bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP61: Improved Routing of Comprehensive Stroke Center Appropriate Patients via Mobile Stroke Unit Conclusive Field Diagnosis
Authors: Villareal Bryan , Brown Kevin , Harrell Kenny , Saver Jeffrey L. , Bahr Hosseini Mersedeh , Restrepo-Jimenez Lucas , Liebeskind David S. , Szeder Viktor , Ghurabi Walid , Kazan Clayton , Bosson Nichole , Gausche-Hill Marianne , Chidester Cathy , Nour May
Published: June 2021

Background:
Mobile Stroke Units (MSUs) are capable of rapid initiation of intravenous thrombolysis and have the potential to improve acute stroke patient routing by providing conclusive imaging diagnosis of LVO (arterial sequences) and intracranial hemorrhage (parenchymal/extraparenchymal sequences). However, the incremental increase in diagnostic accuracy and effect on patient disposition have not been well delineated.

Methods:
Consecutive transports in a regionally-deployed MSU from September 2017-August 2019) were analyzed, comparing patient routing that would have occurred under standard ambulance protocols to routing and process outcomes after CT/CTA MSU imaging. Standard ambulance regional routing policy was direct to nearest PSC if Los Angeles Motor Scale (LAMS) 0-3 and direct to nearest CSC within 30m if LAMS 4-5.

Results:
Among 83 MSU transports, final diagnosis was acute cerebral ischemia in 68% and intracranial hemorrhage in 10%. Among 57 acute cerebral ischemia patients, Los Angeles Motor Scale (LAMS) score was 0-3 in 65% and 4-5 in 35%. All (100%) of patients with ICA/M1 occlusions had LAMS score 4-5. However, among patients with expanded range endovascular target occlusions (M2, basilar), LAMS scores were 0-3 in 56%, and MSU imaging permitted improved routing. Among 8 intracranial hemorrhage patients (2 IPH, 5 SDH, 1 SAH), MSU imaging permitted improved direct-to-CSC routing in the 62% of patients with LAMS scores 0-3. Among all MSU admissions, 15% (13) were rerouted based solely upon in-vehicle imaging, including 7% for radiographically proven endovascularly treatable occlusion, 7% for neurosurgical/NICU intracranial hemorrhage care, and 1% for neurosurgical tumor care. Transport times for re-routed patients was median 12 minutes, compared to closest stroke center median 6 minutes.

Conclusion:
More than 1 in 7 MSU evaluations result in improved routing of comprehensive stroke center-appropriate patients directly to a CSC facility, including AIS patients potentially eligible for thrombectomy, intracranial hemorrhage patients, and acutely-presenting brain tumor patients. In addition to speeding start of intravenous thrombolysis, MSUs can substantially improve timely access to CSC care.
Abstract TMP63: Door-In-Door-Out Process Times at 5 Primary Stroke Centers in Chicago
Authors: Prabhakaran Shyam , Khorzad Rebeca , Parnianpour Zahra , Richards Christopher T , Meurer William , Barnard Amy , Bader Elida , Hillman Maureen , Zobel Rebecca , Lee Jungwha , Mendelson Scott J , Holl Jane L
Published: June 2021

Introduction:
Many patients with acute stroke require inter-facility transfer from primary stroke centers (PSC) to comprehensive stroke centers. Given the time-sensitive benefits of endovascular treatments, door-in-door-out (DIDO) time at the PSC is a target for quality improvement.

Methods:
As part of a funded ongoing study of redesigning the acute stroke DIDO process, we collected data on consecutive patients with acute stroke between February 2018 and February 2019 who required inter-facility transfer from 5 PSCs to one of 3 CSCs in the Chicago region. The stroke coordinators at each site abstracted data on mode of transport (critical care vs. advanced life support [ALS]), medical events and treatments (intubation, intravenous medications including tPA), times from arrival to: triage, telestroke activation and start, CT and CTA start, initial transfer center contact, ambulance request, and ambulance arrival and departure times. We evaluated predictors of DIDO time using linear regression.

Results:
Among 107 patients who met study criteria, 67.6% arrived by EMS, 83.2% had telestroke evaluation, 34.6% had tPA treatment, and 43.9% underwent CTA at the PSC. The median DIDO time was 146 (IQR 99-220) minutes. The largest contributors to DIDO time (Figure) were CT to CTA time (45 [18-86] minutes), ambulance scene time (26 [21-35] minutes), and telestroke to transfer center contact (median 23 [0-61] minutes). Independent predictors of DIDO time were obtaining CTA (+64.1 [29.4-98.5] minutes), use of ALS ambulance (+52.5 minutes [17.5-87.5] minutes), and use of intravenous medications besides tPA (+59.9 [15.7-104.1] minutes).

Conclusions:
We identified major opportunities for reducing DIDO times for inter-facility acute stroke transfers. Reducing the need for or time to CTA, earlier, streamlined transfer center contact, and using critical care ambulances are likely important strategies to decrease DIDO times.
Abstract TMP64: CT Perfusion Imaging in Telestroke Can Assist With Decision Making Without Delaying IV Alteplase
Authors: Hackett Chris , Cerejo Russell , Fishman Robert , Wright David , Rana Sandeep , Tayal Ashis
Published: June 2021

Introduction:
Perfusion based imaging aids in patient selection for endovascular therapy (EVT). Appropriate selection of patients for EVT is an important component of telestroke programs. Thus, telestroke sites could be ideal locations for perfusion imaging. Despite the advantages of perfusion imaging, there is the concern that advanced imaging may delay door to needle time (DTN). We implemented CT perfusion (CTP) using RAPID software at three large primary stroke centers within our telestroke network in December 2017. We aimed to evaluate the proportion of transfers for EVT, door in door out time (DIO) and DTN at telestroke sites before and after CTP implementation.

Methods:
Data was prospectively collected and retrospectively analyzed as part of our telestroke quality database. We compared data for one year before and one year after implementing CTP at the telestroke sites. We hypothesized that the addition of CTP would not delay DTN. Additionally we hypothesized that a greater proportion of transfers for possible EVT would receive a stroke thrombectomy and that DIO would be reduced after utilizing CTP.

Results:
Five hundred and forty patients were evaluated via telestroke and completed CT head and/or CT angiography head and neck imaging prior to CTP implementation. Seven hundred and thirteen telestroke patients received CT head, CTA head and neck and CTP imaging after CTP implementation. Of the 1253 patients, 101 (8.1%) were transferred for a possible EVT. Patients receiving CTP had a significantly shorter DIO time (median 109 minutes) compared to patients without CTP (median 122 minutes), U = 425, p = 0.04, r = 0.26. There was no difference in DTN in the 63 IV alteplase treated patients without CTP (median 66 minutes) and 58 IV alteplase treated patients who received CTP (median 63 minutes), U = 1672, p = 0.42, r = 0.07. There was no significant difference in the proportion of patients transferred for a possible EVT that received a stroke thrombectomy in the patients without CTP 28 (74%) compared to patients with CTP 38 (84%), p = 0.23.

Conclusions:
In conclusion, automated perfusion maps and calculated ischemic penumbra size in CTP allowed telestroke physicians to make quicker transfer decisions, without delaying DTN.
Abstract TMP7: Blood Pressure Goal Post Mechanical Yhrombectomy for Anterior and Posterior Circulation Stroke: A Multicenter Registry Study
Authors: Yang Ming , Huo Xiaochuan , Ma Ning , Gao Feng , Mo Dapeng , Wang Anxin , Zhang Xiaoli , Meng Xia , Wang Yongjun , Miao Zhongrong
Published: June 2021

Background and Purpose:
The effect of blood pressure (BP) within 24 hours post-mechanical thrombectomy (MT) accounts on clinical outcomes for patients with successful reperfusion. We aimed to investigate the relationship between BP during 24 hours post-MT with clinical outcomes individually for anterior circulation stroke (ACS) or posterior circulation stroke (PCS) patients

Method:
Patients with successful recanalization and a full record of systolic BP (SBP) and diastolic BP (DBP) every two hours within 24 hours post-MT were included from the ANGEL study, a multi-centric, prospective registry study of endovascular treatment owing to proximal large-artery occlusion from June 2015 to December 2017. We divided patients into three groups based on maximum SBP: <140 (intensive), 140-160 (moderate) and <180 mmHg (permissive). Clinical outcomes included functional independence (modified Rankin Scale score 0-2), mortality at 90 days follow up and intracerebral hemorrhage (ICH).

Results:
355 eligible patients were enrolled in this study. There were 162, 124, and 69 patients in the intensive, moderate, and permissive group, respectively. A 10mmHg increase of maximum SBP during the first 24 hours post-MT was independently associated with a lower likelihood of functional independence (OR=0.84 [0.75-0.94], p=0.001) at 90 days after adjusting for potential confounders. As to ACS, intensive SBP management was associated with higher odds of 90-day functional independence (OR=0.38 [0.18-0.79], p=0.010), compared with permissive SBP group. As to PCS, moderate SBP management was associated with lower odds of 90-day mortality, either compared with permissive or intensive SBP group.

Conclusion:
Higher maximum SBP post-MT was independently associated with a higher risk of poor clinical outcomes. Intensive SBP control may be more reasonable for patients with ACS, while moderate SBP is more beneficial for PCS. Although more randomized trials are needed.
Abstract TMP78: Heterogeneous Imaging Practices Associated With Emergency Department Work-Up of Transient Ischemic Attack
Authors: Timpone Vincent , Jensen Alexandria , Poisson Sharon , Trivedi Premal
Published: June 2021

Introduction:
Multiple societal guidelines recommend urgent imaging in patients with transient ischemic attack (TIA) to identify and treat risk factors that may lead to future stroke. Recommended studies include brain imaging, preferably with MRI, and neurovascular imaging (cranio-cervical CTA, cranio-cervical MRA or carotid ultrasound). The purpose of this study was to evaluate whether emergency department (ED) imaging utilization practices comply with recommended guidelines.

Methods:
Analysis utilized the Nationwide Emergency Department Sample (NEDS), a comprehensive, nationally representative sample of ED visits. Primary analysis was performed on the 2016 cohort, and a secondary trend analysis was performed on cohorts from 2006-2016. Patients diagnosed and discharged from the emergency department with transient ischemic attack were identified using ICD-9 and ICD-10 codes. Brain and neurovascular imaging obtained during the encounter were identified using CPT codes. Demographics, health insurance, patient income, and hospital type data were analyzed and a survey weighted logistic regression analysis was performed to identify predictors of obtaining neurovascular imaging.

Results:
In 2016 there were 183,216 patients evaluated and discharged from emergency departments with TIA. The percentage of patients receiving brain and neurovascular imaging was 75.73% and 37.99% respectively. Of the top 5 imaging work-ups utilized, the most common (34.06% of cases) was a solitary noncontrast head CT without any neurovascular imaging. Decreased odds of obtaining neurovascular imaging was observed in Medicaid patients (OR: 0.73, 95%CI: 0.66-0.80), non-trauma centers (OR: 0.42, 95%CI: 0.38-0.45), and rural hospital locations (OR: 0.30, 95%CI: 0.27-0.33). Trend analysis demonstrated a steady rise in brain and neurovascular imaging from 34.02% and 6.51% of encounters respectively in 2006 to 75.73% and 37.99% of encounters in 2016.

Conclusion:
The majority of TIA patients discharged from the ED do not receive recommended neurovascular imaging during their encounter. Follow-up studies are needed to determine whether delayed or incomplete vascular screening increases the risk of future stroke.
Abstract TMP80: A Stroke Survivor Pilot Program is Feasible and Improves Patient Satisfaction
Authors: Delgadillo Jorge , Pancoska Eric , Im Jenny , Gaddam Anusha , Gordon Ken , Spokoyny Ilana
Published: June 2021

Background:
For stroke patients, the in-hospital care is focused on the initial stroke treatment, secondary prevention, functional assessment, and discharge planning. Despite focused education by nursing and thorough discharge planning, patients often express frustration and concerns regarding their hospital stay, and patient satisfaction scores remain low at 75%.

Methods:
A pilot program was implemented in the acute care setting in which a stroke survivor, himself a former hospital patient, visited stroke patients and their families during admission. He provided services twice a week on the inpatient units, which included answering questions regarding his own experience surviving a stroke and keeping a log of concerns patients and families expressed during the sessions. These concerns were immediately relayed to the nursing staff caring for the patients, and also reviewed and categorized by the stroke coordinator and program manager.

Results:
Since September 2018, the stroke survivor has visited 96 patients. The majority of patients expressed concerns about their functional recovery. Additional concerns included return to normal life following their stroke, how to obtain state and federal benefits, and how to prepare foods for modified diets. These concerns had not been elicited by the clinical care team.

Prior to the program’s initiation, overall stroke patient satisfaction scores averaged 75% annually with high variability. These scores increased to 89.4% with low variability and have persisted for 8 months. Similarly, nursing communication scores averaged 75% and increased to 90% after implementation.

Conclusions:
A stroke survivor pilot program is feasible and effective for improving patient satisfaction, both overall and related to nursing communication. Patients and family members may find it easier to speak with a person who shares similar experiences, such as a stroke survivor. These additional insights to patients’ concerns allow the care team to optimize patient care and improve patient satisfaction. Future expansion of the program may include a broader role for the stroke survivor, leveraging the effective communication provided by this unique role.
Abstract TMP86: Telestroke Improves Guideline-Based Comprehensive Stroke Care: The TELECAST Trial
Authors: Streib Christopher D , Bentho Oladi , Bard Kathryn , Jaton Eric , Engkjer Sarah , Ronck Matthew , Ngo Monica , Mohl Leighton , Stinson Leah , Salari Apameh , Solei Amelia , Rahangdale Rahul , Kim Jae , Miller Benjamin
Published: June 2021

Introduction:
Limited access to stroke specialist expertise produces disparities in inpatient stroke treatment. The impact of telestroke on the remote delivery of guideline-based inpatient stroke care is yet to be comprehensively studied. The TELECAST trial (NCT03672890) prospectively examined the impact of a 24-7 telestroke specialist service dedicated to inpatient acute stroke care spanning admission to discharge.

Methods:
AHA stroke guidelines were used to derive outcome metrics in the following acute stroke inpatient care categories: diagnostic stroke evaluation (DSE), secondary stroke prevention (SSP), health screening and evaluation (HSE), and stroke education (SE). Adherence to AHA guidelines for stroke inpatients pre-telestroke (July 1, 2016-June 30, 2018) and post-telestroke intervention (July 1, 2018-June 30, 2019) were studied. The primary outcome was a composite score of all guideline-based stroke care. Secondary outcomes consisted of subcategory composite scores in DSE, SSP, HSE, and SE. Chi-squared tests were utilized to assess primary and secondary outcomes. Statistical analysis was performed using STATA 15.0.

Results:
Following institution of a comprehensive inpatient telestroke service, overall adherence to guideline-based metrics improved (composite score: 85% vs 94%, p<0.01) as did adherence to DSE guidelines (subgroup score: 90 vs 95%, p<0.01). SSP, HSE, and SE subgroup scores were not significantly different. See Table 1.

Conclusion:
The implementation of a 24-7 inpatient telestroke service improved adherence to AHA guidelines for inpatient acute stroke care. Dedicated inpatient telestroke specialist coverage may improve inpatient stroke care and reduce stroke recurrence in hospitals without access to stroke specialists.
Abstract TMP87: Stroke Outcomes Related to Initial Volume Status, Diuretic Use, and Potassium Levels
Authors: Renner Christopher J , Bahouth Mona N , Bath Philip M , Kasner Scott E ,   on behalf of the VISTA-Acute Collaborators
Published: June 2021

Background and Purpose:
The relationship between stroke outcome and initial presentation in a volume contracted state (VCS) has not been well established, and may intersect with concomitant diuretic use and serum potassium (K) levels. We hypothesized that stroke outcome is a function of multiple volume related factors.

Methods:
We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset, enrolled in acute treatment trials within the Virtual International Stroke Trials Archive. VCS was defined as a BUN-to-creatinine ratio>20 and hypokalemia as <3.5 mEq/L. The primary endpoint was modified Rankin Scale (mRS) at 90 days. Primary analysis employed generalized ordinal logistic regression over the full mRS range, with adjustment for THRIVE score, onset-to-enrollment time, and intravenous rtPA usage. Secondary analyses dichotomized the mRS.

Results:
Of 5971 eligible patients, 44% were in a VCS and 56% were euvolemic. Patients with VCS were older, had more vascular risk factors, more severe strokes, and were more likely taking diuretics. VCS was not significantly associated with mRS scores after adjustment (Table). Post hoc sensitivity analysis using BUN-to-creatinine ratio>30 yielded similar results. Diuretic use was associated with worse outcomes (Table), mainly driven by non-K sparing diuretics, while K-sparing diuretics tended to have the opposite effect. Hypokalemia had discordant associations with mRS, depending on the analytic approach (Table). There was no evidence of effect modification among the three exposures of VCS, diuretic use, or hypokalemia in relation to outcome (all p>0.30).

Conclusions:
A VCS at the time of hospitalization was associated with more severe stroke but not associated with worse functional outcome when accounting for key measurable baseline characteristics. However, diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.
Abstract TMP89: Impaired Cerebral Autoregulation Increases Risk of Worse Outcome After Endovascular Thrombectomy in Stroke Patients With High Blood Pressure Variability
Authors: Nguyen Cindy Khanh , Silverman Andrew , Wang Anson , Kodali Sreeja , Strander Sumita , Kimmel Alexandra C , Peshwe Krithika Umesh , De Havenon Adam , Gilmore Emily , Matouk Charles , Sansing Lauren , Schindler Joseph , Sheth Kevin N , Petersen Nils H
Published: June 2021

Introduction:
Both increased blood pressure (BP) variability and impaired autoregulation have been associated with increased risk of poor outcome after endovascular thrombectomy (EVT). The combined effect of these two variables, however, has not yet been elucidated. We hypothesized that the detrimental effects of high BP variability may be amplified by impaired autoregulation.

Methods:
We prospectively enrolled patients with large-vessel occlusion (LVO) stroke undergoing EVT. Autoregulatory function was continuously measured for up to 48 hours post-EVT by interrogating changes in near-infrared spectroscopy-derived tissue oxygenation (a cerebral blood flow surrogate) in response to changes in BP (Fig. 1A). BP variability was assessed using the standard deviation of the mean. Values were averaged for the entire recording period and dichotomized based on the median. Functional outcome was assessed using the modified Rankin scale (mRS) at 90 days. We examined the association between BP variability, autoregulatory function, and outcome using ordinal logistic regression, adjusting for age and admission NIHSS.

Results:
Ninety-five patients (mean age 71, NIHSS 14, monitoring time 28±18 hours) were included. BP variability (p=0.043) and autoregulation (p=0.04) were each independently associated with functional outcome. Among patients with high BP variability, worse autoregulation was independently associated with higher (worse) mRS scores at 90 days (OR 3.9, 95% CI 1.1-14.5, p=0.036; Fig. 1B). The proportion of favorable outcome was highest among patients with low BP variability and better autoregulation, and lowest among those with high BP variability and worse autoregulation (p=0.073; Fig. 1C).

Conclusion:
For LVO stroke patients with high BP variability after EVT, worse functional outcome may be exacerbated by impaired autoregulation. These results suggest that autoregulatory status should be considered in the management of BP after EVT.
Abstract TMP92: Serum Markers of Physiologic Stress and Associations With Delirium in Patients With Intracerebral Hemorrhage
Authors: Reznik Michael E , Kalagara Roshini , Moody Scott , Drake Jonathan , Margolis Seth , Mahta Ali , Rao Shyam , Stretz Christoph , Wendell Linda C , Thompson Bradford B , Asaad Wael F , Furie Karen L , Daiello Lori A , Jones Richard N
Published: June 2021

Background:
Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients.

Methods:
We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (>0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or >180 mg/dL), using ordered logistic regression.

Results:
Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p<0.001) and were more likely to have intraventricular hemorrhage (55% vs. 22%, p<0.001). Delirious patients also had higher admission NLR (mean 9.0±10.4 vs. 6.4±5.5, p=0.01) and glucose (mean 146.5±59.6 vs. 129.9±41.4 mg/dL, p=0.008), and were more likely to have elevated troponin (21% vs. 10%, p=0.02). In adjusted models, patients with delirium had higher admission NLR than patients who were never delirious (adjusted mean difference 2.6, 95% CI 0.3-4.9), and were more likely to have elevated admission troponin (OR 2.8, 95% CI 1.2-6.4) and glucose (OR 2.0, 95% CI 1.1-3.6).

Conclusions:
Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.
Abstract TMP95: Structured Screening for Post-Stroke Cognitive Impairment in the Outpatient Stroke Clinic
Authors: Denny M. Carter , Bonojo Esther A , Hinojosa Evelyn , Savitz Sean I , Sharrief Anjail Z
Published: June 2021

Introduction:
Cognitive impairment (CI) affects 30% of stroke survivors and impacts ability to return to work, drive and perform ADLs. However, there is no standardized screening for post-stroke CI. We implemented CI screening in the STEP (Stroke Transitions, Education and Prevention) clinic. We sought to identify demographic and clinical factors associated with early post-stroke CI.

Methods:
Eligible pts had ischemic stroke, ICH or TIA, were seen in the STEP clinic from March 2017 to June 2018, and included in the prospective outpatient clinical registry. Screening for post-stroke CI was performed with a Brief Neurocognitive Screen (BNS), a validated 5-minute subset of the Montreal Cognitive Assessment. BNS 0-8 was defined as abnormal (CI present) and 9-12 was defined as normal. Continuous variables were analyzed with student t-tests or Wilcoxon rank-sum tests and categorical variables with Fisher’s exact test. Logistic regression was performed with the significant variables in the univariate analyses.

Results:
Of 256 patients, 116 completed a BNS at a median of 35 days after hospital discharge. Median NIHSS was 3 (IQR 0.5,6) and follow-up modified Rankin scale (mRS) was 1 (IQR 1,2). Median BNS was 10 (IQR 9,11). Abnormal BNS, was present in 17.2% of pts screened. Of the 20 pts with abnormal BNS, 17 had neuropsychological testing ordered. In the univariate analysis, age, education, admission NIHSS, poor mRS (<2) at follow-up, and atrial fibrillation were significantly associated with early post-stroke CI (Table 1). In the multivariable analysis, only age and follow-up mRS remained significant.

Conclusion:
Early post-stroke CI is common in stroke pts, even with low NIHSS, and associated with older age and worse mRS. The BNS is a post-stroke CI screening tool than can be performed in stroke clinics. Future studies are needed to assess the feasibility of implementing the BNS across multiple sites and outcomes associated with early identification of post-stroke CI.
Abstract TP101: Inhibition of S-nitrosoglutathione Reductase Improves Stroke Outcomes and Stimulates Functional Recovery in an Aged Mouse Model of Stroke
Authors: Khan Mushfiquddin , Singh Avtar K , Kumar Pavan , Qiao Fei , Singh Inderjit
Published: June 2021

Background:
The nitric oxide (NO) metabolome and the NO metabolite-based neurovascular protective pathways are dysregulated after stroke, especially in the aged population. The major NO metabolite S-nitrosoglutathione (GSNO) is essential for S-nitrosylation-based signaling events. Inhibition of S-nitrosoglutathione (GSNO)-metabolizing enzyme GSNO reductase (GSNOR) increases the levels of endogenous GSNO and invokes a protective effect following cardiac ischemia and vascular diseases. However, the roles of GSNOR and GSNOR inhibition-mediated increased GSNO levels have not been characterized in neurovascular diseases, including stroke. We investigated the efficacy of GSNOR inhibition using a GSNOR specific inhibitor N6022 in a clinically relevant aged mouse model of experimental stroke.

Methods:
Transient focal cerebral ischemia was induced for 60 min by occluding the middle cerebral artery (MCA) of middle-aged and aged mice. N6022 (5 mg/kg) was administered intravenously at 2 h after reperfusion, and the same dose was administered daily thereafter until the endpoints (72 h and 4 weeks). Brain infarction was assessed by staining the brain sections with 2,3,5-triphenyl tetrazolium chloride, and the expression/activity of GSNOR was determined using biochemical methods. Cognitive and motor function recovery was assessed by novel object recognition and cylinder test, respectively.

Results:
This study found that IR caused an increased expression/activity of GSNOR and its inhibition by N6022 reduced infarct volume in the acute phase (72 h) of injury. Daily treatment of IR animals with N6022 for 4 weeks improved both motor and cognitive functions in parallel with the decreased activity of GSNOR.

Conclusions:
These results are the first evidence of a new pathway to treat stroke via the inhibition of GSNOR. Based on the efficacy of N6022 in this stroke animal model and its use in humans without toxicity in other indications, we submit that GSNOR is a druggable target and N6022 is a promising candidate for human stroke therapy.
Abstract TP11: CTA Collateral Status and Final Infarct Distribution Following Thrombectomy in Stroke Patients With Large Vessel Occlusion
Authors: Al-Dasuqi Khalid , Payabvash Seyedmehdi , Abou Karam Anthony , Strander Sumita , Kodali Sreeja , Silverman Andrew , Sansing Lauren H , Schindler Joseph L , Matouk Charles , Sheth Kevin N , Malhotra Ajay Malhotra , Petersen Nils
Published: June 2021

Aim:
The angiographic collateral status is a major predictor of final infarct volume in patients with large vessel occlusion (LVO). In this study, we assessed the effects of collateral status on final infarct lesion distribution after thrombectomy.

Methods:
Acute ischemic stroke patients with occluded terminal ICA and/or MCA M1 segment who underwent thrombectomy and had a follow up MRI within a week were included. The angiographic collateral status was evaluated on pre-thrombectomy CTA and graded according to Miteff et al. (Brain 2009;132(8):2231-8). The final infarct lesion was segmented on DWI; and using voxel-wise general linear model, we determined the correlation of final infarct volume with post-thrombectomy TICI (thrombolysis in cerebral infarction) score, and collateral status - as a covariate.

Results:
Among 106 patients with terminal ICA and/or MCA M1 occlusion in analysis, final infarct volume had a significant correlation with TICI reperfusion score (rho=0.384, p<0.001), CTA collaterals (rho=0.221, p=0.023), and TICIxCollaterals interaction term (rho=0.446, p<0.001). Voxel-wise analysis (Figure) showed that better reperfusion after thrombectomy (i.e. higher TICI) was associated with preservation of MCA territory cortex and deep white matter (green). The voxel-wise interaction analysis of TICI and CTA collateral status showed that poor collateral status is associated with infarction of the MCA-PCA border zone (red). Alternatively, good collaterals may preserve the peripheral edges of the MCA territory and MCA-ACA border zone (blue).

Conclusion:
A successful thrombectomy in LVO stroke patients can preserve the cortical and deep white matter of MCA territory - including eloquent speech and motor regions - while CTA collateral status mainly determines the fate of the MCA-PCA border zone. On the other hand, lentiform nuclei tend to infarct despite successful reperfusion and good CTA collateral status.
Abstract TP110: Dissecting the Optimized Cytoprotective Responses of Arctic Ground Squirrels With CRISPR
Authors: Lee Evan M , Singhal Neel S , Bai Meirong , Ma Dengke K
Published: June 2021

Arctic ground squirrels (AGS) have evolved to survive harsh environmental conditions through hibernation. AGS retain resistance to stroke and ischemic injury independent of hibernation, suggesting that genetic cell autonomous changes are also critical to AGS resilience. The mechanistic details of these cytoprotective adaptations are largely unknown.

A functional cDNA expression screen identified AGS candidate genes facilitating stress resilience and a bioinformatics pipeline identified AGS protein sequence changes in regions of high conservation. These unique AGS amino acid substitutions were edited using a combination of CRISPR base-editing and Cas9 knock-out approaches to generate AGS cell lines with loss-of-function variants.

We found that AGS neural cells exhibit marked resilience to diverse metabolic stressors in assays of in vitro survival, function, and mitochondrial morphology. The functional genetic screen identified a network of evolutionarily-conserved AGS transcripts imparting cytoprotection, particularly in endoplasmic reticulum (ER) stress and oxidative phosphorylation (OXPHOS) pathways. CRISPR-based genome editing creating AGS cell lines with loss-of-function mutations indicated that editing of key candidates, such as ATP5G1, ameliorates features of the AGS resilient phenotype including increasing susceptibility to metabolic stressors, decreasing spare respiratory capacity, and altering mitochondrial dynamic organization.

We gained key functional insights into how specific amino acid substitutions in the machinery of the OXPHOS and ER stress responses systems alter mitochondrial function to impart cytoprotection against metabolic insults. This detailed dissection of the AGS optimized adaptive stress response pathway will serve as a template for the development of new neuroprotective treatments.
Abstract TP112: Delayed Oligodendrocyte Maturation Corresponds to Myelin and Motor Recovery After Neonatal Stroke
Authors: Frazier Alexandra P , Wasserman Benjamin R , Macklin Wendy B , Herson Paco S , Dingman Andra L
Published: June 2021

Introduction:
Neonatal stroke is a common cause of lifelong neurologic disability. White matter repair after neonatal stroke has been understudied.

Objective:
Characterize acute myelin injury within striatal white matter and determine if endogenous remyelination occurs chronically.

Methods:
Postnatal day 10 (p10) mice underwent MCAO for 60 minutes, followed by reperfusion, and animals were sacrificed on post-op day (POD) 3, 14 or 28. Immunohistochemistry (IHC) was used to assess oligodendrocyte maturation, and white matter integrity. Gait was assessed on POD 14 or 30.

Results:
On POD3 there is a significant decrease in neuronal density in the ipsilateral striatum compared to contralateral. There is also a significant reduction in mature oligodendrocytes density. At this timepoint, axons are preserved (measured as %SMI34
+
pixels), but there is significant myelin loss (measured as %MBP
+
pixels) in the ipsilateral striatum (fig 1A-D). On POD 14 there is persistently decreased myelin density in ipsilateral striatum compared to contralateral, and the proportion of oligodendrocytes with a mature phenotype (Olig2
+
CC1
+
/Olig2
+
) is significantly lower. Both myelin density and maturational index of oligodendrocytes recover by POD 28. At fourteen days after MCAO there is a significant reduction in gait length on the left side, which recovers by 28 days (fig1 E-G).

Conclusions:
60 minute MCAO in neonatal mice produces striatal injury with oligodendrocyte and myelin loss but preservation of axons, providing a substrate for repair. Myelin deficit persists at 14 days, and there is an oligodendrocyte maturational delay at this same time. Myelination and oligodendrocyte maturation recover between 14 and 28 days, corresponding to recovery of motor function. Future studies will focus on whether interventions that accelerate oligodendrocyte maturation and re-myelination can improve early functional outcome.
Abstract TP115: Nrf2 Plays an Essential Role in Long-Term Neuroprotection of Ginseng in Permanent Cerebral Ischemia
Authors: Skrobach Anna , Liu Lei , Kelly Marie G , Wierzbicki Erika L , Escober-Nario Iana C , Vollmer Mary K , Dore Sylvain
Published: June 2021

Introduction:
Cerebral ischemia is a devastating disease with a high incidence of death and disability; however, effective therapeutics remain limited. The transcriptional factor Nrf2 has been shown to play a pivotal role in the endogenous defense against brain oxidative stress and inflammation; therefore, it represents a promising target for stroke intervention. The natural potential Nrf2-inducer ginseng, extracted from the root of Panax ginseng C.A.Meyer, has been widely used in East Asia for thousands of years, exhibiting potent anti-inflammatory and antioxidative properties. However, the long-term effects of Nrf2 and the standardized Korean red ginseng extract (ginseng) on permanent cerebral ischemic damage have not yet been reported.

Methods:
Wildtype (WT) and Nrf2
–/–
adult mice were treated with either vehicle (water) or ginseng for 7 days and subjected to the permanent distal middle cerebral artery occlusion (pdMCAO). The infarct volume, the reactive astrogliosis and microgliosis, and water regulatory protein aquaporin 4 (AQP4) were examined 28 days after the initiation of stroke. Data acquisition and analyses were performed by an observer blinded to the treatment.

Results:
When compared with the WT matched controls, the Nrf2 disruption significantly enlarged the infarct volume by 40.4±10.1% (n=7 per group; p<0.05), increased levels of reactive gliosis and AQP4 protein after pdMCAO. Interestingly, ginseng significantly reduced the infarct volume and attenuated the reactive gliosis and AQP4 in the ischemic WT mice (47.3±6.9%, n=12; p<0.01), but not in the Nrf2
-/-
mice (25.5±5.6%, n=11; p=0.241).

Conclusion:
Nrf2 plays an important role in the long-term recovery of permanent cerebral ischemic damage and neuroprotection of ginseng.
Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke
Authors: Biose Ifechukwude Joachim , Salmeron Katie E , Parker Anthony , Stowe Ann , Bix Gregory
Published: June 2021

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm
3
; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.
Abstract TP119: Tibia Fracture Leads to Long-Lasting Memory Dysfunction in Mice Through Enhanced Blood-Brain Barrie Breakdown in the Hippocampus and White Matter Damage
Authors: Huang Jinhao , Lyu Haiyan , Hou Kang , Barbosa Do Prado Leandro , Tang Chaoliang , Wang Zhanqiang , Wong Julia , Su Hua
Published: June 2021

Background and Purpose:
Tibia fracture (BF) causes long-lasting memory dysfunction in stroke mice, which is associated with microglia accumulation in the hippocampus ipsilateral to the stroke injury. The underlying mechanism is unclear.

Hypothesis:
BF exacerbates blood brain barrier (BBB) breakdown and fibrin extravasation in the hippocampus enhancing white matter damage of stroke mice.

Method:
C57 mice (8-weeks) were randomly assigned to BF, stroke (pMCAO), BF+stroke (BF 6h before stroke) and sham groups. The integrity of BBB, fibrin deposition and CD68
+
cells infiltration in the hippocampus were analyzed 3 days and the white matter injury in the basal ganglia was analyzed 8 weeks after the surgeries.

Results:
Compared to BF group, stroke and BF+stroke groups had lower level of claudin-5, fewer pericytes, more extravascular fibrin and CD68
+
cells in the ipsilateral side of stroke 3 days after the injuries. BF+stroke group had the lowest level of claudin-5, fewest pericytes, highest extravascular fibrin and most CD68
+
cells among the three groups. BF+stroke group also had a lower level of claudin-5 and fewer CD13
+
pericytes in the contralateral side than the other two groups. Compared to sham group, the white matter bundle areas in the basal ganglia were reduced in stroke and BF+stroke groups in both contralateral and ipsilateral sides 8 weeks after the injuries. Stroke and BF+stroke groups also has smaller white matter bundle areas in the ipsilateral than contralateral side, and the white matter bundle areas in the contralateral side of BF+stroke group were also smaller than stroke group.

Conclusion:
BF shortly before stroke causes long-lasting memory dysfunction in mice through enhancing BBB breakdown and fibrin extravasation in the hippocampus, which exacerbates neuroinflammation and white matter damage.
Abstract TP121: Organic Anion Transporting Polypeptide (Oatp)-Mediated Transport is Required for Statin-Induced Neuroprotection: A Role for Blood-Brain Barrier Transporters in Stroke Treatment
Authors: Ronaldson Patrick T , Lochhead Jeffrey J , Davis Thomas P
Published: June 2021

Objectives:
Treatment approaches for stroke include reperfusion therapies (i.e., recombinant tissue plasminogen activator, endovascular thrombectomy); however, many stroke patients still experience disability. This indicates a need to develop neuroprotective treatments that are effective in the setting of successful recanalization. Post-stroke outcomes are improved by treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins). We have shown that the endogenous blood-brain barrier (BBB) uptake transporter Oatp1a4 facilitates blood-to-brain transport of atorvastatin (ATV). The objective of this study was to show that Oatp-mediated transport at the BBB is an absolute requirement for ATV neuroprotective effectiveness in stroke.

Methods:
Male and female Sprague-Dawley rats (200-250 g) were subjected to transient middle cerebral artery occlusion (tMCAO) for 90 minutes followed by 22.5 h reperfusion. Sham-operated animals were used as controls. ATV (20 mg/kg, i.v.) was injected 2 h following reperfusion. The role of Oatp-mediated transport was determined using the Oatp transport inhibitor fexofenadine (FEX; 3.2 mg/kg, i.v.) injected at the same time as ATV. Following tMCAO, infarction volume and brain edema ratios were calculated from TTC-stained brain slices. Post-stroke outcomes were assessed via measurement of neurological deficit scores, by the adhesive removal test (i.e., sensorimotor function), and by the rotarod performance test (i.e., motor function).

Results:
In tMCAO animals, ATV reduced (p < 0.01) both infarction volume and brain edema ratio in both sexes. ATV improved neurological deficit scores and well as sensorimotor function and motor performance. In the presence of FEX, ATV had no effect on infarction volume or brain edema ratio. Similarly, positive effects of ATV on post-stroke outcomes were attenuated by FEX.

Conclusions:
Our data indicate that pharmacological inhibition of Oatp-mediated transport at the BBB prevents ATV from exerting neuroprotective effects in rats following tMCAO. Our results also suggest that i.v. ATV administered at an early time point following reperfusion (i.e., 2 h) can provide effective neuroprotection in male and female rats subjected to tMCAO.
Abstract TP122: Peri-Procedural Stroke or Death in Stenting of Symptomatic Severe Intracranial Stenosis: A Post-Hoc Analysis of the SAMMPRIS Trial
Authors: Yaghi Shadi , Khatri Pooja , de Havenon Adam , Yeatts Sharon , Chang Andrew , Cutting Shawna , Mac Grory Brian , Burton Tina , Jayaraman Mahesh , McTaggart Ryan , Fiorella David , Derdeyn Colin , Zaidat Osama , Dehkharghani Seena , Amin-Hanjani Sepideh , Furie Karen , Prahbakaran Shyam , Liebeskind David
Published: June 2021

Background and Purpose:
There is limited data on predictors of 30-day stroke or death in patients with symptomatic intracranial atherosclerosis (sICAS) undergoing stenting. We aim to determine these predictors.

Methods:
This is a post-hoc analysis SAMMPRIS including patients who underwent angioplasty/stenting. We determined associations between patient-specific, lesion-specific, and procedure-specific variables, and FDA-approved indications and the primary outcome (stroke or death at 30 days) using logistic regression analyses.

Results:
We identified 213 patients; 30 patients (14.1%) met the primary outcome. The odds of stroke or death was higher with non-smokers vs. smokers (adjusted OR 4.46, 95% CI 1.79-11.1) and increasing lesion length in millimeters (adjusted OR 1.20, 95% CI 1.02-1.39). These had modest predictive value: absence of smoking history (sensitivity=66.7% and specificity=65.4%) and lesion length (Area Under Curve=0.606). Furthermore, event rates were not significantly different between patients with and without the FDA approved indication for stenting (15.9% vs. 12%, p = 0.437).

Conclusion:
In SAMMPRIS patients who underwent angioplasty/stenting, neither clinical and neuroimaging variables nor the FDA indication for stenting reliably predicted the primary outcome. Further work in identifying reliable biomarkers of stroke/death in patients with sICAS is needed before considering new clinical trials of stenting.
Abstract TP126: Evaluation of Pre-Stenotic Hemodynamic Differences in Unilateral Carotid Stenosis After Artificial Carotid Plaque Removal
Authors: Fukuda Shunichi , Shimogonya Yuji
Published: June 2021

Introduction:
There is still insufficient to determine which carotid stenosis is likely to progress. The carotid artery shape is an independent risk factor for intimal thickening. Although it is assumed that hemodynamic factors are strongly involved in the mechanisms, the details are unknown. Here, we removed carotid plaques in unilateral carotid stenotic cases, and reproduced the vessel shape without plaques as after carotid endarterectomy, and compared hemodynamic distributions with the non-stenotic side.

Methods:
We used 30 cases of unilateral carotid stenosis (area stenosis rate > 60%) registered in the National Hospital Organization Prospective Clinical Study; Carotid CFD Study. The plaques in DICOM images were artificially removed (Figure 1), and the vessel shape without plaque was reproduced. Patient-specific arterial geometries and inflow velocities were obtained from 3D-CTA and carotid doppler examinations.We compared distributions of hemodynamic indices (time-averaged wall shear stress (WSS), time-averaged WSS gradient, normalized WSS, normalized WSS gradient, OSI and NtransWSS) at 3 regions; the stenotic site, its proximal and distal sites (10 mm).

Results and Conclusions:
The average age was 71.6 years, male 23 cases, hypertension 20, diabetes 7, dyslipidemia 15, smoking history 22, and average area stenosis rate 72.6%. Normalized WSS was lower (p<0.0001, Wilcoxon signed rank test), and NtransWSS (p=0.0242) and OSI (p=0.0355) were higher in the stenotic sites of vessels after plaque removal (Figure 2). The data suggest that low and disturbed WSS caused by differences in carotid shape may contribute to the progress in stenosis at the carotid bifurcation.