bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP71: Parent Artery Plaque in Acute Lacunar Stroke: A Prospective, Multicenter, Observational Study
Authors: Lin Qianqian , Chen Hui-Sheng , Yang Yi , Fang Le , Zhang Meng , Wu Shiwen , Lu Baoquan , You Yong , Chen Beilei , Liu Changyun , Lu Zhengqi , Lou Min , Hu Hongtao , Li Haifeng , Lu Zuneng , Du Ailian , Zhang Jue , Li Mingli , Huang Yining , Xu Weihai ,   Stroke Imaging Package Study Group
Published: June 2021

Purpose:
We aimed to investigate the prevalence and clinical relevance of the parent artery plaque in acute lacunar stroke.

Methods:
This prospective, multi-center, observational study included patients with first-ever ischemic stroke within 72 hours of symptom onset. Patients were evaluated by three-dimensional T1-weighted high-resolution magnetic resonance imaging (HR-MRI) and conventional MRI sequences. We examined the presence of intracranial plaque, infarction patterns, and infarct volumes in all the patients with acute lacunar stroke. The outcome measurement was 90-day poor functional outcome (modified Rankin Scale >2).

Results:
Of the 756 patients included, 341(45.1%) patients had an acute lacunar stroke. There were 201 (58.9%, 201/341) patients with an infarct in deep basal ganglia area. Among them, 64 (31.8%, 64/201) patients had middle cerebral artery (MCA) plaques identified on HR-MRI. The patients with MCA plaque had a similar infarct volume ( 0.93ml vs. 0.88ml ,
p
=0.9) with those without MCA plaque. However, they more likely had an infarct involving posterior limb of internal capsule (42.2%, 27/64 vs. 25.5%, 35/137,
p
=0.017 ) and had a higher prevalence of cerebral microbleed (68.8%, 44/64 vs. 40.1%, 55/137,
p
<0.001 ), and moderate to severe perivascular spaces in basal ganglia (BG-PVS)(57.8%, 37/64vs.35.0%, 48/137,
p
=0.002) . After adjusting for age and National Institute of Health Stroke Scale (NIHSS) at admission, the presence of MCA plaque was independently associated with 90-day poor functional outcome (OR:3.44, [95% CI,1.26-9.42]). There were 102 (29.9%, 102/341) patients with an infarct in pons. Among them, 66 (64.7%, 66/102) patients had basilar artery (BA) plaques. Patients with BA plaque had a higher prevalence of moderate to severe BG-PVS (42.4%, 28/66 vs. 22.2%, 8/36,
p
=0.041). There were no differences between the patients with and without BA plaque regarding infarction volume and 90-day functional outcome.

Conclusions:
Parent artery plaque is common in patients with acute lacunar stroke. We propose the deep basal ganglia area infarct with MCA plaque as a unique lacunar stroke subtype with poor prognosis. Our data did not show the presence of BA plaque have an effect on the lacunar stroke prognosis.
Abstract WMP77: SUMO1 Plays an Important Role in Cardiac Dysfunction After Intracerebral Hemorrhage in Aged Mice
Authors: Li Wei , Chopp Michael , Venkat Poornima , Chen Zhili , Zacharek Alex , Landschoot-Ward Julie , Chen Jieli
Published: June 2021

Background:
The conjugation of the small ubiquitin-like modifier1 (SUMO1) plays an important role in numerous biological processes, including DNA repair and signal transduction. SUMO1 also reduces cardiac oxidative stress and hypertrophy as well as induces neuroprotective effects. Intracerebral hemorrhage (ICH) induces cardiac deficit in the absence of primary cardiac diseases in young adult wild type mice. In this study, we tested the hypothesis that SUMO1 plays a key role in regulating brain-heart interaction after ICH, and SUMO1 deficit leads to worse brain and heart deficit after ICH in aged mice.

Methods:
Aged (16-20 months) female Sumo1-deficient (SUMO1-/-) mice or wild-type (SUMO1+/+) mice were subjected to ICH by injecting collagenase IV into the basal ganglia. Cardiac function was measured by echocardiography before ICH induction and at 7 days after ICH. Modified neurological severity (mNSS) ,foot-fault and adhesive removal tests were performed at 1, 3, 6 days after ICH to investigate neurological function. Cognitive functional tests (odor and novel objective tests) were performed before sacrificing the mice at 10 days after ICH, and then histological and immunohistochemically staining were used to evaluate the mechanisms.

Results:
Compared to SUMO1+/+ mice, SUMO1-/- mice did not exhibit significant cardiac deficit before ICH in aged mice. Compared to SUMO1+/+ICH mice, SUMO1-/-ICH mice exhibit significantly (p<0.05) increased:
1)
brain hemorrhage volume and induced worse neurological and cognitive deficits,
2)
cardiac dysfunction identified by decreased cardiac contractile function measured by left ventricular ejection fraction (LVEF) and fractional shortening (FS);
3)
cardiac hypertrophy and fibrosis;
4)
ionized calcium binding adaptor molecule (IBA1) positive macrophages/microglia and CD45 positive leukocyte infiltration into both heart and brain tissue.

Conclusions:
Aged SUMO1 deficient mice subjected to ICH not only exhibit increased neurological and cognitive functional deficit, but also significantly increased cardiac dysfunction and inflammatory cell infiltration into heart. These data suggest that SUMO1 plays an important role in brain-heart interaction and SUMO1 impacts brain-cardiac dysfunction after ICH.
Abstract WMP82: Inhibition of Thioredoxin Interacting Protein Attenuates Tissue Plasminogen Activator Induced Brain Damage Under Acute Hyperglycemia in Murine Stroke Model
Authors: Ismael Saifudeen , Li Lexiao , Yoo Arum , Ishrat Tauheed
Published: June 2021

Background and Hypothesis:
Acute hyperglycemia (AHG) worsens stroke outcome and increases the risk of intracerebral hemorrhage after tissue plasminogen activator (tPA) treatment, independent of preexisting diabetes. We have previously reported that genetic deletion of thioredoxin interacting protein exerts neuroprotection after experimental stroke. Here we tested the hypothesis that pharmacological inhibition of TXNIP, with verapamil protects against tPA-induced brain damage under AHG in a mouse model of focal cerebral ischemia.

Methods:
Transient focal cerebral ischemia was induced by a 60 min middle cerebral artery occlusion (MCAO) followed by 23 h reperfusion in mice. AHG was induced by administration of 20% glucose (ip), 15 minutes before MCAO. Verapamil (0.015 mg/kg, iv) and tPA (iv), or saline was administered at 1 h post-occlusion. After 24 h of I/R, mice were tested for neurobehavioral outcome and were evaluated for infarct size and expression inflammatory mediators, and blood brain barrier markers.

Results:
AHG aggravated brain edema, blood brain disruption and neuroinflammation. Treatment with verapamil significantly reduced in the infarct size (41%, p<0.05), hemorrhage (36%) and edema (36%, p<0.05) compared to saline treated controls. Furthermore, verapamil significantly inhibited the TXNIP mediated activation of NLRP3-inflammsome and ameliorated blood brain barrier leakage (Table 1).

Conclusion:
Taken together, these data indicate that inhibition of TXNIP with verapamil may have therapeutic implications on ischemic stroke in the acute hyperglycemic condition.
Abstract WMP93: Risk of Early Ischemic Stroke After Transient Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Sadighi Alireza , Abedi Vida , Shahjouei Shima , Ansari Saeed , Ishaq Farhan , El Andary Nada , Holland Neil , Zand Ramin
Published: June 2021

Objective:
TIA is considered a heralding sign for stroke. Studies have reported a stroke risk of 12 to 20% within 90 days after an index TIA, of which 50% happen within 24 to 48 hours. In the current comprehensive meta-analysis, we calculated the pooled stroke risk at 2, 7, 30, and 90 days post TIA and compared the risk between two study cohorts with study population before and after 1999 (publication year of the consensus guidelines on the management of TIA).

Methods:
Considering PRISMA guidelines, all published studies of early stroke recurrence in TIA from 2000 to 2019 were included. We calculated risk of early stroke following index TIA event at 2, 7, 30, and 90 days. We excluded studies that had a combined early outcome of TIA and stroke, studies without independent encounter for the index TIA event or diagnosis of index TIA after patient encounter for early ischemic stroke. Patients with positive diffusion weighted imaging (DWI+ TIA), or low suspicious for TIA were also excluded.

Results:
In total, 82,292 (mean age: 69.7; man: %53.4) TIA patients out of 25 studies were included. Hypertension was the most common disease among population of the included studies followed by diabetes mellitus and coronary artery disease. Among included studies, the risk of stroke ranged from 0.1 % to 5.5%, 0.4 % to 8.0%, 1.5% to 11.5% and 0.6 % to 22.1% at 2, 7, 30 and 90 days, respectively. Total number of TIA patients included for meta-analysis at 2, 7, 30 and 90 days were 31,366, 29,634, 15,038, and 81,013 respectively. We calculated pooled estimation of stroke risk following index TIA event at 2, 7, 30, and 90 days, by application of random effect models (95% CI), as 1.5, 2.3, 4.0, and 4.4, respectively. These rates among three studies at 2, 30 and 90 days which studied a population before 1999 were 4.9, 5.7 and 15.0, respectively.

Conclusion:
Our study indicated that an early risk of stroke following an index TIA event at 2, 7, and 90 days is 1.5, 2.3, and 4.4, respectively. We also observed a stroke risk reduction among studies with recruited population after 1999.
Abstract WMP98: Post-Stroke Depression Predictors Among Intracerebral Hemorrhage Survivors
Authors: Avadhani Radhika , Thompson Richard E , McBee Nichol , Ostapkovich Noeleen , Carhuapoma Lourdes , Lane Karen , Ziai Wendy , Hanley Daniel
Published: June 2021

Introduction:
Post-stroke depression (PSD) in ischemic stroke is well-documented in the literature, but much less in intracerebral hemorrhage (ICH). We aimed to evaluate the clinical predictors of PSD in a cohort of ICH patients.

Methods:
499 randomized ICH subjects in MISTIE-III trial were followed for 1 year. Center for Epidemiologic Studies Depression Scale (CES-D) was assessed at 180 days (D180) post-ICH. A score of CES-D ≥16 were considered depressed. 300 out of 379 survivors responded. Multivariable logistic regression analysis was performed to identify independent predictors of depression at D180 with adjustment for baseline demographic characteristics, ICH hemisphere and severity, and functional recovery, cognition status and patient disposition at day 30 (Model 1) and day 180 (Model 2). Good functional outcome was defined as modified Rankin Scale (mRS) 0-3 vs. 4-5 (poor mRS), cognitive impairment status was defined as screening Mini-Mental State Examination (MMSE) < 24 and good patient disposition was defined as patient location at home. Prior use of antidepressants was too small to consider.

Results:
Using CES-D, 106/300 subjects (35%) were considered depressed at day 180. Both models found that female gender, Hispanic ethnicity, and right hemisphere ICH location were statistically significant predictors of PSD. Poor mRS at D180 was statistically significant D180. Early (D30), but not late cognitive impairment was also significant.

Conclusion:
Almost 4 out of 10 ICH survivors displayed significant depression as defined by CES-D. Race/ethnicity, gender, ICH hemisphere, and poor functional recovery appear to influence post-stroke depression, while later cognitive impairment, volumetric, age, and later home location were less important.
Abstract WP10: Evaluation of a Novel Liquid Embolic Material Using a Rabbit Model: A Hydrophilic Polymer Composite Activated by the Ca2+ in the Blood
Authors: Yuki Ichiro , Ohkawa Kousaku , Hsu Frank P , Xu Jordan C , Suzuki Shuichi
Published: June 2021

Introduction:
Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by arteriovenous malformation or dural arteriovenous fistula. However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have a cytotoxic effect due to the organic solvents such as Dimethyl Sulfoxide (DMSO). The New Generation Liquid Embolic Material (NGLEM) is a clear liquid that immediately forms a solid hydrogel cast upon exposure to Ca2+ in the bloodstream, and organic solvents are not required (Figure1). The performance of this new liquid embolic material was evaluated using an
in vivo
experimental model using rabbit.

Methods:
Under general anesthesia, a renal artery of New Zealand rabbit (4.5-5.0kg) was catheterized under fluoroscopy using a microcatheter, and NGLEM was injected into the artery. Following factors were assessed; 1) the amount of LEM required for the complete occlusion, 2) injection speed, 3) duration of the injection, 4) radiopacity during the deployment and 5) incidence of catheter entrapment after the injection.

Results:
Five renal arteries in five rabbits were treated, and all arteries were completely occluded without technical complication. The injected materials immediately formed LEM cast in all vessels followed by the reflux over the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The NGLEM mixed with both iodine-based (3 animals) and tantalum based (2 animals) contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.68ml. Average time for the complete occlusion was 237 seconds. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure.

Conclusions:
NGLEM, which is a DMSO free, non-adhesive bio-polymer may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases.
Abstract WP102: Increased Blood Pressure Variability After Acute Ischemic Stroke Correlates With Ischemic Core Growth and Poor Neurological Outcome
Authors: de Havenon Adam H , Mistry Eva , Anadani Mohammad , Yaghi Shadi , Vahidy Farhaan , Tirschwell David , Rost Natalia
Published: June 2021

Background:
Research has shown that increased blood pressure variability (BPV) correlates with worse outcome after stroke. However, the mechanism is unknown.

Methods:
In this secondary analysis of the Albumin in Acute Ischemic Stroke (ALIAS) trial, we calculated BPV for SBP over the first 120 hours. The primary outcome was 90-day modified Rankin Scale of 2-6 (unfavorable outcome). The secondary outcome was difference between the CT ASPECTS at baseline and 24 hours. We fit regression models to the outcomes and used the Baron and Kenny method to estimate causal mediation effects.

Results:
We included 508 patients with a mean (SD) age of 64.3 (12.3) years, 56.1% male, median NIHSS of 11, and mean SBP measurements of 19.8. Unfavorable outcome was seen in 309 (60.8%). BPV was significantly higher in patients with unfavorable outcome (Table 1). In adjusted models, increased BPV was independently associated with unfavorable outcome (Table 2) and ASPECTS decline (Table 3). Mediation analysis revealed that ASPECTS decline accounted for 23.5% of the effect of BPV on outcome, with 16.4% as direct effect.

Conclusion:
We found that increased BPV was associated with both unfavorable outcome and growth of the ischemic core. Future prospective studies are needed to establish causality and confirm BPV’s effect on stroke recovery.
Abstract WP103: Re-Examining the Exclusion Criterion of Early Recurrent Ischemic Stroke in Intravenous Thrombolysis: A Meta-Analysis
Authors: Ignacio Katrina Hannah , Diestro Jose Danilo , Espiritu Adrian , Spears Julian , San Jose Maria Cristina
Published: June 2021

Background:
Current guidelines for intravenous tissue plasminogen activator for acute ischemic stroke preclude the administration of the drug in patients with a history of recent stroke.

Objectives:
Our meta-analysis aims to determine the safety and efficacy of thrombolysis in patients with early recurrent ischemic stroke (within 3 months of initial stroke).

Methods:
Pubmed, Cochrane, Scopus, Embase,
Clinicaltrials.gov
, and HERDIN were searched for studies comparing the outcomes of acute stroke patients undergoing intravenous thrombolysis between those with early recurrent stroke (ERS) and those without. Random-effects meta-analysis was used to evaluate the outcomes in terms of symptomatic intracranial hemorrhage, mortality and good functional outcomes at 3 months (modified Rankin Score
<
2
)

Results:
Three observational studies with a total of 48,459 thrombolysed patients (824 with ERS and 47,635 without) were included in the study. There was no significant difference between patients with ERS and those without in terms of symptomatic intracranial hemorrhage (OR 1.39, 95% Confidence Interval [CI] 0.75-2.58), mortality (OR 1.36, 95% CI 0.60-3.09) and good functional outcomes at 3 months (OR 0.74, 95% CI 0.47-1.16).

Conclusion:
Our meta-analysis suggests that there is insufficient evidence to substantiate excluding patients with ERS from receiving thrombolysis. Further studies to re-examine ERS as an exclusion criterion for receiving thrombolysis are warranted.
Abstract WP105: A Practical Wake up Tpa Protocol at a United States Based Comprehensive Stroke Center Hub and Its Telestroke Spokes
Authors: Sangha Navdeep S , Le Duy , Dhanji Raeesa , Gaffney Denise , McCartney David , Ly An , Rho Howard , Ajani Zahra
Published: June 2021

Background:
IV tPA is established as an effective treatment for acute ischemic stroke. Currently it is endorsed up to 4.5 hours of last known well time by major guidelines. A randomized trial, WAKE-UP, displayed its safety and efficacy in patients who presented within 4.5 hours of waking up with their symptoms.

Objective:
To establish a practical tPA protocol for patients who wake up or are found with stroke symptoms at a large Comprehensive Stroke Center (CSC) and its 13 telestroke spokes (TS) based on the WAKE-UP trial.

Methods:
A wake up tPA protocol was created and given to all teleneurologists. Door to needle times (DTN) and reasons for no tPA were collected for 12 months post implementation and evaluated for differences between wake up (WU) and non-wake up (NW) patients.

Results:
93 WU patients were identified; 23 at CSC and 70 at TS. 11 (47.8%) vs. 4 (5.7%) patients received tPA at CSC and TS, respectively. Median DTN was not significantly different for WU patients at CSC vs. TS (64 vs. 89 mins, p=0.54). Median DTN at CSC was shorter for NW vs. WU (37 vs. 64 mins; p=0.003). Similarly, median DTN at TS trended toward being shorter for NW vs. WU (44 vs. 89 mins; p=0.062). The reasons for no tPA at CSC were no mismatch found in 6 (50%), and MRI unavailability in 6 (50%); at TS were no mismatch found in 11 (16.6%), MRI unavailability in 54 (81,1%) and MRI was contraindicated in 1 (1.5%).

Conclusion:
Treating WU patients using a CSC Hub and TS model is feasible. DTN are longer for WU vs. NW. In the United States, MRI availability is the main barrier to WU tPA at both CSC and community hospitals. The difference between median DTN for WU between CSC and TS did not reach statistical significance, likely due to the small sample size.
Abstract WP113: Impact of Apixaban on Clinical Outcome of the Patients With Large Vessel Occlusion or Stenosis (alvo) Study
Authors: Yoshimura Shinichi , Sakai Nobuyuki , Yamagami Hiroshi , Shibata Masunari , Enomoto Yukiko , Fukawa Norihito , Matsumoto Yasushi , Takeuchi Masataka , Nonaka Tadashi , Shimizu Fuminori , Ezura Masayuki , Ota Takahiro , Hatano Taketo , Ota Hajime , Morimoto Masafumi , Morimoto Takeshi
Published: June 2021

Background:
Efficacy and safety of direct oral factor Xa inhibitor in patients with acute large vessel occlusion (LVO) and nonvalvular atrial fibrillation (NVAF) were questionable because recombinant tissue plasminogen activator (rt-PA) and endovascular therapy (EVT) became the standard therapy.

Methods:
We conducted historical and prospective multicenter registry from July 2016 to Feb 2018 at 38 centers in Japan. The eligible criteria were 20-year old or elder and patients with NVAF and acute LVO who received apixaban within 14 days from the onset. The primary endpoint was a composite of all-cause death, International Society of Thrombosis and Hemostasismajor bleedings, and ischemic events. Ischemic events included ischemic stroke, acute coronary syndrome, acute myocardial infarction and systemic embolism. The secondary endpoints were each component of primary composite endpoint.

Results:
We registered 713 patients but 27 patients were excluded due to logical error or ineligibility. The mean age was 78 (SD 10) years and 52% were male among 686 enrolled patients. The median NIHSS and ASPECTS on admission were 14 (range 0-38) and 8 (range 0-10), respectively. The use of rt-PA and EVT were 39.1% and 52.3% of patients, respectively. The median time from onset to the start of apixaban was 2.5 days (range 0-14). The cumulative incidence of primary composite endpoint at 90 days and 365 days were 9.6% (95%CI 7.4-11.9) and 17.5% (95%CI 14.4-20.5), respectively. The cumulative incidence of primary composite endpoint were 15.6% and 12.2% in those with and without EVT at 365 days (p=0.20) The cumulative incidences of ISTH major bleedings and ischemic events at 365 days were 9.0% (95%CI 6.7-11.2) and 4.4% (95%CI 2.8-6.0), respectively.

Conclusions:
We estimated the cumulative incidences of bleeding and ischemic events as well as all-cause mortality in patients on apixaban for NVAF and acute LVO. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02818868.)
Abstract WP115: Cilostazol Addition to Aspirin Does Not Alter the Short-Term Neurological Outcome in Each Clinical Subtype of Acute Stroke
Authors: Aoki Junya , Abe Koji , Masaaki Uno , Okada Yasushi , Urabe Takao , Fujimoto Shigeru , Matsuoka Hideki , Yamagata Sen , Yamagami Hiroshi , Yamamoto Yasumasa , Yonehara Toshiro , Inoue Takeshi , Yagita Yoshiki , Kimura Kazumi ,   ADS Study Group
Published: June 2021

Hypothesis:
Our previous study, ADS reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. The aim of the present study is to investigate 1) whether the impact of cilostazol addition to aspirin differ among each stroke subtype, and 2) factors associated with neurological deterioration and/or stroke recurrence in order to find therapeutic target.

Methods:
This is a retrospective analysis using the ADS databank. Neurological worsening and the rates of stroke recurrence within 14 day of onset were evaluated. Stroke subtype included large-artery atherosclerosis (LAA), lacunae infarct (LI), branch atheromatous disease (BAD), other, and undetermined.

Results:
Data on 1,160 patients (773 [67%] men; median age, 69 [61-77] years, NIHSS score was 2 [1-4]) were analyzed. At discharge, 167 (14%) were diagnoses as having LAA; LI, 532 (46%); BAD, 173 (15%); other, 132 (11%); and undetermined, 156 (14%). Neurological deterioration and/or recurrence were seen in 130 (11%) patients, and the rates were not different between patients treated with DAPT and aspirin in any stroke subtypes: LAA, 19% (DAPT) vs. 11% (aspirin alone), (p=0.185); LI, 4% vs. 3% (p=0.645); BAD, 33% vs.34%, (p=0.872), other, 8% vs.14% (p=0.272); undetermined, 13% vs. 8% (p=0.301). When we evaluated factors related to the deterioration/recurrence, age (p<0.001), NIHSS score (p<0.001), systolic and diastolic blood pressures (p<0.001, and 0.025), whiter matter change (p=0.002), large infarcts >1.5cm (p<0.001), and intracranial stenosis/occlusion (p<0.001) were found. Multivariate regression analysis revealed older age (p=0.003), systolic blood pressure (p=0.013), larger infarct (p=0.001), intracranial stenosis/occlusion (p<0.035) were the independent factors associated with neurological deterioration/stroke recurrence.

Conclusions:
Dual antiplatelet therapy using cilostazol and aspirin does not reduce the rate of short-term neurological worsening in each clinical stroke subtype. Improvement of hyperacute therapy targeting the elder patients with elevated blood pressure, large infarct and intracranial stenosis/occlusion should be required.
Abstract WP116: Association Between Smoking Status, Platelet Function and Clinical Outcomes of Ticagrelor versus Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack
Authors: Yang Yingying , Wang Yilong
Published: June 2021

Background:
Association between smoking status, platelet function and clinical outcomes of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic stroke (TIA) remains unclear.

Methods:
A subgroup analysis was conducted of Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) trial. PRINCE trial was a randomized, prospective, multicenter, open-label, active-controlled, and blind-endpoint trial, which randomized patients with acute minor stroke, or TIA, to ticagrelor plus aspirin or clopidogrel plus aspirin within 24 hours of symptoms onset. Patients who smoked at least one cigarette per day for at least one year in their lives were defined as smokers. Platelet reactivity was assessed by the VerifyNow P2Y12 assay at baseline, 7+2 days and 90±7 days. High-on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208.Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days.

Results:
Among 675 patients enrolled in the PRINCE trial, 370 patients (54.8%) were smokers. At 7+2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% versus 21.8%) and non-smokers (2.3% versus 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR (
P
=0.058). There were significant interactions between treatment groups and carrier status of
CYP2C19
LOF alleles for the proportion of HOPR among smokers (
P
=0.04), but no significant interactions were found among non-smokers (
P
=0.91). At 90±7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers, 7.0% versus 4.9%, hazard ratio [HR], 1.57 [95%CI, 0.65-3.79],
P
=0.39; non-smokers, 5.3% versus 13.5%, HR, 0.39 [95%CI, 0.17-0.91],
P
=0.01.
P
for interaction=0.02).

Conclusions:
Among patients with minor stroke or TIA, ticagrelor might be superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of stroke, particularly in non-smokers. Carrier status of
CYP2C19
LOF alleles might play a role in the impact of smoking status.

Clinical Trial Registration

:
Clinicaltrials.gov NCT02506140.
Abstract WP119: Alteplase Given Within 4.5 Hours via Telemedicine and in Person to Patients Presenting With a Central Retinal Artery Occlusion
Authors: Khrlobyan Manya , Ali Shayan , Le Duy , Ajani Zahra A , Navdeep Sangha S
Published: June 2021

Introduction:
Central or branch retinal artery occlusion (CRAO/BRAO) results in acute monocular vision loss. Studies on the efficacy of IV t-PA, treated patients up to 30 hours from symptom onset. There has only been one prospective study of early IV t-PA use. With the increasing use of telemedicine (TM), we evaluated the use of IV t-PA within 4.5 hours for CRAO/BRAO and assessed visual outcomes up to 90 days amongst patients evaluated via TM versus in-person.

Methods:
Data were retrospectively abstracted for CRAO/BRAO treated with IV t-PA within a large managed healthcare system. Visual outcomes abstracted at 24 hours were classified as Low Vision (light perception, hand motion, finger counting) and converted to mean LogMAR. Visual outcomes abstracted within 2 weeks and 3 months were classified as normal-mild impairment (LogMAR 0.4-0.5), moderate-severe impairment (LogMAR 0.6-1.3) and blind-low vision (LogMAR >1.3). Descriptive statistics were performed on all variables. Visual outcomes were analyzed using the sign test.

Results:
Between 2013-2019, 16 patients received IV t-PA within 4.5 hours of symptom onset. 11 were evaluated via TM and 5 in-person. All patients were accurately diagnosed with CRAO/BRAO. 24 hours post t-PA, 37.5% of TM vs 25% of in-person patients had at least a one-point improvement on the low vision scale. Within 2 weeks, 12.5% of TM vs 18.75% of in-person, and within 90 days, 13.33% of TM vs 20% of in-person patients improved from low vision to normal-mild impairment in vision. In all patients, at 24 hours post t-PA 56.25% (p= 0.04) had at least a one-point improvement on the low vision scale. Within 2 weeks, 31.25% (p= 0.03) and 90 days, 33.3% (p= 0.03) of patients continued to improve from low vision to normal-mild impairment in vision.

Conclusions:
All patients were correctly diagnosed with CRAO/BRAO irrespective of method of evaluation. More patients improved on the low vision scale at 24 hours via TM than in-person. More in-person diagnosed patients improved from low vision to normal-mild impairment in vision within 2 weeks and 90 days of IV t-PA. IV t-PA use within 4.5 hours for CRAO/BRAO may lead to improved visual outcomes at 90 days regardless of TM or in-person diagnosis. Our study was limited by small sample size and no control group.
Abstract WP122: Refusal of Intravenous Thrombolysis for Acute Ischemic Stroke in San Diego
Authors: von Kleist Tara , Meyer Dawn , Rapp Karen , Meyer Brett , Modir Royya
Published: June 2021

Purpose:
To assess the demographic and clinical characteristics of patients who refuse intravenous thrombolysis (IV tPA) for acute ischemic stroke from the Stroke Registry population collected by the University of California San Diego (UCSD) Stroke Team and to compare outcomes between those who were treated with IV tPA and those who refused.

Methods:
We evaluated patients between July 2004 and July 2019 from the prospective Institutional Review Board (IRB) approved Stroke Registry project. Patients who either received IV tPA or refused IV tPA were included. Baseline demographics, NIHSS, treatment times and 90 day mRS were collected.

Results:
A total of 1056 patients were included in the analysis. Forty-seven patients (4.5%) refused IV tPA. There were no differences in demographics between patients who were treated with IV tPA and those who refused. Patients who refused IV tPA had a significantly lower baseline NIHSS (4 vs 9, p=<0.0001) and higher baseline mRS (1.3 vs 0.6, p=0.00043) compared to patients who received IV tPA. The time from arrival to treatment decision was significantly longer in patients who refused IV tPA (group mean 57.9 min vs 48.8 min, p=0.03). There was no difference in 90 day mRS between groups.

Conclusions:
There is a low rate of IV tPA refusal in our registry population which is similar to what previous studies have shown
1,2
. We found that patients who refuse IV tPA have milder deficits and worse pre-morbid disability. We suspect that the longer “arrival to treatment decision” time in the refuse IV tPA group is due to longer informed consent discussions. This study demonstrates the utility of informed consent in clinical practice and highlights the importance of respecting patient autonomy.
Abstract WP126: Association of 24-Hour Blood Pressure Parameters Post-Intravenous Alteplase With Symptomatic Intracerebral Hemorrhage
Authors: Nisar Taha , Tofade Toluwalase , Liberman Ava , Khandelwal Priyank
Published: June 2021

Introduction:
Higher blood pressure (BP) at presentation is associated with a higher risk of symptomatic intracerebral hemorrhage (sICH) post-intravenous alteplase (IV-rtPA). We investigated the association of different BP parameters post-IV-rtPA with the development of sICH at a tertiary care center.

Methods:
We performed a retrospective chart review of adult patients with an acute ischemic stroke treated with IV-rtPA at a comprehensive stroke center from July 2014 to March 2018. We excluded patients who underwent mechanical thrombectomy. At the comprehensive stroke center, the BP values are documented according to standard post-IV-rtPA care guidelines. We recorded the BP values over a period of 24-hours post-IV-rtPA. A binary logistic regression analysis was performed, controlling for age, sex, pre-treatment NIHSS, atrial fibrillation, onset to treatment time, with the BP parameters as the predictors. The primary outcome was the development of sICH. SICH was defined as an intracerebral hemorrhage (ICH) that causes worsening of NIHSS score by ≥4 points post-IV-rtPA.

Results:
84 patients met our inclusion criteria. 45 (53.57%) patients were male. The mean age was 63.50±15 years. 5 (5.95%) patients developed sICH. In our cohort, the BP parameters of higher maximum systolic blood pressure (SBP) (195.8±9 vs.172.22±17; OR, 1.14; 95% CI, 1.03-1.26; P 0.016), higher maximum diastolic blood pressure (DBP) (120.2±18 vs.104.76±15; OR, 1.08; 95% CI, 1.01-1.17; P 0.04), wider SBP range (79.4±20 vs.58.75±18; OR, 1.06; 95% CI, 1.01-1.12; P 0.033), wider DBP range (74.2±27 vs.47.27±15; OR, 1.11; 95% CI, 1.03-1.2; P 0.008), and coefficient variation (CV) DBP (17.7±6 vs.12.65±4; OR, 1.19; 95% CI, 1.01-1.42; P 0.048) were significantly associated with a risk of sICH post IV-rtPA.

Conclusions:
Our study demonstrates significant risk of sICH with higher maximum SBP and DBP, wider SBP and DBP ranges, and CV DBP post-IV-rtPA.
Abstract WP130: Long Term Outcome of Large and Giant Unruptured Intracranial Aneurysms
Authors: Kan Issei , Ishibashi Toshihiro , Yuki Ichiro , Ebara Masayuki , Arakawa Hideki , Irie Koreaki , Kaku Shogo , Kajiwara Ikki , Kodama Tomonobu , Kato Naoki , Nishimura Kengo , Fujimura Soichiro , Uchiyama Yuya , Murayama Yuichi
Published: June 2021

Objectives:
Long term outcome of large / giant unruptured intracranial aneurysms (LG-UIAs) after endovascular therapy is still unknown. We retrospectively analyzed long-term results of patients with LG-UIAs who were followed up more than 5 years after endovascular therapy.

Methods:
We included patients from our complete database with UIAs greater than 10mm and treated at our hospital from January 2003 to December 2013. Retreatment rate of targeted aneurysms, rupture rate, and the modified Rankin scale (mRS) at last visit were evaluated till December 2018.

Results:
From 142 patients treated during the period were excluded 3 patients with perioperative rupture and 38 patients with less than 5 years follow-up period, finally analyzing 101 patients. The median aneurysm size was 12.0 mm (IQR 10.8-15). The median follow-up period was 9.4 years (IQR: 7-11), the longest being 13.3 years. Retreatment was performed on 36 patients (35.6%). Comparing cumulative re-treatment rates in groups with aneurysm sizes <15 mm and> 20 mm, it was predominantly higher for aneurysms> 20 mm (P = 0.02,
Figure1
). Rupture of targeted aneurysms was observed in 2 cases (1.98%,
Figure2
), and the longest period from last treatment was up to 12 years. The mRS 0-1 at the first treatment and the final visit were 98% and 93%, respectively, and mRS deterioration remained at 5%.

Conclusion:
The retreatment rate tended to increase in proportion to the size of the aneurysm, however the final neurological outcome was favorable when considering the natural history of these aneurysms. Since aneurysmal rupture could occur after 12 years of treatment, long-term follow-up should be considered for LG-UIAs.
Abstract WP135: Engineered Exosomes With Elevated Mir-27a Improve Neurological Outcome in Ischemic Mice
Authors: Zhang Yi , Liu Zhongwu , Chopp Michael , Li Chao , Wang Xinli , Zhang Li , Zhang Zheng Gang
Published: June 2021

Background:
Augmentation of axonal growth enhances improvement of neurological function after stroke. Our previous in vitro study demonstrated that miR-27a promotes axonal growth of embryonic neurons. The present in vivo study investigated whether exosomes carrying elevated miR-27a (27a-exos) enhance axonal growth and neurological outcome after stroke.

Methods and Results:
The 27a-exos were isolated from medium of mesenchymal stromal cells (MSCs) transfected with lenti-miR-27 vector. In order to investigate axonal growth and underlying mechanisms, Emx1-Thy1-YFP mice with selective expression of yellow fluorescent protein (YFP) in pyramidal neurons were subjected to the permanent middle cerebral artery occlusion (MCAO). Quantitative RT-PCR analysis showed that compared with exosomes derived from empty-vector transfected MSCs (empty-exos), 27a-exos had 3.7 fold increased miR-27a. 27a-exos (3x10
11
particles) were injected intravenously into mice at 24h after MCAO. Compared with control mice, the empty-exos (n=7) significantly (p<0.05) reduced the foot-fault (5±0.1 vs 11±0.5 in control) and the times to remove adhesive paper (seconds, 47±3 vs 70±4). However, compared with empty-exos, 27a-exos (n=7) further significantly (p<0.05) reduced foot-fault (3.0±0.2) and times to remove the paper (38±1.7). Histopathological and in situ hybridization analysis showed that 27a-exos localized to neurons and significantly (p<0.05) increased miR-27a in Emx1-YFP+ neurons (4±0.7 vs 1 in empty-exos), and augmented (p<0.05) the density of YFP+/pNFH+ axons (7±2 vs 1 in empty-exos). Moreover, 27a-exos substantially decreased the levels of the inhibitory protein Sema6a in the YFP+ axons in peri-infarct areas.

Conclusion:
Our data suggest that tailored 27a-exos augment the therapeutic effect of exosomes on stroke recovery and that suppression of axonal inhibitory proteins such as Sema6a may contribute to the 27a-exo-enhanced axonal outgrowth to promote neurological recovery post stroke.
Abstract WP141: Cyclic-AMP Induces Nogo-A Receptor NgR1 Internalization and Inhibits Nogo-A-Mediated Collapse of Growth Cone
Authors: Gopalakrishna Rayudu , Zhu Angela , Oh Andrew , Nguyen Julie , Lin Charlotte , Kindy Mark S , Mack William J
Published: June 2021

Recovery of stroke and neuronal injuries requires the promotion of axonal regeneration from the remaining neurons. However, axonal regeneration is inhibited by diverse axonal growth inhibitors, such as Nogo-A. C-terminal domain of Nogo-A, Nogo-66 binds to the Nogo-A receptor 1 (NgR1) and induces the collapse of growth cones and inhibition of neurite outgrowth. NgR1 is also a receptor for additional axonal growth inhibitors. In this study, by using indirect immunofluorescence and biotinylation method, we have found that a cell-permeable cAMP analog (dibutyryl-cAMP) and other intracellular cAMP-elevating agents, such as forskolin, which directly activates adenylyl cyclase, and rolipram, which inhibits cyclic nucleotide phosphodiesterase, all induced rapid internalization of the cell surface NgR1 in Neuroscreen-1 (NS-1) cells. This endocytosis of NgR1 is lipid raft mediated. These cAMP-elevating agents induced a reversible distribution of NgR1 between the cell surface and intracellular compartment; NgR1 distributed to the cell surface at low levels of cAMP and distributed to an intracellular compartment at high levels of cAMP. Using pharmacological activators and inhibitors of protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac), we found that NgR1 internalization is independent of PKA but dependent on Epac. There is a correlation between the decrease in cell surface expression of NgR1 decreased sensitivity of NS-1 cells to Nogo-66-induced growth cone collapse. Therefore, besides axonal growth inhibitors affecting neurons, neurons by themselves self-regulate their own sensitivity to extracellular cues such as axonal growth inhibitors. This normal cellular regulatory mechanism may be therapeutically applied to overcome axonal growth inhibitors and enhance functional recovery after stroke and neuronal injuries.
Abstract WP142: Targeting VCAM1 to Reduce Acute and Chronic Neuroinflammation After Stroke
Authors: Zera Kristy , Peterson Todd , Youdef Hanadie , Lee Davis , Wyss-Coray Tony , Buckwalter Marion S
Published: June 2021

Background:
Ischemia-induced neuroinflammmation is associated with worse outcomes after stroke. The innate immune response can mediate infarct expansion and impair short-term recovery, while adaptive responses lead to chronic neuroinflammation, neurodegeneration remote to the ischemic lesion, and consequent vascular dementia. Vascular cell adhesion molecule 1 (VCAM1) is an endothelial protein that facilitates vascular-immune cell interactions by binding very late antigen-4 (VLA-4). Soluble VCAM1 plasma levels are elevated in stroke patients and in aging people and mice. In aging mice, blocking VCAM1 ameliorates age-induced neuroinflammation and cognitive impairment.

Objective:
To determine if acute anti-VCAM1 treatment in mice would reduce microgliosis and astrogliosis, while delayed treatment would reduce B and T lymphocyte infiltration.

Methodology:
Adult (3-month-old) C57BL/6 mice (N=10/group) underwent permanent distal middle cerebral artery occlusion and were dosed with anti-VCAM1 antibody 4h post-stroke, then sacrificed at 72h. Microgliosis and astrogliosis were quantified as percent area immunostained in the infarct border by Iba1 and GFAP, respectively.

Results:
Acute treatment reduced microgliosis by 30% (p=0.0476) and astrogliosis 39% (p<0.03). Additionally, adult mice (N=10/group) were treated with anti-VCAM1 immediately (4h) or later (4d) post-stroke and euthanized 3 weeks later. B cell infiltration was quantified as percent stroke core immunostained by B220, while T lymphocyte infiltration was quantified as CD3+ cells in the core. Delayed anti-VCAM1 significantly reduced B and T cell infiltration by approximately 25% (p=0.0015) and 50% (p=0.0192), respectively. In contrast, early anti-VCAM1 had no effect on B/T cell infiltration.

Conclusions:
Together, these findings establish VCAM1 as a possible therapeutic target to prevent stroke-induced neuroinflammation in both acute and chronic settings.
Abstract WP143: Identification of Socially-Regulated Circulating Microrna Signatures in Stroke
Authors: Lee Juneyoung , Venna Venugopal R , McCullough Louise D
Published: June 2021

Introduction:
Epidemiological and clinical studies strongly support that social isolation (SI) is associated with higher mortality after stroke. SI has been identified as a risk factor in a wide variety of diseases, including stroke. However, few studies have attempted to identify the underlying mechanisms contributing to the detrimental effect of SI. To better understand systemic and global regulation networks governed by social factors, and in an attempt to identify viable biomarkers, we profiled changes in circulating microRNA (miRNA) expression in aged stroke mice after SI.

Methods:
Aged C57BL/6 mice (18-20 months) of both sexes were pair-housed (PH) or socially isolated (SI) for two weeks prior to sham or a 60-minute middle cerebral artery occlusion surgery. Mice were sacrificed two weeks after surgery and blood samples were obtained for profiling of plasma miRNAs. Using whole miRNAome analysis, differentially expressed miRNAs by isolation, stroke and sex differences were comprehensively identified and compared using bioinformatics. We further used mimic and antagomiR treatments to confirm a potential role of the identified miRNAs.

Results:
Stroke significantly changed 8 miRNAs including miR-467d-3p (
P
=0.0014), miR-376b-3p (
P
=0.013) and miR-297c-5p (
P
=0.016) in PH groups (sham vs. stroke). In a comparison between PH vs. SI in stroke mice, stroke SI mice showed a differential miRNA profile (11 miRNAs) including let-7 family potentially targeting Dicer protein, a key enzyme for miRNA biogenesis. Interestingly, compared to sham SI mice, stroke SI mice had a 2-fold increase in the number of altered miRNAs (21 miRNAs) including miR-129-1-3p (
P
=0.0075), miR-28a-3p (
P
=0.0091) and miR-204-5p (
P
=0.016). Finally, we found a strong sex difference in miRNA expression in response to SI.

Conclusions:
We identified several key miRNAs as potential biomarkers for 1) stroke, 2) SI and 3) SI/stroke. These miRNA signatures are highly unique and create a complex gene-regulatory network that depends on the social environment. Our data provide potential biomarkers and identify several miRNAs that could lead to significant improvements in diagnosis of elderly patients at elevated risk for the detrimental effects of loneliness.
Abstract WP148: The Effect of Mitochondrial Migration From Astrocyte to Glial Cells Under Prolonged Cerebral Hypoperfusion
Authors: Miyamoto Nobukazu , Magami Shunsuke , Ueno Yuji , Hira Kenichiro , Yamashiro Kazuo , Urabe Takao , Hattori Nobutaka
Published: June 2021

Introduction:
Astrocytes play broad roles in the Central nervous system, and are involved in the regulation of cerebral metabolism and blood flow. Normal astrocytes (A2) protect against oxidative stress and excitotoxicity, but unhealthy astrocytes (A1) may release deleterious factors. Oligodendrocytes (OLGs) differentiate from oligodendrocyte-precursor-cells (OPCs) for myelination in white matter, but OPC were vulnerable for ischemia. Therefore, differentiation is impaired when white matter injury occurs in a chronic cerebral hypoperfusion model. Thus, we examined the effects of the interaction between astrocyte and oligodendrocyte lineage cells on myelination focused on mitochondrial migration.

Method:
A microcoil was applied to the bilateral common carotid arteries in male C57BL/6 mice as an in vivo cerebral chronic hypoperfusion model (BCAS model). A nonlethal concentration of CoCl
2
was added to the primary cell culture from the postnatal rat cortex and incubated in vitro.

Results:
White matter injury progressed in the BCAS model as myelin decreased. The numbers of OPCs and astrocytes increased after the operation, whereas that of OLGs decreased at day 28. Increased astrocytes were mainly A1 type, and A2 type were decreased. OPC differentiation was disrupted under the stressed conditions in the cell culture, but improved after administration of astrocyte-conditioned medium (ACM), but injured ACM couldn’t improve maturation. Incubate with CoCl
2
change astrocyte A2 to A1, and mitochondrial migration also reduced. Trkβ agonist could change astrocyte A1 to A2 even in hyperperfused condition, and also help OPC maturation via mitochondrial migration and drug effect in vivo and in vitro.

Conclusions:
The reduction in incrementing A1 astrocytes protect white matter injury. and Trkβ agonist may play an important role in the impairment under chronic ischemic conditions. Mitochondrial migration could be a broad therapeutic strategy for cerebrovascular disorders.