bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P161: Asymmetric Dimethylarginine, C-reactive Protein, and the Risk of Developing Metabolic Syndrome in Middle-Aged Men
Authors: Nishiyama Yasuhiro , Otsuka Toshiaki , Ueda Masayuki , Kimura Kazumi
Published: July 2021

BACKGROUND:
The metabolic syndrome has known as an independent risk factor of stroke. We have recently shown that the measurement of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be useful for identifying individuals with a high risk of stroke among Japanese population. We aimed to examine whether serum levels of ADMA and a high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of developing metabolic syndrome in middle-aged men.

METHODS:
In this longitudinal study, serum ADMA and hs-CRP levels were measured in Japanese men without metabolic syndrome, which was diagnosed according to the currently accepted unified criteria. The subjects were followed-up for a maximum of four years to determine new-onset metabolic syndrome. A Cox proportional hazards model with adjusting for potential confounders was applied to determine the hazard ratio (HR) for developing metabolic syndrome according to serum levels of ADMA and hs-CRP, considered either alone or in combination.

RESULTS:
Of the 848 subjects (mean age, 43 ± 6 years), 100 subjects developed metabolic syndrome. High ADMA levels (≥ 0.45μmol/L) alone did not show a significant HR for developing metabolic syndrome, while high hs-CRP levels (≥ 0.3 mg/L) did (HR 1.82, 95% CI 1.17-2.83). The combination of high levels of both hs-CRP and ADMA had a high HR (2.32, 95% CI 1.30-4.14) as compared to low levels of both markers. In contrast, the HR was not significant in the combination of high hs-CRP and low ADMA levels, as well as low hs-CRP and high ADMA levels.

CONCLUSIONS:
Serum hs-CRP, but not ADMA, levels were associated with the risk of metabolic syndrome. Furthermore, the combination of high ADMA and high CRP levels increased the risk of metabolic syndrome. Hence, further studies are needed, but measuring the new combination of two markers may potentiate the predictive value for developing cardiovascular diseases including stroke.
Abstract T P167: The Relationship Between Stroke Center and Transfer Time on Mortality of Subarachnoid Hemorrhage: An Instrumental Variable Analysis
Authors: Kada Akiko , Nishimura Kunihiro , Kamitani Satoru , Nishimura Ataru , Kurogi Ryota , Sayama Tetsuro , Iihara Koji ,   J-ASPECT study investigators
Published: July 2021

Objective:
Recommendations for comprehensive stroke centers (CSC) have been launched, but evaluations of these with respect to accessibility and mortality have not been clear. We thus examined the relationship between stroke centers and transfer time on mortality of subarachnoid hemorrhage (SAH) from a nationwide survey: J-ASPECT Study in Japan.

Methods:
We approached 1,369 certified training institutions in Japan with a survey regarding acute stroke care capabilities, and 749 hospitals responded. The CSC score was generated to evaluate the capabilities of CSC (Iihara K et al. PLOS One 2014). Data for patients hospitalized with stroke were gathered from the Japanese Diagnosis Procedure Combination database from April 1, 2010 to May 31, 2012. Transfer time was measured using an electronic mapping system based on patients’ postal addresses and hospitals. We examined the effects of CSC scores on mortality using instrumental variable analysis with log-transferred transfer time as an instrumental variable, adjusted by age, gender, and scores of the Japan coma scale (JCS) which was grading with the 1-, 2-, and 3-digit codes (Iihara K et al. PLOS One 2014).

Results:
Data from 265 institutions and 9,648 emergency-hospitalized patients with SAH were analyzed. Mortality rate was 28.8% and median transfer time was 22 min. Longer transfer times were associated with high CSC scores (p < 0.001). Adjusting for log-transformed transfer time, high CSC scores corresponded to lower mortality in patients with SAH, and the adjusted difference between high and low scores was 25.6% (95%CI= 8.5 - 42.6%). The severe SAH patients with JCS of 2- or 3-digit code showed more influence of CSC score on mortality, and the difference was 33.5% (95%CI= 21.5 - 45.5%).

Conclusion:
Longer transfer times were associated with the choice of highly qualified stroke centers measured by CSC scores, and highly qualified stroke centers were associated with lower mortality of SAH.
Abstract T P178: Cerebral Blood Flow and Metabolism Associated with Cerebral Microbleeds in Patients with Non-cardioembolic Stroke Without Major Cerebral Arterial Stenosis
Authors: Hashimoto Tetsuya , Yokota Chiaki , Shimomura Ryo , Koshino Kazuhiro , Uehara Toshiyuki , Morita Naomi , Nakagawara Jyoji , Minematsu Kazuo , Iida Hidehiro , Toyoda Kazunori
Published: July 2021

Background and Purpose:
Cerebral microbleeds (CMBs) are associated with not only higher age but also extensive white matter lesions (WMLs), indicating that CMBs could be a reflection of microangiopathy. CMBs have not yet been examined in association with cerebral blood flow (CBF) and metabolism. The purpose of this study was to clarify the relationships of CMBs with WMLs volume, and CBF and metabolism in patients with ischemic stroke.

Methods:
We enrolled 19 patients who had past history of non-cardioembolic stroke without severe stenosis (>50%) in major cerebral arteries (69±7 years, 9 women). We measured WMLs volume and counted the number of CMBs on a 1.5-T magnetic resonance imaging (MRI) scanner. CBF, cerebral blood volume, oxygen extraction fraction and cerebral metabolic rate of oxygen were measured with
15
O-labeled gas positron emission tomography (PET). We set 36 regions of interest (ROIs) in the cortex-subcortex regions, basal ganglia and centra semiovale in each patient on MRI. MRI was superimposed on PET images and 4 parameters of each ROI were calculated.

Results:
CMBs existed in 14 out of 19 patients (median 5; range 0-39). Patients were divided into 2 groups according to the number of CMBs; less than 5 as the group I (n=9) and 5 or more as the group II (n=10). WMLs volume of the group II was larger than that of the group I (median 38.4 with range of 25.1-91.5 vs. 10.0 with 4.2-73.4 ml, p=0.020). In the centra semiovale, CBF of the group II was significantly lower than that of the group I (12.5±2.5 vs. 15.7±3.5 ml/100g/min, p=0.031). In the other regions, there were no significant differences in all 4 parameters of PET between the 2 groups.

Conclusions:
We showed that the increases in the number of CMBs could indicate cerebral ischemia in the deep white matter of patients with non-cardioembolic stroke without major cerebral arterial stenosis.
Abstract T P202: Implementation of a 24/7 Enrollment Process Improves Recruitment Rate in a Multi-Center, Randomized Clinical Trial
Authors: Shen Loren F , Jacobs Amber N , Rahbar Mohammad H , Ford Gary A , Macdonald Claire , Piechowski Bart , Roffe Christine , Alexandrov Andrei V , Levine Steven R , Sangha Navdeep S , Ajani Zahra G , Mullen Michael , Pandurengan Renganayaki , Grotta James C , Barreto Andrew D
Published: July 2021

Background:
Enrollment into acute ischemic stroke (AIS) trials is usually limited to weekday working hours. At our center, the majority of patients (64%) that receive tPA arrive after-hours. As a result, a large portion of eligible patients do not receive the opportunity to participate in these trials, hence enrollment rate suffers.

Objectives:
Demonstrate ongoing experience regarding feasibility and implementation of a 24/7 enrollment plan for an international AIS trial. Compare differences in patients’ characteristics enrolled during working hours (
WH
- Mon-Fri 07:00-17:00) vs. after hours+weekend (
AH
).

Methods:
Data obtained from an on-going, multi-center, randomized, time-sensitive, tPA-adjunctive clinical trial (ARTSS-2; NCT01464788) Centers capable of doing so, implemented an on-call system for coordinators to respond AH. AH enrollment includes a coordinated effort to reduce time and meet the time challenges of screening, consent, randomization and starting study drug before the end of tPA infusion. The coordinator arrives at the ED to assist in-house physician with study procedures. We conducted descriptive analyses that explore differences between
WH
vs.
AH
.

Results:
As of 08/14, a total of 240 patients were eligible of which 75 were enrolled. Of these, 32 (43%) were enrolled AH at a total of 6 sites. 15 of 32 AH patients were enrolled at non-coordinating centers. AH patients were younger and more likely to be male (Table 1). Compared to WH, AH enrollment did not delay tPA initiation, time to website randomization, or initiation of study drug. No signal of increased harm or trial protocol deviations was evident between the two groups.

Conclusion:
24/7 clinical trial enrollment is safe and feasible in a multicenter, international thrombolysis trial. We increased recruitment by 75% with no delays in randomization or initiation of study treatment. Efforts to provide 24/7 coverage should be implemented to improve trial recruitment rates.
Abstract T P220: Primate Model of Intracranial Aneurysm to Examine the Effect of Drugs on Aneurysm Growth
Authors: Tsuji Keiichi , Saito Makoto , Yokoi Toshihiro , Aoki Tomohiro , Nozaki Kazuhiko
Published: July 2021

Current problem of intracranial aneurysm treatment is a lack of medical therapy for patients without surgical indication. Considered with the high incidence of aneurysm and the devastating outcome by subarachnoid hemorrhage after rupture, the development of a novel therapeutic drug to prevent the enlargement or rupture of aneurysms should be established. To examine the effect of drugs on enlargement of aneurysm in vivo, we established the primate model of intracranial aneurysm. In this model, female Macaca fascicularis was used and aneurysms were induced at bifurcation sites of intracranial arteries by the ligation of one side of carotid artery and bilateral oophorectomy accompanied with the systemic hypertension by salt-overloading. In this model, unlike rodent model of aneurysms, we can keep track of aneurysm formation and enlargement by sequential MRA examinations in same animals without sacrificing them. Indeed, we could detect the induction of intracranial aneurysms defined by the saccular lesion in MRA studies in 43% (3/7) of animals subjected to models. Histopathologically, we confirmed that, all primates examined developed aneurysmal changes evidenced by disrupted elastic lamina and degeneration of media at bifurcation sites of intracranial arteries during 26 months of follow-up. We, further, successfully followed up the therapeutic effect of the drug on enlargement of aneurysms induced in this model. In conclusion, primate models and sequential following up of induced aneurysms by MRA is a powerful tool to assess the effect of drugs on aneurysms and contribute greatly to develop medical therapy for intracranial aneurysms.
Abstract T P23: Posterior Circulation CT Angiography Collaterals Predict Outcome of Endovascular Acute Ischemic Stroke Therapy for Basilar Artery Occlusion
Authors: Goyal Nitin , Tsivgoulis Georgios , Doss Vinodh T , Laster Robert , Hoit Dan , Arthur Adam , Elijovich Lucas
Published: July 2021

Background & Purpose:
The outcomes of patients with acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) are poor. Endovascular therapy (EVT) improves rates of recanalization. We hypothesized that good collateral patterns by pre-treatment CT Angiography (CTA) would predict favorable outcome after EVT.

Methods:
We conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a four-year period. BAO was diagnosed by CTA in all cases, who received EVT as standard of care. Admission stroke severity was documented using NIHSS-score. Pretreatment collateral score (CS) for posterior circulation was defined as follows: 0 - no posterior communicating artery (PCOM), 1- unilateral PCOM, 2- bilateral PCOM. Complete recanalization was defined by Thrombolysis in Cerebral Infarction (TICI) scores of 2b or 3. Favorable outcome was defined as modified Rankin Scale score (mRS) of 0-2 at three months.

Results:
Our study population consisted of 15 AIS patients (age range; 31-84 years, median admission NIHSS-score: 21, range 2-38 points) who underwent EVT. Systemic thrombolysis was administered in 4 patients (27%). Seven of 15 patients (47%) had bilateral PCOMs, while unilateral PCOM was diagnosed in 2 cases (13%). Patients with bilateral PCOMs tended to have less severe stroke (p=0.199) at admission in comparison to patients with absent/unilateral PCOM (median NIHSS-score 18 vs. 28 points). The rate of favorable outcome was higher in patients with bilateral PCOMs (71%) in comparison to patients with absent or unilateral PCOM (0%; p=0.014). Patients with bilateral PCOMs tended to have higher recanalization in comparison with patients with absent/unilateral PCOM (86% vs. 33%, p= 0.076).

CONCLUSION:
Presence of bilateral PCOMs on pre-treatment CTA is associated with lower baseline stroke severity, higher rates of complete recanalization and favorable outcome in patients with AIS due to BAO who are treated with EVT. Future prospective studies including a larger sample of patients are required to define the potential association of posterior circulation collateral status with favorable outcome in this subgroup of ischemic stroke patients.
Abstract T P240: Intravenous Injections of Microrna 363 Mimic Promotes Neuroprotection in Middle Aged Females in an Ischemic Stroke Model
Authors: Selvamani Amutha , Sohrabji Farida
Published: July 2021

Background:
Analysis of circulating microRNA in young and middle aged male and female rats revealed distinct expression patterns of post-stroke microRNAs (Selvamani et al., 2014). Mir-363 expression was inversely related to infarct volume, such that adult females, who display the smallest infarct volumes, had the highest expression of miR363. Based on this association, we hypothesized that mir-363 may promote survival of ischemic neurons. As proof of concept, the present study utilized middle aged females to investigate the role of miR-363 in neuroprotection.

Methods:
Middle aged (12 mo) female rats were subject to middle cerebral artery occlusion (MCAo). At 4h post-stroke, animals received a tail-vein injection of miR-363 or scrambled control. Vibrissae-elicited forelimb placement (VIB) test was performed pre and post MCAo to assess motor deficits. Blood samples were drawn at 2d and 5d post stroke. All animals were terminated at 5d post MCAo and the brains processed for infarct analysis by standard histological procedures. Total RNA isolated from serum and brain was subject to QPCR amplification for miR-363 and U6 (normalization control)

Results:
IV injections of mir363 significantly elevated serum expression of this microRNA as compared to animals injected with scrambles control oligos, when measured 2d post stroke. Infarct volumes (cortex and striatum), at 5d post stroke, were significantly reduced in the miR-363 treated group as compared to controls (p ≤ 0.001). VIB-test indicated significant motor recovery post-stroke in the contralateral limb in miR-363 mimic treated group as compared to controls. RT-PCR analysis of brain tissue showed higher expression of miR-363 in the left (ischemic) hemisphere in the miR-363 mimic group while, no difference was observed in the non-ischemic, indicating that the mimetic is recruited to the ischemic site.

Conclusion:
The present study underscores the value of miRNA profiling in populations with different stroke outcomes as a strategy to identify new therapeutic targets for stroke.
Abstract T P248: Leukemia Inhibitory Factor Induced-Akt Activation Protects Neurons from Ischemic Damage by Increasing Superoxide Dismutase Activity and Expression
Authors: Davis Stephanie M , Collier Lisa A , Leonardo Christopher C , Seifert Hilary A , Ajmo Craig T , Pennypacker Keith R
Published: July 2021

Objective:
To determine the molecular mechanisms by which leukemia inhibitory factor (LIF) protects neurons during permanent middle cerebral artery occlusion (MCAO).

Hypothesis:
LIF protects neurons from ischemic oxidative injury through Akt-mediated increases in superoxide dismutase 3 (SOD3) expression and total SOD activity.

Methods:
Male Sprague-Dawley rats injected with vehicle (PBS) or LIF (125 μg/kg) were euthanized 24, 48, and 72 h post-MCAO or sham surgery for assessment of SOD activity and SOD3 expression. Rat cortical neurons were subjected to 24 h oxygen glucose deprivation or normoxia following treatment with vehicle , 50, 200, or 1000 ng/mL LIF (n=3 per group). In a third experiment, neurons were treated with vehicle, 50 ng/mL LIF,10 μM Akt inhibitor, or 50 ng/mL LIF+10 μM Akt inhibitor (n=3 per group) prior to oxygen glucose deprivation. Lactate dehydrogenase levels in media were measured to assess neuronal death. We used immunocytochemistry to assess expression of SOD3, phospho-Akt (Ser473), and myeloid zinc finger-1 in neurons.

Results:
LIF significantly increased brain SOD activity (2.085 ± 0.476 U/mg lysate; n=5) compared to vehicle (0.919 ± 0.285 U/mg lysate; n=7) 72 h post-MCAO (p<0.05). LIF significantly increased SOD3 protein expression in the brain (3.707 ± 0.541 units; n=3) compared to vehicle (1.401 ± 0.825 units; n=3) at 72 h post-MCAO (p<0.05). Co-localization of phospho-Akt and SOD3 occurred 24 h post-MCAO. Additionally, 50 ng/mL LIF (0.789 ± 0.018 U/mL media; n=3) significantly decreased lactate dehydrogenase levels in vitro compared to vehicle (1.000 ± 0.023 U/mL media; n=3) (p<0.0001). Co-incubation of 50/mL ng LIF with 10 μM Akt inhibitor (1.070 ±0.106 U/mL media; n=3) reversed the protective effect of LIF (0.705 ± 0.050 U/mL media; n=3) (p<0.01). Increases in SOD3, phospho-Akt, and myeloid zinc finger-1 staining after oxygen glucose deprivation and LIF were abolished upon Akt inhibition.

Conclusion:
Our data demonstrates that LIF-mediated protection against ischemia in vivo and in vitro results from Akt-dependent increases in SOD3 expression and SOD activity.
Abstract T P255: QCI-NASCAR - Quality Care Improvement with Nursing-driven Acute Stroke CARe
Authors: Yang Julian P , Stutzman Sonja , Riise Laura , Jones Donald , Dirickson Amanda , Magadan Alejandro , Olson DaiWai M
Published: July 2021

Objective:
To observe the impact on stroke code time metrics after applying a “pit stop” model of bedside nursing for telestroke encounters.

Background:
Despite the recent push for target treatment times in acute stroke codes, no guidelines exist for optimizing practices specific to stroke care via telemedicine. Effective telestroke is dependent on efficient data gathering by remote staff, and lengthy metrics for real-world telestroke often preclude timely tPA treatment. By co-opting “pit stops” as inspiration, an optimized nursing workflow for telestroke can be created on the following principles: Identification of Shared Goals; Organized Urgency with the Removal of Gatekeepers; Multi-personnel, Non-Sequential Processes; Focus on Defined Staged Roles; and Empowered Engagement/Responsibility.

Methods:
The QCI-NASCAR protocol was implemented in Oct 2013, and data was collected prospectively on consecutive stroke code activations through Apr 2014 at St. Paul University Hospital (Dallas, TX), a telestroke spoke site. The nurse-driven protocol was reinforced by a paper checklist (i.e. “Driver Sheet”), which doubled as a data collection form. Timestamps were recorded in real time for: door time, MD at bedside, CT arrival, needle time, and/or code cancellation. The primary outcome was Door-to-CT (D2CT) times to reflect the portion of the stroke code most impacted by the nursing protocol.

Results:
Mean D2CT times were: all cases (n=152, 33.2 min), intervention-eligible cases (n=71, 27.0 min), and thrombolytic-eligible cases (n=57, 22.2 min). A trend for lower D2CT times and standard deviations was noted in comparing the first half of the data (n=76, 38.04 ± 58.1 min) to the second (n=77, 27.8 ± 19.1 min; p<0.05). A similar pattern was noted in the subset of intervention-eligible cases: first half (n=36, 29.4 ± 37.4 min) vs. second half (n=35, 24.3 ± 18.6 min; p<0.05). IV tPA was administered 3 times, including an institutional best door-to-needle time of 32.0 min.

Conclusion:
QCI-NASCAR demonstrates the feasibility of implementing a nursing-driven protocol for telestroke encounters. A larger, multi-institutional trial will demonstrate if such a protocol can significantly and reproducibly lower stroke code metrics to national guideline parameters.
Abstract T P26: Combining Clinical and Imaging Data to Develop a Highly Predictive Model of Outcomes in the MR RESCUE Trial
Authors: Kidwell Chelsea S , Jahan Reza , Gornbein Jeffrey , Alger Jeffry R , Nenov Val , Norato Gina , Ajani Zahra , Feng Lei , Meyer Brett C , Olson Scott , Schwamm Lee H , Yoo Albert J , Marshall Randolph S , Meyers Philip M , Yavagal Dileep R , Wintermark Max , Liebeskind David S , Guzy Judy , Starkman Sidney , Saver Jeffrey L ,   MR RESCUE Investigators
Published: July 2021

Background:
Identifying patient characteristics that predict outcomes in acute ischemic stroke may assist in triaging those who are candidates for endovascular therapies. We sought to identify predictors of outcome in the overall Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) cohort and compare results to the previously validated Totaled Health Risks in Vascular Events (THRIVE) score.

Methods:
MR RESCUE randomized 118 acute ischemic stroke patients with multimodal imaging to embolectomy or standard care within 8 hours of onset. For this analysis, we investigated 17 baseline variables (e.g. age, predicted core volume, time to enrollment) and 8 intermediate variables (e.g. hemorrhagic transformation, day 7 recanalization, final infarct volume) with the potential to impact outcomes (day 90 mRS). The baseline variables were analyzed employing bivariate and multivariate methods (random forest and logistic regression). Two models were developed, one including only significant baseline variables, and the second also incorporating significant intermediate variables.

Results:
A multivariate model (Table) employing only baseline covariates achieved an overall accuracy (C statistic) of 85% in predicting poor outcome (day 90 mRS 3-6) compared to 80.5% for the THRIVE score. A second model (Table) adding significant intermediate variables achieved 89% accuracy in predicting day 90 mRS.

Conclusions:
In the MR RESCUE trial, advanced imaging variables, including predicted core volume and site of vessel occlusion, contributed to a highly accurate multivariable model of outcome. In the development phase, this model achieved higher accuracy than the THRIVE score. Future studies are needed to validate this model in an independent cohort.
Abstract T P291: Hospital Improvement with Scheduling Stroke Specialty Care Follow-up Appointments
Authors: Lender Stacy , Prvu Bettger Janet , Nutter Diane ,   on behalf of the Ohio Coverdell Stroke Program
Published: July 2021

Background:
Follow-up care with stroke specialists can facilitate patient recovery. To improve care continuity post-stroke the Ohio Coverdell Stroke Program aimed to improve the proportion of hospitalized patients who had a follow-up appointment scheduled with specialty care (neurologist, neurosurgeon or neurology provider) prior to discharge.

Methods:
Data from Ohio Coverdell Stroke Program hospitals (N=48) were examined to determine the change in performance over a 12-month quality improvement initiative (quarters 1-2=baseline; quarters 3-4=active improvement phase). Admitted stroke patients of any type, planned for discharge home or to a rehabilitation or skilled nursing facility (post-acute care), and with a follow-up appointment ordered or recommended were included. Patients discharged in quarter 4 with and without an appointment scheduled were compared to identify targeted areas for continued improvement.

Results:
There were 3,920 stroke patients discharged home and 3,530 discharged to post-acute care. Of patients discharged home during the baseline period, 24.4% had a follow-up appointment scheduled before hospital discharge compared with 44.0% of patients in quarter 4 (80.3% improvement). Of patients discharged to post-acute care during baseline, 25.0% had a follow-up appointment scheduled compared with 40.2% of patients in quarter 4 (60.8% improvement). Improvement in the proportion of patients with a follow-up appointment was significant (p<0.001) for those discharged home and to post-acute care. Analysis of patient characteristics showed fewer appointments were scheduled in quarter 4 for patients discharged home who had a stroke type other than ischemic, were White, obese/overweight, or without a history of hypertension (p<0.05; no difference by age, stroke severity, or other co-morbidities). Among those discharged to post-acute care, fewer appointments were scheduled for patients with a NIHSS<5, White, with Medicare, or no history of coronary artery disease or obesity/overweight (p<0.05).

Conclusions:
Hospital performance with scheduling specialty care follow-up appointments improved significantly; however, there is room for continued improvement particularly with targeted patient sub-groups identified.
Abstract T P315: Wake-up Intracerebral Hemorrhage Is Not Different From Intracerebral Hemorrhage With Known Onset Time
Authors: Martí-Fàbregas Joan , Prats Luis , Martínez-Domeño Alejandro , Marín Rebeca , Casoni Francesca , Dorado Laura , Fuentes Blanca , Purroy Francisco , Arias Susana , Jimenez-Xarrié Elena , Delgado-Mederos Raquel ,   RETICS (INVICTUS network)
Published: July 2021

Background:
The frequency of wake-up Intracerebral Hemorrhage (WU-ICH) is uncertain. It is also unknown whether there are clinical, radiological and prognostic differences between WU-ICH and non-WU-ICH. We assessed the hypothesis that both types of ICH do not differ.

Methods:
This is a multicentre (n=6 tertiary hospitals) registry of consecutive patients with ICH. We collected the following variables: Time of onset. WU onset was defined as stroke detected on awakening, independently of the time of the day; Demographics (age, sex); Traditional vascular risk factors; Severity of the neurological deficit at admission (NIHSS score and/or Glasgow coma scale score -GCS-); Neurological deterioration (decrease in >1 point in GCS and/or increase in >3 points in NIHSS score); Etiology; Neuroimaging at admission (location, secondary intraventricular hemorrhage, hematoma volume); Blood pressure, blood glucose, platelet count and INR at admission; and Outcome (modified Rankin scale score -mRS- at discharge and at 3 months; favourable outcome when mRS ≤ 2). Patients were treated according to national guidelines of ICH. Comparison between groups was achieved with Student’s t-test, Chi-square test and Mann-Whitney’s U test.

Results:
We included a total of 270 patients, whose mean age was 70.2 ± 14.4 years, and 60% of them were men. WU-ICH was diagnosed in 49 (18%) patients. We found no significant differences between groups in demographics, frequency of vascular risk factors, severity of the neurological deficit, etiology, blood pressure, blood analysis and neuroradiological findings. Patients with WU-ICH had a lower frequency of neurological deterioration when assessed by the NIHSS scale (p= 0.04) but not by the GCS scale. The outcome at discharge and at 3-months was equivalent between groups.

Conclusions:
In conclusion, 18% of ICHs are detected on awakening. Patients with wake-up ICH do not differ from patients with known onset time either in most clinical and radiological variables or in the long-term prognosis. WU-ICH patients may have a lower likelihood of neurological worsening within the acute stage.
Abstract T P341: Transitions of Care: Increasing Follow-up and Decreasing Readmission Rates After Hospitalization for Acute Ischemic Stroke
Authors: Maygers Joyce , Lawrence Erin , Woolford Cheryl , Llinas Rafael H , Marsh Elisabeth B
Published: July 2021

Background:
Acute ischemic stroke accounts for nearly 800,000 inpatient hospitalizations annually in the United States. Post-discharge disposition varies greatly among stroke survivors. The transition to home or nursing facilities post-hospitalization provides an opportunity to improve quality of life; but also increases the potential for miscommunication between patients, care givers, and health care providers. This may result in the need for hospital readmission, which further complicates patient care. A timely post-discharge neurology clinic visit would be the ideal forum to address miscommunication and reduce readmission. Without dedicated infrastructure, it is difficult to see patients quickly, resulting in a poor follow-up rate. Our Stroke Center sought to improve transitions for stroke survivors with the addition of a neurology nurse case manager, creation of a targeted post-discharge plan, and implementation of the Bayview Stroke Intervention Clinic (BaSIC).

Methods:
Beginning in September 2013, all patients admitted with acute ischemic stroke were assessed by our case manager prior to discharge and a specific post-discharge plan was developed including a plan for follow-up within 4-6 weeks. This was achieved with the implementation of a weekly neurology clinic dedicated to post-stroke care, staffed by two cerebrovascular neurologists. To gauge the effectiveness of our intervention to improve follow-up rates and decrease hospital readmissions, we retrospectively compared stroke patients discharged in fiscal year 2013 (prior to implementation) to those discharged in 2014. Annual readmission rates as well as follow-up rates in neurology clinic at 30, 60 and 90 day post-discharge intervals were assessed.

Results:
With implementation of targeted post-discharge planning and BaSIC clinic, the 30 day follow-up rate (2.6% pre versus 8.4% post; p=0.01), 60 day follow-up rate (8.3% pre versus 16% post; p=0.01), and 90 day follow-up rate (14.4% pre versus 20.6% post; p=0.10) all improved. Hospital readmissions fell from 10.5% to 8.7% (p=0.63).

Conclusion:
Implementation of a targeted post-discharge plan and specialized stroke follow-up clinic decreases readmissions and increases follow-up visits with neurology.
Abstract T P388: Statin Use is Linked to Lower Risk of Recurrent Vascular Events among Ischemic Stroke Patients with Atrial Fibrillation
Authors: Lee Meng , Wu Yi-Ling , Saver Jeffrey L , Lee Jiann-Der , Wang Hui-Hsuan , Ovbiagele Bruce
Published: July 2021

Background:
The efficacy of statin therapy in the prevention of recurrent stroke and major adverse cardiovascularevents (MACE) was clearly established by the SPARCL trial; but SPARCL excluded patients whose index stroke was due to a presumed cardioembolic mechanism. As such, it remains unclear whether statins are beneficial in cardioembolic stroke patients, particularly those with atrial fibrillation (AF).

Objective:
To evaluate the relationship between statin use and future vascular risk reduction among recent ischemic stroke patients with AF

Methods:
We analyzed the Taiwan National Health Insurance registry which comprises beneficiaries aged ≥ 18 years. Code ICD-9 was used to identify a primary hospitalization diagnosis of ischemic stroke and AF among subjects encountered between 2003 and 2009. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction; withdrawal from the registry; and last medical claim before 1/1/2011. Patients were divided into 2 groups based on whether statin was prescribed (at least 30 days vs. never used) during the follow-up period. Patients were excluded if they did not take any antithrombotic agent within 30 days before an endpoint. Primary endpoint was MACE (composite of stroke and myocardial infarction) and a key secondary endpoint was any recurrent stroke. Multivariate-adjusted hazard ratio (HR) and 95% CI for the development of events were estimated using Cox models. Model was adjusted for baseline age, gender, hypertension, diabetes, prior stroke, prior myocardial infarction, hyperlipidemia, hospital level, and antithrombotic agent during follow-up.

Results:
Among 4455 eligible patients, mean age was 71 years and mean follow-up duration was 2.8 years.Compared to non-statin use, statin use was associated with a significantly lower occurrence of MACE (adjusted HR 0.84, 95% CI 0.72 to 0.99, P=0.04) and recurrent stroke (adjusted HR 0.82, 0.69 to 0.97, P=0.02). Statin use was also linked to lower ischemic stroke risk, but had neutral effects on intracranial hemorrhage and myocardial infarction.

Conclusion:
Among patients with an index ischemic stroke and AF, statin use is associated with a lower risk of recurrent vascular events including stroke.
Abstract T P418: The Association Of Cognitive Decline With Cerebral Microbleeds Appearance And Its Risk Factors: 9 Years Follow-up Study
Authors: Nakagawa Tomonori , Onoda Keiichi , Takayoshi Hiroyuki , Mitaki Shingo , Oguro Hiroaki , Nagai Atushi , Yamaguchi Shuhei
Published: July 2021

Aims:
Cumulative evidence indicates that the presence of cerebral microbleeds (CMB) is a highly strong risk factor for future brain hemorrhage. Our recent longitudinal study demonstrated the odds ratio of CMB for future brain hemorrhage was 50.2 (95% CI, 16.7 to 150.9). Since small vessel disease underlies CMB as a histopathological basis, the control of hypertension is supposed to be essential for preventing the occurrence of CMB. It remains unknown whether new appearance of CBM affects cognitive functions. We performed a longitudinal cohort study to clarify risk factors accounting for the appearance of CMB and its effects on cognitive functions.

Methods:
In this study we followed up 97 healthy subjects (mean age 63 y.o. at the entry), who had undertaken brain MRI 9 years ago in our brain check-up system. No subjects had neurological symptoms at the first and second check-up. We assessed the changes of CMB in MRI and risk factors for the appearance or increase of asymptomatic lesions were examined. Cognitive function tests (a concise version of WAIS-R) were also performed at the entry and follow-up time. Age was used as a covariate in all statistics.

Results:
During the 9-year follow-up period, we observed new appearance of CMB in 19 subjects (19.6 %: worsening group). The worsening group showed significantly higher values of systolic blood pressure at the time of entry compared to the no-change group (p=140) is 4.21 (p<0.05). In addition, the worsening group showed significant deterioration in cognitive function tests (p<0.05).

Conclusions:
The present study demonstrates that the optimal control of blood pressure are critical for prevention of CMB appearance, which would contribute to prevention of future cognitive deterioration in addition to brain hemorrhage.
Abstract T P419: Pathological Arterial Wall Correlates of Lumen-based Remodeling: Results From the Brain Arterial Remodeling Study
Authors: Gutierrez Jose , Elkind Mitchell S , Goldman James , Honig Lawrence , Morgello Susan , Marshall Randolph
Published: July 2021

Background:
There is paucity of data about arterial wall characteristics of the smallest and largest caliber cerebral vessels. Determining the relationship between the lumen and the wall might shed new insights into cerebral artery remodeling.

Objective:
To test the hypotheses that arteries with larger luminal diameters have a thinner wall and that arteries with the smallest lumina have thicker walls.

Methods:
Cross-sectional segments from large arteries (N=1392) were obtained from the circle of Willis in 196 autopsied brains (mean age 55 ± 17 yrs, 39% with hypertension, 15% with diabetes and 20% with dyslipidemia). Lumen diameter, stenosis percentage, and thicknesses of intima, media, and adventitia were calculated in digital microphotography after staining. Atheromas and internal elastic lamina (IEL) disruption were rated visually. Arteries were categorized into the top 5% (“dilated”) and bottom 5% (“narrowed”) of the luminal diameters, as well as an intermediate category (90% of sample as reference). We used logistic regression to obtain the odds of association (OR, 95% CI) after adjusting for demographic and vascular variables.

Results:
Narrowed arteries were more frequently found in men (OR 2.7, 95%CI 1.3-5.9) and with dyslipidemia (4.2, 1.6-11.1) while dilated arteries were more frequently found in women (5.6, 2.2-14.0), in smokers (2.6, 1.0-6.5) and those with prior MI (7.7, 1.2-48.7). Narrowed arteries were more likely to have atheromas (20.8, 4.8-90.3), greater luminal stenosis (per %, 1.1, 1.1-1.2), thicker vessel walls (1.3, 1.2-1.4), but thinner medias (0.9, 0.8-1.0). Conversely, larger arteries exhibited less IEL disruption (0.3, 0.1-0.9), atheromas (0.34, 0.1-0.9) and stenosis (0.8, 0.8-0.9), their walls were thinner (0.8, 0.8-0.9) but the media was thicker (1.1, 1.1-1.2).

Conclusions:
Narrowed cerebral arteries were more likely to have atheromas while dilated arteries had thinner walls and were more frequent in subjects with prior MI. These findings suggest that both extremes of the arterial spectrum might be differentially related with vascular disease, underscoring the need to revisit whether standard preventive measures for vascular disease are equally effective in patients harboring such disparate arterial phenotypes.
Abstract T P61: Network Profile Between Neuroprotector and Immune Responses Following Acute Stroke
Authors: Chuang Pei-Ying
Published: July 2021

INTRODUCTION:
The nation’s leading cause of death and disabilities is stroke. The only FDA-approved treatment for ischemic stroke remains tissues plasminogen activator (tPA) within 3-4.5 hours after onset. Humans demonstrate early neuroprotection and immune response prevention in stroke. Neuroglobin (NGB), a promising neuroproteective agent, directly binds with toxic substances and increased the oxygen level within brain tissues after stroke.

PURPOSE:
To analyze the network mechanism between neuroprotective and immune responses in critical hours and to identify personalized intervention for individuals with more aggressive conditions.

METHODS:
This pilot study included 92 Caucasian stroke subjects (ischemia and hemorrhage), with the following inclusion criteria: 1) adults (age 18-75) diagnosed within 24-72 hours of initial symptoms of stroke; 2) CT/MRI image with clinical biomarker-cerebral ischemia/hemorrhage; 3) NIHSS and mRS data available; and 4) tPA infusion and intra-arterial therapy allowed at Memorial Hermann Hospital, Medical Center in Houston, and IRBs approved. Peripheral blood and DNA extracted samples were obtained from baseline to seven days. Neurological outcomes, NGB ELISA, Western blot, mass spectrometry (MS), immunoprecipitation, and coding sequence were collected.

RESULTS:
The average age of stroke was 58.9+12, with NIHSS score 0-40, and mean of admitted SBP/DBP =160/87 mmHg. Earliest Sign/Symptoms included visual (n=60), facial paresis (n=49), motor (n=59) deficiency. Forty-five subjects received tPA within 3-4.5 hours (ICH=41) with 58 had a stroke history; GCS, GOS, NIHSS, mRS, and Barthel were collected. NGB protein expression was higher in ischemic stroke than hemorrhagic stroke. Males had higher NGB protein than females. NGB single nucleotide polymorphisms (rs3783988 and rs10133981) were significantly identified, and MS detected nine peptides associated with NGB. A self-defense pathway was provided.

CONCLUSION:
Natural protective phenomena for individuals are critical. Bridging the bench evidence and clinical practice may promote a more enhanced personalized intervention and better identify main predictors. Future direction will focus on acute network mechanism of self-defense prevention.
Abstract T P92: Remote Ischemic Conditioning (RIC) Attenuates Post-TBI Ischemic Injury and Improves Behavioral Outcomes
Authors: Vaibhav Kumar , Baban Babak , Wang Philip , Khan Mohammad B , Pandya Chirayu , Ahmed Heba , Chaudhary Aizaz , Ergul Adviye , Heger Ian , Hess David C , Dhandapani Krishnan M , Hoda Md Nasrul
Published: July 2021

Background:
Others and we reported that RIC-therapy is safe in humans, and protective in rodents that can be repeatedly used under both, hemorrhagic and ischemic stroke. Since TBI shares some common features of ischemic and hemorrhagic injury as in stroke, we hypothesized that RIC-therapy will remain protective in TBI, too.

Methods:
We tested RIC-therapy in a closed-head injury model of pediatric TBI in male mice (28 days old). Mice were later randomized for either RIC-therapy or its sham-procedure once daily starting 1-hour post-TBI until sacrifice. Cerebral blood flow (CBF) was measured by laser speckle imager (LSCI), and MRI was used to estimate edema and cerebral perfusion. Mice were also tested for functional outcomes. Statistical significance was determined at p<0.05.

Results:
Micro-CT showed a shallow dent along the median suture of skull. Closed-head TBI led to progressive acute ischemia, which was attenuated with time. However, reduced CBF and significant edema was observed at 48-hours post-TBI, which was attenuated by RIC-therapy. Open-field test showed no significant difference at 3 days post-TBI but in the narrow beam-walk challenge, TBI mice showed significantly impaired activity, which was improved by RIC-therapy. Flowcytometry in brain tissue confirmed significantly increased opening of mitochondrial permeability transition pore and necro-apoptotic cell death at 3 days post-TBI that was blocked by RIC-therapy. In a 3-weeks follow up, the mice with TBI were apparently normal but showed depressive phenotype in challenged environments, such as lesser mobility during forced swim test, and reduced cerebrovascular reserve capacity (CVRC). Flowcytometric analysis of the brain tissue at 3-weeks post-TBI showed reduced neuronal activity as detected by the poor population of cFOS positive neurons. RIC-therapy after TBI significantly attenuated the depressive phenotype, improved CVRC and cFOS positive neurons, collectively indicating improved neurovascular coupling and function.

Conclusion:
Post-TBI RIC-therapy is safe and beneficial, and can be translated to prevent ischemic injury.
Abstract W MP10: Outcome and Futile Recanalization in Basilar Artery Occlusion - Systematic Analysis
Authors: Lindsberg Perttu J , Sairanen Tiina , Nagel Simon , Salonen Oili , Silvennoinen Heli , Strbian Daniel
Published: July 2021

Background:
Basilar artery occlusion (BAO) is a most devastating form of stroke, and the current wisdom is to reverse it with revascularization therapies. Pharmacological thrombolysis have been adjuncted or replaced with endovascular thrombectomy devices. The preferred approach remains unknown and most recanalizations are futile with no clinical benefit.

Methods:
To determine whether invasive, endovascular interventions are superior to pharmacological thrombolysis alone we analyzed systematically the reported outcomes produced by variable BAO recanalization protocols. Information was retrieved from 15 reports published from 2005 comprising 803 patients in 17 cohorts. In the largest single-center cohort (162, Helsinki), predictors of futile recanalization (FR;3-month modified Rankin Scale [mRS] score 4 to 6) were determined.

Results:
Good outcome was reported by pharmacological protocols less frequently than by mechanical approaches either alone or on-demand (24.4% vs. 35.5% %, p<0.001), accompanied by lower recanalization rates (70.9% vs. 84.1%, p<0.001)(Figure). Afforded by superior recanalization rate at 91%, good outcome was reached by primary thrombectomy with stent-retrievers in 36%, but at the cost of substantial FR rate at 60%.

In the largest single-center cohort, the single most significant predictor was extensive baseline ischemia, increasing the odds of futility 20-fold (95%CI 4.39-92.29, p<0.001). Other attributes of futility were ventilation support and history of atrial fibrillation or previous stroke.

Conclusion:
Mechanical endovascular approaches have reported superior primary outcome rates over pharmacological thrombolysis in BAO. Stricter patient selection, most notably to exclude victims of already extended ischemia, would assist in translating excellent recanalization rates into improved clinical outcomes and more acceptable futility rates.
Abstract W MP11: Does Intravenous t-PA Before Acute Stroke Intervention Increase Intracranial Hemorrhage? -Subanalysis of Rescue-japan Registry
Authors: Takagi Toshinori , Yoshimura Shinichi , Enomoto Yukiko , Egashira Yusuke , Yamagami Hiroshi , Sakai Nobuyuki , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Tanahashi Norio , Hyogo Toshio ,   Recovery by Endovascular Salvage for CerebralUltra-acute Embolism (RESCUE)-Japan Study Group
Published: July 2021

Objective:
It has not been clarified whether combination therapy of intravenous t-PA (IV t-PA) and acute stroke intervention (ASI) increase intracranial hemorrhage (ICH). The aim of this study was to investigate the relationship between IV tPA and intracranial hemorrhage at every occluded vessel using data of RESCUE-Japan Registry.

Methods:
Among 1,442 acute cerebral infarction patients due to major vessel occlusion within 24 hours who were enrolled in RESCUE-Japan registry, we examined the influence of IV tPA for intracranial bleeding according to a vessel occlusion site in 410 patients who were received ASI. The site of occlusion was classified as Internal carotid artery (ICA), M1 and M2 in Middle cerebral artery, Vertebral artery (VA), and Basilar artery (BA). Intracranial hemorrhage was defined as any intracranial hemorrhage (aICH) and symptomatic ICH (sICH) which worsened more than 4 points in National Institution of Health Stroke Scale (NIHSS).

Result:
Among 410 patients, aICH was found in 127 (30.9%) and sICH was found in 20 (4.9%). According to the occluded vessel, ASI after IV tPA did not increased both aICH and sICH in ICA, M1, VA, and BA. In analysis of M2, ASI after IV tPA significantly increased sICH (0% vs 18.75%, p=0.0245). For multivariate analysis, age over 75 years old, more than 20 points in NIHSS tended to increase sICH (p=0.0507, respectively), and IV tPA was independent risk factor for increase of sICH (p=0.0102). On the other hand, IV tPA did not increase aICH in M2 occlusion (p=0.7059). In multivariate analysis in M2 occlusion, more than 20 points in NIHSS (p=0.0057), heparin use in ASI (p<0.0001), pre-antiplatelet therapy (p=0.0004) were independent risk factors.

Conclusion:
In acute brain infarction, ASI after IV tPA did not increase ICH totally, but sICH was increased in M2. IV tPA before ASI in small vessel was thought to be a risk factor of increase sICH.