bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP74: Implementing CSTK Measures at a High Volume Comprehensive Stroke Center
Authors: DeGuzman Maria I , Indupuru Hari K , Bajgur Suhas , Shaw Sandi , Cooper Stephanie , Glendening Christine , Sline Melvin , Moser Hope , Harrison Nicole , Sarraj Amrou , Savitz Sean I , Vahidy Farhaan S
Published: March 2022

Background:
The Joint Commission mandates implementation of comprehensive stroke (CSTK) measures for Comprehensive Stroke Centers (CSC) effective January 1, 2015. CSTK measures are evidence based metrics targeting quality of care and outcomes for stroke patients.

Purpose:
Share challenges and experiences in implementation of CSTK measures, and present our data highlighting these metrics.

Methods:
Beginning last quarter of 2014 we reviewed the guidelines in multidisciplinary CSC committees, identified the measure specific needs, and assigned responsibilities to team members. We started pilot data collection and re-programmed our CSC data registry to capture these data. We also created live dashboards to provide instant feedback on performance metrics (Fig 1). All CSTK measures were incorporated to the stroke coordinators’ daily review, with emphasis on concurrent follow up, hence preventing fall outs. This approach enabled us to monitor our progress, identify performance improvement opportunities, and develop evidence based PDSA cycles. Efforts were undertaken to train and educate clinical staff, develop process specific scripts and algorithms, and periodically present data for internal review.

Results:
We obtained comprehensive stroke certification in March 2013 and re-certification in June 2015. From January 2014 to April 2015 we treated 2,886 patients (180 patients per month). Meeting the requirements entailed enhanced clinical documentation, alterations in work flow, additional time and resources for tracking data elements, and monitoring. Our CSTK metrics for indicated time periods are presented as Fig 2a - 2j.

Conclusion:
The eight CSTK measures encompass a wide range of system processes. Workflow alterations in a complex health care environment can be daunting. We share our experiences, and provide a successful model for our peers, particularly generalizable for high throughput centers.
Abstract TMP88: Cyp2c19 Polymorphisms Are Not Associated With the Long-term Clinical Outcomes in Stroke Patients Treated With Clopidogrel
Authors: Tanaka Tomotaka , Yamagami Hiroshi , Ihara Masafumi , Hamasaki Toshimitsu , Miyata Shigeki , MIyata Toshiyuki , Yamamoto Haruko , Toyoda Kazunori , Nagatsuka Kazuyuki ,   the Contribution of Genetic Analysis to the Efficacy of Clopidogrel (Cognac) Study Investigators
Published: March 2022

Introduction:
Active metabolite of clopidogrel blocks P2Y12 receptor and consequently reduces cardiovascular events (CVEs) in stroke patients. Since CYP2C19 is the major enzyme involved in the generation of active metabolite, several large-scale studies of the patients who mostly underwent percutaneous coronary intervention have indicated that the genotypes of CYP2C19 are associated with recurrent CVEs. However, reliable prospective data regarding this association in stroke patients are sparse.

Methods:
A multicenter, prospective cohort study of stable stroke patients receiving long-term clopidogrel therapy (for at least 28 days before enrollment) for the secondary prevention of CVEs was conducted at 14 hospitals in Japan. Between September 2010 and March 2012, 511 patients were enrolled and underwent CYP2C19 genotyping to identify loss-of-function polymorphisms (*2 and *3). On-treatment platelet reactivity was assessed by ADP-induced platelet aggregation and vasodilator-stimulated phosphoprotein (VASP) index. We followed all patients for 2 years to evaluate the association of CYP2C19 polymorphisms with the composite outcome including cardiac death, stroke, myocardial infarction and cerebral/carotid vascularization.

Results:
Median follow-up period was 728 days. Of 511 patients, 243 (48%) and 76 (15%) patients were classified as intermediate (IM:*1/*2 or *1/*3) and poor (PM:*2/*2, *2/*3, or *3/*3) metabolizers, respectively. The prevalence of IM/PM was substantially higher than that of studies on Caucasian populations. On-treatment platelet reactivity (mean±SD) assessed by ADP-induced platelet aggregation (52±18% in extensive metabolizer [EM:*1/*1], 60±16% in IM, and 69±71% in PM) or VASP index (43±15% in EM, 52±16% in IM, and 67±14% in PM) was significantly different among the groups (p<0.0001). However, there was no significant difference in the incidence of the composite outcome among the groups (EM vs IM; hazard ratio [HR] 0.99 [95% CI 0.48—2.04], p=0.97, vs PM; HR 0.80 [0.26—2.51], p=0.70).

Conclusions:
Despite the significant association of CYP2C19 polymorphisms with on-treatment platelet reactivity, these parameters did not predict the recurrence of CVEs in stroke patients with long-term clopidogrel therapy.
Abstract TMP94: Treatment With Pravastatin Decreases the Level of Serum Hs-CRP in Ischemic Stroke Patients - Hs-CRP Sub-study of the Japan Statin Treatment Against Recurrent Stroke (J-STARS)
Authors: Kitagawa Kazuo , Hosomi Naohisa , Nagai Yoji , Kagimura Tatsuo , Origasa Hideki , Minematsu Kazuo , Uchiyama Shinichiro , Nakamura Masakazu , Matsumoto Masayasu
Published: March 2022

Background and Purpose:
Serum hs-CRP level has been shown as a reliable marker of vascular inflammation. One of the pleiotropic effect of statin could be anti-inflammation shown as decrease of hs-CRP level. However, it remains unclear whether statin decreases the hs-CRP level in ischemic stroke patients. This is a sub-study of J-STARS, and the primary outcome was change of hs-CRP after statin treatment. The secondary outcome was whether mean hs-CRP level during follow-up period is associated with recurrent stroke and transient ischemic attack (TIA), and all vascular event.

Methods:
Among 1578 patients enrolled in J-STARS, 1095 were included in Hs-CRP sub-study. Those were randomly assigned to pravastatin (n=545) or control group (n=550). The pravastatin group patients received 10 mg of pravastatin/day. Blood samples were obtained at baseline and 2, 6 months, 2 and 5 years after randomization. Hs-CRP levels were log-transformed for statistical analysis.

Results:
Baseline average hs-CRP level was 691 ng/L. Hs-CRP level was significantly decreased 2 months after pravastatin treatment, and remained significantly lower until the end of study. However, hs-CRP level did not show significant change in the control group. One SD increase of mean hs-CRP level during follow-up tended to increase the risk of stroke/TIA recurrence (HR 1.18, 95%CI 0.99-1.40, p=0.065) and significantly increased the risk of all vascular events (HR1.28, 95%CI 1.10-1.49, p<0.01). After adjustment with risk factors, the association between 1SD increase of hs-CRP and all vascular events remained significant. When cut-off level of hs-CRP level during follow-up was determined as 1000 ng/L, higher CRP level significantly increased the risk of stroke/TIA (HR 1.47, 95%CI 1.04-2.09, p=0.03) and all vascular events (HR 1.63, 95%CI 1.20-2.21, p<0.01). After adjustment, the association with stroke/TIA was of borderline significance (p=0.06) but remained significant with all vascular events (p=0.01).

Conclusion:
Low dose pravastatin significantly decreased the level of hs-CRP in ischemic stroke patients. High hs-CRP level during follow-up, particularly beyond 1000 ng/l, tended to increase the stroke/TIA recurrence and was significantly associated with the risk of all vascular events.
Abstract TP101: CaMKII Reverts After Stem Cell Treatment in Ischemic Stroke
Authors: Chelluboina Bharath , Klopfenstein Jeffrey D , Ramanathan Dinesh , Pinson David M , Wang David Z , Veeravalli Krishna K
Published: March 2022

Background:
Loss of calcium/calmodulin-dependent kinase II (CaMKII) after ischemic stroke exacerbates cell death by sensitizing vulnerable neurons to excitotoxic glutamate signaling and inducing neurotoxicity. Our recent study demonstrated the potential of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) treatment in inhibiting apoptosis after ischemic stroke. In this study, we aimed to investigate the effect of focal cerebral ischemia and/or reperfusion on CaMKII expression and the role of HUCB-MSCs treatment on CaMKII regulation. To our knowledge this is the first study that demonstrates the possible involvement of CaMKII in HUCB-MSCs-mediated neuroprotection after ischemic stroke.

Methods:
Male Sprague-Dawley rats were obtained and randomly assigned to various groups. Rats were subjected to a two-hour middle cerebral artery occlusion (MCAO) procedure followed by seven days reperfusion. HUCB-MSCs (0.25x106cells/animal) were intravenously injected via tail vein 24 hours post-MCAO to designated animals. Rats brain tissues obtained seven days after reperfusion from various groups were subjected to real-time PCR, immunoblot and immunofluorescence analysis.

Results:
CaMKII protein expression did not change in animals subjected to 1h, 2h, and 4h of ischemia without reperfusion. However, CaMKII expression is significantly reduced when the animals were subjected to ischemia followed by one day reperfusion. The loss of CaMKII was persistent until 14 days after reperfusion. All CaMKII isoforms (CaMKIIα, CaMKIIγ and CaMKIIδ), except CaMKIIβ, were downregulated. CaMKII expression in neurons was also reduced in the ischemic hemisphere. HUCB-MSCs treatment 24h after reperfusion revert CaMKII mRNA and protein expression. Significant co-localization of CaMKII with neurons was also noticed in rats subjected to stem cell treatment.

Conclusions:
HUCB-MSCs-mediated neuroprotection after ischemic stroke could be mediated by upregulation of neuronal CaMKII expression.
Abstract TP121: Simulated Inanimate Model for Physical Learning Experience (SIMPLE) of Carotid Endarterectomy Using a 3-D Printing Technology
Authors: Santangelo Gabrielle , Stone Jonathan , Mix Doran , Park Jennifer , Ghazi Ahmed , Richards Michael , Stoner Michael , Vates George E
Published: March 2022

Introduction:
Surgical education relies heavily on operative exposure with live patients. However, the carotid endarterectomy (CEA) demands an experienced surgeon with a very low complication rate. The high-risk nature of this procedure and the decline in number of CEAs performed annually has created a training gap. Current surgical skill simulators do not provide a comparable surgical experience.

Hypothesis:
The SIMPLE-CEA is a comprehensive and realistic operative exercise that replicates all vital steps in a CEA and permits measurement of clinically significant metrics.

Methods:
Using a novel method, anatomically accurate models of the human neck and carotid artery were created using poly-vinyl alcohol hydrogels. Relevant structures were also fabricated including the vagus and hypoglossal nerves, internal jugular and facial veins, sternocleidomastoid and sternohyoid muscles, and carotid sheath. 3D models were created based on an amalgamation of patient data using CAD software. Injection molds of the modeled tissues were 3D printed. Graded polymerization of the hydrogel was achieved by inducing crosslinks during freeze/thaw cycles, which stiffened the simulated tissues to realistic tactile properties. Bleeding was simulated using pressure bags and a ventricular assistive device was used to create pulsatile flow in the carotid.

Results:
Realistic models were produced using 3D printed injection models and polymer hydrogels. Preliminary findings show an average of 4/5 for face validity surveys according to experts who performed preliminary testing. Comparison of surgeon performance was feasible using construct metrics such as carotid clamp time, estimated blood loss, and nerve injury.

Conclusion:
SIMPLE-CEA is a realistic, inexpensive model of high fidelity, offering comprehensive training for CEA and allows residents to master required skills prior to operating on a live patient. Next steps include testing content and construct validity of the model.
Abstract TP138: Carotid Endarterectomy for Complicated Carotid Artery Disease∼ Application of Extracorporeal Circulation Technique
Authors: Niiya Yoshimasa , Kawabori Masato , Iwasaki Motoyuki , Mabuchi Shoji , Houkin Kiyohiro
Published: March 2022

Intorduction:
In performing carotid endarterectomy (CEA), indwelling shunt tube placement is necessary in some cases with poor collateral flow. Particularly, in patients with critical hemodynamic insufficiency like contralateral internal carotid artery (ICA) occlusion, shorter cross-clamping duration is preferable. Furthermore, in patients who have common carotid artery (CCA) ulceration, shunt placement can be dangerous because of the risk of embolic complication through the indwelling shunt tube. For such cases, we introduced extracorporeal circulation technique for cerebral perfusion during CEA.

Methods:
In 309 consecutive CEA cases, 16 cases (5.2%) were performed CEA under extracorporeal circulation. Using roller pump, arterial blood was supplied from brachial or femoral artery to the distal portion of the cervical ICA. In cases with contralateral ICA occlusion, distal ICA cannulation was performed without any cross clamping by using Seldinger technique. Other cases with CCA ulceration, distal ICA cannulation was performed with conventional indwelling shunt tube insertion technique.

Results:
In 6 cases with contralateral ICA occlusion and 9 cases with ipsilateral CCA ulceration concomitant with ICA stenosis, and in one case had both contralateral ICA occlusion and ipsilateral CCA ulceration, we successfully performed CEA under extracorporeal circulation. No ischemic event was observed in all the cases.

Conclusions:
This extracorporeal circulation procedure is very useful in patients with carotid artery disease who have extremely poor collateral flow or have severe CCA lesions.
Abstract TP140: Recurrence and Outcomes in Patients Who Experience a Mild Ischemic Stroke: A Systematic Review
Authors: Chan Michael , Westergaard Mogens , Mayhook Andrew , Inglis Steven R , Jennings Em , Johansson Saga
Published: March 2022

Introduction:
Patients experiencing a mild ischemic stroke (MIS) or transient ischemic attack (TIA) are at high risk of further events in the next 90 days. A good understanding of the unmet medical needs in these patients is required to develop evidenced-based treatment options that may improve post-stroke outcomes.

Aims:
This systematic literature review aimed to assess 90-day outcomes in patients following an MIS in routine clinical practice.

Methods:
Ovid MEDLINE and Embase were searched using terms relating to disease, severity and outcomes. Key inclusion criteria were: ≥ 100 patients with MIS (NIHSS score ≤ 5); 90-day outcomes reported; and non-interventional study design.

Results:
In total, 6510 records were identified. Of these, 18 articles reporting outcomes from 16 studies were included in the review. Stroke recurrence at 90 days, reported by 7 studies, varied widely (0.9-24.6%; Table); there were differences in study size, recurrence definition and time to presentation. Mortality at 90 days was 0.2-5.1% (13 studies), with a trend towards higher mortality in studies using higher NIHSS cut-off values to define MIS. Most patients had modified Rankin Scale scores of 0-1 (6 studies) or 0-2 (5 studies) at 90 days.

Conclusions:
The rates of 90-day stroke recurrence in patients following an MIS identified in this comprehensive literature review suggest there is a need for improvement in current clinical practice. However, identified studies reporting stroke recurrence had varied methodologies. Further standardized studies in these patients may be needed to better understand stroke recurrence, severity and mortality.
Abstract TP145: Cystatin C is a Strong Predictor of Short-term Functional Outcome After Ischemic Stroke in Patients With Chronic Kidney Disease
Authors: Kim Tae Jung , Kim Chi Kyung , Kim Yerim , Jeong Han-Gil , Nam Kiwoong , An Sang Joon , Ko Sang-Bae , Yoon Byung-Woo
Published: March 2022

Introduction:
Serum cystatin C has emerged as a risk factor of cardiovascular disease and death. Cystatin C is promoted a better marker of renal function compared to estimated glomerular filtration rate (GFR). However, the impact of cystatin C on the functional outcome after ischemic stroke in patients with CKD remains unclear.

Hypothesis:
We assessed the prognostic value of cystatin C for functional outcome after ischemic stroke in CKD patients.

Methods:
A consecutive 239 patients with CKD who were admitted within 7 days after ischemic stroke onset between January 2010 and February 2014 were included for analysis. An estimated GFR < 60mL/min/1.73 m
2
defined CKD. We compared the demographic information, clinical characteristics and laboratory findings including serum cystatin C level. We evaluated the short-term outcomes using a modified Rankin Scale (mRS) at three-months after onset of ischemic stroke. We divided patients into two groups with favorable outcome (mRS score ≤2) and unfavorable outcome (mRS score ≥3).

Results:
Among the total patients, 36.0% (n=86) patients had unfavorable outcome. These patients were mostly male (52.9%), with a mean age of 73.5 years. Older age, atrial fibrillation and history of previous stroke were significantly higher in the unfavorable outcome group. Participants with unfavorable outcome tended to have lower body mass index, higher initial NIHSS, lower estimated GFR, and higher C-reactive protein concentration. Compared to the favorable outcome group, cystatin C level was significantly higher (1.25±0.41 vs. 1.54±0.64 mg/dL, P = 0.001) in the unfavorable outcome group. After controlling for confounding factors, higher cystatin C levels were independently related to the unfavorable outcome at three-months (Odds ratio, 3.19; 95% Confidence interval, 1.02-9.96). In contrast, estimated GFR did not show any significant association with the unfavorable outcome (Odds ratio, 1.01; 95% Confidence interval, 0.96-1.06).

Conclusions:
In conclusion, our study showed that elevated cystatin C levels were independently associated with the unfavorable functional outcome after ischemic stroke in patients with CKD. Cystatin C may be a potent predictor of short-term functional outcome after ischemic stroke in CKD patients.
Abstract TP155: Robotic Retraining of Finger Movements After Stroke
Authors: Ingemanson Morgan L , Rowe Justin B , Chan Vicky , Cramer Steven C , Reinkensmeyer David J
Published: March 2022

Background:
Robots aid motor rehabilitation, but there has been limited attention to recovery of finger movements. This study evaluated robotic assistance during finger movement training. Functional MRI (fMRI) was acquired at baseline to understand predictors of treatment gains.

Methods:
Patients with chronic stroke underwent a baseline fMRI scan, alternating rest with affected-side finger movements similar to those made during robotic therapy. Next, subjects received therapy 3 hr/wk for 3 weeks using FINGER (Finger Individuating Grasp Exercise Robot), with which subjects moved their paretic index and middle fingers to play a musical game similar to GuitarHero. FINGER used an assistance-as-needed algorithm to facilitate completion of grasping movements, which increased sensory feedback without altering voluntary motor output. Participants were randomized to receive High Assistance (to insure 85% success) or Low Assistance (55% success).

Results:
30 subjects (mean age 58 yr; baseline Fugl-Meyer 46 out of 66; 37 mo post-stroke) completed the study. Significant gains were found in the primary outcome measure, change in Box & Blocks (B&B) score (23 to 25.5, p<0.0001). There was no difference between High and Low Assistance groups in the primary endpoint (p=0.65), though some secondary outcomes favored High Assistance. The fMRI scans found that greater treatment gains were associated with higher laterality index in primary sensory cortex, indicating greater boost in B&B score over time with higher pretreatment balance of activation towards ipsilesional rather than contralesional sensory cortex; laterality index in primary motor cortex lacked predictive value.

Conclusions:
Significant motor gains were found with a robotic device that targets finger movements. Sensory factors appear key: treatment content emphasized augmented sensory feedback, and the hemispheric balance of fMRI activation within sensory but not motor cortex predicted treatment gains. Together these findings suggest Hebbian rules of sensorimotor cortex plasticity during finger robotic therapy after stroke.
Abstract TP158: Haptoglobin Hp2 Variant Associates With an Increased Risk of Ischemic Cardiovascular Death After First-ever Stroke
Authors: Ijas Petra , Melkas Susanna , Saksi Jani , Jula Antti , Jauhiainen Matti , Pohjasvaara Tarja , Kaste Markku , Karhunen Pekka J , Lindsberg Perttu , Erkinjuntti Timo
Published: March 2022

Introduction:
Haptoglobin (Hb) is an acute phase plasma protein which binds free hemoglobin and protects tissues from heme-iron induced oxidative damage. Hp gene exists in two variant alleles, Hp1 and Hp2 giving rise to three protein isoforms, hp1-1, hp1-2 and hp2-2, which differ in their efficiency to limit oxidative stress. Previously, Hp variants have been associated with the risk of ischemic stroke subtypes, Hp1 variant with lacunar stroke and Hp2 with large-artery atherosclerotic stroke.

Hypothesis:
Our aim was to scrutinize previous associations to stroke subtypes and, further, to test association of Hp variants with the extent of white matter lesions (WML) and incidence of cardiovascular death after first-ever ischemic stroke.

Methods:
Hp was genotyped by PCR and gel electrophoresis in Helsinki Stroke Aging Memory Study (SAM, n=378 with DNA) and Cardiovascular diseases -subcohort of Health 2000 Survey (n=1426), who served as population controls.

Results:
Hp genotype frequencies were 15.6% (Hp1-1), 44.2% (Hp1-2) and 40.2% (Hp2-2), within Hardy-Weinberg equilibrium and equal to those described in other Caucasian populations. There were no significant differences in Hp genotypes between stroke subtypes classified according to TOAST within SAM or compared to population controls. Hp alleles did not associate with the extent of WML. In follow-up, the carriers of Hp2 allele (Hp1-2 and Hp2-2) had substantially higher rate of cardiac deaths (24.5% vs 8.5%, P=0.006) and a trend towards more fatal strokes (23.5% vs 13.6%, P=0.122). The combined risk of ischemic cardiovascular death was 2.4-fold increased in Hp2 carriers (95%CI 1.28-4.43) even after adjustment for major cardiovascular risk factors (age, gender, hypertension, diabetes, atrial fibrillation, smoking, high LDL cholesterol).

Conclusions:
Hp2 allele is associated with increased risk of ischemic cardiovascular death after first-ever ischemic stroke. This may result from the impaired capacity of Hp2-containing protein isoforms to alleviate oxidative stress in the vasculopathic arterial tree.
Abstract TP174: Incidence Rate of Transient Ischemic Attack and Subsequent Stroke Incidence Rates: a Meta-analysis
Authors: Kokubo Yoshihiro , Matsumoto Chisa
Published: March 2022

Background and Purpose:
Only a limited number of studies have examined the incidence of transient ischemic attack (TIA) along with the subsequent stroke incidence. There is no meta-analysis of the incident TIA along with the subsequent stroke incidence. The purpose of the present meta-analysis was to identify the annual incidence rate of TIA according to sex and age categories and the incidence rate of stroke after the onset of TIA.

Methods:
Using PubMed, we performed a systematic review and meta-analysis of prospective cohort studies of TIA published between 1985 and July 2015. The search was limited to English-language studies and reports showing the number of subjects according to sex and age categories. The incidence of stroke after TIA onset was calculated. Among 98 articles revealed by the PubMed search, eight studies of Western populations (1,422,037 men and 1,467,254 women) and the single study of a Japanese population met the inclusion criteria for the incidence of TIA. Among 115 articles by the PubMed search, 14 studies (8,763 patients with TIA) were included in our identification of the incidence rate of stroke after TIA search.

Results:
During the follow-ups, the incidence rates of TIA were 1.38 and 1.29 per 1,000 person-years in the Western men and women, respectively. The incidence rates of TIA in Western populations according to the age categories (<45, 45-54, 55-64, 65-74, 75-84, and ≥85 years old) were 0.05, 0.4, 1.1, 2.4, 4.8, and 5.2 per 1,000 person-years in the men and 0.03, 0.3, 0.7, 1.5, 3.7, and 5.4 per 1,000 person-years in the women, respectively. In the Japanese population, the incidence rates of TIA were 0.78 and 0.38 per 1,000 person-years in the men and women, respectively. The incidence rates of stroke which were all Western countries, were 3.8%, 6.3%, 9.7%, 10.5%, and 17.2% at 2 days, 1 week, and 1, 3, and 6 months after the onset of TIA, respectively.

Conclusions:
In this meta-analysis, the incidence rate of TIA in Western populations was 1.3 per 1,000 person-years, which is higher than that in Japanese population. One in 10 patients and one in 6 patients with TIA subsequently suffered from a stroke during a month and a half year, respectively. For stroke prevention, it is important that thorough care is provided for TIAs that occur during the acute phase.
Abstract TP194: Albuminuria Predicts Early Neurological Deterioration in Patients with Acute Ischemic Stoke
Authors: Kanamaru Takuya , Suda Satoshi , Muraga Kanako , Okubo Seiji , Watanabe Yoko , Tsuruoka Syuichi , Kimura Kazumi
Published: March 2022

Background:
Chronic kidney disease (CKD), defined as a reduced glomerular filtration rate (GFR) or albuminuria, is associated with an increased risk of cardiovascular events, including stroke. However, the association between CKD and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of estimated GFR (eGFR) and albuminuria on early neurological deterioration (END) in patients with acute ischemic stroke.

Methods:
In this retrospective study, we enrolled 294 consecutive patients with acute ischemic stroke admitted to our stroke center from January 2011 to September 2012. General blood and urine examinations, including eGFR and urinary albumin/creatinine ratio (UACR), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥ 2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days. Statistical significance between the END and non-END group was assessed using Pearson’s chi-square test for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END.

Results:
END was observed in 60 patients (20.4%). Age (P = 0.003), admission Blood glucose level (P = 0.036), large vessel disease (P = 0.022), small vessel disease (P < 0.001), UACR (P < 0.001), and admission NIHSS score (P < 0.001) were significantly associated with END, but no relationship between eGFR and END was found. The optimal cutoff level, sensitivity, and specificity of UACR levels to distinguish the END group from the non-END group were 39.6 mg/g creatinine, 83.3 and 52.1%, respectively. On multivariable logistic regression analysis showed that END was positively associated with high UACR (≥ 39.6 mg/g creatinine; odds ratio [OR], 3.36; 95% confidence interval [CI], 1.60-7.51; P = 0.0011) and high admission NIHSS score(≥ 6 points, OR, 2.27; 95% CI, 1.11-4.78; P = 0.0245), and negatively associated with diagnosis of small vessel disease (OR, 0.11; 95% CI, 0.0054-0.80; P = 0.0277).

Conclusions:
Our data suggest that high UACR on admission may predict early neurological deterioration in patients with acute ischemic stroke. Larger prospective studies are further required to clarify the correlation between albuminuria and END.
Abstract TP203: Dementia Treatment was Associated with Reduced Risk of Intacerebral Hemorrhage
Authors: Yim Eunji , Sekar Padmini , Moomaw Charles J , Osbourne Jennifer , Martini Sharyl R , Xiong Li , Woo Daniel
Published: March 2022

Background and purpose:
NMDA receptor antagonists have been found to reduce inflammation after intracerebral hemorrhage (ICH) in animal models. Here, we evaluated the potential role for dementia treatment (including memantine, an NMDA receptor antagonist and donepezil, an AchE inhibitor) in decreasing risk of ICH and effect on functional outcome.

Methods:
The study population was comprised of the Genetic and Environmental Risk Factors for Hemorrhagic Stroke study (GERFHS), a case-control study of hemorrhagic stroke that recruited 1,000 cases of ICH and 3,000 controls (1997 -2013), and the Ethnic/Racial Variations of Intracerebral Hemorrhage study, a multi-center, case-control study to recruit 3,000 cases of ICH and 3,000 demographically matched controls from 2010 to the present. A subset of cases and controls with history of or treatment of Alzheimer’s disease or dementia was created to account for the higher risk of ICH with dementia. A review of each subject’s medication history was performed to evaluate the frequency of treated dementia. Three month survival was evaluated using multivariate logistic regression analysis.

Results:
Frequency of memantine use among cases (N=234) and controls (N=36) with Alzheimer’s disease was 19.2% and 25.0%, respectively (OR 0.714, 95% CI [0.314-1.624], p=0.42). Frequency of donepezil use among cases (32.1%) was lower than controls (61.1%) (OR 0.300, CI [0.146-0.619], p=.0011). Cases on Alzheimer treatment did not demonstrate significantly better mortality at 3 months than untreated patients (p=0.15). Overall, treated dementia/AD was associated with a decreased risk of ICH (OR 0.18, CI [0.08-0.44], p=0.0002) independent of anticoagulant use, hypertension, and high cholesterol and prestroke disability.

Conclusions:
While preliminary analysis was unable to identify an association between memantine and risk of ICH, treated dementia was associated with a decreased risk of ICH. In addition, despite putative benefits of NMDA antagonism, no benefit on survival was observed. Further studies are needed to determine the mechanism by which treatment of dementia may be associated with lower risk of ICH.
Abstract TP217: Different Features of Anterior and Posterior Circulation Dissections
Authors: Lee Jun , Kim Min-Gyeong , Gwon Jung-Im
Published: March 2022

Introduction:
The features of vascular images and risk factors might be different according to the location of the cervicocerebral artery dissection.

Hypothesis:
We investigate whether the risk factors, neuroimaging features, and imaging outcomes differ according to the dissection site (anterior vs. posterior circulation).

Methods:
Consecutive patients who presented with ischemic symptoms and underwent brain vascular imaging within seven days after the onset of symptoms were enrolled. Demographic characteristics, putative risk factors, imaging findings, and types of antithrombotic medication were assessed between anterior circulation dissection (ACD) and posterior circulation dissection (PCD). The baseline and follow-up vascular images (6 months or 1 year after the onset of symptoms) were compared to determine the prognostic difference in the reverse of the lesion.

Results:
A total of 117 patients (n=32 with ACD and n=85 with PCD) were eligible for these analysis. The median delay from symptom onset to baseline vascular imaging was a day (IQR 1, 2). Patients with PCD were older (OR=1.5 by increasing 10 years old [1.02-2.03], p=0.038) and had a dissection associated with exercise or neck manipulation more frequently (OR=4.8 [1.2-18.1], p=0.019) compared to patients with ACD. Arterial stenosis or occlusion was the most common imaging feature (94% in ACD vs. 86% in PCD, p= 0.345). Aneurysm or pseudoaneurysm was identified in 9.4% of ACD and 24.7% of PCD (p=0.067). Among patients with PCD, vertebral artery was the most common lesion site (65% [53-74%]). The complete reverse on the follow-up images at the 6 months or 1 year was identified in 9 patients with ACD and 11 patients with PCD (45% vs. 22%, p=0.054). Neither anticoagulation nor antiplatelet demonstrated significant differences between the frequency of the complete reverse on the follow-up vascular images in patients with ACD and PCD (33% vs. 21%, p=0.613 for anticoagulation; 44% vs. 23%, p=0.087 for antiplatelet).

Conclusions:
These results substantiate the difference in the risk factors and radiologic features according to the dissection site. There was no difference in efficacy of antiplatelet and anticoagulant drugs at complete reverse of the lesion after cervicocerebral artery dissection.
Abstract TP243: Emergency Transport of Stroke Patients in a Rural State: Opportunities for Improvement in Arkansas
Authors: Brown Aliza , Bianchi Nicolas , Wei Feifei , Onteddu Sanjeeva R , Balamurugan Appathurai , Culp William C
Published: March 2022

Introduction:
Time delay is the key obstacle for receiving effective stroke treatment. The requirement for Alteplase therapy to begin within 3 hours of an ischemic stroke onset (4.5 hours off-label) causes treatment ineligibility among many patients, such that only 3-5% receives treatment. Rapid transport to a stroke-care qualified facility is vital. Time and destination data for emergency medical system (EMS) first-responders transporting identified strokes in 2013 were provided by the EMS section of the Arkansas Department of Health and analyzed for regional location, mode of transport, transport time and the destination’s qualification for stroke care.

Hypothesis:
Rural regional EMS first-responders were transporting patients to non-qualified facilities even when there were nearby stroke-ready specialty centers available. We aimed at identifying potential areas for improvement within the system.

Methods:
The state’s 75 counties were placed into eight geographical regions (R1-R8). For each region transport times for stroke suspects and the destination’s qualification for stroke care were determined for all EMS 911 ground-transport calls. Destinations were ranked as a Primary Stroke Center (PSC), Acute Stroke Ready Hospital (ASRH), Non-Specialty or unknown Care Facility (NSCF), or out-of-state facility.

Results:
There were 9,688 verified EMS stroke ground transports with median within-region transport times ranging from 29.5 to 40 minutes. Statewide, only 65 percent of EMS-identified stroke 911-call patients were transported to either PSC (12%) or ASRH (53%) facilities. About one-third of the patients (30.4%) were delivered to NSCFs. In the regions (R6, R8) with the highest stroke suspects’ per-capita, up to 57% of transports were made to NSCFs.

Conclusions:
As a rural state with few PSCs, Arkansas benefits from a widespread network of ASRHs, yet almost a third of stroke suspects were delivered to NSCFs, where acute stroke therapy rates and outcomes are unknown. Further work is needed to enhance the ASRH network development and utilization, including EMS destination protocols.
Abstract TP249: Predictors of Arrival by Ambulance Among Massachusetts Ischemic Stroke Patients
Authors: Sauser-Zachrison Kori , Land Thomas , Soare Thomas W , Christie Anita , Nasuti Laura , Schwamm Lee H
Published: March 2022

Introduction:
Rapid evaluation and treatment are critical for improving outcomes of acute ischemic stroke patients. Arrival by ambulance is associated with more rapid imaging and tPA administration. Predictors of arrival by ambulance have not been well described.

Hypothesis:
Ischemic stroke patients with increased stroke severity are more likely to arrive to the hospital by ambulance.

Methods:
Prospective study of all ischemic stroke patients presenting to Massachusetts hospitals participating in the Coverdell Registry from 2005-13 (60 of the states’ 70 hospitals license to receive stroke patients). Logistic regression analysis identified predictors of ambulance use, accounting for clustering by hospital.

Results:
Among 54,164 acute ischemic stroke patients in the sample, 60.2% (n=32,622) arrived by ambulance. Among the 29,236 patients in whom NIHSS was documented, 59.5% (n=17,380) arrived by ambulance. In bivariate analysis, patients arriving by ambulance had higher NIHSS (mean 8.3 versus 4.5, p<0.001). In logistic regression analysis adjusting for patient characteristics and clustering within hospital, increased age, Medicaid insurance, history of atrial fibrillation/flutter, previous stroke, presentation from another healthcare facility, and increased stroke severity remained predictors of arrival by ambulance (Table). Ambulance arrival was less likely among Asian patients, those with stroke onset after hospital arrival, and later year of presentation.

Conclusions:
While patients with increased stroke severity are more likely to present via EMS, the use of ambulance transport by stroke patients decreased significantly over time. Widespread public education efforts are still needed to stress the importance of ambulance use for suspected stroke symptoms.
Abstract TP258: Enoph1-ADI1-MT-MMP-1 Pathway Contributes to Ischemic Brain Microvascular Endothelial Cell Apoptosis
in vivo
and
in vitro
Authors: Zhang Yuan , Wang Ting , Li Yun , Zhao Peiyan , Huang Jianlin , Li Weiping , Liu Wenlan
Published: March 2022

Enolase-Phosphatase 1 (Enoph1), a newly discovered enzyme of the methionine salvage pathway, has been identified as a candidate gene involved in the modulation of stress responses. In the present study, we investigated the effect of Enoph1 on ischemic blood brain barrier (BBB) injury on an in vitro model of oxygen-glucose deprivation (OGD) and an in vivo rat model of middle cerebral artery occlusion (MCAO). Cell death and apoptosis were assessed by measuring 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide formation, lactate dehydrogenase release and TdT-mediated dUTP-biotin nick end labeling staining. BBB disruption was evaluated based on fluorescein-labeled albumin (FITC-albumin) extravasation. ROS generation was assessed by DCFH staining. Real time-PCR and western blot were used to measure mRNA and protein expression, respectively. CRISPR-activated plasmid and siRNA were applied to manipulate Enoph1 expression in brain microvascular endothelial cells (BMVECs). Exposure of BMVECs to OGD for 6 hours markedly increased Enoph1 expression and decreased the protein levels of its substrate aci-reductone dioxygenase 1 (ADI1) protein, which was accompanied by membrane type 1 matrix metalloproteinase (MT1-MMP) upregulation, increased apoptotic cell death and ROS generation. Increased Enoph1 expression was also observed in ischemic cerebromicrovassels where FITC-albumin extravasation was observed, indicating the co-localization of BBB disruption and increased Enoph1 expression. Knockdown of Enoph1 expression with siRNA significantly inhibited OGD-induce apoptosis, ROS generation, ADI1 protein reduction and MT1-MMP upregulation in BMVECs, while overexpression of Enoph1 CRISPR-activated plasmids exacerbated OGD-induced cell death and ROS generation. Of note, overexpression of ADI1 or knockdown of MT1-MMP with siRNA significantly blocked OGD-induced BMVECs apoptosis. In conclusion, our data demonstrate for the first time that cerebral ischemia activates Enoph1-ADI1-MT1-MMP axis to mediate BMVEC apoptosis and BBB disruption, and Enoph1 may represent a new therapeutic target for ischemic stroke.
Abstract TP267: Stroke Induced Respiratory Dysfunction: Effects of Age and Sex
Authors: Patrizz Anthony , Munchi Yashasvee , Mulkey Daniel , McCullough Louise
Published: March 2022

Background:
Stroke induced respiratory dysfunction (SIRD) is a common complication of stroke. SIRD delays recovery and increases mortality. Despite the high prevalence of SIRD, the magnitude of breathing dysfunction in stroke patients and its impact on functional recovery is unknown. Even less is known regarding age and sex differences in SIRD and respiratory instability due to the lack of an appropriate animal model of SIRD.

Methods:
Whole body plethysmography was performed in WT C57/B6 young (2-3 month)/aged (20 month) male and female mice to establish baseline frequency (BPM), tidal volume (TV), minute ventilation (MV-ml/min/g), periods of apnea, duration of apnea and approximate entropy of the system (ApEn). Mice were then subjected to 60 (aged) or 90 (young) minute MCAO, or sham surgery. 72 hours and 21 days after surgery whole body plethysmography was repeated to identify SIRD phenotype across cohorts.

Results:
Three days after stroke aged animals of both sexes exhibit hypoventilation and a reduced ventilatory response to CO2 (Air: male sham 2.13±.1 vs. stroke1.26±.13 MV, p=.01, female sham 2.89±.27 vs. stroke 1.73±.21 p=.001). A significant interaction of age and surgery was noted among males F(1,42)=10.69, p<0.005. At day 21, young males show a recovery in MV (Air: 2.96±.24 vs. day 3 1.95±.35) as a combined result of decreased inter-breath interval (134.6±12.7mS vs. day 3 248.8±37.3,p=.05) and a decrease in apneas (26.6±9.3/min vs. day 3 47.8±11.4).

Conclusions:
We found that both age and sex affect ventilatory response following stroke. Aged females showed higher pre-stroke MV and dropped to similar levels as males after stroke, suggesting a more severe effect on breathing in aged females. Aged males demonstrated a more pronounced hypoventilation following stroke than their young counterparts, with less robust recovery. Stabilizing respiratory dysfunction may improve post stroke recovery and cognitive outcomes.
Abstract TP272: A Novel Designer Lipophilic Curcumin Analog Promotes Clinical Improvement Ii Rabbit Models Of Spinal Cord Neurodegeneration and Ischemic Stroke
Authors: Lapchak Paul A , Chou Daisy , Khoynezhad Ali
Published: March 2022

Introduction:
We studied the pharmacokinetics and pharmacology of intravenously administered CNB-001, a pleiotropic anti-inflammatory molecule with neurotrophic properties in two rabbit neuro-ischemia models.

Hypothesis:
In vitro, we have found that CNB-001 can significantly reduce cell death mediated by glutamate, iodoacetic acid, ATP depletion, oxidative stress (glutathione depletion) and oxygen-glucose depletion. We tested the hypothesis that CNB-001 would attenuate ischemia-induced behavioral deficits in vivo.

Methods:
Abiding by RIGOR guidelines, the study was randomized and the neuro-examiners were naive (blinded) to treatment. CNB-001 (10mg/kg) was administered IV 45 minutes prior to balloon of occlusion of the infrarenal aorta, which reliably produces spinal cord ischemia (SCI) depending upon the occlusion time. Using TARLOV scores and quantal analysis, we quantified the ischemia duration (P50 in minutes) producing SCI in 50% of study rabbits. Second, using a rabbit embolic stroke model (RSCEM), CNB-001(1-25mg/kg) was applied IV 1 hour post-ischemia and behavioral function measured. We calculated the effective stroke clot dose (P50 in mg) producing neurological deficits in 50% of embolized rabbits. Control groups and positive-control drugs were also studied in parallel in both rabbit ischemia models. All behavioral endpoints were measured 2days after ischemia.

Results:
Pharmacokinetic analysis of CNB-001 in normal male rabbits indicated that the t1/2 was 3.37 ± 0.52 hours and clearance rate was 44.2 ml/min/kg in rabbits. In the SCI model, CNB-001 (10mg/kg) significantly increased P50 values to 19.38 ± 2.03 min (n=16) from 13.58 ± 0.90min (n=14; p<0.05); the positive control, memantine (IV 10mg/kg) increased P50 to 22.52 ± 2.98 min (n=23; P<0.05). In the RSCEM, 10mg/kg CNB-001 significantly improved behavior: P50 2.15 ± 0.09 mg (n=18, p<0.05) compared to vehicle 1.11± 0.08 mg (n=20), when the drug was administered 1 hour after embolization; tPA (IV 3.3mg/kg) also increased P50 2.69 ± 0.29mg (n=20).

Conclusions:
CNB-001 can be provided to patients prior to cardiaovascular surgery to reduce the probability of SCI. Moreover, CNB-001 can reduce behavioral deficits associated with brain ischemia when given after an embolic stroke.
Abstract TP278: Complement Cascade Inhibition Abrogates tPA-mediated Hemorrhage and Brain Edema Following Ischemic Stroke
Authors: Zhao Xue-Jun , Larkin Timothy M , Ducruet Andrew F
Published: March 2022

Introduction:
Tissue plasminogen activator (tPA) remains the only approved pharmacologic treatment for patients with ischemic stroke. Although intravenous thrombolysis improves outcome in a subset of patients, tPA also increases symptomatic hemorrhage and worsens brain edema, thus limiting its clinical applicability. Among several putative mechanisms, plasmin-meditated complement cascade activation likely plays a critical role in the deleterious effects of tPA.

Hypothesis:
tPA administration promotes C3 cleavage and complement activation in ischemic brain, and pharmacologic inhibition of the C3a receptor abrogates tPA-mediated hemorrhage and brain edema following reperfused stroke.

Methods:
C3a concentrations were assessed using ELISA. Transient focal cerebral ischemia was induced in mice by 60 minutes of middle cerebral artery occlusion (MCAO), with tPA (10mg/kg) or saline injected intravenously at reperfusion. C3a receptor antagonist (1mg/kg) or vehicle was administered 45 minutes prior to MCAO. Infarct volume was determined at 24 hours by TTC staining, neurological function was assessed on a 5-point scale, and brain hemorrhage was quantified using a spectrophotometric assay. Cerebral edema was determined by calculating the difference in volume between ischemic and non-ischemic hemispheres and normalized to infarct volume.

Results:
The incubation of tPA with native C3 as well as plasma promotes the generation of C3a. Similarly, intravenous tPA administration dramatically increases cerebral C3a levels in the ischemic hemisphere following MCAO. Intravenous tPA significantly reduces infarct volume (p<0.05) and improves neurological function (p<0.05) in our stroke model. However, tPA also dramatically increases cerebral hemorrhage (p<0.05) and relative cerebral edema (p<0.05). Administration of a C3a receptor antagonist abrogates this hemorrhagic conversion (p<0.05) and brain edema (p<0.05).

Conclusions:
Intravenous tPA administration promotes complement activation through C3 cleavage in ischemic brain. Pharmacologic inhibition of the C3a receptor protects against the deleterious side effects of tPA and represents a promising therapeutic strategy for stroke patients.
Abstract TP279: Hyperglycemia Mediates Matrix Metalloprotease 3 Activation Through Tyrosine Nitration After Stroke
Authors: Hafez Sherif , Abdelsaid Mohammed , Fagan Susan , Ergul Adviye
Published: March 2022

Tissue plasminogen activator (tPA) induces hemorrhagic transformation (HT) after stroke and the incidence of hyperglycemia further exacerbates this injury. Matrix metalloprotease 3 (MMP3) amplifies the tPA-induced HT. The influence of the interaction between tPA and HG on activating MMP3 after stroke was not previously reported. Accordingly, we investigated the impact of tPA and HG on MMP3 activity and the mechanisms through which they induce MMP3 activation in hyperglycemic stroke. Methods. Control/normoglycemic and hyperglycemic (blood glucose: 140-200 mg/dl) male Wistar rats were subjected to either middle cerebral artery (MCA) suture occlusion for 90 minutes or thromboembolic occlusion and up to 24 h reperfusion, with or without tPA (1 mg/kg, IV, 2 h after stroke). MMP3 activity and MMP3 tyrosine nitration were evaluated in brain homogenates at 24 h. Brain vascular endothelial cells (BVEC) were subjected to 3 h hypoxia under either normal or high glucose conditions with or without tPA. MMP3 activity and MMP3 tyrosine nitration were assessed at 24 h. Results. HG and tPA significantly increased MMP3 activity in the brain after stroke and in BVECs after hypoxia/reoxygenation. HG significantly increased MMP3 tyrosine nitration in rats subjected to either suture or thromboembolic occlusion as well as in BVECs (Table). Conclusion. HG and tPA significantly increased MMP3 activity in the brain after stroke and this was associated with increased MMP3 nitration. Our findings suggest that tyrosine nitration may be the underlying mechanism through which MMP3 is activated in hyperglycemic stroke.