bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract T P154: Association of Common Variants in Immune Response Genes with Severity of Familial Cerebral Cavernous Malformation Type 1
Authors: Choquet Hélène , Nelson Jeffrey , Pawlikowska Ludmila , McCulloch Charles E. , Akers Amy , Baca Beth , Khan Yasir , Hart Blaine , Morrison Leslie , Kim Helen
Published: July 2021

Objective:
Familial Cerebral Cavernous Malformation type 1 (fCCM1) is an autosomal dominant disease caused by
KRIT1
mutations and characterized by brain lesions, which increase in number over time for unknown reasons. Inflammation and altered expression of immune response genes have been observed in human CCM lesions. We investigated whether common variants in immune response genes are associated with fCCM1 disease severity, as manifested by greater lesion burden.

Methods:
Lesion burden was assessed on susceptibility-weighted MR imaging for 178 fCCM1 subjects, all carriers of the founder common Hispanic mutation (CHM, Q455X in
KRIT1
) and recruited as part of the Brain Vascular Malformation Consortium study. We selected 321 variants in 12 immune response genes up-regulated in human CCM lesions and represented on the Affymetrix Axiom® Genome-Wide LAT-1 Human Array. Linear regression analyses under an additive model were performed to assess association of genotype with log-lesion burden residuals, after adjustment for age at enrollment and gender.
P
-values were generated using 100,000 permutations to account for family structure and multiple testing.

Results:
Lesion burden (range: 0-713; mean ± SD: 60.5 ± 116.3) was highly variable. The minor alleles at rs2272022 (
CD200
), rs75223220 (
CD68
), rs57767447 and rs12587347 (
IGH
), and rs13053345 (
IGL
) were associated with more lesions (≥32%,
P
<0.05) at baseline, independent of age and gender. The minor alleles at rs7639471 (
CD200
), rs9901675 (
CD68
), rs5759959 (
GUSP11
), rs10147756 and rs7144404 (
IGH
), and rs987710 (
IGL
) were associated with fewer lesions (≤45%,
P
<0.05). Variants in
CD247
,
CD3G
,
HLA-DRB1
,
IGJ
,
LOC390714
,
MS4A1
and
SDC1
were not significantly associated with lesion burden.

Conclusions:
Several common variants in immune response genes are associated with lesion burden in fCCM1-CHM subjects. Further studies are needed to confirm whether
CD200, CD68, GUSP11, IGH
and
IGL
genes influence fCCM1 disease severity.
Abstract T P159: Cardiovascular Health and Subsequent Cognitive Function in Patients with Pre-existing Coronary Heart Disease.
Authors: Tanne David , Weinstein Galit , Molshatzki Noa , Goldbourt Uri
Published: July 2021

Background:
Cardiovascular (CV) health factors are associated with lower risk of CV disease, stroke and all-cause mortality. We used a CV health metric in order to examine association with subsequent cognitive function.

Methods:
A subset of patients with coronary heart disease (CHD) that participated in the secondary prevention BIP trial were assessed for cognitive function (Mindstream Computerized Cognitive Battery) after an average of 9.8 ±1.7 years. A CV health metric at baseline was calculated including 3 health factors (glucose, LDL cholesterol, and blood pressure), 4 health behaviors (BMI, physical activity, adherence to a Mediterranean diet, and cigarette smoking), and one marker assessing in-part early life environment (body height), categorizing each of these 8 factors into ideal (2 points), intermediate (1 point), and poor levels (0 points).

Results:
Among 310 patients (mean age 62 yrs, 96.5% men) higher CV health scores were positively associated with educational level (p<0.001) and inversely with age (p=0.003), while no significant associations were identified with ultrasound indices of cerebrovascular disease (impaired CVR, increased common carotid IMT and carotid plaques). In linear regression models adjusted for age, educational level, sex and BIP study arm, increment in the overall CV health score (per 1 point) was associated with higher scores in executive function (p=0.002), memory (p=0.06), visuospatial function (p=0.005), attention (p=0.024) as well as in a global cognitive function score [B coefficient ± SE, 1.19±0.35 (p=0.001)] assessed a decade later. Increment (per 1-point) in the health behavior component was associated with 1.28±0.49 (p=0.009) higher cognitive score, in the early life environment component with 2.55±0.75 (p=0.001) higher cognitive score, while the health factors component was not associated with subsequent cognitive scores [0.24±0.52 (p=0.64)]. In sensitivity analyses excluding patients with stroke similar findings were observed.

Conclusion:
Among patients with pre-existing CHD, better CV health is associated with subsequent higher cognitive functions. Our findings suggest that health behavior and early life environment are important determinants of late-life cognitive function.
Abstract T P160: Are Severity and Outcome of Ischemic Stroke With Paroxysmal Atrial Fiblliration Different From Those With Chronic Atrial Fibrillation?
Authors: Miura Seiji , Yasaka Masahiro , Maeda Koichiro , Uwatoko Takeshi , Kuwashiro Takahiro , Wakugawa Yoshiyuki , Okada Yasushi
Published: July 2021

Background and Purpose:
Previous studies indicated that incidence of ischemic stroke did not differ between patients with paroxysmal atrial fibrillation (PAF) and those with chronic atrial fibrillation (CAF). However, it has been under dispute whether severity and outcome of ischemic stroke in patients with PAF differ from those with CAF. Then, we compared them between ischemic stroke patients with PAF and those with CAF.

Methods:
We obtained data from the medical records of 372 consecutive patients admitted to our hospital, who had acute ischemic stroke with atrial fibrillation, from January, 2008, to December, 2012.We compared neurological severities (NIH stroke scale scores) on admission and discharge, functional outcome evaluated by modified Rankin scale, (mRS) on discharge between patients with PAF and those with CAF.

Results:
Of 372 patients, 123 patients had PAF (men 62.6%, 78.0 +- 10.0 years old) and 249 patients (men 62.1%, 77.9 +- 9.5 years old) had CAF. There were no significant differences in NIH stroke scale on admission between the PAF group (media 5 with IQR 2-14) and the CAF group (6, 2-16)(P=0.2772). NIH stroke scale scores (1, 0-8.75, vs. 2, 0-10, p=0.1549) and mRS(2, 1-4, vs. 3, 1-4, p=0.2105) on discharge did not differ between the two groups, either. After adjustment for age, sex, modified Rankin scale before admission, diabetes, hypertension, dyslipidemia, there was no significant difference in mRS at discharge between the two groups. (P=0.1416).

Conclusion:
It seems that the severity and outcome of ischemic stroke with PAF are not different from those with CAF.
Abstract T P187: Regionalization of Endovascular Therapy for Acute Ischemic Stroke in California, 2009-2010
Authors: Choi Jay Chol , Hsia Renee Y , Kim Anthony S
Published: July 2021

Background:
The regional availability of hospitals with expertise in applying endovascular therapy for acute ischemic stroke is critical to ongoing efforts to develop effective interventions for this time-sensitive indication. We sought to assess the geographic proximity of stroke patients in California to centers that perform endovascular stroke therapy.

Methods:
We identified all hospitalizations for ischemic stroke at all 366 non-federal acute care hospitals in California from 2009 to 2010, including the subset where endovascular stroke therapy was employed, using data from the Office of Statewide Health Planning and Development. ZIP code centroids were used to estimate the geographic distance between a treating hospital and the patient’s residence. Using these distances, we estimated the proportion of stroke patients that lived within 2-hour (65 mile) transport distance to a hospital that performed certain threshold volumes of endovascular stroke cases each year.

Results:
From 2009-10, endovascular stroke treatment was used in 643 of 104,350 (0.6%) hospital discharges for ischemic stroke in California. A majority (60%) of these procedures were performed at hospitals that performed at least 12 procedures per year, and 83% of these procedures were performed at hospitals that performed at least 6 procedures per year. Of the 366 hospitals, 54 (15%) performed at least one endovascular stroke procedure per year. The median number of procedures per hospital per year was 3.5 (IQR 1-9). In-hospital mortality for endovascular stroke therapy was 21%, and a higher procedural volume at the hospital level was not associated with lower mortality. Most (86%) stroke patients lived within 65 miles of a center that performed at least 6 procedures per year (median with IQR, 9.5[7-17]), and 97% were within 65 miles of a center that performed at least 1 procedure per year.

Conclusion:
In 2009-10, less than 1% of ischemic stroke hospitalizations in California involved the use of endovascular stroke therapy. Most patients lived within a 2-hour transport distance from a center that performed at least one endovascular procedure per year.
Abstract T P188: Equivalency in Intravenous Thrombolytic Treatment Rates Between Primary Stroke Centers and Non-Primary Stroke Centers Through the Use of Telestroke
Authors: Bhatt Archit , Barban Elizabeth , Corless Leslie , Stuchiner Tamela , Kansara Amit
Published: July 2021

Background:
Research has shown that subjects evaluated at (Primary Stroke Centers) PSCs are more likely to receive rt–PA than those evaluated at non–PSCs. It is unknown if telestroke evaluation affects rt-PA rates at non-PSCs. We hypothesized that with a robust telestroke system rt-TPA rates among PSCs and non-PSCs are not significantly different.

Methods and Results:
Data were obtained from the Providence Stroke Registry from January 2010 to December 2012. We identified ischemic stroke patients (n=3307) who received care in Oregon and Southwest Washington, which include 2 PSCs and 14 non-PSCs. Intravenous rt–PA was administered to 7.3% (n=242) of ischemic patients overall, 8.4% (n=79) at non–PSCs and 6.9% (n=163) at PSCs (p=.135). Stroke neurologists evaluated 5.2 % (n=172) of all ischemic stroke patients (n=3307) were evaluated via telestroke robot. Our analysis included AIS (Acute Ischemic Stroke) patients, those presenting within 4.5 hours of symptom onset. We identified 1070 AIS discharges from 16 hospitals of which 77.9 % (n=833) were at PSCs and 22.1 % (n=237) non-PSCs. For acute ischemic stroke patients (AIS) patients, those presenting within 4.5 hours of symptom onset, 22.1% (n=237) received rt-PA; 21.5% (n=74) presented at non–PSCs and 23.7% (n=163) presented at PSCs. Among AIS, bivariate analysis showed significant differences in treatment rates by race, age, NIHSS at admit, previous stroke or TIA, PVD, use of robot, smoking and time from patient arrival to CT completed. Using multiple logistic regression adjusting for these variables, treatment was significantly related to admit NIHSS (AOR=1.67, p<.001), history of stroke (AOR=.323, p<.001), TIA (AOR=.303, p=.01) and PVD (AOR=.176, p=.02), time to CT (.971, p<.001), and use of robot (7.76, p<.001). PSC designation was not significantly related to treatment (p=.06).

Conclusions:
Through the use of a robust telestroke system, there are no significant differences in the TPA treatment rates between non-PSC and PSC facilities. Telestroke systems can ensure stroke patients access to acute stroke care at non-PSC hospitals.
Abstract T P19: “Futile” Interhospital Transfer for Endovascular Recanalization Treatment in Acute Ischemic Stroke. The Madrid Stroke Network
Authors: Fuentes Blanca , Alonso de Leciñana Maria , Ximenez-Carrillo Alvaro , Martínez-Sánchez Patricia , Cruz-Culebras Antonio , Zapata Gustavo , Ruiz-Ares Gerardo , Masjuan Jaime , Vivancos Jose , Diez-Tejedor Exuperio ,   Madrid Stroke Network
Published: July 2021

Objectives:
The complexity of endovascular revascularization treatment (ERT) in acute ischemic stroke (IS) and the small number of patients eligible for that treatment justifies the development of Stroke Center networks with interhospital transfer of eligible patients. But it is possible that this approach generate “futile“ transfers (i.e. shift of patients who finally do not receive ET) generating unnecessary costs. Our aim is to analyze the frequency of “futile” transfers, the reasons for rejection for ERT and to identify the possible associated factors.

Methods:
We analyzed a prospective registry of ERT from a Stroke Network integrated by three hospitals with facilities for ERT for acute stroke patients. These hospitals share a common stroke protocol and have established a weekly rotatory shift with inter-hospital transference to the on-call center for ERT in those patients in whom this therapy is indicated, both primarily, after completing IV thrombolysis or in patients attended in outside hospitals (drip and shift). We analyzed: demographic data, vascular risk factors, stroke severity, frequency of prior intravenous thrombolysis, time from stroke onset and reasons for rejection. Study period: 1/02/2012 to 07/05/2013.

Results:
ERT protocol was activated in 199 patients, receiving ERT 129 (64.8%). 120 (60.3%) patients required inter-hospital transfer, among them 50 (41%) were not finally treated (futile transfer). These were more often male (74.1% vs. 25.9%, P = 0.04), with no differences in age, vascular risk factors, time-lapse from stroke onset or delay of inter-hospital transfer, baseline NIHSS, baseline ASPECTS or rate of prior intravenous thrombolysis between transferred patients treated with ERT and those non-treated. Reasons for rejection were: clinical improvement (16%), arterial recanalization (24%), clinical deterioration (8%); ASPECTS <7 in the 2nd TC (20%), absence of mismatch (20%); delay in shipment (2%), revocation of consent (1%).

Conclusions:
40% of shipments for ERT are “futile”. None of the baseline patient characteristics predict this fact, being arterial recanalization and findings in a second imaging test done in the receiving hospital the main reasons for ERT rejection.
Abstract T P192: Interventional Stroke Assessment Scale for Eligibility in Endovascular Therapy (ISAS-ET)
Authors: Dababneh Haitham , Bashir Asif , Hussain Mohammed , Misthal Sara , Moussavi Mohammad , Kirmani Jawad F
Published: July 2021

Background and Purpose:
During the last two decades, we have witnessed advancements in the field of endovascular treatment of stroke, especially after showing the benefit of Intravenous tissue plasminogen activator (IV tPA). Despite these innovations in the field, only 55% or less of patients were shown to have good outcomes in multiple randomized clinical trials.

Methods:
This is a retrospective analysis of all patients (n= 97) who presented to our hospital with ischemic stroke and received mechanical thrombectomy with or without IV tPA between January 2009 and July 2012 and had all possible variables documented in their charts. Statistical analysis was performed using the R statistical package and XLSTAT-Pro 2011. Spearman correlations (P value <0.05) for non-normally distributed data were used to independently evaluate the correlation of all the variables including age, gender, site of occlusion, time to intervention, baseline NIHSS, volume of infarct core at presentation, hypertension, diabetes, hyperlipidemia, atrial fibrillation (AFib), coronary artery disease, prior strokes and disability and smoking with the patient functional outcome at discharge using a modified rankin scale (mRS). mRS of 2 or less represented a good functional outcome.

Results:
80 patients had all previously mentioned variables. Group analysis including gender, mean age, mean NIHSS, percentage of AFib and mortality at discharge was as follows: Female 50%, 72.9, 14.5, 31.0% and 13%. There was a significant negative correlation with the outcome if a patient had a NIHSS more than 20, age above 65, presence of AFib, prior strokes or disability, volume of infarct core on perfusion studies or reformat CT angiography more than 75 cm3 (P value <0.05). The scoring system was developed with a score range (0-8), where a high score predicts a better outcome. Infarct core volume 75 cm3 received 2, 1, 0 points respectively; NIHSS20 received 2, 1, 0 points respectively; Age <65 received 1 point; absence of AFib received 1 point, time of onset <3 hours received 1 point, no prior stroke or disability received 1 point.

Conclusion:
The ISAS scoring system might help with assessment of patient qualification for endovascular treatment. Further prospective studies validating the score are warranted.
Abstract T P198: Cerebrovascular Disease Patterns among Emergency Room Admissions in 4070 Consecutive Patients of Haiti
Authors: Barthelemy Ernest , Jean-Pierre Marie Y , Benjamin Ernest , Télémaque Louis-Franck , Pierre Bernard , Osborn Irene , Germano Isabelle
Published: July 2021

Introduction:
No study to date has examined cerebrovascular disease patterns in the country of Haiti. Our objective was to describe the patterns of presentation and outcomes of neurological patients presenting to the emergency room (ER) of a major public hospital in Port-au-Prince.

Methods:
After obtaining ethical approvals from institutions in the US and in Haiti, de-identified data on neurologic disease were prospectively collected from patients consecutively admitted to the ER of Hôpital de L’Université d’État d’Haïti (HUEH) from November 2012 to January 2013. Data were collected over a period of 90 days using Microsoft Excel, analyzed with standard statistical analysis and is shown as mean±SD.

Results:
Out of 4070 consecutive patients, there were 792 neurological admissions (19%; age 42y±20; 40%man). The diagnosis of stroke accounted for 25% of admissions (age 58y±16; 41%man), while hypertensive encephalopathy accounted for 14% (age 49y±16; 30%man). Absence of onsite CT imaging prohibited distinction of ischemic from hemorrhagic stroke in 196 (99%) stroke patients. Data on the time lapse between symptom onset and ER admission was available in 154/197 (78%) of stroke patients. In this group, median and mean time frame were 24-hours and 85±210-hours with 22/134 (16%) presenting in <3-hours and 11/134 (8%) presenting between 3 and 6 hours. The most common presenting symptom among patients with hypertensive encephalopathy was headache (73%); the average presenting blood pressure (BP) in this group was systolic 174±27mmHg and diastolic 108±24mmHg. The most common presenting symptoms among stroke patients included speech disturbance (47%), and altered mental status (56%). Overall in-hospital stroke mortality was 19% (38/197).

Conclusions:
To our knowledge, this is the first study addressing cerebrovascular disease patterns in Haiti. Limitations on diagnostic imaging and resources contribute to high observed morbidity and mortality. Prevention, diagnosis, and treatment of cerebrovascular diseases should be prioritized in Haiti, while additional studies are necessary to better define the epidemiology of this disease.
Abstract T P200: CD13 is an Immune Regulator in the CNS Following Ischemic Stroke
Authors: Tarabishy Sami , Patrizz Anthony , Mancini Nikolas S , Shapiro Linda , McCullough Louise D
Published: July 2021

Background:
Focal cerebral ischemia results in marked inflammatory response initiated by microglia and astrocyte activation, upregulation of pro-inflammatory cytokines, and disruption of the blood brain barrier leading to invasion of peripheral immune cells. CD13 (Aminopeptidase N), a 150 kD type II transmembrane metalloprotease highly expressed on myeloid cells, has recently been shown to possess several non-enzymatic functions involving the regulation of processes related to inflammation including antigen presentation and cell trafficking into sites of inflammation. We hypothesized that deletion of CD13 would alter the innate immune response after stroke leading to smaller infarcts and neuroprotection.

Methods:
C57BL/6 WT and CD13 KO male mice were subjected to transient focal ischemia by middle cerebral artery occlusion for 90 minutes. Motor and sensory deficits were assessed using the Benderson neurological deficit score and open field analysis. Mice were sacrificed at 48hrs and brain slices stained with Cresyl Violet for infarct analysis. Immunohistochemistry was performed on fresh frozen slices to visualize microglial activation.

Results:
There was significant reduction in total hemispheric and cortical infarct in KO compared to WT at 48 hours post stroke (Hemispheric 50.8 ± 2.0 WT vs. 40.7 ± 3.8 KO p=.04, Cortical 56.5 ± 4.0 WT vs. 40.1 ± 5.8 KO p=.04, n=6-10). Behaviorally, CD13 KO mice performed better in the open field test than WT, displaying less motor dysfunction (p=.047). 48hrs post stroke. CD13 KO mice had lower neurological deficit scores (3 WT vs. 2 KO, IQR=0, U=0, n=6-10). CD13 mice had less mortality at all time-points. IHC revealed increased microglia activation in the infarct hemisphere of KO mice when compared to WT.

Conclusions:
CD13 KO mice had smaller infarct sizes and better acute behavioral outcomes than WT mice. Furthermore, initial IHC results displayed a phenotypically different immune response in KO animals. Flow cytometry is characterizing the differences in the immune response between the groups and microglial phenotypes. Further identifying and targeting of the non-enzymatic functions of CD13 in the CNS may lead to novel therapeutic clinical treatments to reduce morbidity and mortality from ischemic stroke.
Abstract T P208: Diabetes Exacerbates Neurovascular And White Matter Disruptions in Older Rats After Stroke
Authors: Zhang Li , Chopp Michael , Zhang Yanlu , xiong ye , Zhang Zheng Gang
Published: July 2021

Background and Purpose:
Diabetes mellitus (DM) is a common metabolic disease in the aged population, which leads to an increase of stroke incidence, poor stroke outcome, and slower neurological recovery. A better understanding of the pathological cascades of brain injury in the aged DM population is of major clinical importance for stroke management. The present study was designed to characterize the behavioral and pathological changes in older DM rats after embolic stroke.

Methods:
Male Wistar rats at age of 13 months were subjected to intraperitoneal nicotinamide (NTM, 210mg/kg) and streptozotocin (STZ, 60mg/kg) injection (n=19). Rats were subjected to embolic middle cerebral artery occlusion (MCAo) 30d after induction of DM (n=10). Aged matched normal rats (n=9) and ischemic rats (n=11) without induction of DM were used as controls.

Results:
Rats subjected to STZ-NTM administration exhibited persistent hyperglycemia and reduction of insulin producing pancreatic β-cells, and have clinical manifestations of type 2 DM (T2DM). These rats exhibited substantial spatial learning deficits measured by the Morris water maze (39±3 vs 50±4% of time spent in the correct quadrant in age matched non-DM rats, p<0.05) 65d after induction of DM. Histological analysis revealed that there was patchy vascular and parenchymal fibrin deposition mainly in the hippocampus and white matter, which were associated with significant (p<0.05) reductions in neurofilament positive axonal density (14±3 vs 23±4% in non-DM rats) and myelinating oligodendrocytes (78±11 vs 98±13/mm
2
). Stroke in DM rats exacerbated vascular and parenchymal fibrin deposition (32±8 vs 17±6 mm
2
in non-DM ischemic rats), decreased axonal density (9±2 vs 17±4%) and dendritic spines (10±4 vs 19±5/μm), and increased loss of oligodendrocytes (47±12 vs 73±14/mm
2
), which were associated with spatial learning and neurological deficits 35d after stroke onset, although the primary infarct volumes within the MCA territory were not different between groups.

Conclusions:
T2DM exacerbates neurovascular and white matter damage, leading to neurological deficits in older rats, which closely resembles pathological symptoms observed in stroke patients with T2DM.
Abstract T P225: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke Injury in Mice
Authors: Atochin Dmitriy , Buys Emmanuel , Swanson Helen , Dordea Ana , Fukumura Dai , Feil Robert , Huang Paul L
Published: July 2021

The signaling pathways by which NO protects against stroke injury are mediated by cyclic guanosine monophosphate (cGMP) formation. However, the mechanisms of downstream signaling from cGMP to smooth muscle cells (SMC) remain incompletely understood. The cGMP-dependent protein kinase I (cGKI) is a key mediator of cGMP signaling.

The goal of this study is to test the hypothesis that cGKI in SMC protects against stroke injury.

Animals:
We used the novel mouse line for highly efficient tamoxifen-inducible SMC-specific gene knockout, SMA-CreERT2, which expresses the CreERT2 recombinase under the control of the smooth muscle alpha-actin promoter (cGKI KO mice). The litter mate wild-type (WT) mice (no Cre gene) receiving the same tamoxifen treatment were used as control (cGKI WT) mice.

Methods and Results:
Mean blood pressure measured acutely from the common carotid artery under anesthesia (30% oxygen, 70% nitrous oxide and 1.5% isoflurane) was higher in cGKI KO mice (107±8 mmHg, Mean±SD) than in cGKI WT mice (95±1 mmHg, n=4/group, P<0.05). One hour of middle cerebral artery (MCA) occlusion by filament with 23 hours of reperfusion produced increased cerebral infarct volume (TTC staining, indirect calculation) in cGKI KO mice (123±39 mm3) as compared with cGKI WT (85±17 mm3, n=5/group, p< 0.05). Neurological deficit by 5 point scale was worse in cGKI KO mice (4.0 points) as compared with cGKI WT (2.4 points). Cerebral blood flow monitored by laser Doppler flowmetry above the core of the MCA territory indicated that reperfusion was less in cGKI KO mice than in cGKI WT mice, suggesting that cGKI mediates cerebrovascular SMC relaxation and protects against ischemic stroke. Vascular relaxation of mesenteric resistance arteries to acetylcholine, and the NO donor, NONOate after preconstriction with phenylephrine was dramatically impaired in cGKI KO mice. It suggests the importance of cGKI in the vascular SMC for NO-induced relaxation.

In conclusion, stroke injury was more pronounced in cGKI SMC specific inducible conditional knockout mice than in cGKI WT mice, suggesting a protective role for cGKI in SMC against cerebral reperfusion injury. These studies identify the cGKI in cerebral vasculature as a potential target for therapies aimed at reducing stroke injury.
Abstract T P228: Greater Effect of Early Intensive Blood Pressure Lowering on Hematoma Growth in Non-Chinese Participants in the Interact2 Trial
Authors: Anderson Craig , Huang Yining , Wang Jiguang , Arima Hisatomi , Heeley Emma , Wang Xia , Lindley Richard , Parsons Mark , Chalmers John ,   the INTERACT2 Investigators
Published: July 2021

Background:
We aimed to assess the effects of early intensive blood pressure (BP) lowering on hematoma growth separately for Chinese and non-Chinese participants in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2).

Methods:
INTERACT2 was an open, randomised, multicentre clinical trial involving 2839 patients with spontaneous ICH and elevated systolic BP (150-220 mmHg) and capacity to receive intensive BP lowering treatment within 6 hours of onset. Participants were centrally randomized to receive intensive (target systolic <140 mmHg) or standard (target systolic <180 mmHg) BP management using intravenous agents. Vital status and disability were assessed over 90 days. Baseline and 24 hour CT digital images were analysed centrally in 964 (34%).

Results:
Compared to non-Chinese participants, the Chinese were significantly younger, had milder clinical severity, less co-morbid diabetes and coronary disease, and were randomised slightly later after the onset of ICH. However, baseline hematoma volumes were similar (median 11 ml). There were also significant differences in medical management. Effects of treatment on mean (95% CI) absolute hematoma growth at 24 hours (adjusted for baseline hematoma volume and time from onset of CT) were: (i) non-Chinese - intensive 2.8 (0.7-4.9) vs standard 6.2 (4.1-8.4), [[Unable to Display Character: ∆]]-3.5 (-6.5-0.5) groups, P=0.02; (ii) Chinese - intensive 3.4 (1.5-5.3) vs standard 2.0 (0.04-3.9), [[Unable to Display Character: ∆]]1.4 (-0.8-3.6) groups, P=0.21.

Conclusions:
There was a significantly greater effect of early intensive BP lowering on hematoma growth in non-Chinese participants, which could relate to less effective BP reduction and greater use of background medical therapy including mannitol, in the Chinese participants
Abstract T P238: Microglial CX3CR1 Required for M2 Polarization and Recovery After Intracerebral Hemorrhage
Authors: Taylor Roslyn A , Hammond Matthew D , Ai Youxi , Sansing Lauren H
Published: July 2021

Introduction:
Intracerebral hemorrhage (ICH) results in the activation of microglia, the resident immune cells of the central nervous system. Microglia may polarize into an M1, pro-inflammatory phenotype, or an M2 phenotype associated with repair. CX3CR1 is a chemokine receptor on microglia and monocyte subsets. CX3CR1-null microglia have been shown to have dysregulated inflammation. We hypothesize that CX3CR1-null microglia have a prolonged M1 phenotype, contributing to worse functional outcome after ICH.

Methods:
ICH was modeled by injection of 20μl of blood into the right striatum. Neurological deficit was quantified using digital gait analysis, cylinder test, and beam walking. Mice were sacrificed 14 days after ICH; brains were harvested for flow cytometry and immunohistochemistry (IHC). C57BL/6 (WT) and CX3CR1
GFP/GFP
(CX3CR1-null)

mice were irradiated and reconstituted with bone marrow from WT mice carrying the congenic marker CD45.1 to generate bone marrow chimeras (CD45.1WT or CD45.1CX3CR1-null). M1 microglia were identified as expressing MHCII and M2 microglia with CD206.

Results:
The CD45.1CX3CR1-null mice show worse functional outcome 14 days after ICH by cylinder test (p=0.002), beam walking (p=<0.001) and gait analysis (p=0.02). By flow cytometry, few peripheral leukocytes remain in the brain at 14 days, indicating that F4/80
+
and CD11b
+
cells visualized by IHC are likely microglia, not peripheral macrophages. By IHC, CD45.1 CX3CR1-null mice have significantly more amoeboid F4/80
+
MHCII
+
cells per field (M1 microglia) than CD45.1WT mice (p=0.02). CD45.1 CX3CR1-null mice have significantly fewer CD11b
+
CD206
+
cells per field (M2 microglia) compared to CD45.1WT mice (p=0.04).

Conclusions:
Our results suggest microglial CX3CR1 signaling is necessary for microglia to transition from M1 to M2 and contribute to recovery after ICH.
Abstract T P240: Sex-specific Differential Gene Expression in a Murine Model of Experimental Intracerebral Hemorrhage
Authors: Gokhale Sankalp , Kernagis Dawn , Lei Beilei , Li Yi-Ju , Warner David , Laskowitz Daniel , James Michael
Published: July 2021

Introduction:
Decreased mortality and improved functional outcome in female compared to male mice after experimental intracerebral hemorrhage (ICH) has been demonstrated. We postulate that sex-specific differences in post-ICH gene expression may provide mechanistic insight.

Methods:
Ten to 12 week old C57/Bl6 male (M) and female in low estrus (LE-F) or high estrous state (HE-F) mice (n=3/group) underwent ICH induction via left intrastriatal collagenase injection. Whole brain samples were collected at baseline, immediately after sham injury and 6 hours after injury. Genome-wide expression profiling was performed with Affymetrix GeneChip Mouse Genome 2.0 to identify genes differentially expressed between baseline and 6 hours in males and females. Probes showing expression levels greater than log2 (10) for all samples were selected for differential analysis. Comparisons were made between baseline and 6-hour time points to determine significant differential gene expression in both sexes. An adjusted p < 0.05 was considered significant.

Results:
A total of 12136 probes qualified for our filtering criteria, representing 9830 genes. Of the genes tested, 119 in M, 76 in LE-F, and 420 in HE-F were expressed differently at 6 hours as compared to baseline. Of these genes, a total of 37 were shared in M and HE-F groups, 32 in M and LE-F groups, and 42 in HE-F and LE-F groups. Several pathways were identified based on the top list of genes in each group comparison, including coagulation and inflammatory mediator signaling.

Conclusions:
Sex-specific differential gene expression exists at 6 hours after experimental ICH. Further experiments will be designed to test whether these observed differences in gene expression are associated with outcome after experimental ICH and, thus, may yield novel therapeutic targets for translation into the human disease.
Abstract T P249: Improving Door to Needle Times With Emergency Medical Services Collaboration
Authors: Smith Kimberly M , Gaunt Susan M
Published: July 2021

Background and Purpose:
The AHA/ASA Stroke Guidelines recommend intravenous Recombinant Tissue Plasminogen Activator (rtPA) within 60 min from hospital arrival in eligible patients. Patient outcomes are time dependent and require a multidisciplinary approach between the hospital and Emergency Medical Services (EMS). In 2012, we implemented a process improvement initiative that included pre-hospital EMS lab draws, emergency department (ED) patient flow changes, immediate physician evaluation and EMS direct transport to CT. The purpose of this project was to improve stroke care by minimizing door to needle time (DTN) in patients with acute ischemic stroke.

Methods:
We used the Plan-Do-Check-Act method of performance improvement in our implementation process. A multidisciplinary performance Improvement team was established which included EMS, ED Laboratory, and Imaging participants. The four highest volume EMS stations were chosen to participate in the pilot process improvement strategy. Education was provided to EMS, ED physicians and staff, radiology, laboratory and patient registration personnel. Concurrent review of 100% of the stroke alert cases was conducted. We analyzed the door to CT result, the door to laboratory result and the DTN time for the four pilot stations. Based on the results, the decision was made to extend this process countywide.

Results:
Twenty-nine patients were enrolled in the pilot, and 15 labs were successfully drawn in the field for an average door to result time of 30.4 min. Fourteen labs were drawn on arrival for an average of 46.6 min. The door to CT result for the patients sent directly to CT by EMS was an average of 16 min. Seven out of the 29 patients were diverted to a room, and their average door to result was 30.6 min. Four patients received IV rtPA with an average DTN time of 47 min, and 100% of the 4 patients received IV rtPA within 60 min. During the same time period, IV rtPA was given to 9 patients that were not in the pilot for an average DTN of 61 min, and only 5/9 (55%) received IV rtPA within 60 min.

Conclusion:
The performance improvement initiative decreased our door to lab result, door to CT result and DTN time in this small sample and was implemented county wide.
Abstract T P255: Post-Stroke Care In a Rural Community; Need For Improvement
Authors: Kline Ann M , Rankin Pauline , Perry Christine , McLaughlin James
Published: July 2021

Primary care evidence based literature contains quality care indicators covering general aspects of post-stroke care; but few of these are routinely implemented. As part of the ongoing process improvement program at our 180 bed primary stroke care center in rural northwestern Pennsylvania, we hypothesized the potential need for a comprehensive multidisciplinary long term post-stroke strategy. We used a sample population of 48 participants representing all those discharged with a diagnosis of stroke from January through June of 2013. Stroke survivors / caregivers were contacted by telephone and interviewed using the Global Stroke Community Advisory Panel 11 item post-stroke checklist. Results revealed that of the 11 long term areas assessed, three were identified as having the greatest need for intervention. In our community, 39.5% required advice on secondary prevention, 39.5% for evaluation of mood changes, and 37.5% for assessment of cognitive changes. In conclusion, we identified three post-stroke care issues which if effectively addressed, would potentially improve post-stroke quality of life. Our goal is to evaluate the availability of current resources and implement measures appropriate to this rural setting; including the potential to incorporate telemedicine as a resource to improve the standard of post-stroke care.
Abstract T P26: Predictors of Clinical and Angiographic Outcomes in Acute Stroke Treatment: Subgroup Analysis From the Star Study
Authors: Mendes Pereira Vitor , Chapot Rene , Davalos Antoni , Bonafé Alain , Castano Carlos , Nogueira Raul , liebeskind David , Goyal Mayank , Brown Scott , Moreno Antonio , Besselman Michael , Arnold Marcel , Sztajzel Roman , Schroth Gerhard , Lovblad Karl-olof , Liebig Thomas , Gralla Jan
Published: July 2021

Endovascular acute stroke treatment (AIS) has changed dramatically last years. Stent retrievers are progressively substituting other devices and old practices like intra-arterial thrombolysis. We present the subgroup analysis of the largest prospective multicentre study using stent retrievers on the treatment of AIS. The study was realized in 14 high volume and experienced stroke centres in Europe, Canada and Australia. 202 patients harbouring anterior circulation occlusions were included within 8 hours after onset. All procedures were performed with balloon guiding catheter. We observed that the occlusion location did not change the successful (TICI 2b or 3) recanalization rates (ICA - 76.5% and MCA - 86.4%: p=0.187) or good clinical outcomes (mRS 0-2) (ICA - 47.2% and MCA - 61.3%: p=0.137). However, it was significant when we considered excellent (mRS 0-1) outcomes only (ICA - 25% and MCA - 47.5%: p=0.016). There were no differences concerning the previous use of rtPA on the angiographic (TICI scores) (p=1.0) or clinical (mRS) (p=0.564) outcomes. The anaesthetic management also did not influence the revascularization (p=0.7) or patient’s status (p=0.343). Angiographic collateral status determined using the ASITN/SIR grading system was significantly correlated to good clinical outcomes (Grades 0-2 and Grades3-4, p=0.034). Also the time from the stroke onset to groin puncture influence clinical progress (0-3h, 3-4.5h, over 4.5h: p=0.002). Multivariate regression analysis on prediction of good outcomes was significant for age (OR-0.93 (0.89, 0.97)), baseline NIHSS (OR-0.87(0.79, 0.96)), absence of haemorrhage (OR-5.01 (1.65, 15.16)), time to treatment (OR-0.62(0.45-0.83)) procedure performed under conscious sedation (OR4.83(1.78,13.11)) and successful recanalization (OR-3.37(1.12,10.14)). Early and efficient revascularization is ideal situation for AIS. Conscious sedation can save time for endovascular procedure using a stent retriever in experienced centers.
Abstract T P281: Facilitating Best Practices in Rehabilitation for Persons With Stroke: Use of a Triage Tool in Toronto
Authors: Sharp Shelley , Willems Jacqueline , Linkewich Elizabeth , Tahair Nicola , Levy Charissa , Bayley Mark
Published: July 2021

Background:
Best practice indicates all stroke patients (including severely affected) benefit from timely and intensive rehabilitation care. Currently in Toronto 27% of patients with stroke are discharged to inpatient rehabilitation from acute care (Canadian Institute for Health Information (CIHI) 11/12). Sixty percent of admissions to rehabilitation were patients with moderate stroke, 17% mild and 22% severe CIHI (FY12-13 Q1-3). Access to rehabilitation in Toronto is not equitable as admission criteria and rehabilitation programming are not standardized for stroke.

Purpose:
Develop a triage tool to support clinical decision making, equitable access to care and early referral to appropriate rehabilitation based on best practice Methods Acute and rehabilitation leaders collaboratively developed the triage tool. Provincial expert panel recommendations and existing referral frameworks were considered. The AlphaFIM® tool was used as the basis for categorizing stroke severity. Agreement was reached to support automatic acceptance of patients referred to rehab with AlphaFIM® score of 60-80. The tool was implemented Feb 1, 2013. All rehabilitation organizations agreed to standardized admission criteria and are working toward best practice for stroke inpatient rehabilitation care.

Results:
Baseline data (January to August 2012) for patients referred with an early AlphaFIM® of 60-80 indicated only 66% were accepted to rehab, 15% were declined and 8.5% had a decision pending. For those declined, 10% were identified as having special needs that could not be met, 29% were considered more appropriate for slow stream rehab, and 14% because of limited sitting tolerance and balance. An analysis of data following implementation will be presented.

Conclusion:
The triage tool creates a standard of best practice for the system. Agreement on common admission criteria and standard of practice for rehabilitation referral management for patients with AlphaFIM® 60-80 have been established between referrers and rehab providers. It is expected that transition barriers for this group should be minimal unless special needs are identified.
Abstract T P285: In-hospital Complications Affected Stroke Recurrence in Patients With Ischemic Stroke
Authors: Wang Penglian , Zhao Xingquan , Wang Yongjun , Liu Liping , Wang Anxin , Ji Ruijun , Wang Yilong , Du Wanliang , Dong Kehui ,   the China National Stroke Registry (CNSR) investigators
Published: July 2021

Objective:
In-hospital medical complications are common and costly. Outcomes of stroke patients are affected by medical complications. However, there are limited data investigating the effect of medical complications on stroke recurrence worldwide. We prospectively and systematically investigated the effect of in-hospital medical complications on recurrent stroke of patients with acute ischemic stroke at 3, 6 and 12 months in the China National Stroke Registry (CNSR).

Methods:
Prospective cohort study collected data of adult patients with acute ischemic stroke in 132 clinical centers distributed in 32 provinces and 4 municipalities (including Hong Kong region) of China, from September 2007 to August 2008. Data on in-hospital medical complications, recurrent stroke, adherence to stroke secondary prevention and other relative information were obtained from paper-based registry forms. Medical complications were associated with stroke outcomes using multivariable logistic regression.

Results:
Of the 10306 study patients, recurrent stroke occurred in 1637 (15.9%) within 12 months after stroke onset. In-hospital medical complications were independent risk factors for stroke recurrence in patients with acute ischemic stroke at 3 months (adjusted OR=2.19; 95% CI 1.85 to 2.60), 6 months (adjusted OR=2.04; 95% CI 1.74 to 2.38), and 12 months (adjusted OR=1.88; 95% CI 1.62 to 2.19) after onset. In-hospital medical complications decreased the adherence to stroke secondary prevention, may indirectly resulting in increased recurrent stroke events.

Conclusions:
The results demonstrated that the short-term and long-term stroke recurrence of acute ischemic patients is significantly affected by in-hospital medical complications, possibly through decreasing the persistence of secondary prevention following acute ischemic stroke.
Abstract T P287: Reasons for Delays in Door to Needle Time
Authors: Smith Eric E , Kashyap Devika , Bohm Victoria , Hill Michael D , Demhuk Andrew M ,   for the HASTE-2 Investigators
Published: July 2021

Background:
The National Quality Forum recently endorsed a performance measure for door-to-needle (DTN) time less than 60 minutes, with exclusion criteria for acceptable reasons for delay. However, the reasons for delay in timely treatment with tPA, and their impact on DTN times, are largely unknown. At our center we initiated the Hurry Acute Stroke Treatment and Evaluation-2 (HASTE-2) project to identify reasons for longer DTN.

Methods:
From 06/2012 to 06/2013 we encouraged treating physicians to fill out a 1-page case report form on opportunities for improvements and reasons for delays in treatment times, categorized according to systems-related delays (e.g. in patient registration, or in recognition of stroke symptoms and activation of the stroke) vs. medical/eligibility delays (e.g. management of concomitant emergent conditions or initial patient refusal). DTN data were analyzed from 113 consecutive patients presenting directly to the ER, treated with IV tPA within 4.5 hours of symptom onset.

Results:
Mean age was 71, 60/113 (53%) were women, median NIHSS was 13.5 and DTN was 57 minutes. Prospective data were recorded on the presence of absence of potential delays in 48/113 (42.5%); patients with missing data were somewhat younger (mean age 68.5 vs. 75.3, p=0.04) but did not differ in DTN or NIHSS. 52 different systems delays were identified in 30/48 patients (63%), and 15 different medical/eligibility delays were identified in 13/48 patients (27%). Medical/eligibility delays had the greatest impact on DTN: median 67 min [interquartile range 54-120] in patients with medical/eligibility delays, 47.5 min [40-66] in patients with only systems delays and 51 min [34-65] in patients with no delays (p=0.01).

Conclusions:
DTN may be prolonged for a variety of reasons. Up to 27% of patients have delays due to medical or eligibility-related causes that may be legitimate reasons for providing tPA later than the benchmark time of 60 minutes. Our difficulty in obtaining complete prospective physician documentation of reasons for delays suggests a need for improved chart documentation regarding DTN times.
Abstract T P292: Baseline Infarct Volume Predicts Disability in TIA and Minor Stroke Patients
Authors: Asdaghi Negar , Coulter jonathan , Modi Jayish , Qazi Abdul , Goyal Mayank , Butcher Kenneth S , Coutts Shelagh B
Published: July 2021

BACKGROUND:
Despite their mild presenting neurological deficit, over one third of patients with transient ischemic attack (TIA) and minor stroke are dead or disabled at the time of hospital discharge. This is predominantly related to either symptom progression or recurrent stroke, although predicting outcome can be difficult. We sought to determine whether baseline radiographic MR characteristics could predict disability at 3months in this population.

METHODS:
Consecutive TIA/minor stroke (National Institutes of Health Stroke Scale<4) that were not disabled at baseline and had an MRI within 24 hours of symptom onset were prospectively included. Disability was assessed at 90 days using the modified Rankin Scale (mRS). The impact of perfusion (PWI) and diffusion (DWI) variables on disability (mRS≥2) at 90 days was assessed.

RESULTS:
418 patients were included; 55.5% had positive DWI lesions. 292 patients had PWI imaging of whom 35% had PWI deficit (Tmax≥2s) and 26.5% had mismatch (Tmax≥4s-DWI) at baseline. The median DWI, PWI and mismatch volumes were 1.14 ml (IQR=3.43), 9.8 ml (IQR=29.8) and 9 ml respectively. A total of 56/418 (13.4%) patients were disabled at 90days. In multivariable analysis we adjusted for baseline predictors of disability (age, DM, premorbid mRS 1, ongoing symptoms, baseline NIHSS, CT/CT angiography-positive metric and DWI or PWI volume). DWI volume (OR=1.05, p=0.007), and age (OR=1.03, p=0.003) remained independent predictors of disability. PWI or mismatch volume did not predict functional outcome.

CONCLUSIONS:
A substantial proportion of patients with TIA and minor stroke are disabled at 90days. The degree of tissue injury as measured by DWI volume is an independent predictor of disability regardless of the mechanism of disability.