obtained for all patients and strict radiation safety guidelines followed.

Results:
13 consecutive patients having CTA on-board the MSU and then ET were compared to 84 patients in the pre-on-board CTA group. Baseline characteristics including median NIHSS score (20 in both groups) and frequency of tPA (85% on-board CTA vs 89% pre-on-board CTA) were comparable. Median DTPT was 60 minutes shorter with on-board CTA and direct notification of the interventional team from the MSU; 34 minutes (IQR 30-57) vs 94.5 minutes (IQR 69.75-117.25) (p < 0.001). Despite the additional time to obtain the CTA on the MSU, on-scene time was only slightly prolonged and did not offset the reduction in DTPT (on-board CTA 30 minutes (IQR 28-33) vs pre-on-board CTA 27 minutes (IQR 23-31) (p = 0.01).

Conclusion:
Pre-hospital identification and notification of LVO by a MSU allows a one hour reduction of DTPT, and can be utilized to establish a direct to angiosuite protocol.
Abstract NS3: A Comprehensive Post-Acute Stroke Services (COMPASS) Website for Public Use
Authors: Coleman Sylvia , Radman Meghan , Sissine Mysha , Duncan Pamela , Bushnell Cheryl , Taylor Karen , Lundy-Lamm Gladys
Published: June 2021

Background:
Stroke patients, caregivers, and health and human services are in need of organized, evidence-based resources to improve post-acute care and outcomes. Educational materials vetted by stakeholders are scarce and difficult to develop. The COMprehensive Post-Acute Stroke Services (COMPASS) Study developed online resources by discipline for clinical providers, patients, caregivers, and health and human services teams.

Purpose:
This presentation introduces the COMPASS website content available and ready for immediate use to support post-acute stroke care quality improvement.

Methods:
Materials were developed as a component of the PCORI-funded COMPASS Study designed to implement and evaluate comprehensive transitional care (TC) for stroke survivors. Patients discharged home from 41 NC hospitals after a stroke or TIA received COMPASS TC which incorporated Centers for Medicare and Medicaid (CMS) recommendations: a follow-up phone call within two days of discharge; a comprehensive follow-up clinic visit; and delivery of a patient care plan. An interdisciplinary team of health care providers, stakeholders, and researchers developed patient and caregiver educational materials tested for sixth grade literacy, a community resource directory, and training materials for implementation of COMPASS TC that are available on the COMPASS website at www.nccompass-study.org/.

Results:
Educational products, including a directory of resources, training manuals, recorded webinars, instructional handouts, animated videos, and patient/caregiver materials are on the COMPASS website. An electronic application called COMPASS-Care Plan (CP) also developed can be readily integrated into Epic and Cerner electronic health records. COMPASS-CP was developed to streamline the delivery of the TC model. Since the website was made public July 1, 2019, there have been 616 views from 15 countries with the majority reviewing patient/caregiver resources.

Conclusions:
The COMPASS website provides health and human services teams with organized, evidence-based resources to support delivery and management of post-acute transitional care for patients and caregivers.
Abstract NS6: Early Mobility Initiated at 12 Hours Post Thrombolytic Therapy for Stroke Increases Likelihood for Discharge to Home
Authors: Gwilliam John , McNicholas Mechelle
Published: June 2021

Purpose:
To assess patient safety and discharge outcomes of initiating early mobility after 12 hours of receiving thrombolytic therapy (tPA) for stroke at a Primary Stroke Center.

Background:
Patients receiving tPA are traditionally maintained on bedrest for 24 hours due to an alleged risk of increased complications or falls, however this standard is not supported by data. Prior data among patients receiving tPA supports the concept of providing early mobility before 24 hours without an increased risk of falls or other adverse response. There is also evidence that early mobility in other critical care populations has positive impact on discharge disposition and decreasing the length of stay (LOS).

Methods:
A validated Early Mobility Protocol was implemented within 24 hours for all patients receiving tPA for stroke with a focus to progress each patient through the stages of the mobility protocol based on clinical presentation. Data from pre-implementation (January – May 2018) and post implementation (June 2018-December 2018) were compared for outcomes, including discharge disposition, adverse responses and LOS. T-test and Chi-square were used to determine significant difference in outcomes between groups.

Results:
Between January to December 2018 44 patients received tPA (18 pre-implementation and 26 post implementation). For the post implementation group 18/26 early mobility was initiated with 24 hours, 4/26 were placed on comfort care and 4/26 were transferred to a comprehensive stroke center. Among the early mobility group, there were no falls or adverse physiological events. Patients that participated with early mobility were more likely to discharge home, 46.15% vs 33.33%, less likely to require post-acute services, 15.38% vs 27.78%, and less likely to require transfer to a higher level of care, 15.38% vs 33.78%. There was not a significant difference in LOS.

Conclusion:
Providing early mobility to patients post thrombolytic therapy between 12-24 hours does not cause an increase in adverse physiological events. Additionally, providing early mobility has a positive impact on patient discharges to home. Further study may include initiating mobility at an early timeframe to examine the correlation to LOS and discharge outcomes.
Abstract TMP1: Predicting Scale Design and Derivation to Select Acute Ischemic Stroke Patients for Direct Angiosuite Intervention
Authors: Ren Zeguang , Wangqin Runqi , Mokin Maxim , Wang Anxin , Zhao Liang , Li Tao , Miao Zhongrong , Wang Yongjun , Burgin W Scott
Published: June 2021

Introduction:
Vascular imaging after head CT to confirm large vessel occlusion (LVO) for acute stroke patients requires additional time and delays recanalization. We developed the
T
hrombectomy
A
cute
M
echanical re
P
erfusion
A
ssessment (
TAMPA
) scale for selecting patients with LVO for direct angiosuite transfer and intervention to improve recanalization time.

Methods:
The TAMPA scale was developed from our prospectively collected “Get with the Guidelines” database. We included all “stroke alert” patients between 1/2017 and 8/2018 with vascular imaging and National Institutes of Health Stroke Scale scores between 5 and 25. We excluded patients with immediately obvious non-stroke diagnoses, those lacking subsequent vascular imaging, or those with incomplete records. Different variables were collected. The TAMPA scale receiver operating characteristics curve (ROC) was compared with the ROCs of other commonly used scales.

Results:
571 eligible patients from 2115 “acute stroke alerts” were identified for developing the TAMPA scale. The scale was established with a combination of 5 items with a total score of 9: CT hyperdense sign, parenchymal hypodensity, lateralizing hemiparalysis, gaze deviation and speech disturbance. A cutoff of ≥ 4 yielded a sensitivity of 68.98%, specificity of 72.91%, false positive rate of 27.09%, and false negative rate of 31.02%. Compared with other scales, such as total NIHSS, C-stat/CPSSS, RACE, FAST-ED and 3I-SS, the TAMPA scale had the best ROC for the selected group of patients.

Conclusions:
The TAMPA scale accurately predicts presence of clinically amenable LVO in patients with moderate to severe ischemic stroke. Use of the TAMPA scale to identify high probability mechanical embolectomy candidates for direct transfer to the angiosuite could potentially reduce revascularization times and increase treatment rates.
Abstract TMP10: Real-World Analysis of Endovascular Stroke Therapy Outcomes for Patients With Large Vessel Occlusions After Inter-Hospital Transfer
Authors: Fan James , Lopez-Rivera Victor , Lee Songmi , Savitz Sean , McCullough Louise , Chen Peng , Blackburn Spiros , Day Arthur , Kim Dong , Harrison Nicole , Wells Meredith , Sheth Sunil ,   Memorial Hermann Hosp System Stroke Coordinators
Published: June 2021

Introduction:
Prior studies suggest that patients with large vessel occlusion (LVO) who undergo endovascular stroke therapy (EST) after inter-hospital transfer (IHT) have worse outcomes than those who present directly to EST centers. However, these studies were largely derived from clinical trials or registries and may not be representative of real-world clinical practice.

Methods:
We performed a multicenter, observational cohort study on acute ischemic stroke (AIS) patients with LVO that presented to EST-capable centers directly (LVO-D) or after IHT (LVO-T) between 1/1/2018 to 2/1/2019. The study included 11 hospitals in the Houston area, of which 4 are EST-capable. Clinical data were collected using our cerebrovascular data registry. All transfers were from non-EST capable hospitals to EST-capable hospitals. Logistic regression adjusted for age, NIHSS, occlusion location and direct vs transfer arrival was used to assess the likelihood of good outcome, defined as discharge to home or rehabilitation. Results are given as median [IQR] and OR [95% CI].

Results:
Among 4,313 patients with AIS, 772 (18%) patients had LVO. Among LVO patients, median age was 68 [59-79], 47% were female, 51% were white, 378 (49%) were LVO-D and 394 (51%) were LVO-T. Median IHT time was 152 min [114-198]. LVO-D patients arrived at EST-treating hospitals with superior ASPECTS compared to LVO-T (9 [7-10] vs 7 [6-9], p<0.0001), but comparable CTP RAPID infarct cores (5 mL [0-31] vs 7 mL [0-38], p=0.59). LVO-D and LVO-T patients were just as likely to have ICA occlusions (13% vs 12%; p=.64) and proceeded to have equivalent rates of EST (43% vs 47%, p=0.95). Among LVO patients who did not receive EST, good discharge outcomes were comparable (34% vs. 35%, p=0.66, LVO-D vs. LVO-T). Good discharge outcomes were also similar for those receiving EST (34% vs. 37%, p=0.57, LVO-D vs. LVO-T). In logistic regression adjusted for age, NIHSS, and occlusion location, likelihood of good discharge outcome was comparable between the two groups (OR 0.98 [0.71-1.36]).

Conclusion:
In this real-world cohort of a multi-center stroke network, IHT was not associated with worse outcomes for patients with LVO, for both patients who did receive EST and those that did not.
Abstract TMP101: Epigenetics in Blood Brain Barrier Formation and Maintenance
Authors: Thankamani Pandit Peeyush , Kulkarni Tanuja , McBride Devin , Elizebeth Mathew Iny , Blackburn Spiros
Published: June 2021

The blood brain barrier (BBB), unique to the central nervous system (CNS) vessels, tightly controls the passage of molecules between the blood and the brain. BBB breakdown is documented in many pathological conditions including, stroke, and contributes to the severity of disease and poor outcome. Currently,
there is no efficient treatment strategy to prevent BBB breakdown or restore disrupted BBB
. Despite BBB’s importance in the CNS function, t
he genetic program and mechanism, that regulates BBB formation and maintenance is poorly characterized.
To understand the molecular features underlying BBB gene regulation during development we utilize endothelial cell (EC) cultures derived from brain of both embryonic (E-13.5) and adult mice and investigated differences in BBB gene expression and epigenetic status using real time PCR analysis and ChIP-qPCR. We found that a
distinct BBB profile exist in the CNS ECs during BBB formation and maintenance
. When compared to embryonic ECs, adult ECs showed a significant down regulation in expression of tight junction (TJ) genes such as
CLDN-1
,
CLDN -11
,
ZO-1
and
OCLN
. Conversely, another important TJ gene
CLDN- 5
shows a significant increase in adult ECs. Further, we found that epigenetic-histone modifications are involved in the repression in the TJ gene in adult ECs. To more fully understand the role of Wnt/β-catenin in BBB formation and maintenance we block the downstream of the Wnt/β-catenin signaling pathway using LF3 (block the interaction of β-catenin and transcription factor TCF4) in developing ECs. This results in a
adult BBB phenotype
in developing ECs indicating,
silencing of Wnt/β-catenin pathway is required for BBB maturation
. Further, epigenetic component HDAC2 was increased significantly in developing ECs when Wnt/β-catenin signaling is blocked demonstrating this
pathway can modulate the epigenetics of CNS ECs
.

In summary, we describe that BBB genes have distinguished expression pattern during BBB formation and maintenance, guided by the Wnt/β-catenin pathway through epigenetic modifications. Understanding the fundamental epigenetic and regulatory mechanisms of BBB formation and maintenance is critical for developing therapeutic interventions against BBB breakdown.
Abstract TMP102: Sex Differences in the Structure and Function of the Middle Cerebral Artery
Authors: Wang Shaoxun , Zhang Huawei , Guo Ya , Liu Yedan , Gonzalez-Fernandez Ezekiel , Roman Richard J , Fan Fan
Published: June 2021

There are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD), including stroke and dementia. Understanding the influence of differences in cerebrovascular structure and function between males and females will provide essential insight into the rationale to identify new pharmaceutical targets to improve treatment of CVD. In the present study, we compared sex differences of the structure and function of the middle cerebral artery (MCA, M2) in young healthy SD rats. We found that female rats had a thinner vascular wall and a smaller inner diameter of MCA compared to males. However, there was no significant difference in the wall-to-lumen ratio between sexes. Female MCAs exhibited less vascular smooth muscle cell (VSMC), more elastin and less collagen I content per wall cross-sectional area than males detected by confocal microscopy using immunostaining as well as protein expression by Western blot. Female SD rats had elevated vascular tone, lower MCA distensibility, and higher wall stress. In addition, the stress/strain curves shifted to the left compared to males. Primary cerebral VSMCs isolated from females displayed lower contractile capabilities than males using a collagen-based cell contraction assay. The diameter of the MCA in males decreased by 14.7 ± 2.0% when perfusion pressure was increased from 40 to 180 mmHg. In contrast, the MCA in females failed to constrict under the same pressure changes. Female MCAs had a greater response to Ach than males. Cerebral blood flow (CBF) measured by laser Doppler flowmetry rose by 27.7 ± 4.8% and 57.4 ± 4.4% in males and females, respectively, when perfusion pressure increased from 100-180 mmHg. Functional hyperemia responses using whisker-barrel stimulation and learning and memory examined with eight-arm water maze were not different between males and females. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which lead to decreased cerebral vascular reactivity and CBF autoregulation to elevations in pressures in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause.
Abstract TMP106: Decisions on Life-Sustaining Treatments After Stroke: The OASIS Project
Authors: Zahuranec Darin B , Ortiz Carmen , Lank Rebecca J , Hsu Chia-Wei , Kim Sehee , Case Erin , Morgenstern Lewis B
Published: June 2021

Introduction:
Surrogate decision makers are commonly asked to make critical decisions after stroke, though there has been little formal study of stroke surrogates. We report initial results on surrogate decisions in a community that does not have an academic medical center from the Outcomes Among Surrogate decision makers In Stroke (OASIS) project.

Methods:
Patients with ischemic stroke or intracerebral hemorrhage (ICH) from the Brain Attack Surveillance in Corpus Christi (BASIC) project, Texas, USA, were screened for presence of a surrogate decision maker. Surrogates self-identified as being involved in decisions about life-sustaining treatments: do-not-resuscitate (DNR), brain surgery, ventilator, feeding tube, or transition to hospice/comfort measures only. The scope of decisions including surrogate report of patient and healthcare team participation are presented.

Results:
Between 4/2016 and 8/2018, 230 stroke patients with at least one eligible surrogate were identified; 199 surrogates for 160 stroke patients enrolled (160/230=70% enrolled). Patient characteristics were mean age 74, female 53%, Mexican American 56% ICH 24%, median NIHSS 11.5 (IQR 4, 21), ICU admission 51%, deceased at time of surrogate interview 38%. Surrogates had a mean age of 55 years, were mostly women (74%), and were most commonly the child of the patient (64%) followed by the spouse (21%). Treatments discussed with the healthcare team are shown in the table. DNR was the most common discussion (90%). While physicians typically discussed brain surgery, surrogates reported that a nurse or other non-physician was the primary person talking to them in nearly half of the other discussions about life-sustaining treatment.

Conclusions:
Women are responsible for a large proportion of surrogate decision making after stroke. Further study of the role of nursing participation in decisions on life-sustaining treatment is warranted, particularly in non-academic medical centers.
Abstract TMP107: Impact of a Stroke Transitional Care Navigator at a Comprehensive Stroke Center
Authors: Larsen Darren T , Lesko Alexandra , Baraban Elizabeth
Published: June 2021

Background:
The Stroke Transitional Care Navigator (STCN), was implemented at our Comprehensive Stroke Center (CSC) in January 2017 in order to bridge care from the inpatient to outpatient setting. The STCN nurse meets with patients prior to discharge to address secondary stroke risk factors and discuss the follow up plan in an effort to improve patient outcomes. The purpose of this study was to determine whether implementation of a STCN improved compliance with follow up stroke neurology care and reduced unplanned readmissions and Emergency Department (ED) visits.

Methods:
Retrospective data review, included ischemic stroke or ICH patients, 18 or over, discharged from February 2017 through February 2018. Subarachnoid hemorrhages and hospice discharges were excluded. Patients were grouped into a “Followed’ cohort if they had documented contact with the STCN prior to discharge or within 30 days; otherwise they were categorized as “Not Followed”. Outcomes of interest were percentage of patients compliant with attending an outpatient visit with a stroke provider within 45 or 120 days post-discharge and percentage of unplanned readmission and ED visits 30 days post-discharge. Analyses comparing those with and without STCN contact were performed using Fisher’s Exact test and Pearson’s chi square test.

Results:
There were 689 patients that met inclusion criteria with 47.2% (n=325) in the Followed and 52.8% (n=364) in the Not-Followed cohorts. The Followed cohort was more likely to comply with attending a follow-up visit within 45-days (67.2% vs. 32.8%, p<.001) as well as 120 days of discharge (61.0% vs 39.0%, p<.001). No differences were found between the Followed and Not Followed cohorts for readmissions (9.5% vs. 11.5%, p=.394) or ED visits (9.5% vs. 10.2%, p=.783).

Conclusion:
The STCN had a significant positive impact on patients returning to clinic for follow up stroke neurology care. Though follow up care has been shown to reduce readmission rates in some studies, in this study there was no impact on 30-day readmissions or ED visits. Given the unique, individualized care and coordination provided by the STCN, which is very well received by patients and providers, qualitative measures may be more useful in the future to determine the effectiveness of the STCN.
Abstract TMP110: Antithrombotic Therapy and Risk of Stroke Recurrence in Children With Congenital and Acquired Cardiac Disease
Authors: Pulcine Elizabeth , Seed Mike , Brandao Leonardo , Slim Mahmoud , Shroff Manohar , Moharir Mahendranath , deVeber Gabrielle , Dlamini Nomazulu
Published: June 2021

Background:
Antithrombotic therapy (ATT) is currently recommended for stroke prevention in pediatric cardioembolic arterial ischemic stroke (CE-AIS) where the risk of recurrence is high.

Methods:
We conducted a retrospective study of a prospectively enrolled cohort of neonates and children with radiologically-confirmed cardioembolic arterial ischemic stroke (CE-AIS) from January 2003 - December 2017. We evaluated the clinical and radiographic predictors of hemorrhagic transformation (HT) and stroke recurrence to assess the safety and efficacy of ATT.

Results:
Eighty-two children met inclusion criteria [53.7% males and 28% neonates; median age 0.43 (IQR: 0.08 - 4.23) years]. Stroke recurred in 11 children at a median of 32 days (IQR: 5.5 - 93) from the index event. Most recurrent infarcts were silent (n=6; 54.5%) and found on follow-up neuroimaging with an average follow-up interval of 4.1 ±3 .5 years. Procedure-related recurrence took place in 1 (9.1%) child. Ten (90.9%) children were receiving antithrombotic therapy at the time of recurrence: 8 (72.7%) were on anticoagulant therapy (ACT) and 2 (18.2%) were on a combination of antiplatelet (ATP) and ACT. HT occurred in 20 of 82 children (24.4%), all of whom were receiving ACT, 5 (6.1%) of whom were symptomatic. Four (4.9%) had systemic hemorrhage. There was no difference in the frequency of stroke recurrence between those with and without HT [3 (15.0%) vs. 8 (12.9%); p=1.00]. Children with univentricular physiology were less likely to have HT [15% vs. 43.5%; p=0.03] and had higher rates of recurrent stroke, prior to definitive cardiac repair, despite receiving ATT. Stroke recurrence was highest in those with cyanotic congenital heart disease (CHD) pre-surgery (3/11), cyanotic CHD post-palliative surgery with residual right-to-left-shunt (3/11) and in those with cardiomyopathy (4/11). HT was not associated with ATP vs. ACT use nor combination therapy.

Conclusion:
ATT appears to be relatively safe in children with CE-AIS. However, ATT warrants further optimization to prevent stroke recurrence, particularly in those with single ventricle physiology and reduced left ventricular function.
Abstract TMP112: Increased Large Vessel Diameter is Associated With Increased Cerebral Metabolic Stress in Children With Sickle Cell Anemia
Authors: Guilliams Kristin , Fields Melanie , Gupta Niket , Goyal Manu , Fellah Slim , Chen Yasheng , Shimony Joshua , Hulbert Monica , McKinstry Robert , An Hongyu , Ford Andria , Lee Jin-Moo
Published: June 2021

Background:
Children with sickle cell anemia (SCA) invoke compensatory mechanisms to meet cerebral oxygen demand in the setting of low oxygen carrying capacity. Whereas cerebral blood flow (CBF) is largely regulated by cerebral arterioles as one compensatory mechanism, we sought to determine if the cross-sectional area of the large in-flow arteries was also increased.

Methods:
Children and young adults with SCA underwent 3 Tesla magnetic resonance angiography (MRA) and imaging (MRI) with pseudocontinuous arterial spin labeling (pCASL) and asymmetric spin echo sequence to measure CBF and oxygen extraction fraction (OEF) respectively. Using the double oblique method, we measured artery diameters and calculated the area (A) of the vessel as A=πr
2
. The total inflow area (A
T-inflow
) was the summation of the areas of distal portions of both internal carotid arteries and basilar artery. CBF, OEF, arterial oxygen content [(CaO
2
) = 1.36*Hemoglobin*%saturation on pulse oximetry] and A
T-inflow
were compared between groups with nonparametric statistics. Spearman’s correlation determined relationship of A
T-inflow
with other variables.

Results:
Data was available for 29 subjects with SCA (median age 15 years (range 9-26), 45% male) and 17 age-matched controls (15y (range 9-18), 47% male) underwent scanning. Children with SCA had larger A
T-inflow
(36 [29, 40] mm
2
) compared to age-matched controls (29 [26, 31] mm
2
, p=0.01). CBF and OEF were higher (p=0.001, p=0.002), and CaO
2
was lower (p<0.001) in SCA compared to controls. A
T-inflow
positively correlated with CBF (p=0.002) and OEF (p<0.001), and negatively correlated with CaO
2
(p=0.02;
Figure
).

Conclusion:
Increased cross sectional area of large cerebral arteries may provide an additional compensatory mechanism in SCA to augment CBF and aid in meeting cerebral oxygen demand. Further work is needed to determine if MRA measurements provide a non-invasive precursor to increased cerebral metabolic stress and stroke risk.
Abstract TMP19: MRI Characteristics and Predictors of Diffusion Weighted Hyperintense Lesions After Spontaneous Intracerebral Hemorrhage: A Secondary Analysis of MISTIE-III
Authors: Cho Sung-Min , Murthy Santosh , Li Yunke , Ali Hasan , Avadhani Radhika , Hanley Daniel , Ziai Wendy
Published: June 2021

Introduction:
Mechanisms of diffusion weighted hyperintense lesions (DWIHL) after spontaneous intracerebral hemorrhage (ICH) are controversial. We evaluated mechanism and outcome of DWIHL.

Methods:
Protocolized MRI scans within 7 days from ICH were reviewed from MISTIE-III trial. Imaging analysis included DWIHL, leukoariosis (Fazekas score), enlarged perivascular space (EPVS), and cerebral microbleeds. Multivariable logistic regression analysis was performed to assess predictors and outcomes of having DWIHLs. Favorable outcome was defined as modified Rankin Score 0-3 at 12 months.

Results:
Of 499 patients, 300 underwent DWI studies (62% lobar ICH; 38% deep ICH) and 178 (59%) had acute DWIHLs (66% lobar; 34% deep). DWIHL locations were perihematomal in 140 (79%); and remote in 96 (54%). In multivariable regression analysis, DWIHLs were associated with initial mean arterial pressure [MAP] (odds ratio [OR]: 1.004; 95% confidence interval [CI]: 1.002-1.01), initial ICH volume (OR: 1.004; 95%CI: 1.001-1.01), NIHSS at randomization (OR: 1.01; 95%CI: 1.01-1.02), hypertension history (OR: 1.41; 95%CI: 1.04-1.93), and Fazekas score (OR: 1.04; 95%CI: 1.01-1.08). Patients with DWIHLs were less likely to have favorable outcome (66% vs. 50%; OR: 0.89; 95%CI: 0.81-0.99) after adjusting for ICH severity; however, the presence of DWIHLs did not confer an independent mortality risk at 12 months. In addition, perihematomal DWIHLs were associated with ICH volume (OR: 1.003; 95%CI: 1.00-1.01), NIHSS (OR: 1.01; 95%CI: 1.00-1.02), deep location (OR: 1.25; 95%CI: 1.10-1.42), and centrum semiovale EPVS score (OR: 0.99; 95% CI: 0.99-1.00). Remote DWIHLs were associated with Fazekas score (OR: 1.17; 95%CI: 1.06-1.29), centrum semiovale EPVS score (OR: 1.01; 95%CI: 1.00-1.01), atrial fibrillation (OR: 1.40; 95%CI: 1.04-1.90), and maximal ΔMAP on first 24 hours (OR: 1.004; 95%CI: 1.001-1.006).

Conclusions:
DWIHLs were common (59%) in patients after spontaneous ICH, predominantly in lobar locations and were associated with unfavorable neurologic outcome. While perihematomal DWIHLs were associated with ICH severity, remote DWIHLs suggested different mechanisms including acute blood pressure reduction, cardiac emboli, and white matter disease severity.
Abstract TMP20: The Therapeutic Gas Carbon Monoxide (CO) Attenuates Vasospasm and Improve Neurobehavioral Function After SAH
Authors: Kamat Pradip K , Ahmad Abdullah , Dore Sylvain
Published: June 2021

Introduction:
Subarachnoid hemorrhage (SAH) is one of the most devastating forms of hemorrhagic stroke and it is a serious medical condition caused by bleeding of a ruptured aneurysm. The etiopathology of the disease includes early brain injury, vasospasm, and delayed cerebral ischemia. Blood byproducts cause the walls of arteries to constrict and spasm. At physiological concentrations, we and others have reported that carbon monoxide (CO) has functional roles in neuroprotection through anti-inflammation, anti-oxidative stress, and improving blood flow. Hence, this study focuses on the safe noninvasive therapeutic strategy to treat SAH by using CO as therapeutic medical gas.

Hypothesis:
We propose that CO may prevent SAH by mitigating vasospasm, limiting brain injury and improving functional outcomes.

Methods:
SAH was induced in adult mice using the endovascular perforation method. Mice were treated either with 250ppm CO or medical Air (at the same flow rate) after 2h of SAH for 1h daily for 7d. Such CO administration protocol keeps carboxyhemoglobin within normal range. Neurobehavioral outcomes such as focal neurological deficit score, open field activity, and motor functions were monitored at day 1 and day 7. Data acquisition and statistical analysis were performed by an investigator blinded to the intervention.

Results:
At 7d after SAH, CO decreased neurological deficit score (47.4±10.5%, p<0.05), and increased activity (30.0±9.1%, p<0.05) and stereotypic counts (261.5±62.1%, p<0.01) as compared to the air control group. No significant changes in motor function were observed in CO treated mice as compared to SAH at either day 1 or day 7). Of interest, there was a significant increase in CO treated group’s lumen area/wall thickness ratio in the middle cerebral artery (173.5±19.3%, p<0.01) and trended to increase in the anterior cerebral artery (25.5±4.3%, p=0.58) at 7d.

Conclusion:
This is a first report to demonstrate that CO prevents delayed SAH-induced neurobehavioral deficits, which suggest that post-treatment with CO should be considered a therapeutic strategy against SAH.
Abstract TMP21: Cilostazol for Prevention of Cerebral Vasospasm and Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Lobanova Iryna , Qualls Kathryn , Martin Renee L , Arora Niraj , Nattanmai Premkumar , Siddiq Farhan , French Brandi R , Gomez Camilo R , Huang Wei , Qureshi Adnan I
Published: June 2021

Introduction:
Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and associated cerebral ischemia and improve outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to its anti-platelet, anti-proliferative, and vasodilatory effects. Due to recent publication of randomized controlled clinical trials, a meta-analysis was performed to identify the common treatment effect.

Methods:
We performed a meta-analysis of four randomized controlled clinical trials. The primary endpoint of interest was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the 90 days following randomization. Using random-effects models with study as a random effect, relative risks (RR) and 95% confidence intervals (CI) were generated

Results:
A total of 405 subjects (200 randomized to oral cilostazol 100 mg twice per day) were included in the meta-analysis. The proportion of subjects with cerebral ischemia related to vasospasm was significantly lower in those who were assigned to cilostazol treatment (RR 0.46; 95% CI 0.21-1.00; p< 0.050) without any heterogeneity between the trials (Cochran’s Q statistic 1.52, df 2; P = .468, I
2
=0.0%). The proportion of subjects who had new cerebral infarction was significantly lower in subjects who were assigned to cilostazol treatment (RR 0.40, 95% CI 0.32-0.49, p=0.0009). There was a lower rate of death or disability at 90 days in subjects who were assigned to cilostazol treatment (RR 0.44, 95% 0.28-0.70, p=0.011) without any heterogeneity between the trials (Cochran’s Q statistics 1.49, df 3; P = .685, I
2
=0.0%). The proportion of subjects who had any adverse events was not significantly different in subjects who were assigned to cilostazol treatment (RR 1.24, 95% 0.68-2.25, p=0.26).

Conclusion:
The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aSAH in a phase III large randomized clinical trial.
Abstract TMP28: Serotonin Transporter Polymorphism Impact on Cortisol Level and Outcome After Stroke
Authors: Ben Assayag Einor , Seyman Estelle , Molad Jeremy , Tene Oren , Korczyn Amos , Shenhar Shani , Bornstein Natan , Hallevi Hen
Published: June 2021

Background:
The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke.

Methods:
Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter.

Results:
Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers.

Conclusions:
We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.
Abstract TMP29: Mesenchymal Stromal Cell Administration Attenuates Post-Stroke Susceptibility to Spontaneous Infection Through Prevention of Caspase-1-Dependent Splenic Marginal Zone B Cell Death
Authors: Huang Yinong , Lu Zhengqi
Published: June 2021

Spontaneous infection is one of most common complications of acute ischemic stroke (AIS) and leads to increased mortality and morbidity in stroke patients. However, current interventions fail to improve clinical outcomes in these patients. Since stroke-induced immunodeficiency is thought to contribute to the risk of infections, we suppose mesenchymal stromal cells (MSCs) therapy, based on its potent immunomodulatory capacities, could be a potential solution to this problem. Here, we show MSCs administration successfully ameliorates post-stroke infections and reduces the mortality in mouse middle cerebral artery occlusion (MCAO) model of AIS. Additionally, the intravenously infused MSCs preferentially migrate to the spleen and mainly distribute around the marginal zone (MZ). These grafted MSCs rescue stroke-induced splenic atrophy, especially the marginal zone B (MZB) cells loss, a subset of innate-like lymphocytes localized in MZ. Using the CD19-deficient mice model lacking MZB cells, we found that MSCs transplantation could not reduce post-stroke infections or mortality in CD19
-/-
mice, reconfirming MZB cells are indispensable for the immunoprotective effects of MSCs. In terms of mechanism, we demonstrate that MSCs attenuate caspase-1-dependent MZB cells death partially through direct mitochondrial transfer and subsequent inhibition of NLRP3 activation. Taken together, this study suggests MSCs administration alleviates post-stroke immunodepression and spontaneous infections via MZB cells protection.
Abstract TMP32: Transcriptome Changes of Brain Myeloid Cells After Ischemic Stroke in Type 2 Diabetic Mice
Authors: Omodaka Shunsuke , Kanoke Atsushi , Wong Suwei , Aran Dvir , Liu Jialing
Published: June 2021

Introduction:
Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Brain myeloid cells are considered to play a pivotal role in modulating brain damage and recovery after stroke, but how myeloid response to stroke under diabetic condition is largely unclear. We used single-cell RNA sequencing (scRNA seq) to determine the transcriptome profiles of brain myeloid cells under diabetic and ischemic conditions using T2DM mouse model.

Hypothesis:
The altered gene expression in the brain myeloid cells under diabetic condition leads to the aggravation of ischemic brain injury.

Methods:
We performed scRNA seq in Percoll gradient-isolated brain mononuclear cells from middle-aged
db/db
and
db/+
mice three days after direct middle cerebral artery occlusion (MCAO) or sham-operation. Clusters of brain myeloid cells were predominantly annotated as macrophages (mp) or microglia (mg) according to the expression of marker genes in each cell type. We identified DM-unique differentially expressed genes (DEGs) and stroke-unique DEGs, and assessed the biological role of these DEGs by enrichment analysis.

Results:
Myeloid cell population was increased in DM (
db/db
without MCAO; mp 37.3% mg 10.6%) and stroke (
db/+
with MCAO; mp 26.2% mg 33.2%) group compared to control (
db/+
without MCAO; mp 3.4% mg 0.8%) group. In macrophages, 91 DM-unique (64 up- and 27 down-regulated) and 464 stroke-unique (458 up- and 6 down-regulated) DEGs were identified, whereas 258 stroke-unique (254 up- and 4 down-regulated) DEGs were identified in microglia. Enrichment analysis revealed that DM-unique down-regulated DEGs in macrophages were related to MHC class II antigen processing involved in
Staphylococcus aureus
infection pathway, indicating a possible relationship between immunosuppression and stroke aggravation in diabetes. DM-unique and stroke-unique up-regulated DEGs were related to oxidative phosphorylation, phagocytosis, and protein metabolism.

Conclusions:
The present study demonstrated altered gene expression profile and molecular network of brain myeloid cells in response to diabetic and ischemic conditions by scRNA seq, providing a clue to the underlying mechanism of the adverse effect of T2DM on stroke.
Abstract TMP4: Impact of Bridging Therapy With Intravenous Thrombolysis Prior to Mechanical Thrombectomy in Patients With Large Vessel Occlusion- Insights From the STAR Registry
Authors: Al Kasab Sami , Almallouhi Eyad , Alawieh Ali , Holmstedt Christine A , Chalhub Reda M , Psychogios Marios , Arthur Adam , Kim Joon-Tae , De Leacy Reade , Rai Ansaar , Keyrouz Salah , Fargen Kyle M , Dumont Travis , Kan Peter , Starke Robert M , Spiotta Alejandro M
Published: June 2021

Introduction:
Clinical trials have proven the safety and efficacy of mechanical thrombectomy (MT) with intravenous alteplase (tPA) compared to tPA alone in patients presenting with large vessel occlusion (LVO). The impact of tPA prior to MT on procedural metrics, successful revascularization, symptomatic hemorrhage and long-term functional outcome has not been established from large scale real-world studies. In this study we evaluate the impact of tPA prior to MT on procedural times, immediate and long-term outcomes.

Methods:
The STAR registry combined prospectively maintained databases of 11 thrombectomy-capable stroke centers in the US, Europe and Asia. Patients who received mechanical thrombectomy with or without intravenous tPA prior to MT were included in these analyses. Baseline characteristics, procedural time, successful revascularization (TICI ≥ 2B), symptomatic intracranial hemorrhage (PH2), and long-term functional outcomes were compared between the two groups.

Results:
Total of 1869 patients were included in this analysis. Of those, 907 received tPA prior to MT. Baseline features and outcomes are summarized in table 1. There were more white patients in the non-tPA group, and more patients in this group had atrial fibrillation and hyperlipidemia; otherwise there were no differences in baseline features between the two groups. Median NIHSS on admission was 16 in both groups, median ASPECTS was 9 in the tPA group versus 8 in the non-tPA group, p=0.208. Patients in the tPA group had higher rate of successful revascularization, lower number of revascularizations attempts and were more likely to achieve excellent long-term functional outcome. There was no difference in procedural time, rate of symptomatic hemorrhage or length of hospital stay.

Conclusion:
Bridging therapy with intravenous tPA prior to mechanical thrombectomy may facilitate MT and yield to better long-term functional outcome.
Abstract TMP40: Pharyngeal Electrical Stimulation for Early Decannulation in Tracheotomised Stroke Patients With Dysphagia: A Meta-analysis of Individual Patient Data From Randomised Controlled Trials
Authors: Bath Philip M , Woodhouse Lisa J , Suntrup-Krueger Sonja , Hamdy Shaheen , Dziewas Rainer
Published: June 2021

Background:
Dysphagia is common after stroke and associated with a poor outcome. Pharyngeal electrical stimulation (PES) increased decannulation rates in tracheotomised stroke patients with dysphagia following ventilation in two trials. We report the results of an individual patient data meta-analysis assessing PES in severely dysphagic tracheotomised stroke patients.

Methods:
We searched for randomised controlled trials of PES in dysphagic tracheotomised stroke patients and obtained individual patient data for demographic and clinical (stroke severity, NIHSS; functional oral intake scale, FOIS; decannulation) variables from trialists. Data are number (%), median [interquartile range], mean (standard deviation) and mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CI).

Results:
Two completed trials were identified (n=30, PHAST-TRAC n=69 [funded by Phagenesis Ltd]), with data for 99 participants (PES 55, 56%; sham 44, 44%). Mean age 64 (13) years, female 40 (40%), NIHSS 18 [14-21], time from onset to randomisation 27 days [20-38], and FOIS=1 (nil by mouth). As compared with sham, PES was associated with an increased proportion of patients who were ready for early decannulation, 59% versus 11% (OR 11.4, 95% CI 3.86-33.33; p<0.001) and improved FOIS score at discharge (MD 1.13, 95% CI 0.25-2.00; p=0.011). Treated participants who were ready for decannulation tended to have a shorter hospital length of stay: 23 vs 41 days (p=0.070) than those who were not ready. No device-related serious adverse events were reported.

Conclusions:
PES was associated with an increased proportion of stroke patients who were ready for decannulation and less dysphagia, in two randomised trials.