bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 129: Older Age and Shorter Time from Symptom Onset Positively Impacts Outcomes in Moderate Severity Stroke Patients in SENTIS Trial
Authors: Shuaib Ashfaq ,   on behalf of the SENTIS Investigators
Published: March 2022

Background:
A number of recent acute ischemic stroke trials have shown that patients with moderate severity strokes respond most positively to interventional treatments. Similarly, the SENTIS Trial showed that patients with moderate severity stroke had significantly better outcome when treated with NeuroFlo. The current report is a post hoc analysis of patients with moderate stroke in the SENTIS Trial.

Methods:
SENTIS was a prospective randomized trial of the safety and efficacy of NeuroFlo treatment. A total of 515 patients were enrolled at 68 centers in 9 countries. Modified Rankin Scale (mRS) scores at 90 days were dichotomized into 0-2 versus 3-6 for patients with baseline National Institute of Health Stroke Scale (NIHSS) scores of 8 to 14, and compared between the treated and non-treated groups. Additionally, we evaluated the impact of age, time from symptom onset (TFSO) to randomization, and occlusion location on outcomes in this patient cohort.

Results:
Of the 515 patients enrolled in SENTIS, 219 patients (42%) with NIHSS 8 to 14 were available for analysis. The
table
below lists the odds ratio (OR) with 95% confidence intervals (CI) and p-values for the cohorts evaluated.

Conclusion:
Patients with moderate stroke severity had significantly better outcomes in the treated group compared to the non-treated group in this post hoc analysis of over 40% of patients enrolled in the SENTIS Trial. Additionally, patients 70 years and older and those with TFSO ≤5 hours had significantly better outcomes. To ensure the best efficacy analysis of new ischemic stroke treatments, future studies may focus on patients with moderate severity strokes.
Abstract 139: Preclinical In-vivo Safety Evaluation Of Thrombectomy Devices In The Canine Cerebrovasculature
Authors: Mehra Manik , Hendricks Gregory H , O'Callaghan Jaime M , Wakhloo Ajay K , Gounis Matthew J
Published: March 2022

Introduction:
Thrombectomy devices have become an integral tool in the armamentarium of neuro-interventionalists to treat acute ischemic stroke (AIS). Previous preclinical evaluation of these devices has not assessed their safety in the native cerebrovasculature. We assessed the operation of stent-trievers in the canine basilar artery (BA), with a goal to evaluate their vascular safety on angiography and histopathology.

Methods:
Four mongrel canines (female, mean weight:12.53kg,n=2 each arm) were randomly assigned to receive the Solitaire FR Revascularization device (4mm X 22mm;eV3, Plymouth, MN) or the Enterprise VRD (4.5mm X 22mm ;Codman Neurovascular, Raynham, MA). The canine basilar artery (BA) was accessed through the anterior spinal artery (ASA, control vessel). The device was deployed in the basilar artery and withdrawn in the expanded state to the vertebrobasilar junction. The ASA, in which only the microcatheter was deployed, served as the control. Angiographic scoring of the vasospasm and histopathological assessment using a quantitative grading of the scanning electron microscopy (SEM) and cross-sectional hematoxylin and eosin histology was used to assess for the vascular integrity.

Results:
The Enterprise VRD and the Solitaire performed equally with grade 3 vasospasm on the first pass, which quickly resolved with intra-arterial Nicardipine administration and minimal vasospasm on subsequent passes. Based on the qualitative histopathological and SEM assessment the Solitaire and the Enterprise VRD device performed comparably when tracked through the canine basilar artery. Based on the luminal surface assessment from the SEM, the most likely damage expected from an intervention with either of these devices is expected to be partial damage to the internal elastic lamina and an exposure of the smooth muscle cells. Microcatheter navigation in the control vessels induced focal endothelial injury along the path in which the catheter was tracked.

Conclusion:
In an attempt to emergently re-vascularize the ischemic vascular territory, the vulnerability of the cerebrovasculature to manipulation by thrombectomy devices is often overlooked. Deployment of stent-trievers induces intimal damage that does not impact vessel integrity.
Abstract 143: Baseline Pre-Diabetes Boosts Future Stroke Risk
Authors: Lee Meng , Saver Jeffrey L , Hong Keun-Sik , Song Sarah , Chang Kuo-Hsuan , Ovbiagele Bruce
Published: March 2022

Background:
Recent national US estimates indicate that up to 35% of adults have pre-diabetes. Pre-diabetes is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), and has been associated with modest increase of cardiovascular events. However, the role of pre-diabetes in conferring greater stroke risk is unsettled. Furthermore, it is not clear what impact recent lowering of the IFG threshold of pre-diabetes diagnosis (from 110 to 100 mg/dL) has had on this relationship.

Objective:
To conduct a systematic review and meta-analysis to - 1} investigate the magnitude and direction of the relation of pre-diabetes with stroke risk, 2} evaluate whether this relationship varies based on IFG threshold or inclusion of IGT criteria in the diagnosis.

Methods:
We searched PUBMED and EMBASE. We included studies that prospectively collected data within cohort studies or clinical trials, assessed stroke, had follow-up of at least one year, and reported estimates of the multivariate adjusted relative risk and 95% confidence interval for stroke associated with pre-diabetes. We combined data using the inverse variance approach.

Results:
The final primary analysis included 16 prospective cohort studies comprising 767,813 participants. In 9 publications with information about IFG (100 to 125 mg/dL), the summary estimate did not show increased risk of stroke (RR 1.08, 0.94 to 1.23, P=0.26) (
Fig
1). In 6 publications with information about IFG (110 to 125 mg/dl), the summary estimate showed increased risk of stroke (RR 1.21, 1.02 to 1.44, P=0.03). In 11 publications with information about IGT (140 to 199 mg/dL) or combination of IFG/IGT, the summary estimate showed increased risk of stroke (RR 1.24, 1.10 to 1.39, P=0.0003) (
fig
2).

Conclusion:
Baseline pre-diabetes, defined by fasting glucose 110-125 mg/dL or combination of IGT/IFG certainly raises future stroke risk. However, the current IFG definition (100-125 mg/dL) is not associated with increased stroke risk. Given the high prevalence of pre-diabetes, randomized trials to evaluate the efficacy of blood sugar lowering therapies in persons with this condition are warranted, but may need to focus on persons with IFG 110-125 mg/dL or a combination of IGT/IFG.
Abstract 160: Intravenous rt-PA is Not Associated with Increased Risk of Symptomatic Hemorrhage in Patients with Intracranial Aneurysms
Authors: Sheth Kevin N , Shah Nikeith , Morovati Tanya , Hermann Lisa D , Cronin Carolyn A
Published: March 2022

Introduction:
Recent American Heart Association guidelines for acute ischemic stroke suggest a prominent role for CT angiography. As vascular neuro-imaging is used more commonly in the acute setting, the incidental detection of intracranial aneurysms is likely to increase. In the protocols of some stroke centers, the presence of an intracranial aneurysm is a relative or absolute contraindication for the administration of rt-PA. This study was designed to test the hypothesis that administration of rt-PA is safe in patients who have an unruptured intracranial aneurysm.

Methods:
We performed a retrospective analysis of all acute ischemic stroke patients treated with rt-PA at our tertiary care academic medical center from June 2006 to June 2010 who also received intracranial vessel imaging during their hospitalization. Patients who received rt-PA but did not receive vessel imaging were excluded. Baseline clinical characteristics were prospectively determined. Identification of hemorrhage and presence of aneurysm was obtained from radiology report and neuro-imaging findings were confirmed by study investigators. Symptomatic ICH (sICH) was defined according to NINDS criteria.

Results:
Five percent of patients (8/172) had at least one intracranial aneurysm on vessel imaging. There were no differences in baseline clinical characteristics including age, NIHSS, INR, or atrial fibrillation between patients who did and did not have an aneurysm. A total of seven patients (4%) had sICH. There was no significant difference in intracranial aneurysms between patients with or without sICH (1/7 (14%) vs. 7/165 (4.2%), p=0.29). Risk factors for sICH included history of atrial fibrillation (4/7 vs. 31/134, p=0.032; RR = 5.22) and final infarct volume (mean 155 ml
3
(SEM 45) vs. 36 ml
3
(SEM 6); p=0.0004). There was a trend towards increased hemorrhage in patients with elevated serum glucose (mean 153 mg/dl (SEM 19) vs. 123 mg/dl (SEM 4); p=0.068). In the one patient with sICH and an intracranial aneurysm, the location of hemorrhage was distant from the aneurysm.

Conclusions:
Incidental intracranial aneurysms are common in patients who present with acute ischemic stroke. Administration of rt-PA in these patients appears to be safe, and the presence of an intracranial aneurysm should not be a contraindication to thrombolysis.
Abstract 167: High Resolution MR Imaging Of Intracranial Arterial Vessel Walls In Moyamoya Disease
Authors: Sagar James , Lee John , Shimony Joshua , Zazulia Allyson , Davis Patricia , Aiyagari Venkatesh , Ivan Cristina , Prabhakaran Shyam , Zipfel Gregory , Derdeyn Colin
Published: March 2022

Background:
The pathogenesis of the primary occlusive vasculopathy or vasculopathies involving the basal arteries in patients with moyamoya phenomenon is unknown. Newer Magnetic Resonance (MR) techniques have been developed to characterize atheroma in the arterial wall. This is a pilot study of vessel wall imaging using high field-strength, high-spatial resolution MR techniques in patients with moyamoya.

Method:
Twenty patients with idiopathic moyamoya were recruited. MR imaging was performed on a 3T head MR system. Imaging included a time-of-flight (TOF) magnetic resonance angiography (MRA) and high-resolution T2-weighted sequences through the circle of Willis. Images were inspected for evidence of an intramural occlusive lesion or atheroma. Vessel wall thickness of the internal carotid artery (ICA) at the points of maximal narrowing as determined by catheter angiography was compared to the wall thickness of the distal basilar artery in each patient. Vessel wall thickness was calculated as the difference between the intraluminal diameter measured on MRA and the extraluminal diameter measured on the T2 image, divided by 2.

Results:
All patients demonstrated diminished arterial diameters on T2 imaging corresponding to sites of luminal stenosis on catheter angiography and time-of-flight MRA sequences. No focal or diffuse intramural thickening was subjectively observed at the sites of stenosis. Objective measures of vessel wall thickness found no difference between the sites of maximal stenosis of involvded vessels and univolved vessels of similar diameter. The mean thickness of the basilar artery was 0.66 mm (standard deviation 0.14). The mean thickness of the diseased ICA was 0.61 mm (s.d. 0.22) in patients with bilateral disease. The mean thickness of the uninvolved ICA in patients with unilateral disease was 0.69 mm (s.d. 0.07). The figure includes sequential high resolution T2 images of a patients with unilateral right sided moyamoya phenomenon (a,b) demonstrating a small right ICA (arrow) compared to the unaffected contralateral ICA. TOF MRA (c,d) illustrate luminal stenosis without evidence of intramural thickening. Multiple moyamoya collateral vessels are also evident (c).

Conclusion:
These data suggest that the pathological process underlying vessel narrowing and occlusion is not a static structural lesion in the vessel wall leading to luminal compromise. In addition, these imaging techniques may be useful in distinguishing idiopathic basal occlusive disease from other processes such as atherosclosis.
Abstract 17: Motor Relearning Effects of Functional Electrical Stimulation in Lower Limb Hemiparesis
Authors: Sheffler Lynne R , Taylor Paul , Buurke Jaap , IJzerman Maarten , Chae John
Published: March 2022

Objective:
The primary objective of this study was to assess the effect of peroneal nerve stimulation (PNS) on lower limb motor impairment among chronic stroke survivors. The secondary objective was to assess the effect of PNS on lower limb functional mobility (disability) and overall quality of life.

Design:
A single-blinded randomized controlled trial, which enrolled 110 chronic hemiparetic stroke survivors (>90 days post-stroke), compared the effect of ambulation training with a PNS device to ambulation training with usual care (ankle foot orthosis or no device). Subjects were treated for 12-wks (Device Usage period) and followed for a total of 6-mos post-treatment. Outcome assessments were performed at baseline, end of the Device Usage period, and 3-mos and 6-mos post-treatment. The primary outcome measure was the Fugl-Meyer Motor Impairment scale. Secondary outcome measures were the Modified Emory Functional Ambulation Profile (mEFAP) and the Stroke Specific Quality of Life scale (SSQOL). Change scores were analyzed via repeated measure ANOVA with treatment and baseline dorsiflexion status (absence or presence of partial dorsiflexion) as independent factors and the baseline measure as a covariate.

Results:
Change in Fugl-Meyer scores was not significantly influenced by either treatment group (PNS or usual care) or by the presence (DP) or absence (DA) of volitional dorsiflexion at baseline. However, there was a significant treatment group by dorsiflexion status interaction (F=13.46, p=.00) on change in mEFAP scores. Post-hoc subset analysis of the DP and DA subjects using treatment group as an independent factor and baseline mEFAP score as covariate showed a significant treatment group effect (DP subjects: F=6.57, p=0.012 and DA subjects: F=4.24, p=.05) on mEFAP changes scores. A series of independent t-tests which compared the mean mEFAP change in the DP subjects relative to treatment group showed significant differences in favor of the usual care group. However, the same series of independent t-tests in the DA subjects showed the opposite effect with significant differences in favor of the PNS group. SSQOL change scores were not significantly influenced by treatment group or dorsiflexion status.

Conclusions:
Ambulation training for 12 weeks with either PNS or usual care had similar effects on lower limb motor impairment and overall quality of life in chronic stroke survivors. However, post-hoc analysis found that while PNS enhanced functional mobility in chronic stroke survivors with absent dorsiflexion, usual care was superior in chronic stroke survivors who demonstrated preservation of volitional ankle dorsiflexion.
Abstract 175: Applying Toyota Lean Manufacturing Principles to Stroke Care: Accelerating Door-to-Needle times
Authors: Panagos Peter , Ford Andria L , Williams Jennifer A , Khoury Naim , Sampson Tomoko , McCammon Craig , Lee Jin-Moo
Published: March 2022

Background:
Recent analysis of National Get-with-the-Guidelines data has shown that less than one third of all patients treated with intravenous tissue plasminogen activator (tPA) had door-to-needle times (DTN) within the ‘Golden Hour’ recommended by current guidelines. Accumulating evidence indicates that shorter DTN is associated with improved outcomes. In March 2011, we began a fundamental transformation, employing Toyota Lean manufacturing principles to improve Emergency Department (ED) DTN in acute ischemic stroke (AIS) patients receiving IV tPA.

Methods:
A multi-disciplinary team of ED physicians, Neurologists, Radiologists, Nurses, Patient Care Technologists, Radiology Technologists and Lean Performance Management Engineers critically analyzed the chain of events required to evaluate and treat AIS patients with intravenous tPA. A “current state” value stream Map (VSM) was created to identify barriers and inefficiencies in the process. To address the identified inefficiencies, a “future state” VSM was created and implemented. Time metrics were prospectively collected prior to and after implementation of the “future state” VSM.

Results:
The “current state” VSM identified several barriers to rapid evaluation for treatment, including: 1) Inefficient patient flow, requiring patients to be routed by EMS to an ED room, then to CT, then back to the room; 2) Redundant procedures (patient was initially hooked up to cardiac monitors, then removed, and re-hooked up after imaging); 3) Serial processing of multiple tasks; 4) Inefficient use of available staff; 5) Difficulties locating witnesses to determine time of onset (TOO); 6) Delays due to laboratory sample processing; 7) Delays due to non-uniform organization of supplies within each room. A “future state” VSM was created, addressing many of the identified inefficiencies: 1) Patients were routed directly to the CT scanner by EMS; 2) A formal team of 6 members was created to initiate work after the stroke pager activation; 3) Each team member was assigned pre-arranged tasks (e.g. social worker to identify and contact witnesses to determine TOO, alternation of NIHSS and medical history duties between EM and Neurology); 4) Point of care tests were implemented for labs that were critical to the decision-making process; 5) Patient registration occurred in the CT suite. Median DTN prior to the “future state” VSM (N=132) was 60 min; after implementation (N=37), median DTN decreased to 37 min (0<0.0001). Initial safety, outcomes data and mimic treatments were statistically insignificant.

Conclusion:
Lean manufacturing principles can successfully be applied to improve stroke care in an acute hospital setting. We show in this study that DTN times can be dramatically reduced after a Lean intervention. Future analysis will be needed to examine if this intervention is safe, sustainable and leads to improved outcomes.
Abstract 178: In-vitro Fluid Dynamic Investigation of a Novel Hyper Elastic-Thin Film Nitinol Stent and the Pipeline Embolization Device for Cerebral Aneurysm Treatment
Authors: Babiker Haithem , Kealey Colin , Chun Youngjae , Carman Greg P , Levi Daniel , Frakes David
Published: March 2022

Introduction:
Fusiform and wide-neck intracranial aneurysms (ICAs) can be challenging to treat with conventional endovascular or surgical means. Recently developed low porosity stents, such as the pipeline embolization device (PED), are designed to treat these ICAs by diverting flow away from the aneurysmal sac. However, low porosity stents rely on a dense metal mesh to divert flow, which reduces flexibility and increases the risk of perforator blockage. In this study, we compare fluid dynamic performance between the PED and a novel high porosity stent fabricated from Hyper Elastic-Thin Film Nitinol (HE-TFN).

Methods:
An idealized model of a sidewall ICA with a collateral branch, located immediately upstream of the aneurysm, was constructed from transparent silicone. A blood analog solution was circulated through the model at steady and pulsatile flow rates spanning a range of physiologic conditions. The PED and two HE-TFN stents, with pore densities of 8 and 21 pores/mm
2
for 500 and 300 υm pore meshes respectively, were deployed into the model. Each stent was placed across the aneurysm and collateral. Volumetric flow velocity data were acquired before and after stent placement using particle image velocimetry. Computational fluid dynamic (CFD) simulations were also conducted.

Results:
For both

steady and pulsatile conditions, the 300 HE-TFN stent led to the largest drops in RMS Velocity Magnitude in the aneurysmal sac and in cross-neck flow. Under pulsatile conditions, the average drops in aneurysmal RMS Velocity Magnitude over the cardiac cycle, for the range of parent-vessel flow rates investigated, were 42.8-73.7% for the PED, 46.4-58.1% for the 500 HE-TFN, and 68.9-82.7% for the 300 HE-TFN. The largest drops were observed at lower parent-vessel flow rates and at peak systole. Examination of collateral flows showed that the PED led to the largest drops in collateral RMS Velocity Magnitude. Under pulsatile conditions, the average drops in collateral RMS Velocity Magnitude over the cardiac cycle were 38.3-46.1% for the PED, 14.0-25.9% for the 500 HE-TFN, and 34.5-40.8% for the 300 HE-TFN. For steady flow, both the aneurysmal and collateral performance metrics followed similar trends.

Conclusion:
The 300 HE-TFN stent led to larger reductions in cross-neck flow than the PED. This may be due to the higher pore density of the HE-TFN, which may be of greater importance for aneurysm occlusion than absolute porosity. Additionally, the ultra low profile, thin struts of the HE-TFN reduce perforator blockage as demonstrated by increased post-treatment collateral flows as compared to the PED. Overall, the 300 HE-TFN device performed best among the flow diversion devices examined by this study. CFD results characterizing the flow dynamics of each device will also be presented.
Abstract 1905: Arterial Spin-Labeled MRI of Leptomeningeal Collateral Perfusion in Acute Ischemic Stroke
Authors: Liebeskind David S , Wang Danny J , Fong Albert K , Sanossian Nerses , Hao Qing , Qiao Joe X , Saver Jeffrey L , Ali Latisha K , Kim Doojin , Abcede Hermelinda G , Adamczyk Peter , Salamon Noriko , Alger Jeffry R ,   for the UCLA Collateral Investigators
Published: March 2022

Background:
Leptomeningeal collaterals and associated cortical perfusion downstream from a proximal arterial occlusion or stenosis are potent predictors of outcome in acute stroke. Arterial spin-labeled (ASL) MRI may depict delayed arterial transit effects (DATE) of these collaterals and cerebral blood flow (CBF), utilizing noninvasive techniques without the use of contrast. We conducted a prospective validation study of ASL DATE and CBF as biomarkers of leptomeningeal collateral perfusion compared to digital subtraction angiography (DSA) and dynamic susceptibility contrast (DSC) perfusion MRI in acute ischemic stroke.

Methods:
Consecutive anterior circulation acute ischemic stroke patients admitted during a 1-year period were evaluated with pseudo-continuous ASL, DSA and DSC perfusion MRI within 12 hours of symptom onset. ASL DATE extent was scored using a 3-point scale and angiographic collaterals on the DSA graded using the ASITN/SIR collateral score. ASL CBF and DSC CBF maps were co-registered to derive comparative ROI statistics on perfusion in the symptomatic territory. ASL CBF lesions < 15 mL/100 g/min were used to measure DSC CBF values within coregistered ROIs.

Results:
Among 39 patients meeting entry criteria, mean age was 66±19 years and 51% were male. All 39 patients were imaged with ASL and DSA, with DSC perfusion MRI in a subset of 27. Sites of vascular occlusion or stenosis were: terminal ICA - 10, M1 MCA - 20, M2 MCA - 5 and more distal MCA - 4. ASL DATE scores ranged from 0-2, with a median of 1. DSA collateral grade ranged from 0-4, with a median of 2. Overall, there was strong correlation (r=0.702, p<0.001) between the ASL and DSA measures of leptomeningeal collateral supply. In the downstream territory from these leptomeningeal collaterals, ASL CBF and DSC CBF maps both revealed hypoperfusion in regions that closely matched. Only limited correlation, however, was noted between exact ASL CBF and DSC CBF values within the co-registered ROIs.

Conclusions:
ASL MRI provides an accurate, noninvasive measure of leptomeningeal collateral perfusion in acute ischemic stroke due to anterior circulation stenosis or occlusion. ASL CBF measures of collateral perfusion likely are arterially weighted, like DSA collateral grades, and unlike conventional DSC perfusion MRI CBF values.
Abstract 197: Post-stroke Inhibition of TGF-β-activated Kinase by 5Z-7-oxozeaenol Improves Histological and Behavioral Outcomes in a Mouse Model of Ischemic Stroke
Authors: White Benjamin , Tarabishy Sami , Benashki Sharon , Venna Venugopal R , Manwani Bharti , Li Jun , McCullough Louise
Published: March 2022

Background:
Transforming growth factor-β activated kinase 1 (TAK1) activates several intracellular signaling cascades, affecting cell proliferation, inflammation, and apoptosis. It is also a putative kinase for adenosine monophosphate protein kinase (AMPK). 5Z-7-oxozeaenol is a selective inhibitor of TAK1. We and others have previously reported that this drug reduced infarct volume and levels of activated TAK1when administered prior to ischemia in a mouse model of ischemic stroke. We investigated the possible clinical utility of the drug by administering it after ischemia and measuring infarct volumes and behavioral outcomes at 7 days. We also explored the relationship between TAK1 and AMPK by examining outcomes of TAK1 inhibition in AMPK knockout (KO) mice.

Methods:
Stroke was induced by 90 minutes of reversible middle cerebral artery occlusion (MCAO) in male mice. In one cohort, wild-type (WT) and AMPK KO mice were treated with drug or vehicle via intraperitoneal (IP) injection 2 hours after stroke onset and stroke severity was measured by tissue staining at 24 hours. In a second cohort, WT and AMPK KO mice were treated with drug or vehicle 3.5 hours after stroke onset and stroke severity was measured using the novel-object recognition test (NORT) and by tissue staining at 7 days. Proteins were analyzed by western blot in a third cohort of mice that were sacrificed 4 hours after onset of ischemia.

Results:
IP injection of 5.0 mg/kg of drug 2 hours after onset of MCAO resulted in a significant reduction in whole-hemisphere infarct volume after 24 hours of reperfusion (49.18±4.18% vehicle vs.17.81±5.86% drug, p=0.001, n=7 vehicle, 8 drug) and after 7 days of reperfusion (57.16±2.38% vehicle vs. 38.35±8.97% drug, p=0.049, n=8 vehicle, 8 drug), and significantly increased the percentage of time that the mice spent exploring a novel object (59.85 ± 3.62% drug vs. 33.15 ± 5.04% vehicle, p=0.001, n=7 vehicle, 7 drug). In AMPK KO mice, there was also a reduction in whole-hemisphere infarct volume. The drug reduced levels of the TAK1 target JNK as well as the JNK target c-Jun.

Conclusions:
Post-stroke inhibition of TAK1 was neuroprotective and this effect was sustained for 7 days. It was also associated with improvement in the NORT, suggesting preservation of memory function. Together, these findings suggest that 5Z-7-oxozeaenol may have clinical utility for patients suffering ischemic stroke. 5Z-7-oxozeaenol reduced levels of the TAK1 target JNK and its target, c-Jun, suggesting that the benefits of inhibition are due to decreased levels of the transcription factor complex AP-1, of which c-Jun is a major component. The sustained protective effect in AMPK KO mice suggests that AMPK is not important to the mechanism of neuroprotection following TAK1 inhibition.
Abstract 198: The Spleen Is A Pivotal Target Of Functional Recovery After Treatment With Multistem For Acute Ischemic Stroke
Authors: Yang Bing , Schaar Krystal , Hamilton Jason , Xi Xiaopei , Mays Robert , Savitz Sean I
Published: March 2022

Background:
There is increasing evidence to suggest that some types of stem cells enhance recovery after stroke by exerting immunomodulatory effects on the peripheral immune system.

Methods:
We studied the effects of MultiStem
®
, an adherent, human pluripotent adult stem cell product, in a model of focal ischemic stroke in rats with and without a spleen. Long Evans male rats were subjected to middle cerebral artery occlusion (MCAo) for 90 minutes. At 24 hrs after stroke, animals were randomly assigned to either receive MultiStem
®
12 million cells/kg (N= 9) or saline vehicle (N= 8). A separate group of animals underwent splenectomy two weeks prior to stroke and then were randomized to receive MultiStem
®
(N=9) or vehicle (N=9). All animals were serially evaluated on a battery of behavioral tests for 28 days. Stroke lesion volume was measured at 28 days after stroke. In another experiment, animals with and without spleens were subjected to MCAo, randomized to cell or saline treatment and then serum cytokines were analyzed at 3 days after treatment (N=5).

Results:
MultiStem
®
improved functional recovery compared with saline treatment at 28 days after stroke in animals with intact spleens; however, in splenectomized rats, there was no difference in neurological deficits between MultiStem
®
and saline treated groups at 28 days after stroke. MultiStem
®
treatment reduced lesion size compared with saline-treated controls at 28 days after stroke in both groups with intact spleens or without spleens. Lesion size was reduced in saline-treated animals without spleens compared with animals that had intact spleens. At 4 days after stroke, serum levels of IL-10 were elevated in MultiStem treated animals compared with saline treated animals with intact spleens (p<0.05); however, this elevation in IL-10 was abolished in splenectomized animals treated with MultiStem
®
compared with vehicle. At 4 days after stroke, the proportion of CD4+ or CD8+ cells significantly decreased and Treg cells significantly increased in the spleens derived from MultiStem
®
treated animals compared with saline-treated controls. In the same animals at 4 days after stroke, splenocytes were cultured: IL-1β and TNF-α levels in the medium of cultured splenocytes derived from MultiStem
®
treated animals were significantly reduced (p<0.05) while IL-10 levels were significantly increased (p<0.05) compared with medium of cultured splenocytes derived from saline-treated animals.

Conclusion:
MultiStem
®
improves neurological recovery after stroke through mechanisms involving the spleen. Our data suggest that MultiStem
®
modulates the immunophenotypes of splenocytes and alters their output of inflammatory cytokines, promoting a protective, anti-inflammatory environment. Regulatory T cells may be one of the pivotal sources of IL-10 and other anti-inflammatory mediators to reduce injury and/or enhance recovery in the brain after stroke.
Abstract 2: Outcomes Of Carotid Endarterctomy In The Elderly: A Report From The Care Registry
®
Authors: Rajamani Kumar , Kennedy Kevin F , Ruggiero Nicholas J , Spertus John A , Chaturvedi Seemant
Published: March 2022

Background:
Although stroke affects the elderly disproportionately, benchmark clinical trials of CEA often did not include this population at all or in insufficient numbers. Because trial patients are chosen rather strictly, the results may not be easily generalized and must be applied cautiously to the general population. The CARE Registry is a hospital wide web based data collection tool designed to assess use quality and outcomes of cardiovascular procedures including CEA. We determined the perioperative outcomes of CEA based upon age.

Methods:
Details of data collection and management in the CARE Registry has been previously published. Using the dataset we analyzed the outcome of CEA procedures done in elderly symptomatic and asymptomatic patients (age > 70 years). We compared outcomes (discharge status, and risk of stroke or death) stratified by age. Statistical analysis was performed by using Student’s t- test for continuous variables and Chi square or Fisher’s exact test for categorical variables

Results:
There were a total of 4149 symptomatic and asymptomatic patients > 70 who underwent CEA. Mean age was 78.1 + 5.2 years of which 59% were male. 96% were Caucasian, 89.7% had hypertension, 32.4% had diabetes, and 65% were smokers. The overall mortality rate after the procedure was 0.5%. New stroke or TIA was documented in 2.0%. Risk of combined stroke or death was 2.3%. The risk of death was highest in the 85 years and over group compared to the 70-75, 75-80 and the 80-85 years groups (p=0.002). The combined risk of death or stroke was also highest in the >85 years group (4.9%, p=0.001) compared to the other groups. Among symptomatic elderly patients, the risk of death (0.5% vs. 0.4%, p=1.00) and risk of combined perioperative stroke and death 2.8% vs. 3.2%,p=0.67) was not statistically different between those <75 years compared to those >75 years. Among asymptomatic elderly patients who underwent CEA, the risk of death was significantly higher among those >75 years compared to those < 75 years 0.7% vs 0.0% p=0.006) and the combined risk of death or perioperative stroke was 2.2% vs. 1.6%, p=0.25)

Conclusions:
In the CARE Registry, elderly patients more than 85 years of age are at increased risk of death or perioperative complications of stroke compared to those relatively younger. Elderly patients undergoing CEA for asymptomatic carotid stenosis also had higher mortality than the younger counterparts.
Abstract 209: The Most Accurate Definition of Clinically Relevant Hemorrhagic Transformation after Thrombolytic Therapy for Stroke: Analysis of the NINDS-TPA Trials
Authors: Rao Neal M , Gornbein Jeffrey A , Levine Steven R , Saver Jeffrey L
Published: March 2022

Background:
Multiple contending definitions have been advanced to distinguish clinically relevant from incidental hemorrhagic transformation (HT) after intravenous tissue plasminogen activator (IV TPA) for acute ischemic stroke. We examined which definition best identified hemorrhages that altered patient final outcome in the two NINDS-TPA trials.

Methods:
Ten definitions of clinically relevant hemorrhage were analyzed, based on radiologic (HI, PH, both) and clinical (asymptomatic, any early worsening, early NIHSS worsening by 4 or more) findings. Candidate definitions included any radiologic hemorrhage, any parenchymal hematoma, and definitions of SICH from the NINDS-TPA Study (any HT judged causally related to any worsening), ECASS 3 (any HT and ≥ 4 NIHSS worsening), and modified SITS-MOST (PH and ≥ 4 NIHSS worsening). Using a 15-variable prognostic model derived from the placebo group, we compared the actual 3 month global disability outcomes for patients following TPA and HT with their predicted outcomes had they not received TPA.

Results:
Among the 312 patients treated with IV tPA, 48 (15.4%) experienced any radiologic ICH. Among the ten candidate definitions, the ECASS 3 definition best distinguished hemorrhages that altered final outcome (
figure
). ECASS 3 positive hemorrhage patients had worse actual (with TPA) vs predicted (without TPA) outcomes, with mean final mRS 5.6 vs 3.6 and death in 75% vs 26.8%. ECASS 3 hemorrhage patients without ≥ 4 NIHSS worsening had no difference between actual and predicted outcomes, with mean final mRS 4.2 vs 4.1 and death in 35% vs 37%. In the two NINDS-TPA trials, rates of ECASS 3 hemorrhages in the TPA vs placebo group were 5.1% (95CI 3.2–8.2%) vs 1.3% (95CI 0.5–3.2%).

Conclusions:
The clinically important hemorrhage definition that best identifies hemorrhages that alter final global disability and fatal outcome is any radiologic HT associated with ≥ 4 early NIHSS worsening. Asymptomatic hemorrhages have no adverse impact on final outcomes.
Abstract 2189: Pre-existing Dementia, Death And Disability After Ischemic Stroke: Results From A Propensity-score Matched Analysis
Authors: Saposnik Gustavo , Kapral Moira , Cote Robert , Rochon Paula , Raptis Stavroula , Wang Julie , Mamdani Muhammad , Black Sandra
Published: March 2022

Background:
With an aging population, patients are increasingly likely to present with stroke and pre-existing dementia, which may lead to greater death and disability.

Objective:
To assess the risk of all-cause mortality and poor functional outcomes after ischemic stroke in patients with and without pre-existing dementia.

Design, Participants, and Setting:
We conducted a multicenter cohort study of all patients presenting to 12 tertiary care institutions participating in the Registry of the Canadian Stroke Network (RCSN) with a first ischemic stroke between 2003 and 2008. Individuals with pre-existing dementia were matched using propensity score methods with patients without dementia during their index hospitalization based on these characteristics: age (within 3 years), sex, stroke severity, stroke subtype (lacunar vs. non-lacunar), level of consciousness, vascular risk factors, dysphagia, glucose and creatinine on admission, Charlson index, residence prior to hospitalization (home vs. other), pre-admission dependency, hospital arrival via ambulance, admission to stroke unit, thrombolysis, and palliative care. A propensity score model for dementia was estimated that balanced prognostically-important baseline covariates between subjects with and without dementia.

Data Sources:
Registry of the Canadian Stroke Network (RCSN) and Registered Persons Database (RPDB)

Main Outcome Measures:
The primary outcome was all cause mortality at 30-days. Secondary outcomes included mortality at discharge and at 1 year, disability at discharge (modified Rankin scale ≥3), medical complications (pneumonia), and discharge disposition. A subgroup analysis assessing the risk of intracerebral hemorrhage among those receiving thrombolysis was also conducted.

Results:
We matched 877 patients with an acute ischemic stroke and pre-existing dementia to 877 stroke patients without dementia. Patients were well-matched. The mean age was 82 years and 58% were women. Mortality at discharge, 30 days and one year after stroke was similar in patients with and without dementia [for mortality at discharge: RR 0.88 (95% confidence interval (CI) 0.74 to 1.05); mortality at 30-days: RR 0.88 (95%CI 0.75 to 1.03) and mortality at 1 year: RR 1.01; 95%CI 0.92 to 1.11). Patients with pre-existing dementia had similar disability at discharge and home disposition. In the subgroup of patients who received thrombolysis, there were no differences between those with and without dementia in the risk intracerebral hemorrhage (RR 1.27; 95%CI 0.69- 2.35) and no differences in mortality or disability at discharge.

Conclusions:
Pre-existing dementia is not independently associated with mortality, disability, or institutionalization after ischemic stroke. Pre-existing dementia should not necessarily preclude access to thrombolytic therapy and specialized stroke care.
Abstract 2195: Early Menopause and the Risk of Silent Brain Infarction in Community-dwelling Elderly Subjects
Authors: Yao Hiroshi , Takashima Yuki , Yahara Koji , Fukuda Kenji , Uchino Akira , Yuzuriha Takefumi , Hashimoto Manabu
Published: March 2022

Background and Purpose:
Brain infarction is more common in men. Our previous study showed the male predominance of silent brain infarction (SBI), which was largely due to higher prevalence of alcohol habit and smoking in men than in women (Hypertens Res. 2010;33:748). However, early menopause could be a risk factor for SBI.

Methods:
We conducted a population-based analysis of brain magnetic resonance imaging (MRI) findings to examine whether early menopause contribute to SBI. The subjects (n=712) were living independently at home without apparent dementia. The National Hospital Organization Hizen Psychiatric Center Institutional Review Board approved the study, and written informed consent was obtained from all subjects. Participants underwent a structured clinical interview, a neurological examination, general hematology tests, biochemistry tests, and electrocardiograms. Natural menopause was considered to occur if a woman had ceased menstruating naturally for at least 1 year. Early menopause was defined as menopause before age 40. Women were also queried as to the cause of menopause (natural, surgical, other), whether a hysterectomy was performed, number of ovaries removed, the use of hormone replacement therapy, the total number of children, and the age at giving birth to her last child. T1-weighted, T2-weighted, and FLAIR images were obtained with a MRI (1.0T, Shimadzu Magnex XP). SBI was shown as low signal intensities on T1-weighted images, and their size was 5 mm or larger. The data were analyzed with the IBM SPSS Statistics 18 software for Windows (SPSS Japan Inc.).

Results:
Among 303 female subjects aged 60 years or older, the median age at menopause was 50 years, the median number of children was 3, and the median age at the last parity was 30 years. Early menopause (total or natural) was more frequent in subjects with SBI. Age at natural menopause, number of children, and age at the last parity were not significantly associated with SBI. In the 712 subjects (283 men and 429 women with a mean age of 67.1 years), SBI, DWMLs and PVHs were detected in 89 (12.5%), 240 (33.7%) and 154 (21.6%) of 712 participants, respectively. The prevalence of SBI was more frequent in men (15.5%) than in women (10.5%). In the forward stepwise method of logistic analysis, natural early menopause (OR 4.239, 95% CI1.060-16.960), age (OR 2.447/10y, 95% CI 1.849-3.240), hypertension (OR 4.045, 95% CI 2.413-6.780), alcohol intake (OR 2.091, 95% CI 1.230-3.553), and smoking (OR 2.936, 95% CI 1.520-5.671) were significant factors concerning SBI.

Conclusions:
The present study showed “natural” early menopause as one of the potential risk factors for SBI. Although the prevalence of natural early menopause was low (3.3% of 303 female subjects aged 60 years or older), natural menopause before the age of 40 years may be the basis for SBI or small vessel disease of the brain.
Abstract 2205: Effects of a Stroke Awareness Promotion Intervention for Community Living Adults with Prehypertension in Korea.
Authors: Song Hee-Young
Published: March 2022

Introduction :
People with prehypertension that is systolic blood pressure (BP) over 120 mmHg or diastolic BP over 80 mmHg are known to be at increased risk for stroke compared to normotensive people. For primary prevention of stroke, community-level interventions that equip prehypertensive individuals with relevant knowledge and self-care strategies are of paramount importance, and may lead to substantial reduction in morbidity and economic burden due to stroke. This study assessed effectiveness of an educational intervention utilizing individualized risk assessment and highlighting importance of self-initiated lifestyle modifications on stroke awareness and compliance with self-BP monitoring and healthy lifestyle for stroke prevention.

Methods :
This was a single blinded, randomized, pretest, posttest study with 47 participants (23 in the intervention group and 24 in the control group) recruited by a convenience sampling in community culture centers and churches in two urban areas. The intervention consisted of 3- weekly, 2-hour face to face educational sessions accompanied by an individualized counseling session on individual stroke risk assessment using Framingham stroke risk profile; and 2 booster sessions by telephone calls. The intervention aimed to improve participants' awareness about stroke and their own risk of stroke; and active involvement in self-care management of their own health as primary prevention of stroke. All participants completed pretest, 4 weeks and 12 weeks measurements after intervention including stroke awareness, self-BP monitoring and lifestyle modification of regular physical activity and low-fat diet. Data were analyzed using descriptive statistics, χ
2
test, two sample and paired t-test, and repeated measures ANOVA with PASW statistics 18.0.

Results :
Mean age of experimental group participants was 46.5 (standard deviation (SD) 10) and of control group, participants, 48.3 (SD 18). Mean BPs in experimental and control groups were 123.8 (SD 12.1) and 125.7 (SD 13.1) mmHg, respectively. After the intervention, significant improvements were found in the experimental group for stroke awareness (p=.001), self-BP monitoring and record keeping (P < .001), and lifestyle modification of regular physical activity and low-fat diet (p =.017). Effects of stroke awareness and self- BP monitoring were sustained over time.

Conclusions :
Results indicate effectiveness of a stroke prevention intervention to promote awareness of the key risk factors and their control for people with prehypertension on taking responsibility for their own self-care behavior on a daily basis. Further studies are warranted to refine and validate intervention strategies for sustained lifestyle modification.
Abstract 2215: Utility of Upfront Arterial and Perfusion Imaging among Ischemic Stroke Patients Presenting within the 4.5 hour Time Window
Authors: Noorian Ali R , Aiken Ashley , Nicholson Andrew D , Edwards Adam B , Markowski Mason P , Bouloute Jemisha C , Abney Jacquelyn , Nahab Fadi
Published: March 2022

Background:
Although perfusion imaging is being evaluated as a tool to select acute ischemic stroke patients who are most likely to benefit from reperfusion therapies beyond the standard time windows, there is limited data on the utility of perfusion imaging within the IV thrombolytic time window.

Methods:
A new upfront comprehensive stroke imaging protocol was initiated at Emory University Hospital on July 1, 2010 to include CT angiography (CTA) of the head and neck and CT perfusion (CTP) of the head after non-contrast head CT. All patients presenting within 4.5 hours from last known normal time to Emory University Hospital with suspected stroke were prospectively identified from July 1 to December 31, 2010. Patients with POC Creatinine >1.7, allergy to contrast dye, current metformin use, pregnancy, intracranial hemorrhage (ICH) on non-contrast head CT or who declined consent were excluded from the protocol. Impact of CTA and CTP on the clinical management was recorded prospectively by stroke team members.

Results:
During the study period, 87 patients met eligibility criteria for the CTA/CTP protocol of which 83 (95%) underwent this upfront comprehensive imaging protocol and 30 (34%) received IV thrombolytic. CTA identified large vessel occlusion in 24 (29%) patients, including 5 with NIHSS ≤ 10 and 3 with NIHSS ≤ 5. CTP identified decreased cerebral blood volume > 1/3 of the ipsilateral MCA territory in 38% of anterior circulation large vessel occlusions. Overall, stroke team members reported that CTA and/or CTP aided their clinical management in 39 (47%) cases, including aiding in identification of a non-stroke diagnosis (n=18), triage to the NICU (n=9), early triage to endovascular therapy (n=4) and initiation of IV thrombolytic for low NIHSS with large vessel occlusion (n=3). There were no symptomatic ICHs and no contrast-induced nephropathy requiring dialysis during the study period. Door-to-needle time ≤ 60 minutes was achieved in only 23% of patients receiving IV thrombolysis during the study period but had improved to 39% in the subsequent 6 month period, similar to the pre-CTA/CTP protocol.

Conclusions:
An upfront CTA/CTP protocol to evaluate patients with acute ischemic stroke presenting within 4.5 hours aided stroke team decision making in nearly half of cases. Implementation of a CTA/CTP protocol was associated with a learning curve of 6 months before door-to-needle time ≤ 60 minutes returned to similar rates as the pre-CTA/CTP protocol.