bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP123: Automated Pupillometry In Large Hemispheric Infarctions And Effects On Therapeutic Interventions - A Retrospective Analysis
Authors: Abburi Nandini , Sterenstein Andrea , Breit Hannah , Song Sarah , John Sayona , Koffman Lauren , Da Silva Ivan
Published: February 2022

Background:
Cerebral edema is a complication of large hemispheric infarctions (LHI), and automated pupillometry (AP) may be used to monitor for worsening cerebral edema. We hypothesized that AP may recognize earlier clinical deterioration and lead to earlier interventions, ultimately improving outcomes.

Methods:
This is a retrospective study of acute ischemic stroke patients admitted to a tertiary care hospital from 1/2012-12/2019, with admission imaging of ≥2/3 MCA territory with or without other territory involvement. Patients with AP documented every 4 hours were compared to patients admitted before AP was utilized (2012-2015). Neurologic pupil index (NPi) value <3 and a difference of >0.7 between eyes were recorded along with clinical change, defined as Glasgow coma scale (GCS) decrease of >2. Demographics and hospitalization data were recorded; including mechanical ventilation (MV), hyperosmolar therapy, decompressive hemicraniectomy (DHC), and mortality. Logistic regression was used for association measures.

Results:
Total of 77 patients were in the AP group (mean age 60, 55% females, mean admission NIHSS was 22, and mean admission GCS 9) and 169 patients in the non-AP group (mean age 64, 55% females, mean admission NIHSS 21, and mean GCS 10.4). Admission GCS was significantly lower in the AP group (p=0.04). There was higher use of MV in the AP group (54 patients, 70%), vs 88 (52%) in the non-AP group (p=0.0084). Hyperosmolar therapy was used more in AP patients (79%), vs 55% in the non-AP group (p=0.0004). There was a trend towards higher rates of DHC in the AP group (35%) compared to the non-AP group (24%), but not significant. Mortality rate was 37% in both groups, and there was no difference in mean discharge modified Rankin scale (mRS).

Conclusion:
More patients in the AP group were treated with hyperosmolar therapy and underwent DHC, suggesting use of AP may have triggered more therapeutic interventions. The patients in which AP was utilized seemed more critically ill on admission, based on GCS and need for MV; however, the mortality rate and discharge mRS were not significantly different. Prospective studies may determine if using AP in LHI patients would lead to earlier intervention, ultimately improving mortality and morbidity.
Abstract TP129: Periventricular Hyperintensity On Magnetic Resonance Imaging Predicts Unfavorable Outcomes After Intracerebral Hemorrhage
Authors: Okumura Motohiro , Sato Takeo , Kida Hiroyuki , Takahashi Junichiro , Maku Takahiro , Nakada Ryoji , Kitagawa Tomomichi , Takatsu Hiroki , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: February 2022

Background and Purpose:
To determine the association between the markers of cerebral small vessel disease (CSVD) and cerebral brain atrophy evaluated by magnetic resonance imaging (MRI) and outcomes after intracerebral hemorrhage (ICH).

Methods:
Consecutive patients with ICH ≤72 h from onset to door who underwent MRI during the hospitalization were included. We evaluated the CSVD markers as white matter hyperintensities scale (separately scored by periventricular hyperintensity [PVH] and deep and subcortical white matter hyperintensity [DSWMH]), the number of cerebral microbleeds, the number of old lacunes, and enlarged perivascular spaces scale and the degree of cerebral brain atrophy as global cortical atrophy scale. An unfavorable outcome was defined as a modified Rankin Scale score of 3 to 6 at 3 months from onset. We evaluated whether markers of CSVD and cerebral brain atrophy all assessed by MRI could be associated with prognosis of ICH.

Results:
We screened 361 consecutive patients with ICH, including 231 patients (161 [70%] male, median age 62 years). Of 231 patients, 83 (36%) patients had unfavorable outcomes. PVH, not DSWMH, was independently associated with unfavorable outcomes (odds ratio 2.059, 95% confidence interval 1.029-4.120,
p
= 0.041, Figure). There were no significant relationships between other CSVD markers and cerebral brain atrophy and prognosis after ICH.

Conclusions:
Severe PVH on MRI might predict unfavorable outcomes after ICH.
Abstract TP130: Racial Differences In Palliative Care Utilization And Impact On Inpatient Mortality Length Stay And Costs Among Patients With Intracerebral Hemorrhage
Authors: Chaudhry Mohammad Rauf , Fadah Kahtan , Kherani Danish , Chaudhry Saqib A , Singh Baljinder , Kausar Naila , Moreno Jorge , Ghatali Mohammad , Vellipuram Anantha Ramana , Piriyawat Paisith , Gupta Vikas , Sheriff Faheem , Maud Alberto , Rodriguez Gustavo , Cruz-Flores Salvador
Published: February 2022

Background and Purpose:
Palliative is increasingly used in critically ill patients which has lead to shorter length of stays, higher inpatient mortality and lower utilization of aggressive treatment. We performed analysis to evaluate trends in utilization of palliative care among patients with subarachnoid hemorrhage and its effect on in-hospital outcomes over a 10-year period.

Methods:
We obtained data for patients admitted to hospitals in the United States from 2009 to 2018 with a primary diagnosis of intracerebral hemorrhage (ICH) using a large national database. We determined the overall and among different races, rate of utilization of palliative care in patients with ICH and associated in-hospital outcomes consisting of mean hospital charges, mean length of stay and in-hospital mortality.

Results:
Out of 711787 patients admitted with primary diagnosis of ICH, palliative care was used in 105354 (14.8%). There was a 2.5-fold increase in utilization of PC (8.9% in 2009 vs 22.9% in 2018; p<0.001). Similarly, there were 2.4, 2.6, 3.7 and 2.4-folds increase in utilization of PC among different races: whites, blacks, hispanics and others respectively, p<0.001. Overall rates of PC utilization among different races: whites, blacks, hispanics and others were: 17.4%, 9.8%, 10.1% and 12.2%, p<0.001 respectively. The length of hospitalization remained significantly lower (4.8±7.8 versus 7.7±10.8, p<0.001) in patients undergoing PC compared with those who did not. The cost of hospitalization remained significantly lower ($54736 ± 94502 versus $ 79426 ± 124617, p<0.001) in patients undergoing PC compared with those who did not. Patients with PC utilization had significantly higher (64.9% versus 13.7%, p<0.001) in-hospital mortality compared ones with out.

Conclusions:
Between 2009 and 2018, there has been a significant increase in utilization of PC among patients with ICH along with shorter length of stay and lower hospital charges. ICH patients with PC had significantly higher in-hospital mortality.
Abstract TP140: Loss Of Fibroblasts Aggravates Hemorrhagic Brain Injury By Diminishing Timp2 Secretion
Authors: Xu Lingling , Yao Yao
Published: February 2022

Although Col1a1
+
fibroblast-like cells have been identified in large blood vessels in the CNS, their function remains largely unknown. To answer this important question, we generated mutant mice (Col1a1-DTR) with ablated fibroblast-like cells by crossing the Col1a1-Cre mice with DTR mice, which contain a loxP-flanked STOP sequence before diphtheria toxin receptor. The Col1a1-DTR mice were grossly normal after diphtheria toxin injection, suggesting that Col1a1
+
fibroblast-like cells are dispensable under homeostatic conditions. After hemorrhagic stroke, however, these mice demonstrated exacerbated brain injury, including enhanced blood-brain barrier (BBB) leakage and aggravated injury volume. In addition, the expression of Collagen-1 and PDGFRα, two fibroblast markers, was significantly reduced. These findings highlight a beneficial role of Col1a1
+
fibroblast-like cells in hemorrhagic stroke. Consistent with these results, similar results were also observed in vitro. Specifically, fibroblast-conditioned medium (FCM) attenuated endothelial damage (increased TEER and decreased FITC-Dextran leakage) in an in vitro model of hemorrhagic stroke. Subsequent mechanistic study revealed that FCM up-regulated the expression of various tight junction proteins (occludin, ZO-1, and claudin-5) without affecting that of caveolin-1, a key protein in transcytosis. These results indicate that fibroblasts protect BBB via paracellular rather than transcellular mechanism. To further investigate how exactly fibroblasts exert this beneficial role in hemorrhagic stroke, we performed mass spectrometry analysis, and identified TIMP2 (a protein with known BBB-protecting function) in the FCM. Using both pharmacological and genetic approaches, we further showed that ablating TIMP2 abolished the neuroprotective effect of FCM. Altogether, these findings suggest that Col1a1
+
fibroblasts secrete TIMP2, which inhibits tight junction protein loss and paracellular leakage, promoting BBB repair and hemorrhagic stroke recovery. These results suggest that fibroblasts and TIMP2 may be targeted in the therapy of stroke.
Abstract TP141: Impacts Of Dysnatremia On Outcomes In Aneurysmal Subarachnoid Hemorrhage
Authors: Helliwell Alexandra , Snow Ryan , Stretz Christoph , Potter Nicholas S , Wendell Linda C , Thompson Bradford , Reznik Michael , Furie Karen L , Mahta Ali
Published: February 2022

Disturbances in serum sodium levels are common following aneurysmal subarachnoid hemorrhage (aSAH) and may lead to increased morbidity, mortality, and poor functional outcomes. This study aims to examine the relationship between abnormal sodium levels following aSAH and patient outcomes. A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Dysnatremia was categorized as either mild or moderate-severe and patients were sorted accordingly. Multivariable logistic regression was used to test the association of any dysnatremia and outcomes, including modified Rankin Scale (mRS) at 3 months after discharge, vasospasm (based on transcranial Doppler criteria), delayed cerebral ischemia (DCI) and refractory hydrocephalus requiring ventriculoperitoneal shunt. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia (categorical variables). We included 320 patients (mean age 57.8 years (SD 14.3), 61% female, 70% white). Hyponatremia was seen in 58% for a median of 3 days [IQR 1-6], with moderate-severe hyponatremia occurring in 5%. Hypernatremia was observed in 49% for a median of 5 days [IQR 2-8], 56% of whom had moderate-severe hypernatremia. Of 156 hypernatremic patients, 80% were treated with hypertonic saline for cerebral edema. Hypernatremia was independently associated with a higher odds of vasospasm (OR 1.75, 95% CI 1.02-303,
p
=0.04) when adjusted for Hunt and Hess grades, cerebral edema and modified Fisher scales. There was no independent association between any dysnatremia and mRS, DCI or refractory hydrocephalus. Hospital length of stay was longer in patients with hypernatremia (8.11 more hospital days, 95% CI 5.4-10.8;
p
<0.001) independent of age, Hunt and Hess grades, modified Fisher scales and hospital complications, including cerebral edema, vasospasm, DCI and refractory hydrocephalus. In conclusion, although dysnatremia may not directly affect functional outcome, hypernatremia may prolong hospital length of stay by increasing risk of cerebral vasospasm. These findings underscore the importance of judicious use of hypertonic saline and avoidance of hypernatremia in aSAH patients.
Abstract TP152: A Comparison Of Thrombus Characteristics In Patients With Anterior Circulation Stroke And Posterior Circulation Stroke In The Mr Clean Registry
Authors: Bruggeman Agnetha A , Boodt Nikki , Kappelhof Manon , Hoving Arnolt-Jan , Brouwer Josje , Tolhuisen Manon , Arrarte Terreros Nerea , Konduri Praneeta , van Kranendonk Katinka R , Dippel Diederik W , van der Lugt Aad , van Zwam Wim , van der Leij Christiaan , van Es Adriaan C , Cornelissen Sandra , Brans Rutger , Marquering Henk , Majoie Charles B , Emmer Bart
Published: February 2022

Introduction:
In posterior circulation stroke (PCS), large artery atherosclerosis at the occlusion site or dissection is most often reported as underlying stroke etiology, while cardio embolism is less common than in anterior circulation stroke (ACS). As thrombus characteristics are related to the underlying stroke etiology, we hypothesized that differences in radiological thrombus characteristics between PCS and ACS are fully explained by differences in underlying etiology. We compared radiological thrombus characteristics between PCS and ACS to gain insight in the differences in order to optimize treatment options for PCS.

Methods:
In patients treated with endovascular treatment (EVT) for acute ischemic stroke in the MR CLEAN Registry, radiological thrombus characteristics (perviousness, density, and length) were assessed on thin-slice (<2.5mm) non-contrast computed tomography and computed tomography angiography imaging acquired within 30 minutes from each other. Radiological thrombus characteristics between PCS and ACS patients were compared with univariable and multivariable linear regression with adjustments for baseline differences which could influence thrombus characteristics (age, gender, TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria and intravenous alteplase treatment.

Results:
We analyzed 1052 patients: 118 PCS and 934 ACS patients. PCS thrombi were significantly longer and denser than ACS thrombi: median 23 mm vs 18 mm (p<0.001) and median 53 HU vs 50 HU respectively (p=0.04) (Table 1). After adjustments, thrombus length was significantly different: PCS thrombi were 15 mm longer compared with ACS thrombi (aβ 15, 95% CI 12-18), while thrombus density and perviousness did not significantly differ between ACS and PCS (Table 1).

Conclusion:
PCS thrombi are significantly longer and denser than ACS thrombi. After adjustment for stroke etiology, only thrombus length was significantly different between PCS and ACS patients.
Abstract TP16: Post Stroke Cognitive Impairment (PSCI): Contribution Of Brain Endothelin B Receptor (ETB) In Post Stroke Recovery
Authors: Abdul Yasir , Karakaya Eda , JAMIL SARAH , Ergul Adviye
Published: February 2022

Introduction:
Endothelin (ET) system contributes to cerebrovascular dysfunction and acute neurovascular injury after ischemic stroke. While some clinical and preclinical studies suggests, dual inhibition of ET receptors prevent poststroke cognitive impairment (PSCI), also recent advances suggests systemic ETB receptor agonism improves PSCI. Current, study aimed to investigate the role of ETB receptors in post stroke recovery by selectively silencing cerebral ETB receptors in rats. We hypothesized that ETB receptors are protective, and inhibition of ETB receptors will worsen PSCI.

Methods:
ETB receptors were knocked down by intra-cerebroventricular injections of GFP tagged lentiviral vectors with ETB-shRNA particles (ETBR-KD) or scrambled (sc-shRNA) in male Wistar rats. Middle cerebral artery occlusion (MCAO; 30 minutes) was performed 10 days post lentiviral transfection. Animals were monitored for motor functions with adhesive removal time (ART) and composite score. Cognitive functions were measured at baseline and 28 days post MCAO with novel object recognition (NOR), novel object placement recognition (NOP), 2-trial Y-maze and open field (OF).

Results:
Animals of both the groups had significant deficits in ART and composite score, indicating consistent ischemic injury (table 1). By day 28, NOR-RI and NOR-d2 in sc-shRNA group (n=3) was significantly lower than the ETBR-KD group (n=5). There was a trend for lower NOP-d2 in the ETBR-KD group. Number of alterations and forced alternation scores (Y maze) were lower in ETBR-KD group at baseline and were significantly different between groups at day 28. Animals of both the groups moved around the same amount in OF.

Conclusions:
NOR scores suggest ETBR silencing improves working memory but worsens spatial memory. Y-maze scores also suggest that ETBR-KD worsen deficits. Longer monitoring of animal will provide more definitive answers with respect to the role of ETB receptors in stroke recovery and PSCI.
Abstract TP167: Unanticipated Platelet Function Fluctuations Occur During The First 8 Hours After Neurointerventional Procedures In Patients Receiving Dual Anti-platelet Therapy
Authors: Allen Travis S , Austin Matthew , Santillan Alejandro , LOY DAVID
Published: February 2022

Antiplatelet agents are administered before and after neuroendovascular surgery to minimize implant-associated thromboembolic events. Dual antiplatelet therapy (DAPT) uses aspirin plus P2Y12 receptor inhibitors: clopidogrel, ticagrelor, or prasugrel. Effects are quantified in P2Y12 reactivity units (PRU) and aspirin reactivity units (ARU) by the point-of-care assay, Accumetrics VerifyNow. We hypothesized that intraoperative events such as anesthesia may affect platelet inhibition, increasing the risk of unanticipated ischemic events in the early postoperative period.

This retrospective study was approved by the institutional review board. 50 patients who underwent Verify Now testing preoperatively and within 12 hours postoperatively after placement of cervical or intracranial stents at a single institution (January 1, 2018 - May 25, 2021) were included. PRU values > 194 and ARU values > 550 were considered subtherapeutic. Anesthetic agents, heparin dosage, clopidogrel responsiveness, platelet count, liver function, procedure type and length, NIH stroke scale scores, and demographics were compared to perioperative platelet inhibition values.

Our results indicate that P2Y12 inhibition is likely affected by intraoperative events. Approximately 25% of patients exhibited marginal (170-193) or subtherapeutic (> 194) PRU values during the first 8 hours following neuroendovascular procedures. The greatest variation occurred in the ticagrelor group (PRU median change 84) and was more likely to occur with reduced doses of both ticagrelor and clopidogrel. A single prasugrel patient (clopidogrel non-responder) exhibited the greatest absolute change (PRU 156 -> 316). ARU variations were less pronounced suggesting that perioperative aspirin platelet inhibition is more resilient.

In conclusion, patients undergoing elective neuroendovascular procedures may be at risk for thromboembolic ischemic complications during the first 8 hours postoperatively due to shifts in P2Y12 mediated platelet inhibition. ARU values were less effected, supporting the use of DAPT as an ongoing clinical standard of care.
Abstract TP184: Urban-rural Influence On Readmission After Acute Ischemic Stroke In Younger Adults
Authors: Barfield Leeann , McGee Blake T
Published: February 2022

Introduction:
Complications and mortality after ischemic stroke are higher in rural areas. Identifying predictors of readmission is important, especially for younger patients who represent a growing share of new strokes, but studies differ in how they define rurality.

Hypothesis:
There is an association between urban-rural influence and readmission after acute ischemic stroke among younger adults, and this association depends on how urban-rural influence is defined.

Methods:
Data from the AHRQ State Inpatient Databases for ischemic stroke survivors aged 19-64 years during 2012-2014 were analyzed for six states: Arkansas, Florida, Georgia, Maryland, New Mexico, and Washington. In-state hospitalization within 30 days of discharge was deemed a readmission, excluding admissions for rehabilitation, psychiatry, or cancer treatment. A four-level urban influence code was used as the patient location variable. To further explore the impact of how rurality was defined, this variable was dichotomized three ways: large metropolitan vs. all others, metropolitan vs. non-metropolitan, and rural vs. all others. Chi-square tests were used to determine if planned and unplanned readmission were associated with each urban-rural variable to determine which variables to advance to multivariable analysis. Logistic regression models were then fitted for both planned and unplanned readmission, using the large metropolitan variable and adjusting for length of stay of the first hospitalization, age, race, sex, payer type, and number of chronic conditions.

Results:
Patients who lived in a large metropolitan area compared to those who did not had 0.885 (95% CI: 0.697, 1.122) times the odds of planned readmission when controlling for covariates; however, this difference was not statistically significant. The odds of unplanned readmission, however, were 1.071 times higher (95% CI: 1.004, 1.142) if the patient lived in a large metropolitan area compared to those who did not, controlling for covariates.

Conclusions:
Urban residence can be described as an independent predictor of unplanned readmission for younger adult ischemic stroke survivors. However, researchers should be attentive to the impact of how urban-rural influence is operationalized.
Abstract TP190: Association Of Age, Sex, Race, Weight, And Height With Biomarkers Of Atrial Cardiopathy In Patients With Embolic Stroke Of Undetermined Source
Authors: Schutz Rachael , Kronmal Richard , Heckbert Susan R , Meinzer Caitlyn , Tirschwell David L , Kamel Hooman , Elkind Mitchell , Longstreth W T
Published: February 2022

Introduction:
Elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) and prolonged P-wave terminal force in V1 (PTFV1) on 12-lead ECG are associated with increased risk of atrial fibrillation and stroke. Age is positively associated with NT-proBNP, men have lower levels than women, and Blacks have lower levels than Whites. Although both weight and height are positively related to risk of atrial fibrillation, both are negatively associated with NT-proBNP. We explored associations among these variables in patients with embolic stroke of undetermined source (ESUS).

Methods:
In an ongoing randomized trial of secondary stroke prevention, AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA), as of 2021 August, 2616 ESUS patients were consented for the trial and screened for atrial cardiopathy with serum NT-proBNP and PTFV1. Baseline information on age, sex, race, weight, and height were used in sequential linear regression analyses to understand associations with ln(NT-proBNP) and ln(PTFV1).

Results:
In age-adjusted models of ln(NT-proBNP), significant negative associations were found for weight (beta -0.004, p=0.02) and height (beta -0.013, p<001). When sex was added to these models, significance was lost for weight and height. In a final model including all of these variables (N=2400), significant associations were found for age (beta 0.044, p<0.001), sex (men with lower levels than women, beta -0.448, p<0.001) and race (Blacks with lower levels than Whites, beta -0.141, p=0.027 and Asians with lower levels than Whites, beta -0.512, p=0.009). In similar sequential models for ln(PTFV1), only race was significant; in a final model, Blacks had higher values than Whites, beta 0.275, p<0.001. No evidence was found in these models to suggest violation of linearity.

Conclusions:
In a population of patients with ESUS, associations of weight and height with NT-proBNP are confounded not by age but by sex. Key associations with NT-proBNP include age, sex, and race. In ARCADIA, understanding these associations may be important in individualizing predictions about which ESUS patients with atrial cardiopathy are most likely to benefit from apixaban over aspirin for secondary stroke prevention.
Abstract TP195: A Comprehensive Epidemiology Of Stroke In A Multi Ethnic Society: An Analysis Of A Nationwide Stroke Data From 2014 - 2020
Authors: Bhutta Zain A , AKHTAR NAVEED , Pathan Sameer A , Puolakka Tuukka , Harris Tim , Ganesan Gowrii Saswathy S , Kamran Saadat , Thomas Stephen H , Cameron Peter , Castren Maaret K
Published: February 2022

Introduction:
The prevalence of stroke is progressively increasing in developing countries owing to the increase in vascular risk factors in the population. Risk factors vary significantly in different population groups leading to variations in disease progression, management and outcomes. This study aims to describe the epidemiology, prevalent risk factors and outcomes in a multi ethnic society of Qatar.

Methods:
We conducted a retrospective cohort study that included all patients with suspected stroke admitted to Hamad General Hospital, Doha Qatar between April 30, 2014 till September 15, 2020.

Results:
A total of 11,892 patients were admitted during this period with suspected stroke. Of these, Ischemic stroke (IS; 48.8%), Transient ischemic attack (TIA; 10.3%), Intracerebral hemorrhage (ICH; 10.9%), Stroke mimics (28.6%) and Cerebral venous sinus thrombosis (CVST; 1.3%). Mean age was 53.1
+
14.1 and a male to female ratio of 3:1. Study population was majorly Asian (56.8%) and Arab (36%); while African (4.5%), Caucasian (2.6%) and Others (0.1%) formed minority of the population. Asian population (South Asian; 49.7
+
11.6 and Far Eastern; 47.4
+
9.9) were younger as compared to Arabs (58.9
+
15.9). Majority of the patients were hypertensive (66.8%), diabetic (47.9%) and dyslipidemic (45.9%) on admission, while cardiac diseases (14.7%) and DVT (0.3%) were observed in fewer patients. Patients with a history of prior stroke were 11.7%, while 0.9% had a prior TIA. In IS patients, 31.7% of the patients arrived ED within the 4.5-hour thrombolysis window, 12.5% received thrombolysis and 4.6% received thrombectomy. The average Door-to-Needle time for IS patients was 58.9
+
39.5 minutes. The average length of stay was 5.2
+
9.0 days with 71.5% discharged home, 13.8% transferred to rehabilitation, 9.3% to other specialties, 3% to long term care and 2.4% suffered in-hospital mortality.

Conclusion:
The patients suffering Stroke in Qatar are relatively younger than western population. Highly prevalent vascular risk factors could explain younger presentation and relatively high burden of stroke. Further analysis of epidemiological differences between ethnic subgroups can help tailoring effective preventive and management policies to reduce the burden of disease.
Abstract TP205: Associations Of Admission And Follow-up Neutrophil-lymphocyte Ratios With Clinical Outcomes In Patients With Ischemic Stroke Undergoing Endovascular Therapy
Authors: Bartt Russell , Sercy Erica , Tang Xu , DiManna Kimberly , Frei Donald , Bar-Or David
Published: February 2022

Introduction:
Neutrophil-lymphocyte ratios (NLRs) can be used to assess inflammatory status, with higher NLRs indicating inflammation and physiologic stress. NLRs after ischemic stroke have been shown to predict both short- and long-term outcomes.

Methods:
This was a retrospective study of adult patients admitted to a high-volume stroke center in 1/1/2018-12/31/2020 for ischemic stroke who underwent endovascular therapy (ET). The primary outcomes were successful reperfusion (TICI score ≥2B), favorable discharge NIH Stroke Scale/Score (NIHSS≤4), and favorable discharge and 3-month modified Rankin Scale (mRS≤2) scores. The primary predictor was neutrophil-lymphocyte ratio (NLR), measured at admission and throughout the hospital stay, as well as change in NLR between admission and post-ET. Logistic regression and generalized estimating equations assessed associations between NLRs and the outcomes.

Results:
The study included 131 patients, with a median admission NIHSS of 13 and median discharge NIHSS of 1. Almost all patients (94%) achieved successful reperfusion, and only 2 (1.5%) developed symptomatic ICH. The median discharge mRS was 3, and the median 3-month mRS was 2. The median admission NLR was 6.5 (range 0.8-18.0), and the median NLR change (admission to first post-ET) was 0.0 (range -13.8 to 12.0). Each 1-unit increase in admission NLR was associated with a 19% decreased odds of successful perfusion, 16% decreased odds of favorable discharge NIHSS, 15% decreased odds of favorable discharge mRS, and 14% decreased odds of favorable 3-month mRS. Higher post-ET NLRs on various days were also associated with decreased odds of favorable outcomes (Table 1).

Conclusions:
Admission and select follow-up NLRs were predictive of successful reperfusion and condition at discharge and at 3-months post-discharge in this patient population. These results show that NLRs, a readily available biomarker, can identify individuals at risk for poor outcomes after ET.
Abstract TP225: Socioeconomic Status And Etiologies Of Ischemic Stroke In Peru
Authors: Ridha Mohamed , Guerra Castanon Felix S , Aziz Yasmin , Ades Laura M , Quispe-Orozco Darko , Otiniano-Sifuentes Ricardo , Flores-Rodríguez Néstor , Zunt Joseph , Tirschwell David L , De Los Rios La Rosa Felipe , Abanto Carlos
Published: February 2022

Background:
Studies have reported an association between lower socioeconomic status (SES) and an elevated risk of ischemic stroke. It is unclear whether low SES is correlated with a specific etiology of ischemic stroke. Few studies have investigated the relationship in LMIC nations with wide disparities in SES. We analyzed data from a hospital-based stroke registry in Lima, Peru to determine the association between level of education as an indicator of SES and ischemic stroke etiology.

Methods:
All patients hospitalized with ischemic stroke at the National Institute of Neurologic Sciences from 2015-2018 were prospectively collected in a registry including demographics, risk factors, highest attained level of education, and diagnosed etiology of stroke by TOAST criteria. Association between ordinal level of education and stroke etiology was assessed after adjusting for differences in demographics and comorbidities by a multinomial multivariate logistic regression model.

Results:
A total of 461 cases of ischemic stroke were ascertained with 38.4% female and a mean age of 66.2 (SD 13.0). Stroke etiology was composed of 7.5% atherosclerotic, 29.7% cardioembolic, 14.2% small vessel disease, 24.7% cryptogenic, and 24.0% with incomplete evaluation. Higher education level strata had more men, younger mean age, and lower rates of hypertension. After multivariate adjustment, lower level of education was associated with an increased odds of large artery atherosclerosis compared to all non-cardioembolic etiologies (OR=2.27; 95% CI, 1.12-4.55). There was no significant association with level of education and odds of cardioembolic stroke after multivariate adjustment.

Conclusion:
Lower SES is associated with an increased odds of atherosclerotic etiology in patients with non-cardioembolic ischemic stroke. The associated between SES and stroke may be attributed to a higher burden of atherosclerotic disease in lower SES.
Abstract TP233: Activation Of Alpha 7 Nicotinic Acetylcholine Receptor Protects The Ischemic Brain Via Reductions In Jak2/stat3 Signaling In Mice.
Authors: Chauhan Anjali , Marino Lee Shirley , Ahmad Mian , McCullough Louise
Published: February 2022

Introduction:
The alpha7 nicotinic acetylcholine receptor (α7nAChR) is the principal mediator of the cholinergic anti-inflammatory pathway (CAP). CAP is mediated through several signaling pathways, including the JAK2/ STAT3 pathway. Studies have shown decrease in brain α7nAChR and increase in phosphorylation (p) of JAK2 and STAT3 expression after stroke. Increase JAK2/STAT3 signaling induces expression of high mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE), which promotes release of cytokines. Pharmacological activation of α7nAChR reduced microglial activation and inflammatory cytokines and improved functional outcomes after experimental stroke. However, little is known about how the activation of α7nAChR modulates JAK2/STAT3 signaling after stroke.

Hypothesis:
We hypothesized α7nAChR activation by PNU120596 (PNU), an allosteric modulator will decrease JAK2/STAT3 signaling and improve neurological deficits (ND) after stroke.

Methods:
Young (8-12 weeks, n=5-6) male mice underwent 60-minute middle cerebral artery occlusion (MCAo) or sham surgery and euthanized at 24 hours. In second cohort (n=5-6), PNU or vehicle was administered for 3 consecutive days. One hour after the last injection, MCAo or sham surgery was done. Twenty-four hours after MCAo, body weight, ND scores were recorded and brains harvested for western blotting. Brain α7nAChR, pSTAT3, HMGB1 and RAGE expression was determined.

Results:
At 24 hours after MCAo, the brain expression of α7nAChR decreased (p=0.006) while pSTAT3 expression increased (p=0.001) as compared to sham. PNU treatment prevented a decrease in α7nAChR expression in the brain (p=0.017) and decreased pSTAT3 expression (p=0.005) compared to the vehicle group after MCAo. No difference in the HMGB1 expression was seen between groups. An increase in RAGE expression was observed in vehicle MCAo (p=0.006) compared to sham. A decline (p=0.08) in RAGE expression in PNU MCAo compared to vehicle MCAo was observed. NDS and percent body weight loss were lower in the PNU MCAo compared to vehicle MCAo.

Conclusions:
Activation of α7nAChR downregulated inflammatory JAK2/STAT3-HMGB1/RAGE signaling and may be a druggable target to improve recovery after stroke.
Abstract TP248: Nos Inhibitor Is An Effective Adjuvant To Reperfusion Therapy In Ischemic Stroke In Mice
Authors: Wisen William P , Evans Wesley R , Sure Venkata N , Sakamuri Siva S , Kolli Lahari , Albuck Aaron L , Mostany Ricardo , Katakam Prasad V
Published: February 2022

Background:
Inhibition nitric oxide synthase (NOS) has been shown to paradoxically protect against ischemic brain injury by an unknown mechanism. Recently, we found that NOS inhibitor, N (gamma)-nitro-L-arginine methyl ester (L-NAME), protects primary cultures of endothelial cells and neurons against oxygen-glucose deprivation-reoxygenation injury by preventing NOS uncoupling. Thus, the objective of the present study was to demonstrate the effectiveness of locally administered L-NAME against ischemia-reperfusion (I-R) injury.

Methods:
Transient focal cerebral ischemia in male mice (C57Bl/6, 2-4 months) was achieved by filament method of MCAO with a 60 min occlusion. We employed a novel approach to inject L-NAME (1 mg/Kg dosages at a rate of 60 ug/minute) locally into the ischemic zone by threading a catheter up the middle cerebral artery. This was timed to the onset of reperfusion by rapidly followng the removal of the occlusion with silicon suture. Following 24-hour reperfusion, infarct size was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining and neurological functioning was recorded employing standard neurological score (0-4 range) and Rotarod performance test.

Results:
Admnistration of FITC Dextran 40K and fluroscence microscopy of the brain slices 1 hour post-ischemia confirmed the effective delivery of injected L-NAME into ischemic tissue. Localized injection of L-NAME was protective against I-R injury and promoted significant recovery of neurological and motor function (Figure).

Conclusion:
NOS inhibition could serve as an adjuvant for reperfusion therapies of ischemic stroke.
Abstract TP254: Reduction Of Behavior Deficits Following Delivery Of Sox2 To Stroke Rats Using Mixed-Surface PAMAM Dendrimer Nanomolecules
Authors: Srinageshwar Bhairavi , Andrews Melissa , Malkowski Clayton , Toth Alexa , Stadler Justin , MacDonald Bethany , Schalau Raegan , Singh Nirvisha , Thompson Cassandra , Poudel Arjun , Evers Smith Johnathon , Blackwell Collin , Richmond Joshua , Otero Paulina , Raymor Grant , Bennett Heather , Mersino Lawrence , Reigler Morgan , Zdun Josie , Folkert Grant , Swiontek Jared , Mansfield Emily , Swanson Douglas , Sharma Ajit , Dunbar Gary , Rossignol Julien
Published: February 2022

A major drawback of current stroke treatment strategies (such as the use of tPA) includes time sensitivity to achieve maximum therapeutic efficacy. Alternative treatments include less time-sensitive approaches and utilize
in vivo
reprogramming of resident reactive astrocytes to repopulate the lost neurons in sufficient numbers. In this study, we tested whether a transcription factor,
hSOX2,
when expressed under a glial cell-specific GFAP promoter, could sufficiently reprogram astrocytes in and around the infarct to enhance their differentiation into neurons. To achieve delivery of the hSOX2 gene, we utilize PAMAM dendrimers, which are nanomolecules with a well-established capacity of delivering drugs/ large biomolecules to the brain across the BBB and confer intrinsic anti-inflammatory properties. Dendrimers are comprised of an interior dendritic structure with modifiable sizes, and an exterior surface with functional surface groups. The G4 PAMAM dendrimers used in this study has 10% of the surface covered with amine groups and 90% of the surface covered with hydroxyl groups (G4-90/10). These dendrimers are less toxic and readily form complexes with plasmids up to 14 kb in size (dendriplex) and successfully deliver cargo
in vitro
and
in vivo
. Four days following stroke inductions in Sprague Dawley rats via MCAo, the hSOX2 dendriplex was injected into the ipsilateral corpus callosum. A battery of behavior tests, such as cylinder and ladder tasks, were used to assess motor abilities of the treated and untreated stroked and sham-operated control rats. Moreover, the animals underwent In vivo Imaging System to confirm the presence of dendriplex in the brain. Five weeks following the injections, the brains were collected and processed, using immunohistochemistry, to detect the complex and measure the amount of
hSOX2
gene expression. The size of the brain infarct was measured using the conventional H&E staining. Our results indicated that the dendrimers were able to deliver the hSOX2 gene to the stroke brain and this significantly reduced motor deficits, relative to untreated stroked rats. These results indicated that PAMAM dendrimers effectively deliver genes into the brain and that the hSOX2 gene can successfully reduce motor deficits following stroke.
Abstract TP26: Changes In Health-seeking Behavior Of Stroke Patients During Three Covid-19 Outbreaks: Data From The Korean Stroke Registry
Authors: Jeong Han-yeong , Lee Eungjoon , Park Jong-moo , Bae Hee-joon , Jung Keun-hwa
Published: February 2022

Introduction:
The coronavirus disease 2019 (COVID-19) pandemic has changed the medical use of stroke patients. This study evaluated the health-seeking behavior of stroke patients and changes in stroke care services at the time of three domestic COVID-19 outbreaks in Korea using the Korean Stroke Registry (KSR) data.

Methods:
We reviewed data from patients with acute stroke and transient ischemic attack (TIA) from Jan 2019 to May 2021. There were three domestic COVID-19 outbreaks (1st: Feb to Mar 2020, 2nd Aug to Sep 2020, 3rd Nov 2020 to Jan 2021). Outcomes included patient characteristics, times from stroke onset to hospital arrival, and in-hospital stroke pathways.

Results:
The study included 34,271 patients who visited hospitals that contribute to the KSR. In the first outbreak, in Daegu city (the main epicenter), the number of patients decreased by two-thirds compared to the pre-COVID period, and the number of TIA patients was particularly decreased (9.97% to 2.91%). Unlike other regions, the median onset-to-door time increased significantly in the epicenter (361 min vs. 526.5 min, p=0.016), and longer times were common for patients with mild symptoms and who were in their 60s or 70s. The median onset-to-door time increased in the epicenter during the second outbreak, but it was not statistically significant. At the third outbreak, the median onset-to-door time was reduced even in the epicenter compared to the previous one. The number of patients decreased with each outbreak compared to the previous one, but the decrease gradually became smaller.

Conclusions:
Korean stroke patients in a COVID-19 outbreak region showed clear changes in health-seeking behaviors and showed a pattern of adaptation to the COVID-19 environment. There is a need for continued attention to an appropriate triage system and public education on the importance of early treatment during the COVID-19 pandemic.
Abstract TP29: Physician-driven Dysphagia Screening Protocol For Expedited Medication Delivery In Acute Ischemic Stroke
Authors: Siegler James , Kamen Scott E , Niles Jennifer , Goss Jessica , Heslin Mark , Vigilante Nicholas , Thau Lauren , Edwards Christopher E , Marden Kyle , Siegler James E
Published: February 2022

Background:
We implemented a multi-disciplinary process improvement (PI) intervention at a Comprehensive Stroke Center in cooperation with speech/language pathology in order to expedite oral medication delivery in patients with dysphagia. Following a failed nurse dysphagia screen, trained neurology providers were able to evaluate dysphagia further and approve the use of oral medications.

Methods:
We analyzed prospectively collected data from the PI intervention for timing of dysphagia screen, first oral antithrombotic, and aspiration pneumonia in ischemic stroke patients (9/2019-07/2021). Patients were included if they passed a dysphagia assessment by any provider, with comparisons made between patients who passed by physicians (Ph), nurses (RN) or speech/language pathologists (SLP).

Results:
Of the 789 included patients, 673 were passed by RN, 104 by SLP, and 12 by Ph. Compared to patients passed by SLP, those passed by Ph were younger and had less severe deficits (Table). Patients passed by Ph were screened more quickly than those screened by RN or SLP (median 38 vs. 182 vs. 1330 min after arrival, p=0.0001), and received first oral antithrombotic far more quickly (median 335 vs. 774 vs. 1409 min, p=0.0001). No patients passed by Ph experienced an aspiration pneumonia (0%), although there were non-significantly more pneumonias among patients passed by SLP (5%) and RN (2%, p=0.11).

Conclusions:
We safely conducted a physician-driven dysphagia screening paradigm which led to faster oral medication delivery, and no signal of patient harm.
Abstract TP30: Retention And Trial Coordinator Outreach In A Multicenter Clinical Trial During Covid 19
Authors: Powers Jennifer , Sayles Emily B , Demel Stacie L , Stanton Robert J
Published: February 2022

Introduction:
Human subjects research requires the retention of enrolled patients in order to provide accurate data. The COVID-19 pandemic introduced unique challenges for clinical trial coordination. AtRial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) is an NIH StrokeNet national clinical trial designed to test superiority of apixaban over aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. We sought to explore the methods that allowed our site to maintain a high retention rate in our local ARCADIA population.

Methods:
Prior to COVID-19, our trial coordinator (JP), conducted home visits to enroll and complete study visits every 3 months for the first year. This was approved by our local institution, IRB and study sponsor. During COVID-19 precautions, phone contact was maintained and encouraged. Face-to-face visits were not possible, but our coordinator continued to deliver study drug while maintaining distancing precautions. This was followed by a phone call to remind patients of drug instructions and dosages, and inquiring about any adverse events that may have occurred since the last visit. We evaluated the number of follow up visits before and during the COVID lockdown (March through June 2020).

Results:
Enrollments decreased during the pandemic, in large part due to a study-wide pause in recruitment efforts. The median monthly follow-up prior to COVID-19 was 3, and increased to 5 during lockdown. Before, during and after COVID, our local retention rate has remained 100%.

Conclusions:
In conclusion, despite complicating factors of COVID-19, our local coordinator’s retention rate remained 100% during the COVID-19 pandemic and our median number of monthly follow up visits increased, which may be attributable to our coordinator’s efforts of socially distanced home visits and frequent communication.
Abstract TP32: From Stroke Code To Stroke Clinic; The Emerging Role Of The Stroke Nurse Navigator
Authors: Nystrom Karin V , Neuschatz Kaile , Petrucci Dawn , Coppola Anna , Parker Ranisha L
Published: February 2022

Background:
With numerous stroke centers across the US now caring for complex stroke patients, the role of the stroke nurse navigator has catapulted to be one of the critical elements of a successful stroke program. Our hospital developed an innovative model that addresses the transitions of care after stroke and describes the unique nurse navigator model for stroke patients and families.

Methods:
Under a triple aim mission statement to support patients and families throughout the care continuum, five practice domains were identified spanning the patient’s stroke journey - see table 1. For each domain, expected experiences were described and best practices were outlined.

Results:
Our hospital supported hiring stroke nurse navigators to develop best practices as a complementary role to the stroke care teams during each phase of the patient’s hospitalization to promote a seamless from stroke code to stroke clinic. After discharge, the navigators aligned with acute and subacute rehabilitation teams, visiting nurse agencies, and with patients and caregivers at home. In addition to clinical care, the navigators participated in quality improvement projects, regulatory readiness for certification, and community outreach programs - see Table 2.

Discussion:
The stroke nurse navigator, as a critical member of the stroke program, is uniquely positioned to optimize the transitions of care for patients and families recovering from stroke. This evolving model of acute and recovery stroke care identifies the practice domains and outlines the navigator practice responsibilities that compliments the medical care along the stroke recovery care continuum.Table 1.

Table 2.