bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19: Neurophysiological Responses Of Recovery In Pediatric Mice Compared To Adult Mice With Transient Focal Cerebral Ischemia
Authors: Orfila James E , Grewal Himmat , Bernard Timothy J , Macklin Wendy B , Traystman Richard J , Herson Paco S
Published: March 2022

Introduction:
Ischemic stroke is the fourth leading cause of death in the United States and is increasingly being recognized as a disease that occurs in people of all ages, not just the elderly. Studies suggest that the immature developing brain may have a greater degree of plasticity compared to the adult, thereby enhancing functional recovery to a greater extent during development.

Hypothesis:
Pediatric mice exhibit greater recovery from hippocampal synaptic function following experimental stroke than adults.

Methods:
Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared at 24 hrs, 7 or 30 days after recovery from middle cerebral artery occlusion (MCAO) and compared to sham control mice.

Results:
In adult mice, hippocampal long-term potentiation (LTP) is impaired as early as 24 hrs after experimental stroke and remains impaired for at least 30 days in both the ipsilateral and contralateral, non-injured hemisphere. However, in pediatric mice, LTP is impaired as early as 24 hrs after MCAO and remained impaired in the ipsilateral side 7 days after MCAO, but recovered in the contralateral side at 7 days after MCAO. At day 30 post-stroke, pediatric mice display a full recovery of synaptic function in both hemispheres. Furthermore, significant experimental data is emerging demonstrating an imbalance between inhibitory and excitatory cortical pathways after ischemic stroke, suggesting that reducing GABAergic inhibitory transmission enhances recovery. To test this, hippocampal slices were incubated in L655,708 (100nM), an inverse agonist selective for α5 subunit-containing GABAA receptors. Our data shows that synaptic plasticity was rescued in both pediatric and adult mice in the presence of L655,708 at all-time points tested.

Conclusion:
The present study demonstrates that transient focal ischemia causes functional impairment in the hippocampus at various time points after MCAO and that recovery of synaptic function is more robust in the young brain. In addition, we observed that excessive GABA activity may contribute to impaired synaptic function following ischemic injury, thus inhibition of specific GABA activity may provide a new therapeutic approach to improve functional recovery after stroke.
Abstract 194: Epigenetic And Neuro-glia-vascular Alternations After Stroke In Type-1 Diabetes
Authors: Kalani Anuradha , Kamat Pradip K , Tyagi Neetu
Published: March 2022

Background and Purpose:
Diabetes is a major risk factor for ischemic cerebrovascular disease that increases morbidity and mortality in type-1 diabetes mellitus (T1DM) population. The undefined mechanism for diabetic stroke severity delayed the therapeutic options to deal with this clinically relevant problem. Therefore, the purpose of this study was to determine the mechanism of severity during diabetic stroke by observing epigenetic, neuro-glia-vascular components of the brain with regard to non-diabetic stroke.

Methods:
To test this hypothesis we employed 8-10 weeks old male diabetic Ins2+/- Akita (genetic T1DM) and wild type mice. The experimental mice groups were: 1) sham, 2) IR, 3) sham
Akita
, and 4) IR
Akita
. Mice were subjected to ischemic injury (40 min) followed by reperfusion for 24 h. Infarct area was measured with TTC. The brain tissues were analyzed for inflammation, glial, neuronal, vascular, MMP-9 expressions and global epigenetic alterations (5-methylcytosine, 5-mC and 5-hydroxymethylcytosine, 5-hmC). Intra-carotid FITC-BSA infusion was used to evaluate venular leakage.

Results:
Diabetic
IR
Akita
mice showed more infarct, edema, inflammation, and vascular MMP-9 expressions as compared to non-diabetic and sham mice groups (p<0.05). Intense vascular impairment was determined by reduced expressions of the vascular junctions in IR-injured diabetic mice as compared to other mice groups (p<0.01). FITC-BSA infusion exemplified severe venular leakage in diabetic mice as compared to other experimental mice (F=3, 103, p<0.01). Interestingly, we also found differential regulation of epigenetic [5-hmC; (F=3, 236.8, p<0.01)], vascular [eNOS (F=3, 74.98, p<0.01)], glial [Cx43 (F=3, 37.24, p<0.01); GFAP (F=3, 40.48, p<0.01); CD11b (F=3, 18.36, p<0.01)], and neuronal [NSE (F=3, 292.2, p<0.01); nNOS (F=3, 116.8, p<0.01)] markers in IR-injured diabetic mice as compared to non-diabetic mice.

Conclusion:
We conclude that IR-injury during T1DM exhibits intense inflammation, cellular injury and BBB dysfunction leading to worse stroke outcomes. The data also indicate that severity in IR-injured T1DM mice might be amplified by differential epigenetic and neuro-glio-vascular cascades. This work was supported by NIH grant HL107640.
Abstract 199: Maximal Admission Core Lesion Compatible with Favorable Outcome in Acute Stroke Patients Undergoing Endovascular Procedures
Authors: Ribo Marc , Tomasello Alejandro , Lemus Miguel , Rubiera Marta , Flores alan , Vert Carla , Coscojuela Pilar , Bonet Sandra , Muchada Marian , Molina Carlos A
Published: March 2022

Infarct volume is a strong predictor of outcome. Multiparametric imaging are meant to identify infarct core or non-reversible lesions, and therefore predict on admission the minimum volume of final infarct even if recanalization is rapidly achieved. We aimed to confirm this hypothesis and define the Maximal Admission Lesion volumes Compatible with favorable OutcoMe (MALCOM) in stroke patients receiving endovascular treatment.

Methods:
We studied consecutive patients with ICA/MCA occlusion and multiparametric CT/MRI, who underwent endovascular procedures. Indication for procedure was based on ASPECTS>6 and presence of mismatch (visually>20%). Admission infarct core was later measured on initial imaging (CBV-CTP or DWI-MRI) and infarct volume was measured on follow-up CT-scan. Lesion growth was calculated: final lesion–admission core. We defined MALCOM: cut-off admission core volume (CBV or DWI) above which probability of mRS0-2 is <10%

Results:
57 patients were studied (29 MRI, 28 CT-perf). For all patients mean core volume was 28±22cc, recanalization TICI2b-3:77%. At 24h mean infarct volume was 64±97cc; mean lesion growth: 37±92cc and at 3 months favorable outcome 45% (mRS 0-2). Infarct growth was larger in non-recanalizers (118±182 Vs 29±77; p=0.04). In patients who recanalized admission core was 29±23cc and final lesion was 57±84cc. Overall the maximal lesion volume compatible with favorable outcome (MALCOM) was 39cc. When recanalization was achieved, up to 62% of patients within MALCOM (<39cc) achieved favorable outcome, whereas despite recanalization only 12% of patients beyond MALCOM (>39cc) achieved mRS0-2 (p=0.01). A regression model adjusted for age and recanalization showed that the only predictor of favorable outcome was having an admission core lesion <MALCOM (OR: 9.3, 95%CI: 1.9-46.4; p<0.01) Analysis according to imaging modality showed that CT-CBV allowed larger MALCOM (42cc) than MR-DWI (29cc). In octogenarians, MALCOM (15cc) was lower than in younger patients (40cc)

Conclusion:
Admission lesion core is associated with final infarct volume and is a strong predictor of favorable outcome. MALCOM according to imaging modality and patient age could be set and used on admission to select candidates for endovascular procedures.
Abstract 204: Validity of Etiologic Stroke Classification: Comparison of Different Classification Systems
Authors: Arsava Ethem M , Avery Ross , Sorgun Mine , Pontes Neto Octavio , Park Kwang-Yeol , Kim Gyeong-Moon , Ay Hakan
Published: March 2022

Background and Purpose:
The goal of etiologic ischemic stroke classification is to generate determined subtypes with discrete phenotypic, therapeutic, and prognostic characteristics. Although several new etiologic classification systems have been developed in recent years, their ability to unambiguously generate discrete subtypes is not known. We prospectively examined predictive ability of TOAST, Causative Classification of Stroke System (CCS), and ASCO (based on grade-1 definitions) for various hard stroke features in 2284 consecutive patients within the context of an NIH-funded study.

Methods:
Three raters blinded to each other’s assignments as well as to the study end points performed subtype assignments based on information available at discharge. The primary validation end-point was 90-day stroke recurrence. Secondary validation end-points were admission infarct volume on DWI, admission NIHSS score, and 90-day mortality. We assessed predictive ability of each system by ROC analysis and determined within-category / between-category variance by calculating F values from ANOVA for continuous variables.

Results:
CCS demonstrated larger area under the ROC curve (AUC, 0.71, 95%CI: 0.66-0.75) for stroke recurrence when compared to ASCO (0.66, 95%CI: 0.61-0.71, p=0.04) and TOAST (0.61, 95%CI: 0.55-0.67, p<0.01). The difference in AUC between ASCO and TOAST for recurrent stroke was borderline (p=0.052). There was no difference in AUC for 90-day mortality among the systems [0.67 (95%CI, 0.63-0.70) for CCS, 0.67 (95%CI, 0.64-0.70) for ASCO, and 0.65 (95%CI, 0.62-0.68) for TOAST]. The size of undetermined category was 33% with CCS, 40% with ASCO, and 52% with TOAST (p<0.01). CCS demonstrated larger F values for admission NIHSS (41.8) and infarct volume on DWI (12.0) than ASCO (38.1, 11.4 respectively) and TOAST (37.7, 9.5 respectively).

Conclusion:
This study demonstrates that etiologic stroke subtypes confer predictive information for early stroke recurrence regardless of the classification system used to identify them. Our results also indicate that CCS exhibits greater capacity to generate homogenous categories with different features and assigns a larger proportion of strokes into determined subtypes as compared to other systems.
Abstract 206: Incidence and Duration of Atrial Fibrillation Among a Large, Real-World Population of Cryptogenic Stroke Patients with Insertable Cardiac Monitors
Authors: Richards Mark , Ferreira Scott W , Nichols Allan , Rogers John D , Koehler Jodi L , Sarkar Shantanu , Warman Eduardo N , Ziegler Paul D
Published: March 2022

Introduction:
The characteristics of atrial fibrillation (AF) episodes in cryptogenic stroke patients have recently been explored in carefully selected patient populations. However, the incidence and duration of AF episodes among a large, real-world population of unselected patients with an insertable cardiac monitor (ICM) placed for the detection of AF following a cryptogenic stroke have not been investigated.

Methods:
All patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for the purpose of AF detection following a cryptogenic stroke and who had at least 30 days of device data were included. AF episodes underwent expert adjudication and were at least 2 minutes in duration. We quantified the AF detection rate using Kaplan-Meier survival estimates and compared this to the results from the CRYSTAL AF study, which rigorously excluded patients with evidence of AF prior to enrollment and ICM insertion. The maximum duration of AF episodes was also analyzed.

Results:
A total of 1247 patients were included and followed for 84±34 days. The mean age at the time of device insertion was 65.3±13.0 years. AF episodes (n=657) were detected in 91 patients, resulting in an AF detection rate of 9.22% at 120 days (Figure) which was 15% higher than CRYSTAL AF at the same time-point. The median duration of the longest detected AF episode was 3.9 [IQR 1.0-11.5] hours.

Conclusions:
AF episodes of clinically important durations were detected via continuous monitoring with ICMs in a significant proportion of cryptogenic stroke patients, despite relatively brief follow-up thus far. The real-world incidence of AF among patients being monitored with an ICM after a cryptogenic stroke appears to validate a recent randomized controlled trial and may be slightly higher when adjusted for the duration of follow-up, possibly due to differences in the rigor of the stroke work-up or inclusion/exclusion criteria.
Abstract 211: Socioeconomic and Patient Factors Associated with Pre-stroke Treatment of Hypertension
Authors: Chatterjee Pia , Roberts Eric T , Boden-Albala Bernadette
Published: March 2022

Background:
Identifying high risk populations for stroke that are not receiving treatment for hypertension can help improve targeted care. Hypertension is the major modifiable risk factor for stroke. Treatment of hypertension is mainstay of primary and secondary stroke prevention and is usually conducted by physicians in primary care settings. New York City has private and public health systems that theoretically make access to hypertension treatment available to its citizens regardless of socioeconomic status and insurance status.

Objective:
To determine if socioeconomic or other patient factors may be associated with pre-stroke treatment of hypertension.

Methods:
This cross sectional analysis used data from SWIFT (Stroke Warning Information and Faster Treatment), a prospective population-based ethnically diverse stroke preparedness cohort of ischemic stroke/TIA survivors. The study population of untreated hypertension (UHTN) was defined as SBP ≥ 140 mmHg, DBP ≥ 90, and no history of hypertension prior to event. Regression models examined relationship between UHTN and race/ethnicity, gender, age, level of education, nativity, primary care visits, native languages, and insurance status.

Results:
Among 1193 stroke/TIA patients, 809 had hypertension and of that group, 94 (11.6%) were undiagnosed prior to the index event. Bivariate and logistic regression models for race, gender, age, language, education, nativity do not explain differences in pre-stroke treatment of hypertension. In the full model, patients without health insurance (2.29, 95% C.I. 1.29, 4.13) and those with less than 1 visit per year to a primary care physician were (2.94, 95% C.I. 1.86, 4.65) were significantly associated with untreated hypertension.

Conclusion:
Alternate strategies that do not rely on primary care may be necessary to reach patients without insurance or primary care physicians to treat hypertension prior to stroke. Future studies should investigate other screening opportunities such as health fairs, emergency department visits, or workplace screening.
Abstract 214: Risk and Risk Factors of Perioperative Myocardial Infarction After Carotid Endarterectomy and Carotid Angioplasty and Stenting: Systematic Review and Meta-analysis
Authors: Boulanger Marion , Cameliere Lucie , Trinquart Ludovic , Rerkasem Kittipan , Berger Ludovic , Kazémi Apolline , Rothwell Peter M , Touzé Emmanuel
Published: March 2022

Background and purpose:
Carotid Angioplasty and Stenting (CAS) is associated with higher risk of periprocedural stroke and death compared with carotid endarterectomy (CEA). By contrast, the risk of myocardial infarction (MI) was higher after CEA than after CAS in randomized trials. However, numbers were small and risk factors are unknown. We therefore aimed to estimate the 30-day absolute risk of periprocedural MI after CAS and CEA and to determine which subgroups are at higher risks.

Methods:
We performed a systematic review and a meta-analysis of studies published from 01/1980 to 06/2014 and also collected unpublished data. We selected observational and randomized studies with data available on MI in at least one subgroup. We calculated pooled absolute and relative risks and identified differential effects on risks of MI (CAS vs CEA) with interaction tests using meta-regressions.

Results:
The 30-day absolute risk of MI after CEA was 0.82% (95%CI, 0.67-0.99; 66 studies, 75191 patients) and 0.64% (95%CI, 0.50-0.79; 76 studies, 40431 patients) after CAS (Pint=0.08). Risk of MI has slightly decreased over time in CAS studies but has not changed in CEA studies (Pint=0.14). After CAS, patients with symptomatic stenosis, restenosis were at higher risk of MI whereas males were at lower risk (figure). After CEA, age, history of coronary artery disease, peripheral artery disease, and restenosis increased the risk of MI. Only the effect of gender differed between CAS and CEA with males being at lower risk of MI than females after CAS whereas there was no difference between after CEA (Pint=0.01).

Conclusion:
The risk of MI is slightly higher after CEA than after CAS. Risk factors for periprocedural MI are overall very similar in both techniques except that males are at lower risk of MI after CAS but not after CEA (p int=0.01).
Abstract 22: Usefulness of P wave-triggered Signal-averaged Electrocardiogram for the Estimation of Paroxysmal Atrial Fibrillation Risk in Cryptogenic Stroke
Authors: Rha Joung-ho , Park Jeong-Jin , Ahn Jong-Hyun , Choi Jun-Yong , Lee Eung-Seok , Yoon Cindy , Park Hee-Kwon
Published: March 2022

Backgrounds:
Detection of atrial fibrillation(AF) is important especially in cryptogenic stroke. The P wave-triggered signal-averaged electrocardiogram(signal ECG) is useful method for identifying paroxysmal AF risk. However, signal ECG study in stroke patients remains limited. We investigated the role of signal ECG in stroke patients by comparison between cryptogenic stroke and stroke with determined etiology.

Methods:
We prospectively recruited the acute ischemic stroke patients who admitted from June to September 2012, and underwent routine work up and signal ECG. Patients with known AF at the time of study were excluded. In signal ECG, P wave duration(PWD) and root mean square voltages for the last 20ms (RMS20) were measured. The criteria of RMS20≤3.5μV and PWD>120ms was defined as atrial late potential. We analyzed the difference in signal ECG between the patients with cryptogenic infarct and those with known stroke etiology.

Results:
A total of 160 subjects were enrolled. Patients with cryptogenic stroke (n=66) had significantly longer PWD (140±16ms) and lower RMS20 (2.50±1.91μV) compared to the subjects with known etiology (n=94; PWD 123±17ms, RMS20 3.36±2.11μV; P<0.01, respectively). Also the cryptogenic stroke patients showed more frequent atrial late potential than the other patients (80% vs 43%, P<0.01). The atrial late potential group (n=84) was more likely to have stroke involving right insular cortex (16%) than the other group (6%, p=0.05). During follow-up period of 1 & 1/2 year, AF newly appeared in 9.7% in the atrial late potential group and 4.5% in the others.

Conclusion:
Our results suggest that the signal ECG could be a useful tool for screening the stroke patient with the risk of paroxysmal AF. Prolonged monitoring is required in the patients with atrial late potential in the signal ECG.
Abstract 220: Contralateral Myogenic Dysfunction Contributes to Stroke Outcomes after Acute Hyperglycemic Stroke
Authors: Coucha Maha , Li Weiguo , Hafez Sherif , Abdelsaid Mohammed , Johnson Maribeth H , Fagan Susan C , Ergul Adviye
Published: March 2022

Background:
Admission hyperglycemia (HG) amplifies vascular injury and neurological deficit in acute ischemic stroke but the mechanism remains controversial. We recently reported that copper/zinc-superoxide dismutase (SOD1) overexpression preserves the myogenic tone of ischemic arteries, achieving neurovascular protection after ischemia/reperfusion (I/R) with or without HG. Experimental studies showed that I/R impairs myogenic response in ischemic and contralateral hemispheres. However, the impact of HG on contralateral vascular reactivity and its role in stroke outcomes still unexplored. Hypothesis: Contralateral myogenic dysfunction worsens stroke outcomes after acute hyperglycemic stroke. Methods: SOD1 adenovirus or an empty vector was stereotaxicly injected in the contralateral hemisphere of control Wistar rats. 2-3 weeks after injection, acute hyperglycemic stroke was induced by injecting saline or 40% glucose solution 10 min before 30 min ischemia/45 min or 24 hr reperfusion. Myogenic tone and neurovascular outcomes were determined. Results: HG exacerbated loss of myogenic tone in contralateral side only (p<0.0001), which was associated with infarct size expansion, increased edema (p<0.05) and more pronounced neurological deficit (p<0.01). Contralateral SOD1 overexpression restored myogenic reactivity in contralateral side only. Cerebral blood flow after reperfusion was increased in both sides (p<0.01), which was accompanied with better neurovascular outcomes (p<0.01). Conclusion: Our results showed that SOD1 overexpression nullified the detrimental effects of HG on contralateral myogenic dysfunction and stroke outcomes, and that contralateral hemisphere may be a novel target for the management of acute hyperglycemic stroke.
Abstract 222: Serum Adiponectin Level and Incident Dementia in Patients with Vascular Risk Factors - Sub-analysis of OSACA2 Follow-up Study
Authors: Kitagawa Kazuo , Miwa Kaori , Sakaguchi Manabu , Yagita Yoshiki , Mochizuki Hideki
Published: March 2022

Background and Purpose:
Involvement of metabolic factors on dementia development has received much attention. However, several previous studies have yield contradictory results for the involvement of blood adipocytokine levels on cognitive decline and dementia. The aim of this study is to clarify whether serum adiponectin level is related to incident dementia in patients with vascular risk factors.

Methods:
OSACA2 is a prospective cohort study for cardiovascular events and dementia in which patients with vascular risk factors undergo carotid ultrasound and blood sampling. Between 2001 and 2009, 1106 outpatients were enrolled. Among them, 466 patients who underwent brain MRI and had normal cognitive function were included in this study. High molecular weight adiponectin level was measured with frozen serum. Follow-up data for dementia occurrence were collected in June 2013.

Results:
Among 466 subjects (mean: 67.8 years), serum adiponectin level was 4.33 + 2.95 μg/mL. Adiponectin level was lower in male than in female, and positively associated with body mass index. During the follow-up period of median 6.9 years, 47 patients had incident dementia (27 AD, 17 vascular dementia, 3 others). Age, baseline MMSE, eGFR and the presence of lacunar infarction were related to incident dementia. No difference in adiponectin level was found between patients with and without incident dementia (4.31+3.07 vs. 4.33+2.94 μg/mL). The survival analyses for dementia-free rate curves, determined with respect to median level of adiponectin, are shown in Figure. Risk of incident dementia in patients with high and low adiponectin levels were almost similar (Log-rank test: p = 0.868). Risk of AD and vascular dementia were also similar between two groups.

Conclusion:
This study suggested that serum adiponectin level have little association with future dementia. The impact of metabolic factors on dementia would need to be evaluated not by adiponectin level but other biomarkers or parameters.
Abstract 24: Race/Ethnic Differences in Microbleed Characteristics and Association of Microbleeds with Poor Outcomes in the ERICH Study
Authors: Kidwell Chelsea S , Norato Gina , Osborne Jennifer , Rosand Jonathan , Elkind Mitchell S , James Michael L , Flaherty Matthew , Worrall Bradford B , Vashkevich Anastasia , Langefeld Carl D , Moomaw Charles J , Woo Daniel
Published: March 2022

Background:
Microbleeds have been reported in up to 60% of patients with primary intracerebral hemorrhage (ICH) and are an important marker of a progressive, small vessel cerebral vasculopathy. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study explored the characteristics of microbleeds and their impact on long-term functional outcome.

Methods:
ERICH is a multi-center prospective study designed to recruit white, black, and Hispanic cases of ICH. At least every 5th ICH patient enrolled undergoes an MRI. All MRIs are interpreted by a core laboratory blinded to clinical data.

Results:
Among 642 patients with a gradient echo (GRE) sequence, 49% had ≥1 microbleeds (mean 13, median 4). Blacks had the highest rate of microbleeds at 54% compared to 48% for Hispanics, and 42% for whites (overall p=0.046; blacks vs. white p=0.018). There was a significant racial/ethnic difference in the overall rate of microbleeds in lobar locations (79% in whites, 73.5% in blacks, 61% in Hispanics, p<0.0001). A multivariable logistic regression model predicting the presence of microbleeds included hypertension (OR=1.62, p=0.037), severity of white matter disease (12 point scale, 1 point OR=1.36, p<0.0001), elevated white blood cell count (10
3
/μL OR=1.06, p=0.012), and race/ethnicity (overall p value 0.111; compared to white, black OR=1.53, p=0.056; Hispanic OR=1.49, p=0.078). The presence of microbleeds was associated with poor outcome (6 month mRS 4-6, OR=2.21, p=0.001) in a logistic regression analysis that included ICH volume (1 cc OR=1.04, p<0.001), Glasgow Coma Scale score (OR=0.82, p<0.001), intraventricular hemorrhage (OR=1.98, p=0.003), and age (5 year OR=1.21, p<0.001).

Conclusions:
This study demonstrates substantial differences in microbleed rates across race/ethnicities. This is the first study to report an intermediate microbleed rate among Hispanics relative to white and black ICH cases. In addition to hypertension and leukoaraiosis, our model suggests that inflammation may be an important factor contributing to microbleeds. As a biomarker of progressive vasculopathy and poor outcome, microbleeds may provide a valuable surrogate measure in future studies of therapies targeting optimal approaches to risk factor control.
Abstract 35: B-cell Mediated Recovery of Motor Function in a Murine Model of Stroke
Authors: Noorbhai Ibrahim , Ortega Sterling , Selvaraj Uma Maheswari , Monson Nancy , Plautz Erik , Goldberg Mark , Stowe Ann
Published: March 2022

Background:
Increasing evidence shows a link between the central nervous system and the immune system in mediating damage, as well as regeneration and repair, following stroke, though most studies focus on T-cell-mediated pathology. While previous work links the B-cell secretion of IL-10 with acute neuroprotection following experimental stroke (PMID: 24374817), the role of B cells in long-term functional recovery is unknown.

Hypothesis:
The purpose of this study was to assess the protective role of B-cells in improving post-stroke motor function in B-cell deficient mice.

Materials and Methods:
Adult male transgenic mice expressing human CD20+ (hCD20+) or wild-type (WT) littermate controls (PMID: 17709552) were trained on rotorod for a 2 week duration. Following training, all mice were administered Rituximab (50g ip; PMID: 21359213) daily for 3 days and weekly thereafter. Stroke was induced by a 60-min transient middle cerebral artery occlusion (tMCAo). Post-stroke functional recovery was evaluated 2, 4, 7 and 14 days post-tMCAo. Lymphocytes were isolated from spleen 2 weeks post-tMCAo, stained with antibodies, profiled on a FACS Canto flow cytometer, and analyzed with FlowJo.

Results:
WT mice recovered to near pre-stroke rotorod performance by 4 days post-tMCAo. In contrast, hCD20+ mice exhibited deficits through 7 days (p<0.05). We confirmed that Rituximab depleted CD20+ B-cells (p<0.05) in the spleen of hCD20+ mice. This post-stroke B-cell depletion reduced CD45+ (p<0.0001) populations, as well as pro-inflammatory CD11b+ macrophage populations (p<0.01). Overall, B-cell depletion increased splenic T-cell percent representation (p<0.001), while decreasing monocyte (p<0.0005) and macrophage (p<0.0001) representation.

Conclusions:
B-cell depletion in hCD20+ mice prolonged motor deficits in rotorod performance beyond WT mice. B-cell depletion also enhanced a post-stroke immunosuppression of splenic immune cell populations. These data suggest a potential role for B-cells as a therapeutic tool to enhance functional recovery, and counter potentially detrimental post-stroke immunosuppression that contributes to comorbidity during recovery.
Abstract 36: Hormone Replacement Therapy Increases The Risk Of Subarachnoid Hemorrhage In Post Menopausal Women
Authors: Saeed Omar , Malik Ahmed A , Qureshi Adnan I
Published: March 2022

Background:
The incidence of subarachnoid hemorrhage (SAH) increases after menopause and anecdotal data suggest that hormone replacement therapy (HRT) may reduce the rate of SAH and aneurysm formation in women.

Objective:
To determine the effect of HRT on occurrence of SAH in a large cohort of women.

Methods:
We analyzed the data for 93,676 women aged 50-79 years who were enrolled in the observational arm of the Women's Health Initiative Study. We determined the effect of HRT on risk of SAH over a mean period (±SD) of 12±1 years using Cox Proportional Hazards analysis after adjusting for potential confounders. We performed additional analysis to identify the risk associated with “estrogen only” and “estrogen and progesterone” HRT among women.

Results:
A total of 114 (0.1%) of the 93676 participants developed SAH during the follow-up period. The rate of SAH was higher among women on HRT compared with those without HRT (0.14% versus 0.11%, p= <.0001). The rate was non significantly higher with “estrogen only” (32.5%) compared with “estrogen and progesterone” (18.4%, p=0.2) among women. The risk of SAH was higher among women on HRT compared to those without HRT (relative risk [RR] 1.5, 95% confidence interval [CI] 1.0_2.2) after adjusting for age, systolic blood pressure, and active cigarette smoking. The risk of SAH was higher among women on “estrogen only” HRT (RR 1.5 95% CI 1.0_2.2) and “estrogen and progesterone” HRT (RR 1.1, 95% CI 0.7_1.8).

Conclusions:
Post menopausal women, particularly those at risk for SAH due to presence of unruptured aneurysms, family history, or cardiovascular risk factors, should be counseled against use of HRT.
Abstract 43: Cortical Structure Alterations in Cerebral Amyloid Angiopathy
Authors: Fotiadis Panagiotis , Martinez-Ramirez Sergi , Reijmer Yael , Ayres Alison , Schwab Kristin , Rosand Jonathan , Viswanathan Anand , Greenberg Steven M , Gurol M. Edip
Published: March 2022

Background/Objective:
Multiple lines of evidence suggest that Cerebral Amyloid Angiopathy (CAA) leads to ischemic subcortical tissue injury, but its relationship to cortical changes is unknown. We tested the hypothesis that CAA is associated with cortical tissue loss.

Methods:
Three age-matched cohorts of 63 subjects each (non-demented patients with probable CAA, Healthy Controls [HC] and patients with Alzheimer’s Disease [AD], the latter two from AD Neuroimaging Initiative) underwent multimodal MRI. FreeSurfer was used to calculate cortical thickness, white matter hyperintensity (WMH), and hippocampal volumes (HV). In patients with intracerebral hemorrhage, the measures were obtained from the contralateral hemisphere, and all were corrected for intracranial volume. CAA patients also had functional MRI to calculate Blood-Oxygen-Level-Dependent Time-to-Peak (BOLD-TTP), a measure of vascular reactivity. Lobar microbleeds (LMB) were counted on SWI.

Results:
The mean age of each cohort was 72±5. CAA patients had thinner cortices compared to HC (2.17±0.11 vs 2.31±0.07 in mm, p<0.001), especially in the occipital, temporal, posterior parietal, and medial frontal regions [Figure]. Patients with AD had significantly thinner cortices than both CAA and HC (2.1±0.14, p<0.01 for both comparisons, also see Figure). Similarly, HV was lower in CAA than controls but both CAA and HC had higher HV than AD (p<0.01 for all comparisons). The number of LMBs and WMH did not correlate with cortical measures in CAA (p>0.2). There was a significant negative correlation (r=-0.4) between BOLD-TTP delay and cortical thickness (p=0.005 after adjustment for covariates).

Conclusions:
Cortical thickness of CAA patients is significantly reduced when compared to age-matched HC but higher than in AD. Analyses within the CAA cohort suggest that CAA-related vascular dysfunction might contribute to cortical atrophy.
Abstract 53: Multimodal CT Imaging: Time to Treatment and Outcomes in the Interventional Management of Stroke (IMS) III Trial
Authors: Vagal Achala , Foster Lydia , Menon Bijoy , Livorine Anthony , Shi Junzi , Qazi Emmad , Demchuk Andrew , Yeatts Sharon , Hill Michael , Tomsick Thomas , Goyal Mayank
Published: March 2022

Introduction:
The importance of time in acute stroke is well established. Using the Interventional Management of Stroke (IMS) III trial data, we explored the effect of imaging on time to treatment and outcomes for subjects those receiving multimodal imaging [CT angiogram (CTA) + CT perfusion (CTP) versus CTA alone] versus those who did not.

Materials and Methods:
Multimodal CT was not a prerequisite for IMS III entry .We examined 3 subgroups; those with baseline CTA alone, CTA + CTP, versus those with no CTA or CTP. The baseline demographics and imaging and treatment time parameters of these 3 subgroups were studied.

Results:
Of the 656 subjects enrolled, 98 (14.9%) underwent baseline (pre-IV t-PA treatment) CTA+CTP. 8 out of these 98 patients received only CTP. 216 (32.9%) received CTA alone and 342 (52.1%) had neither.

Time parameters for the CTA+CTP, CTA alone, and no CTA/CTP groups were as follows: median from stroke onset to IV t-PA (120.5 vs. 117.5 vs 120 min; p=0.5869), median IV t-PA bolus to groin puncture (GP) (78 vs. 81 vs. 91 min; p=0.0043) and median GP to start of endovascular therapy (EVT) (31 vs. 38 vs. 44 min; p=0.0001). Pairwise comparison demonstrated no significant difference in time from IV tPA to GP and time from GP to IA therapy between CTA+CTP and CTA alone groups (p=0. 9883 and p=0.1421, respectively). With removal of drip n’ ship subjects, no statistical differences were seen between groups for time from onset to IV t-PA bolus (p=0.5509) or time from imaging to GP (p=0.8459). Time from GP to start of EVT was still shorter in the CTA+CTP and CTA alone paradigms (p =0.0019).

In the IV t-PA treatment arm, no differences in 90d mRS 0-2 outcome were seen in the 3 subgroups (36.4% versus 40.9% versus 38.2%; p=0.8941). In the EVT arm, differences in good outcome were seen (38.5% versus 52.0% versus 33.8%; p=0.0020). CTA alone remained strongly associated with good outcomes in EVT arm (adjusted OR, 2.117; 95% CI, 1.35- 3.30), irrespective of age, stroke severity and time from onset to IV tPA initiation.

Conclusion:
Multimodal imaging did not delay treatment times in IMS III. The CTA alone group was associated with favorable clinical outcomes in the endovascular arm. The CTA+CTP paradigm resulted in worse outcome over the CTA alone paradigm in the endovascular arm.
Abstract 55: Automated, Real-Time, Electronic Health-Record Initiated Alerts Expedite Study Team Notification of Potentially Eligible Subjects for an Acute Stroke Trial
Authors: Meurer William J , Fansler Amy , Jennings Kathleen , Lyman Jason , Barsan William G , Johnston Karen
Published: March 2022

Introduction:
Patients must be quickly identified to be eligible for enrollment in acute stroke studies. Clinical providers are often too busy with patient care to be responsible for identification of study patients. Electronic health records quickly incorporate a wealth of data, including laboratory results, into patient level records and can be used to potentially identify subjects in real-time. Our objective was to describe the implementation and performance of an automated screening tool for an acute stroke trial.

Methods:
The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial (http://www.nett.umich.edu/nett/shine) is an ongoing NIH funded, multicenter, acute stroke trial. Two health systems that use EPIC electronic health record (EHR) developed automated screening (AS) alerts that notify the study team when potentially eligible patients meet the basic criteria for the study in real time. The procedures used are summarized in the figure. Our primary outcome measure was the number of alerts per month at each site.

Results:
From January 2014 through July 2014, a total of 331 patients (UM:259, UVA:72) were identified using AS algorithms; UM: 47.7, UVA: 10.3 per month. A total of 10 patients were eligible (UM:2, UVA:8) during this time period. Both UM patients were identified by the AS alert, along with four at UVA (transfers from other hospitals not captured)..

Conclusions:
While automated screening for acute stroke trials using the electronic health record is feasible, we found substantial implementation issues at two sites. At one site, less than 1% of alerts were for eligible patients and at the other site, half of actual eligible patients were missed. Despite challenges, the systems were useful to the research teams and helped study coordinators taking call from home identify cases which would be the highest yield to travel to the hospital to screen. EHR based acute stroke screening tools for research have both promise and a need for further refinement.
Abstract 64: Utilization of Best Practice Guidelines and Multidisciplinary Work Flow Analysis to Improve System Wide Post-Cerebral Angiogram Assessment
Authors: Johnson Vicki , van Groos Kimberly
Published: March 2022

Background:
as a Joint Commission (TJC) certified Comprehensive Stroke Center (CSC), we managed a total of 797 cerebral angiogram cases over the last 15 months. During a TJC survey site visit, inconsistencies between post-angiography nursing hand-offs and documentation of assessments were identified. As a result, a large scale process improvement initiative was organized by a team of Stroke Nurse Practitioners. Objectives: The key objective was to improve the post-angiography hand off and assessment performance to > 90%; Complete a work flow analysis of this process and define critical barriers; Compare existing practice to best practice guideline and develop, implement, and evaluate a comprehensive PI plan. Methods: Search of common electronic databases and guidelines to identify post-cerebral angiography complications and evidence based guidelines for post-procedure nursing assessment and transition; Auditing of 100% of the cerebral angiogram cases during the defined time period. Survey of practice policies utilized by other certified CSCs and GWTG sponsored CSC collaborative networking activities; Coordinated development of an EMR based abstraction program for data capture and designed a desktop analysis tools. Results: TJC compliance standard of > 90% performance was demonstrated and sustained. Multiple barriers were identified which lead to the development of targeted interventions associated with nursing practice and policies, electronic order sets that highlighted inconsistency in post-procedure orders and discrepancies in knowledge and practice among nurses. The most crucial intervention proved to be standardization of the cerebral angiogram order sets resulting in an almost immediate 14% improvement. Conclusion: This clinical application project validated the importance of standardizing care practices, pathways, documentation, training and tools to sustain a system wide improvement in post-angiography assessment. The project also demonstrated the value added role of a team of specialized advance practice nurse practitioners and clinical specialists in leading multidisciplinary stroke practice change.
Abstract 67: Using Patient Activation to Transition Patients from Hospital to Home
Authors: McLaughlin Davis Mary
Published: March 2022

Background:
The community hospital as a part of a large health care system participates in the Ohio Coverdell Stroke Program. The Coverdell Goals are to improve the quality of patients’ care transitions, reduce avoidable complications, and support the reduction of patients’ unnecessary readmissions. The purpose of the project was to evaluate if the tools, Patient Activation Assessment (PAA), Personal Health Record (PHR), and the Patient Activation Measure (PAM) improve transitions from the Inpatient Rehabilitation Facility (IRF) to home, without patients experiencing an unnecessary readmission. The nurse used the tools to teach patients stroke fundamentals and self-management strategies.

Methods:
The population consisted of all stroke patients discharged home from the IRF over twelve months (n=177). The intervention was patient stroke education based on the PAM and the PAA scores while utilizing the PHR. The nurse taught stroke fundamentals within the structure of the PAA four pillars directed to the patient and the care advocate.

Results:
The project goal to transition stroke patients safely from the IRF to home with a decrease in unnecessary readmissions was met. The patients in the project experienced a 50% decrease in readmissions in less than thirty days from patients discharged the previous year (n=172). The team compared stroke patients' PAM and PAA scores prior to discharge instruction, after instruction, and then prior to discharge to home with a significant improvement in the PAA scores P < 0.005. Patients with a PAA score of 7 and above were discharged to home. Similarly patients with a PAM of 40 and above were discharged home.

Conclusions:
The initial three month phase of the project demonstrated an improvement in the PAM and PAA scores. There was a trend of increased patients’ activation scores related to discharge disposition, and a decrease in readmission rates. Therefore the use of the PAM, PAA, and PHR was incorporated into the IRF nursing practice for all stroke patients. The nurses focus their stroke teaching on patients with lower activation scores with the goal of increasing the scores and improving patients’ ability to return home and avoid an unnecessary readmission. The results over one year mirror the original three month pilot project.
Abstract 75: Sex Differences in the Renin-angiotensin System In Middle Aged Adults at Risk for Stroke
Authors: Bushnell Cheryl , Evans Gregory , Diz Debra , Brosnihan K Bridget
Published: March 2022

Background/Objective:
Angiotensinogen is the substrate for renin, which then converts angiotensinogen to angiotensin I. Sex differences in multiple components of the renin angiotensin system (RAS) have been described. We examined sex differences in angiotensinogen (Aogen) and renin activity in middle aged men and women at risk for stroke, accounting for sex hormone binding globulin and use of RAS-influencing drugs.

Methods:
The Sex Age and Variation in Vascular functionalitY (SAVVY) study measured sex differences in subclinical vascular disease and biomarkers in men and women aged 45 to 64 with at least one stroke risk factor, but free of cardiovascular events using a cross-sectional design. Women were oversampled to assess pre- and post-menopausal time points. Aogen, renin activity, and sex hormone binding globulin (SHBG) were performed using commercial ELISAs/RIAs. We compared biomarker levels by sex using parametric statistical tests, and multiple linear regression models were developed to determine if sex, SHBG, and other RAS-related factors were associated with Aogen level and renin activity.

Results:
In total, 113 subjects (78 women, 35 men) were included. Men (mean 55 y; std 5.3 y) and women (56.6 y; std 5.8 y) were similar in age; Black race (9% in men and 14% in women) and risk factors: hypertension (men 63% vs. women 58%), diabetes (20% vs 18%), hyperlipidemia (80% vs. 76%), and smoking (6% vs. 10%). Systolic and diastolic blood pressures were similar. Women had significantly higher levels of Aogen (mean 35,123 ng/ml; std 12,557) than men (mean 26,601 ng/ml; std 4578; p<.0001), whereas men had higher renin activity (median 2.4 ng/ml/hr; IQR 0.9, 5.0) vs women (median 1.0; IQR 0.6, 2.6; p=0.058). Multiple regression modeling showed that Aogen levels were positively associated with female sex (p=0.018) and SHBG levels (p<.001) after adjustment for hypertension, and concurrent ACE-I/ ARB use. Renin levels were associated with ARB (p=0.008) and ACE-I (p=0.001) use but not sex (p=0.103).

Conclusions:
Aogen, but not renin, is influenced by female sex after accounting for SHBG, hypertension, and use of RAS-influencing drugs. This suggests that potentially different mechanisms may contribute to the identified risk factors for stroke in men and women.
Abstract 85: The Important Role of Drip and Ship Administration in Expanded Use of Thrombolytic Therapy in the United States
Authors: Sheth Kevin N , Smith Eric E , Grau-Sepulveda Maria V , Kleindorfer Dawn , Fonarow Gregg C , Schwamm Lee H
Published: March 2022

Introduction:
Interhospital transfer after use of IV tissue plasminogen activator (tPA) in acute stroke (“drip and ship”) may be increasing, but there are limited data on national trends.

Methods:
We analyzed data from 44,667 patients with ischemic stroke treated with IV tPA <3 hours of symptom onset in the Get With The Guidelines-Stroke Program from 2003-2010 in 1440 hospitals. The main outcomes were the frequency of “drip and ship” tPA use over time. Patient and hospital-level characteristics including bed size, geographic region, academic status, ischemic stroke volume, and Joint Commission primary stroke center certification (PSC) were collected.

Results:
Amongst 44,667 tPA patients, drip and ship was a common method (n=10,475; 23.5%). The median age was 72 years, 49% were women, 12% were Black and 5% Hispanic. The percentage of all tPA eligible patients treated via drip and ship increased during the study period (4.0% to 7.6%, p<.0001) (Figure 1). Compared to front door patients, drip and ship patients were younger, more often male, and more often white. Drip and ship patients were more likely to arrive off hours (outside of Monday-Friday, 7 AM-5 PM) (71% vs 53%, p<.0001). Hospitals that received drip and patients, compared to hospitals with predominantly front door patients, had more beds (488 vs 385, p<.0001), were more likely to be an academic medical center (81% vs 61%, p<.0001), have a higher volume of annual ischemic stroke cases (273 vs 206, p < .0001) and more likely be PSC (70% vs 63%, p<.0001). As a proportion, drip and ship hospitals were more common in the Midwest.

Discussion:
In the largest study of its kind to date, these results show that the drip and ship method of intravenous tPA treatment accounts for one out of every four acute ischemic stroke patients treated with tPA in GWTG hospitals. These results suggest that drip and ship is an important strategy to bring the benefits of tPA treatment to patients.
Abstract NS11: Missed Opportunities: Closing the Loop
Authors: Burns Jo-Ann , Donelly Rose , Thomas Calvin , Shoemake Anne
Published: March 2022

In a Comprehensive Stroke Center, which admits 1200-1300 stroke patients annually, patients are leaving sooner due to many factors, including insurance and financial constraints. Many patients are admitted over the weekend and holidays and 15 to 20 % of all patients are admitted to a non-neurological floor, which resulted in no stroke education being completed. Some patients were not identified as strokes until the day of discharge, also resulting in no stroke education.

The purpose of this project was to ensure all patients discharged received comprehensive stroke education and that regardless of where the patient was in the facility, education was completed either during the hospitalization or post discharge.

A lean evaluation was performed to identify successes and missed opportunities. As a result, several initiatives were implemented. Tip sheets were designed outlining step by step the stroke education that is required and also included the stroke coordinators contact information. This was disseminated throughout the entire facility. Special float pool and float pool nurses were given stroke education, as they staff all through the facility. Stroke Coordinators review all stroke admissions every day and identify those who did not receive the required education, and then phone contact is made. Stroke education is reviewed in depth and stroke materials are mailed out to the patient. In the event the patient is unavailable, this education is done with a family member/significant other. This process is followed regardless of the patient’s discharge disposition.

In conclusion, our 7 day phone follow up post discharge indicated that the satisfaction with stroke education went from 40% to 95% within a 6 month period. The missed opportunities dropped from an average of 20 a month to 0, especially with the follow up by the Stroke Coordinators to ensure that stroke education was completed.