bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP42: Remote Ischemic Stroke Decreases Quiescence and Increases Neurogenic Activation of Radial Glia-like Precursors in the Subgranular Zone of the Dentate Gyrus in Adult Mice
Authors: Sahin Bogachan , Bonaguidi Michael A , Zeiler Steven R , Song Hongjun
Published: July 2021

Adult neurogenesis occurs in two discrete neurogenic niches in the mammalian brain: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampal formation. Under physiologic conditions, neurogenesis in these regions is thought to be important for the maintenance and reorganization of interneurons in the olfactory bulb (SVZ), and the modulation and refinement of existing circuits in the dentate gyrus (SGZ). In rodents, stroke enhances neurogenesis in these regions, and stroke-induced neurogenesis appears to play a role in functional recovery. However, little is known about the behavior of quiescent vs. activated pools of neural stem cells in response to stroke, or the mechanisms of stroke-induced neurogenesis at the cellular level. Here we tested the hypothesis that stroke-induced neurogenesis involves the activation of quiescent stem cell pools, either alone or in combination with further differentiation of activated precursors. We used a genetic labeling strategy for in vivo lineage tracing of quiescent, nestin-expressing radial glia-like (RGL) precursors in the SGZ to elucidate the effect of remote focal ischemic infarction on RGLs at a clonal level. Unilateral infarction of the visual cortex by photothrombosis in transgenic mice caused an increase in the number of differentiated neuronal precursors and a decrease in the number of quiescent RGLs in the ipsilateral SGZ. Furthermore, among activated RGL clones, there was an increase in symmetric and neurogenic RGL divisions in response to stroke, with a concomitant loss of astrogliogenic RGL divisions. These preliminary results suggest that stroke may alter hippocampal neurogenesis from a distance by activating quiescent RGL pools in the SGZ through an as-of-yet unidentified mechanism and pushing them toward a neuronal fate. In turn, this may accelerate the time-dependent depletion of this RGL population. We speculate that this phenomenon contributes to cognitive changes associated with stroke and may represent a target for pharmacological intervention.
Abstract WMP59: A Simple Clinical And MRI Score To Assess A Risk For Development Of Malignant Middle Cerebral Artery Infarction In Large Hemispheric Acute Ischemic Stroke.
Authors: Shimoyama Takashi , Uemura Junichi , Yamashita Shinji , Shibazaki Kensaku , Inoue Takeshi , Iguchi Yasuyuki , Kimura Kazumi
Published: July 2021

Background:
Early surgical decompression has reduced case fatality and improved functional outcome in patients with malignant middle cerebral artery (MCA) infarction. Therefore, identifying patients who will develop life-threatening brain edema is imperative. The aim of the present study was to devise a simple clinical and MRI score for assessing a risk for malignant course in patients with large MCA infarction within 48 hr after admission.

Methods:
Patients with MCA infarction ≥2/3 of the territory and proximal vessel occlusion (ICA or M1) within 24 hr of onset were retrospectively studied. We defined malignant MCA infarction as follows: (1) secondary decline of consciousness ≥1 point on the NIHSS with midline shift ≥5 mm at the level of septum pellucidum at follow-up CT or MRI; (2) anisocoria or death attributable to herniation. We created a simple score to determine a risk for development of malignant MCA infarction using factors selected by multivariate logistic regression analysis.

Results:
Subjects comprised 119 patients (55 men, median age 78.0 years). Fifty-seven patients (47.9%) developed malignant MCA infarction within 48hr after admission. Multivariate logistic regression analysis revealed the following independent factors associated with malignant MCA infarction: involvement of ACA territory [odds ratio (OR), 15.33; 95% confidence interval (CI), 0.39-59.77; P<0·001], glucose value >145mg/dl [OR, 6.68; 95% CI, 2.19-20.42; P=0.001], and M1 vessel sign on T2*-gradient echo imaging [OR, 5.82; 95% CI, 1.71-19.78; P=0.005]. Those three variables were selected for use in the score, with involvement of ACA territory as 2 points, glucose value >145 mg/dl as 1 point, and M1 vessel sign as 1 point. Frequencies of patients developing malignant MCA infarction for each score were as follows: score 0, 10.0%; score 1, 23.5%; score 2, 71.4%; score 3-4, 96.3%. The C statistic for the score was 0.875 (95%CI, 0.810-0·940, P<0.001).

Conclusion:
Our simple clinical and MRI score reliably assessed a risk for development of malignant MCA infarction in large hemispheric acute ischemic stroke, and it should support clinical decision making in early surgical decompression.
Abstract WMP83: Prediction of Intracerebral Hematoma Expansion: Multicenter External Validation of the CTA Spot Sign Score
Authors: Huynh Thien J , Demchuk Andrew , Dowlatshahi Dar , Krischek Ölem , Kiss Alex , Hill Michael D , Molina Carlos A , Rodriguez-Luna David , Dzialowski Imanuel , Silva Blas Yolanda , Czlonkowska Anna , Lum Cheemun , Boulanger Jean-Martin , Gubitz Gordon , Bhatia Rohit , Padma Vasantha , Roy Jayanta , Kase Carlos S , Gladstone David J , Aviv Richard I ,   PREDICT/Sunnybrook ICH CTA study group
Published: July 2021

Background and Purpose:
The spot sign score (SSS) stratifies hematoma expansion risk in patients with acute intracerebral hemorrhage (ICH) but is not externally validated. We sought to validate the SSS and assess prognostic spot characteristics associated with hematoma expansion in a prospective multicenter study.

Methods:
We studied 228 ICH patients presenting < 6 hours post-onset enrolled in the PREDICT (PREdicting hematoma growth anD outcome in ICH using contrast bolus CT) study, a multicentre prospective observational cohort study of ICH patients evaluated with baseline non-contrast CT, CT angiography (CTA), and 24-hour follow-up CT. Primary outcome was significant hematoma expansion (>6ml or >33%). Secondary outcomes were absolute and relative expansion. Blinded CTA spot sign characterization (spot number, maximum axial size and attenuation, and relative attenuation compared to the ipsilateral internal carotid artery and superior sagittal sinus) and SSS calculation was performed independently by two neuroradiologists and a radiology resident. Multivariable regression for prediction of hematoma expansion was performed and diagnostic performance of the SSS and spot characteristics was examined with ROC analysis and tests for trend.

Results:
SSS independently predicted significant, absolute, and relative hematoma expansion (p-values of 0.001, <0.001, and 0.009, respectively), adjusting for initial hematoma volume, INR, mean arterial pressure, and time from onset-to-baseline CT, and demonstrated near perfect interobserver agreement (κ = 0.82). Spot number and SSS demonstrated similar area under the curve (AUC 0.69 vs. 0.68, p=0.149) for hematoma expansion. Incremental risk of hematoma expansion was demonstrated with increasing SSS however a significant trend was not identified (p trend=0.720). Of all spot characteristics, only spot number was independently associated with expansion (p<0.001) providing incremental risk stratification (p trend=0.050) and near perfect agreement (κ=0.85). Median absolute hematoma growth for 0, 1, 2 to 3, ≥4 spots was 0.4, 4, 12, 82 ml respectively.

Conclusion:
Spot number is the single best predictor of significant ICH expansion and appears to be as good as the total SSS in predicting expansion.
Abstract WMP98: Economic Impact Of Dabigatran For Prevention Of Stroke In Patients With Atrial Fibrillation In Colombia
Authors: Alfonso-Cristancho Rafael , Vecino Andres I , Herran Santiago
Published: July 2021

INTRODUCTION:
Dabigatran is a novel oral anticoagulant considered as an alternative to warfarin in patients with non-valvular Atrial Fibrillation (AF) to prevent Stroke.

Hypothesis:
dabigatran compared to warfarin for stroke prevention in AF is a good investment for the health care system in Colombia.

Methods:
We developed a Markov model to represent the health states of AF and its complications: 6 health states (disabling and non-disabling stroke, myocardial infarction, pulmonary embolism and death) and 2 transitional states (major and minor hemorrhage). Probabilities were derived from clinical trials; resource use was estimated from the guidelines of the Colombian Society of Cardiology and validated to adjust to usual practice. Direct medical costs were extracted from public and private insurers and hospitals, and indirect costs (e.g. wages lost, transportation costs, etc.) were obtained from the most recent National Health Survey. Utilities were obtained from a systematic literature review. Two separate analysis, payer and societal perspective, were performed in a 20-year horizon. Multivariate sensitivity analysis was also performed and results were discounted at 3% annually.

Results:
After 20 years of follow up, cumulative discounted direct medical costs per patient accounted for USD$70,500 for warfarin and $78,840 and $79,860 for 150mg and 110mg of dabigatran, respectively. When taking into account indirect costs, warfarin increased their costs by 13% while dabigatran costs were increased by 7%. Estimated life years (LY) for Dabigatran were higher (9.4 and 9.3 for 150mg and 110mg) as well as the QALYs (8.5, 8.4) than for warfarin 9.1 LY and 8.1 QALYs. The calculated ICER was $23,760 and $34,690 per additional QALY gained with dabigatran 150mg and 110 mg from the payer perspective and $19,380 and $28,730 from the societal perspective. The budget impact of including coverage for dabigatran would not surpass 3% of the current unit of payment per capita.

CONCLUSIONS:
In Colombia, coverage for dabigatran for the management of non-complicated AF could increase LY and QALYs at a modest financial impact.
Abstract WP103: Endothelial Nitric Oxide Synthase Regulates White Matter Changes after Stroke
Authors: Cui Xu , Chopp Michael , Yan Tao , Ning Ruizhuo , Roberts Cynthia , Zacharek Alex , Venkat Poornima , chen jieli
Published: July 2021

Background:
Stroke induced white matter damage is associated with neurological functional deficits, but the underlying mechanisms are not well understood. Endothelial nitric oxide synthase knockout (eNOS-/-) mice exhibited a higher mortality, more severe neurological functional deficit, and decreased neurogenesis, angiogenesis and arteriogenesis after stroke than wild type mice. There are no reports as to whether eNOS is related to the white matter change post-stroke.

Methods:
Adult male C57BL/6 WT and eNOS
-/-
mice were subjected to permanent middle cerebral artery occlusion (MCAo) by a filament and sacrificed 7 days after MCAo. Functional evaluation, infarct volume measurement, and immunostaining for analysis of white matter changes were performed.

Results:
There is no significant difference in the infarction volume between wild type and eNOS
-/-
(wild type : 23.09%±3.32%; eNOS-/-: 27.83%±4.92%, p=0.436, n=9/group). However, eNOS
-/-
mice showed significantly decreased functional outcome tested by the singal pellet reaching test (wild type: 38.46%%±1.43%, eNOS-/-: 27.45%±2.41%, p=0.0017). eNOS
-/-
mice also exhibited increased white matter damage compared to wild type mice, including decrease:
1.
Axonal density stained by Bielshowsky Silver in the ipsilateral striatal bundles (wild type: 22.06%±3.0%, eNOS-/-: 13.32%±2.18%,, p=0.031), and in the contralateral striatal bundles (wild type: 65.35%±3.97%, eNOS-/-: 29.38%±5.84%, p=0.02);
2.
Density of phasphorylated neurofilament by SMI31-immunoflureoscent staining (wild type: 24.11%±2.06%, eNOS-/-: 7.90%±1.70%, p=0.009);
3.
The number of CNPase-positive oligodendrocytes in the ischemic border (wild type: 52.23±5.10, eNOS-/-: 35.59±5.33, p=0.041);
4.
The number of NG2-positive oligodendrocyte progenitors in the ischemic border (wild type: 26.22±2.31, eNOS-/-: 18.38±1.95, p=0.0187). There is no significant difference in the density of Luxol fast blue stained myelin in the ipsilateral striatal bundles between wild type and eNOS
-/-
mice (wild type: 25.21%±3.64%; eNOS-/-: 21.39%±6.29%, p=0.260).

Conclusions:
We are the first to report that eNOS not only regulates vascular changes and neurogenesis, but also plays an important role in white matter changes after stroke.
Abstract WP106: Remote Ischemic Per-Conditioning (RIPerC) is Protective after Embolic Stroke in Ovariectomized Female Mice
Authors: Hoda Md Nasrul , Bhatia Kanchan , Ahmad Saif , Hafez Sherif S , Periyasamy-Thandavan Sudharsan , Samuel Herberg , Hill William D , Ergul Adviye , Fagan Susan C , Hess David C
Published: July 2021

RIPerC by sub-lethal limb ischemia is protective in multiple animal models of reperfusion injury including stroke, and in certain clinical trials. We reported that RIPerC is effective with and without IV-tPA after embolic stroke (eMCAO) in young male mice (
Hoda et al; Stroke. 2012: MS ID# 660373; in press
). Our objective here was to determine if RIPerC is also effective in ovariectomized (OVX) female mice.

Methods:
eMCAO was induced in 68 WT C57/BL OVX females by injecting fibrin-rich clot into the right hemisphere, and occlusion was confirmed with laser Doppler instruments (LDI). Animals were randomized for the treatments after eMCAO and outcome measurements were blindly performed. RIPerC therapy or sham procedure was performed non-invasively using a rodent blood pressure cuff on the left hind limb at 2 hrs post-eMCAO (4 cycles/ each cycle 10 minutes/ 10 minutes interval). Either IV-tPA or IV-saline was infused at 4 hours post-eMCAO. Cerebral blood flow (CBF) by LDI and plasma nitric oxide (NO) was measured at 6 hours post-eMCAO. At 24 hours post-eMCAO, Bederson neurological deficit score (NDS) was assessed, and infarct size was estimated by TTC-staining.

Results:
RIPerC alone significantly improved the CBF, plasma NO level and NDS (P<0.05), and also reduced the infarct size (Relative reduction ~31%; P<0.01) as compared to eMCAO control group. IV-tPA alone at 4 hours post-eMCAO neither improved NDS nor reduced the infarct, although IV-tPA improved the CBF as compared to eMCAO control group due to its recanalization effects (P<0.01). In comparison to IV-tPA alone treatment, RIPerC combination with IV-tPA did not show significant improvement in CBF. But when compared to eMCAO control group, the combination therapy showed further improvements in CBF at 6 hours post-eMCAO (P<0.001). Combination therapy also significantly improved the NDS (P<0.05) and reduced the infarct size (Relative reduction ~21%; P<0.05) as compared to eMCAO control group at 24 hours post-eMCAO.

Conclusion:
RIPerC is an effective therapy after eMCAO in females. Further work is needed to determine the effectiveness of RIPerC in aged animals and in animals with comorbidities.
Abstract WP110: TLR5 Is Related To Neuroprotective Mechanism Of Postconditioning Through NF-κB-Akt Survival Pathway In Cerebral Ischemia
Authors: Jeong Jaewon , Yang Jiwon , Kim Soojin , Jeong Hyesun , Kim Bokyung , Jung Siyun , Kim Jeong-Soo , Song Yun Seon
Published: July 2021

Background and Purpose:
Although postconditioning following stroke has indicated neuroprotective mechanisms, little is known about the mechanisms that lead to neuroprotection. Using flagellin, NF-kB activators and agonists of TLR5, we tested whether TLR5 plays an integral role in NF-kB activation and postconditioning-induced neuroprotection.

Method:
For the postconditioning group, 30 min of MCAO was induced, then 5 min of reperfusion was performed, after which the MCA was again occluded for 5 min. Using an anaerobic chamber, bEnd.3 and BV-2 cells in the postconditioning group were subjected to 180 min OGD (oxygen and glucose deprivation) and were allowed to recover for 10 min before being subjected to 10 more min of OGD. The control group was subjected to 180 min of OGD. Flagellin, an agonist of TLR5, was used to clarify the association between TLR5 and postconditioning
in vivo
(ICV; 50, 100 ng/mouse) and
in vitro
(0.1, 0.25, 0.5, 1 ng/ ml) experiments. Immunoprecipitation and immunoblotting were used to determine the interactions of TLR5, MyD88, p-Akt, and NF-κB.

Results:
Animals treated with postconditioning showed significant differences in infarct volumes compared with the MCAO group up to 60.51%. Postconditioning elevated NF-κB translocation to the nuclei (p<0.001) as early as 1 hour after postconditioning following tFCI and OGD. The protein interactions and expressions of TLR5, MyD88 and p-Akt (p<0.05) were increased in
in vivo
and
in vitro
postconditioning. Additionally, inhibition of Akt phosphorylation by Akt inhibitor IV decreased NF-κB translocation after postconditioning. To clarify the role of NF-κB in postconditioning, flagellin was used as a postconditioning mimicking agent. The treatment of flagellin reduced hypoxic-ischemic injury and increased nuclear accumulation of NF-κB and activation of Akt up to 4 hr.

Conclusions:
Postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathway under TLR5 after stroke. Agonist of TLR5, flagellin simulated NF-κB and Akt survival pathways in cerebral ischemia. Our results suggested new mechanisms of postconditioning through TLR-5 and NF-κB, which leads to the possibility of development of a postconditioning mimicking agent using NF-κB activators such as flagellin.
Abstract WP130: Association of Large Inter-arm Blood Pressure Difference With Mortality And Systemic Atherosclerosis In Acute Stroke Patients
Authors: Kim Jinkwon , Song Tae-Jin , Song Dongbeom , Oh Seung Hun , Kim Ok Joon , Nam Hyo Suk , Kim Young Dae , Heo Ji Hoe
Published: July 2021

Backgrounds:
Large inter-arm difference of blood pressure (IAD) is associated with development of cardiovascular events and increased mortality in the general population and in patients with cardiovascular risk factors. However, it is unknown whether the presence of large IAD has prognostic value in acute stroke patients and whether it is associated with atherosclerosis on other vascular beds (cerebral, coronary, and peripheral arteries, and aorta). We evaluated the prognostic value of large IAD measured in acute ischemic stroke, and the association between large IAD and atherosclerosis on multiple arterial beds (cerebral, coronary, and peripheral arteries, and aorta).

Methods:
We included 836 consecutive patients with acute ischemic stroke. Large IAD was defined by more than 10 mmHg absolute difference of systolic blood pressure between the arms. The presence of systemic atherosclerosis was determined based on cerebral angiography, coronary CT angiography, transesophageal echocardiograpghy and ankle-brachial index examination.

Results:
Large IAD was observed in 7.4 % of patients. During a mean study period of 419.4 ± 250.2 days, 48 patients (5.7 %) died (including 34 cardiovascular deaths). The Kaplan-Meier survival curves showed significantly higher mortality in the group with large IAD than those without (Figure, a log-rank test, (A) p<0.001 in all-cause death, (B) p<0.001 in cardiovascular death). In multivariate Cox regression, large IAD was associated with increased all-cause mortality (adjusted HR is 3.040, p=0.002), and cardiovascular mortality (adjusted HR is 3.612, p=0.002). The presence of large IAD was associated with peripheral artery disease in the lower limbs (p=0.005), but not with atherosclerosis in the cerebral artery, coronary artery or the aorta.

Conclusions:
The presence of large IAD is a strong independent prognostic marker in acute ischemic stroke.
Abstract WP136: Enhanced Carotid Plaque on Contrast-enhanced Ultrasound is Asociated with Plaque Instability and Symptomatic Patients
Authors: Matsumoto Noriko , Kimura Kazumi , Uno Masaaki , Sakai Kenichirou , Sadahira Yoshito , Nishimura Hirotake
Published: July 2021

Background:
Presence of neovascularization in plaque was reported as a reliable maker of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of intraplaque neovascularization. The aim of the present study was to investigate the neurological symptom and histopathologic findings of enhanced carotid plaque using CEUS.

Methods:
We studied consecutive 30 patients (27 men, age 68.2 ± 7.6 years) who underwent carotid endarterectomy. Enhanced plaque (enhanced group) was classified into two subgroups: a spotty pattern as moving bright spots within plaque (spotty subgroup, Figure A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque (linear subgroup, Figure B).Sonazoid, perflurobutane microbubbles, was used as the contrast agent. We investigated the association between the neurological symptom, CEUS findings and histopathologic findings.

Results:
CEUS revealed enhanced plaque in 22 (73.3%) of 30 patients. 10 patients were spotty subgroup, and 12 patients were linear subgroup. Symptomatic patients were more frequent in enhanced group than non-enhanced group (82.6% vs. 50%, p=0.037).The amount of neovascularization was larger in enhanced group than in non-enhanced group (6.3±4.2/2.5mm
2
vs. 1.5±1.6/2.5 mm
2
, P=0.001, Figure C). Furthermore, the enhanced group had more macrophage aggregation (11.1±12.5% vs. 4.2±1.5%, P=0.001) and intraplaque hemorrhage (20.2±15.9% vs. 9.4±12.2%, P=0.031) compared with the non-enhanced group. 11 of the linear subgroup (91.7%) had fibrous cap rupture, but this was observed in only 20% of those with a spotty subgroup (P=0.001, Figure D). Symptom and other histopathological findings were not different between the two subgroups.

Conclusions:
Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque and patients.
Abstract WP137: Improvement of Cerebrovascular Reactivity After Carotid Stenting is Greater in Non-Diabetic than in Diabetic Patients: a Bold-FMRI Study.
Authors: Mazzetto-Betti Kelley C , Castro-Affonso Luis H , Leoni Renata F , dos Santos Antonio C , Abud Daniel G , Leite JoãP , Pontes Neto Octavio M
Published: July 2021

Background:
Cerebrovascular reactivity (CVR) has been suggested as an independent predictor of stroke in patients with severe carotid stenosis. Functional-MRI (fMRI) can be used to assess CVR by comparing latency parameters of the neurovascular coupling, i.e. BOLD response at baseline and during hypercarbic challenge. We aim to compare BOLD amplitude and latency parameters in the ipsilateral (IH) and contralateral hemispheres (CH) induced by auditory stimulus, under different hypercapnia levels in diabetic and non-diabetic patients with symptomatic carotid stenosis, before and after carotid stenting.

Methods:
seven diabetic and eight non-diabetic patients with unilateral severe symptomatic carotid stenosis and similar clinical characteristics were evaluated. The protocol was undertaken one week before and three months after the endovascular intervention. Subjects were submitted to auditory stimulus (3s) under normocapnia and EtCO2 increase of 5 and 10mmHg. The images were acquired with a 3T MRI-scanner, preprocessed and BOLD response amplitude and latency parameters were analyzed.

Results:
We observed decreased BOLD amplitude in the IH compared to the CH (p<0.05) in non-diabetic patients in hypercapnic conditions, and was compromised bilaterally in diabetic patients before the stenting. In diabetic patients the mean change on BOLD latency parameters were not significant with CO2 increment. After carotid stenting, BOLD amplitude (p<0.05) under hypercapnic conditions and area under the curve (P<0.05) were increased for non-diabetic patients but not for diabetic patients.

Conclusions:
diabetic patients have diffuse baseline compromise of CVR and their cerebrovascular reactivity measured on BOLD fMRI does not respond to carotid stenting as non-diabetic patients.
Abstract WP164: Role of Risk Factors in the Paradoxical Effect of Smoking on Peri-procedural Stroke in SAMMPRIS
Authors: Holmstedt Christine A , Turan Tanya N , Lynn Michael J , Lane Bethany F , Montgomery Jean , Derdeyn Colin P , Fiorella David , Janis L. S , Chimowitz Marc I
Published: July 2021

Background:
A previous SAMMPRIS analysis of patients randomized to stenting showed that peri-procedural ischemic infarcts were significantly associated with diabetes, basilar stenosis, age, and smoking status with never smokers having a higher risk (odds ratio = 8.8, p< 0.001). We sought to determine if this finding could be due to a higher burden of other risk factors in never smokers.

Method:
Baseline features in 213 patients undergoing stenting in SAMMPRIS were compared between never smokers vs. former and current smokers in univariate and multivariate analyses. Logistic regression was used to determine the effect of smoking on peri-procedural ischemic infarcts after adjusting for factors related to smoking.

Data:
Univariate results are shown in Table 1. Never smokers were significantly (P<0.05) more likely to be female, diabetic, hypertensive, and have another intracranial stenosis, but in multivariate analyses only hypertension and another intracranial stenosis remained significantly (P<0.05) associated with smoking status. In a multivariate model that incorporated hypertension and another intracranial stenosis along with smoking status, diabetes, basilar stenosis, and age, smoking status remained significant with an increased risk among patients who never smoked (odds ratio = 5.3, p = 0.005).

Conclusion:
While never smokers had significantly higher rates of some risk factors compared to active or previous smokers, these risk factors do not explain all the increased risk of early stroke in never smokers after stenting in SAMMPRIS. Another contributory factor may be that smoking accelerates the conversion of clopidogrel to its active form.
Abstract WP167: Effects of Selective Serotonin Reuptake Inhibitors versus Tricyclic Antidepressants on Cerebrovascular Events
Authors: Lin Jou Wei , Chang Chia-Hsuin , Lin Chin-Hsien
Published: July 2021

Background: The objective of this study was to
examine the effects of selective serotonin reuptake inhibitors (SSRIs) versus tricyclic antidepressants (TCAs) on cerebrovascular events in patients with depression or anxiety.

Methods:
We performed a retrospective cohort study in a nationwide population. The patients who started to take SSRIs and TCAs with a diagnosis of depression or anxiety between January 1, 2001 and December 31, 2009 were identified from the Taiwan National Health Insurance claims database. We examined the association between the two types of antidepressants and incidence of stroke using a proportional hazard model adjusted for risk factors for stroke.

Results:
Among of the 24,662 SSRI and 14,736 TCA initiators, the crude incidence rate for stroke was 10.03 and 13.77 per 100 person-years respectively. SSRI use was associated with a significantly reduced risk as compared with TCAs with the adjusted hazard ratio of 0.67 (95% confidence interval 0.47 to 0.96) in a dose-dependent manner. No significant effect modification was found among subgroups, such as hypertension, diabetes, previous cardiovascular and cerebrovascular diseases. The adjusted hazard ratio was 1.09 (95% confidence interval 0.65 to 1.85) for those aged more than 65 years, suggesting only a potential trend for a higher risk of stroke with SSRIs in the geriatric group.

Conclusions:
As compared with TCAs, the use of SSRIs was associated with a reduced risk for cerebrovascular events in a clear dose-response manner. Further researches are needed to examine the potential risk and benefit of SSRI use for patients with high risk of stroke.
Abstract WP17: Rates and Outcomes of Neurosurgical Evacuation for Thromboytic Related Intracerebral Hemorrhage in Patients with Acute Ischemic Stroke
Authors: Norby Kiersten E , Adil Malik M , Rahman Haseeb A , Siddiq Farhan , Qureshi Adnan I
Published: July 2021

Background:
Thrombolytic related intracerebral hemorrhage (ICH) is an infrequent occurrence in patients with acute ischemic stroke. There is controversy surrounding the value of neurosurgical evacuation of hematomas and decompression in these patients and whether such availability is a necessary pre-requisite for administration of thrombolytics.

Objective:
To report the frequency and outcomes of patients who suffer from thrombolytic related ICH and undergo a craniotomy.

Materials/Methods:
Using the Nationwide Inpatient Sample (NIS) from 2002 to 2010, acute ischemic stroke patients who suffered from thrombolytic related ICH were identified using ICD-9 codes. Patients were divided into those who received craniotomy and those who received medical management alone. Discharge destination and mortality were primary endpoints.

Results:
A total of 7359 patients suffered thrombolytic related ICH, 125 (1.7%) of those patients underwent craniotomy and 7234 patients (98.3%) received medical treatment alone. Patients who underwent craniotomy were younger (58±5 versus 72±11 years, p=0.09). Patients in the craniotomy group were frequently in extreme severity APR-DRG category compared with medical management group (92.2% versus 55.5%, p=0.0003). The craniotomy group had greater requirements for gastrostomy (47.8% versus 16.7%, p=0.02) and mechanical ventilation (55% versus 13.8%, p=0.005) compared with the medical management group. The mean length of stay was also longer in the craniotomy group (21.5±7 versus 10±2 days, p<0.0001). The in-hospital mortality and discharge to nursing home/long-term care facility was 24.2% and 72% among those treated with craniotomy, respectively. The corresponding proportions were 30.5% and 57% for medically treated group (p=0.5 and p=0.1, respectively).

Conclusion:
Emergent craniotomy for thrombolytic related hematoma evacuation or decompression in acute stroke is a salvage treatment offered to a small proportion of patients. There may be evidence that this reduces mortality, however long term disability may be higher in those patients. More detailed analysis may be required to understand the impact of emergent craniotomy on patient disability in thrombolytic related hemorrhage for acute ischemic stroke.
Abstract WP179: Effects of Stroke Lesson Using A Comic Book and Animated Cartoon on Elementary School Children
Authors: Sakamoto Yuki , Yokota Chiaki , Miyashita Fumio , Amano Tatsuo , Shigehatake Yuya , Oyama Satoshi , Itagaki Naruhiko , Okumura Kousuke , Toyoda Kazunori , Minematsu Kazuo
Published: July 2021

Background and purpose:
Efforts to increase the knowledge of stroke risk factors and warning signs for youth are expected to reduce the time from stroke onset to hospital and to be effective in stroke prevention. Although there were a few studies about stroke enlightenments for younger individuals, the effective means of stroke enlightenments for elementary school children have not been clarified. The aim of this study is to evaluate the effectiveness of stroke lesson which we developed for elementary school children using a comic book and animated cartoon.

Methods:
We developed a comic book and a 10-minutes animated cartoon introducing stroke risk factors, stroke sign and symptoms, and encouraging immediate calling for emergent medical service (EMS) on identification of stroke signs and symptoms. Using these materials, a 30-minutes lesson was performed by the school teacher for school children. Questionnaires on stroke knowledge (including a total of 7 correct items for risk factors and 6 for stroke signs and symptoms), consisted of multiple-choice and closed type questions, were filled out by school children before, immediately after, and 3 months after the lesson. The score was calculated as total numbers of correct answers in assessing stroke knowledge.

Results:
A total of 219 school children (10 or 11 years old) in 2 public elementary schools were received the stroke lesson. The knowledge about stroke risk factors at the point of immediately after the lesson increased significantly compared with that of before the lesson (mean ± standard deviation, 4.75±1.40 vs. 4.25±1.51, p<0.001), and it preserved at the points of 3 months after the lesson (4.55±1.55). Correct answers for stroke symptoms immediately after the lesson also improved significantly compared with that before the lesson (3.48±1.00 vs. 2.96±1.21, p<0.001), and it conserved at 3 months after the lesson (3.35±1.06). The proportion of calling EMS on identifying stroke signs and symptoms immediately after the lesson were significantly higher than that before the lesson (97% vs. 91%, p=0.007).

Conclusion:
Stroke lesson by a school teacher using a comic book and animated cartoon which we developed was effective on the stroke enlightenments for elementary school children.
Abstract WP180: The Association between Neighborhood Socioeconomic Disadvantage, Fish Consumption, and Stroke Risk Factors: the Cardiovascular Health Study
Authors: Liang Li-Jung , Vassar Stefanie D , Longstreth W. T , Merkin Sharon S , Escarce Jose J , Obviagele Bruce , Brown Arleen F
Published: July 2021

Background:
Fish consumption has been associated with reduced risk of stroke, and residence in low income neighborhoods has been associated with higher risk of stroke, either directly or through biologic risk factors for stroke, such as hypertension, diabetes, and subclinical disease. No studies, however, have examined the relationship between neighborhood characteristics, fish consumption, and stroke risk factors.

Methods:
We analyzed data from 3907 adults from the Cardiovascular Health Study (CHS), a population-based, longitudinal study of adults ages ≥65 years from 4 US counties. The outcomes were fish consumption (non-fried fish: ≥5 times/wk, 1-4 times/wk, 1-3 times/mo, <1 time/mo; fried fish: ≥1 times/wk, 1-3 times/mo, <1 time/mo) and stroke risk factors (Framingham stroke risk score [FSRS], diabetes, subclinical CVD [sCVD], hypertension). Neighborhood socioeconomic status (NSES) was measured using a composite of 6 census variables. Hierarchical generalized mixed-effects regression models with census-level random-effects were fit to continuous, binary, and ordinal outcomes adjusted for sociodemographic characteristics.

Results:
In adjusted analyses, residents of the most disadvantaged neighborhoods had lower consumption of non-fried fish (OR=0.55, 95% CI: 0.41-0.74) and higher consumption of fried fish (OR=1.61, 1.28-2.03). Eating non-fried fish was independently associated with a lower stroke risk score, but not with diabetes, hypertension, or sCVD. However, these relationships differed by neighborhood. Among those who consumed non-fried fish 1-4 times/wk, residents of the most disadvantaged neighborhoods had higher odds of diabetes (OR=1.78; p=0.03) and sCVD (OR=1.59; p=0.003), a trend towards higher odds of hypertension (OR=1.33; p=.054), and a higher FSRS (OR=1.09; p=.03). Eating fried fish was not associated with differences in stroke risk factors or FSRS.

Conclusions:
Residents of disadvantaged neighborhoods consumed less non-fried fish and more fried fish. Even with the same level of non-fried fish consumption, residents of more disadvantaged neighborhoods did not get the same benefit in stroke risk reduction as residents of higher SES neighborhoods.
Abstract WP190: Assessing The Performance Of The Framingham Stroke Risk Prediction Score In The REGARDS Cohort
Authors: McClure Leslie A , Kleindorfer Dawn O , Cushman Mary , Soliman Elsayed Z , Howard George , Kissela Brett M
Published: July 2021

INTRODUCTION:
The most well-known stroke risk score is the Framingham Stroke Risk Score (FSRS). However, the FSRS was developed during the higher stroke risk period of the 1990’s, and has not been validated for African Americans.

Methods:
Among participants in the Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we compared expected annualized stroke rates predicted from the FSRS to observed stroke rates overall and within strata defined by FSRS risk factors (age, sex, systolic blood pressure, use of antihypertensive medications, diabetes, smoking, atrial fibrillation, left ventricular hypertrophy and prevalent coronary heart disease).

Results:
Among 27,748 participants stroke-free at baseline, 715 stroke events occurred over 5.6 years of follow-up. FSRS-estimated incidence of stroke was 1.6 times higher than observed rates for black men, 1.9 times higher for white men (Table 1). This overestimation was consistent among most subgroups of FSRS factors including by categories of predicted FSRS level and blood pressure (Table 1). The overestimation was smaller for low predicted-risk blacks and among white females with higher SBP.

Conclusions:
While higher FSRS was associated with higher stroke risk, the FSRS overestimated observed stroke rates in this study, particularly in certain subgroups. This may be due to temporal declines in stroke rates, secular trends in prevention treatments, or differences in populations studied. More accurate estimates of event rates are critical for planning research, including clinical trials, and targeting health-care efforts.
Abstract WP191: Framingham Stroke Risk Score and Stroke Mortality Among Canadian Adults
Authors: Katzmarzyk Peter T , Reeder Bruce A , Elliott Susan , Joffres Michel
Published: July 2021

Background:
Stroke is a leading cause of mortality among Canadian adults. There is currently very little information on the utility of stroke prediction algorithms for the Canadian population. The purpose of this study was to determine if the Framingham stroke risk prediction model (D’Agostino et al.
Stroke
1994;25:40-43) was associated with stroke mortality in a population-based sample of Canadian adults.

Methods:
The sample included 3,163 adults 55-74 y of age who participated in the Canadian Heart Health Surveys (1986-95) and were free from stroke at baseline. The analysis includes all deaths that occurred between baseline data collection and December, 2004. A modified Framingham Stroke Score was assigned to each participant at baseline based on their age, sex, treated or untreated systolic blood pressure levels, diabetes, smoking, and history of cardiovascular disease. Data on history of atrial fibrillation and left ventricular hypertrophy were not available. Hazard ratios for all-cause and stroke mortality were estimated using Cox proportional hazards regression with exam year as a covariate, and multivariable models also included body mass index, alcohol consumption and education level as covariates.

Results:
There were 915 deaths (70 from stroke) over 12.2 y (0.5 to 16 y) of follow-up. The hazard ratios (95% C.I.) for all-cause mortality associated with the Framingham Stroke Score were 1.12 (1.10 - 1.15) in men and 1.18 (1.15 - 1.22) in women. The hazard ratios for stroke mortality were 1.15 (1.06 - 1.25) in men and 1.22 (1.11 - 1.36) in women. When comparing men and women with scores greater than 8 and 9, respectively (median) to those with lower scores, the hazard ratios were 2.34 (1.20 - 4.58) in men and 4.81 (1.85 - 12.50) in women. The additional inclusion of body mass index, alcohol consumption and education to the models did not appreciably change the results.

Conclusions:
The Framingham Stroke Score is a significant predictor of all-cause and stroke mortality in Canadian adults, and the risk is independent of body mass index, alcohol consumption and education level.
Abstract WP218: Assessment of Carotid Plaque Vulnerability Using Quantitative Expansive Remodeling Evaluation and MRI Plaque Signal Intensity
Authors: Kurosaki Yoshitaka , Yoshida Kazumichi , Fukumitsu Ryu , Koyanagi Masaomi , Sadamasa Nobutake , Chin Masaki , Handa Akira , Yamagata Sen
Published: July 2021

Background:
Assessment of plaque vulnerability is important in evaluating the future risk of stroke. Plaque characteristics and plaque volume are important components of plaque vulnerability. Expansive remodeling (ER) is one of the criteria for vulnerable plaque in the coronary arteries, and influences the plaque volume. The aim of this study is risk stratification of carotid plaque through the evaluation of quantitative ER and MRI plaque signal intensity.

Methods:
We studied and obtained both pre-operation carotid MRI T1-weighted axial and long axis images of 72 patients who underwent carotid endarterectomy or carotid aretery stenting. ER ratio (ERR) was calculated from the ratio of the linear diameter of the artery at the thickest segment of the plaque to the diameter of the artery beyond any poststenotic dilatation on the long axis image on carotid MRI. We also calculated relative plaque signal intensity (rSI) from the axial image and grouped the patients as follows: Group A, rSI≥1.4 and ERR≥1.8; Group B, rSI<1.4 and ERR≥1.8; Group C, rSI≥1.4 and ERR<1.8; Group D, rSI<1.4 and ERR<1.8. Ischemic events within 6 months were retrospectively evaluated in each group.

Results:
Of the 72 patientis, the number of patients in each group was as follows: Group A, 20 patients; B, 12 patients; C, 19 patients; D, 21 patients. Fifteen patients (75%) in Group A, 6 patients (50%) in Group B, 8 patients (42%) in Group C and 7 patients (33%) in Group D had ischemic events within 6 months. Ischemic events in Group A was significantly higher than in Group C and D (p<0.05, p<0.001).

Conclusion:
The combined assessment of plaque characterization with MRI and morphological evaluation using ERR are useful in risk stratification for carotid lesions.
Abstract WP271: Epicatechin Protects Neurons from in vitro Ischemia through the Nrf2 Pathway.
Authors: Agrawal Megha , Dore Sylvain
Published: July 2021

Introduction:
Foods rich in polyphenols, such as flavanols, can lower the risk of ischemic heart disease and we recently demonstrated beneficial outcomes in ischemic stroke; however, the mechanism of protection has not been fully established. In this study, we assessed the hypothesis that epicatechin provides neuroprevention against oxygen glucose deprivation (OGD) in primary cortical neurons, and this protection occurs through activation of Nrf2. Epicatechin targets genes regulating expression of heme oxygenase 1 (HO1), ferritin and biliverdin, which can prevent free radical.

Methods:
Experiments were carried out to optimize and standardize various conditions for OGD and reoxygenation. Seven day old cultures from wildtype and Nrf2 knockout mice were pretreated with 50 and 100uM of epicatechin before 4h oxygen glucose deprivation followed by 24h reoxygenation. Neuronal survival was assessed by live calcein AM, LDH and MTT assay after 24h reoxygenation. Changes in protein expression levels were measured by Western blotting.

Results:
OGD of 4h followed by a reoxygenation of 24h with 4-6mg/ml glucose concentration in culture medium was found to be the optimum conditions to create ischemic stroke like situations under in vitro environment using primary postnatal neurons. Significant increase in live cells (35.7±4.3 vs 64.3±4.9 and 87.5±9.7, p<0.05 and p<0.0001) was recorded in OGD induced cultures pretreated with 50 and 100uM epicatechin respectively by calcein-AM assay and increase in viability (0.2±0.1 vs 0.3±0.1 and 0.3±0.1, p<0.0001) by MTT assay. Significant decrease in cytotoxicity (3102.0±180.4 vs 2684.0±53.5 and 1752.0±64.5, p<0.0001) was also recorded by LDH assay. Western blots from epicatechin pretreatment showed an increase in HO1 and L-ferritin protein expression. Interestingly, pretreatment of epicatechin could not protect Nrf2 knockout neurons from OGD.

Conclusion:
Cell viability assays suggested that pretreatment with epicatechin protect neurons against oxidative stress induced by OGD. Interestingly, the epicatechin-associated neuroprotection was mostly abolished in neurons derived from Nrf2 knockout mice. These results suggest that epicatechin exerts part of its beneficial effect through activation of Nrf2.
Abstract WP285: Hemicraniectomy Outcomes in Patients with Malignant Middle Cerebral Artery Infarctions Plus
Authors: Sangha Navdeep S , Irani Malcolm , Peng Hui , Wu Tzu-Ching , Barreto Andrew D , Savitz Sean I , Grotta James C , Gonzales Nicole
Published: July 2021

Hemicraniectomy (HC) is a proven treatment to reduce mortality and improve outcomes in patients with malignant middle cerebral artery (MCA) infarction.

The benefit of HC in patients with MCA strokes plus infarctions in other vascular territories has not been well defined. We hypothesized that there would be no difference in outcomes in patients with MCA strokes compared to those with MCA Plus infarctions.

We retrospectively reviewed our registry from 07/2003 to 12/2011, and identified consecutive patients diagnosed with an ischemic stroke that underwent HC. Outcome measures included mRS at discharge, mRS at day 90 and death at one year. A good outcome was defined as mRS 0-4. The vascular territory of infarction was established by a vascular neurologist who reviewed the nearest CT scan prior to the procedure and compared it with the official interpretation of a neuroradiologist. The MCA Plus infarctions included MCA + anterior cerebral artery

(ACA), MCA + posterior cerebral artery (PCA) and MCA + ACA + PCA.

Ninety seven patients had a HC. Sixty four were MCA and 33 were MCA Plus. The mean MCA and MCA plus ages were 51.9 (± 14.2) and 51.3 (± 12.8) years respectively.

Median NIHSS was 12.5 (IQR 10.0-15.0) in MCA vs. 12.2 (IQR 9.5-14.0) in MCA Plus. MCA group had a good outcome at discharge in

25% of subjects vs. 21% in the MCA Plus cohort, OR 0.72 (95% CI: 0.24-2.15). For patients with available data, 40% of MCA was dead at 90 days and 50% in MCA Plus, and for those who survived, 33% of MCA had a good outcome compared to 15% of the MCA Plus, OR 2.4 (95% CI: 0.45-7.61).

Forty eight percent of MCA patients were dead at one year vs. 76% of the MCA Plus patients.

We found no difference in good outcomes at discharge and 90 days in our cohort of patients who received a HC with MCA or MCA plus infarctions. Limitations include a high rate of missing data at day 90 and at one year, and poor standardization of HC timing. Further prospective studies are necessary to evaluate the clinical implications of HC in MCA Plus syndromes.
Abstract WP289: The Impact of Infection on Neurological Deterioration and Outcome in Acute Ischemic Stroke Patients
Authors: Boehme Amelia K , Kumar Andre D , Dorsey Adrianne M , Siegler James E , Lyerly Michael J , Monlezun Dominique J , Albright Karen C , Beasley Timothy M , Martin-Schild Sheryl
Published: July 2021

Introduction:
To date, few studies have assessed the influence of infection on neurological deterioration (ND) and other outcome measures in acute ischemic stroke.

Methods:
Patients admitted to our stroke center (07/08-12/10) were retrospectively assessed. Patients were excluded if they had an in-hospital stroke, unknown time of symptom onset, or delay from symptom onset to hospital arrival >48 hours. Positive blood or urine culture, or chest x-ray consistent with pneumonia were classified as infection and stratified according to whether the infection was diagnosed within the first 24 hours of admission or after 24 hours. ND was defined as an increase ≥2 points on the NIHSS score within a 24hr period. Poor functional outcome was defined as a mRS score of 3-6 on discharge.

Results:
Of the 334 patients included in this study, 78 had an infection (19 on admission). The majority of infections were found in the urinary tract (64%), while pneumonia (37%) and bacteremia (24%) were also common. Infection on admission was predictive of ND (Table 1; OR=2.79, 95% CI 1.18-6.64, p=0.0211) and poor functional outcome (OR=3.0, 95% CI 1.1-7.9, p=0.0182). Developing an infection during acute hospitalization was an even stronger predictor of ND (OR=11.9, 95% CI 5.8-24.5, p<0.0001) and poor functional outcome (OR=56.4, 95% CI 7.7-414, p<0.0001). After adjusting for age, NIHSS at baseline and glucose on admission, the development of an infection during acute hospitalization remained a significant predictor of ND (OR=8.9, 95% CI 4.2-18.6, p<0.0001) and poor functional outcome (OR=41.7, 95% CI 5.2-337.9, p=0.005) while an infection on admission was no longer predictive of ND (OR=1.5, 95%CI 0.59-3.99, p=0.3738) or poor functional outcome (OR=1.09, 95%CI 0.3-3.9, p=0.8984).

Conclusion:
Our data suggest that ischemic stroke patients who develop an infection during their acute hospitalization are at increased odds of experiencing ND and of being discharged with significant disability.