bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 22: Accuracy of Perceived Stroke Risk among Young to Middle-Aged Rural African Americans
Authors: Aycock Dawn M , Clark Patricia C
Published: March 2022

Background & Purpose:
Stroke has increased among young adults, which is concerning for African Americans (AA) who have more severe stroke-related outcomes than Caucasians. Since stroke is more common in older adults, younger adults may not recognize stroke as a threat or take action to reduce modifiable stroke risk factors. The purpose of this study was to examine accuracy of perceived stroke risk by comparing perceived risk of future stroke with actual risk of stroke among rural AA aged 19-54 years.

Methods:
A cross-sectional design was used and AA were recruited from rural Alabama. Perceived risk of stroke was measured using a single-item subjective rating of 10-20 year risk of stroke and factors participants attributed to their risk were also explored. Actual stroke risk was calculated based on the presence of eight risk factors: history of hypertension, high cholesterol, diabetes, atrial fibrillation, cigarette smoking, family history of stroke, BMI > 30 and lack of exercise. Based on the number of actual risk factors, participants were categorized into one of three groups; no risk, low risk (1-2 factors); or moderate-high risk (> 3 risk factors).

Results:
Participants (N=66) had a mean age of 43.3+9.4 years, were 71% female, with at least 12 years of school (89%), and unemployed (62%). The majority (66%) perceived their risk of future stroke as no or low risk. However, actual risk factors averaged 2.97+1.63 out of 8 with 59% in the moderate-high actual stroke risk category. In comparing perceived versus actual risk, 44% underestimated, 47% were accurate, and 9% overestimated their risk. Sample characteristics were not associated with accuracy. Most (69%) participants with hypertension (n= 35); 80% of cigarette smokers (n= 25), 93% of diabetics (n= 13) and 88% of overweight/obese participants (n= 49) did not identify their personal risk factors as contributing to their risk of future stroke.

Conclusion:
Despite the number of risk factors observed, participants did not perceive a high risk of future stroke, almost half underestimated their risk of stroke, and few recognized personal risk factors. Strategies to address risk misperceptions should be explored to improve accuracy of perceived stroke risk and facilitate tailoring of interventions to reduce stroke.
Abstract 30: Is NR2 Peptide Promising Biomarker for Acute Cerebrovascular Events?
Authors: Dambinova Svetlana A
Published: March 2022

Introduction:
Feasibility studies of NR2 peptide, a cleavage product of NMDA neuroreceptors that released into the bloodstream due to cerebral ischemia were conducted at 8 clinical sites. The following indications were probed: acute IS vs non-stroke, IS vs hemorrhage, risk of TIA/stroke and secondary ischemic events. The diagnostic potential of NR2 peptide assay in emergency, vascular surgery, neurology, and neurosurgery settings is summarized.

Methods:
Pilot studies were performed according to protocols approved by Ethic Committees at 7 clinical sites in USA, Germany, and UK. The total of 380 patients with hyper-acute (n=186) and acute hemispheric stroke (n=194), mild TBI (n=356) were enrolled. Controls consisted of age- and gender-matched non-stroke (n=91), vascular risk factors (n=89), and healthy volunteers (n=187) were recruited at KSU. The final diagnosis was determined based on clinical observations and radiological findings (CT, MRI, DWI). Blinded plasma was assayed by rapid magnetic particles (MP) ELISA (30 min). Results for different groups were compared using univariate and multivariate statistical analyses.

Results:
When the biomarker cut off was set at 1.0 ng/mL, this resulted in a sensitivity of 92% and a specificity of 96% to detect acute IS within 24 h of onset. In hyper-acute IS, NR2 peptide showed sensitivity of 88% and specificity of 99% (0.5 ng/mL cut off) within 0.5-4.5 h of onset.

Conclusions:
The statistical significance of NR2 peptide values in acute IS has been demonstrated with timely corresponding cut off value. The assay might be used in conjunction with neurological assessment and followed up by neuroimaging. The NR2 peptide plasma assay could assist in ruling-out individuals without acute cerebrovascular events. Further studies are needed.
Abstract 32: N-terminal Probrain Natriuretic Peptide Shows Diagnostic Accuracy For Atrial Fibrillation
Authors: Fonseca Ana Catarina , Sampaio Matias Joaquim , Pinho e Melo Teresa , Geraldes Ruth , Canhão Patricia , Brito Dulce , Caplan Louis R , Ferro José M
Published: March 2022

Introduction:
The diagnosis of paroxysmal atrial fibrillation (pAF) in patients with stroke is of paramount importance and has therapeutic implications. However identifying pAF can be difficult. N-terminal probrain natriuretic peptide (NT-proBNP),a peptide produced by the heart, may be useful to identify pAF in patients with cryptogenic stroke.

Hypothesis:
Cut-off points of serum NT-proBNP at the time of stroke onset can help identify pAF in cryptogenic stroke patients.

Methods:
Among 263 ischemic stroke patients admitted to a stroke unit NT-proBNP serum levels were measured within 72 hours of stroke onset. Etiological evaluation included: TTE, ECG and 24-Holter. Etiology was classified using TOAST criteria. In patients with cryptogenic stroke, 24-Holter was done to look for pAF within the first week, three and six months after admission. First, patients with a defined etiology were used to construct a Receive Operating Characteristic (ROC) curve for the diagnosis of AF. From this curve, the sensitivity and specificity of pre-established cut-off points was calculated. A logistic regression was done to assess the independent relationship of lnNT-proBNP with AF controlling for confounders. In a second phase the cut-off points previously established were evaluated, in patients with cryptogenic stroke, for the diagnosis of pAF.

Results:
In 179 patients a stroke etiology could be established. Fifty five patients had the diagnosis of cardioembolic stroke related to AF. Using multivariate analysis the lnNT-proBNP was independently associated to AF (OR - 2.7, 95% CI 1.5-4.8; p=0.01). The Area Under the Curve (AUC) of the ROC curve of lnNT-proBNP for the diagnosis of AF was excellent - 0.91, 95% CI (0.87-0.95). The previously defined cut-off of 265.5 pg/ml had a sensitivity of 100% and specificity of 72.6%. The cut-off point of 912 pg/ml had a specificity of 87.9%. 83 patients had a cryptogenic stroke. In 16 (19%) pAF was found during follow-up. The cut-off point of 265.5 pg/ml had a sensitivity of 93.8% and a specificity of 58.8% for the diagnosis of pAF. The cut-off point of 912 pg/mL had a specificity of 88.2%.

Conclusion:
NT-proBNP had good accuracy to predict pAF in patients with cryptogenic stroke and can help evaluate these patients.
Abstract 35: Early Diffusion Weighted Imaging and Perfusion Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2
Authors: Wheeler Hayley M , Mlynash Michael , Inoue Manabu , Tipirneni Aaryani , Liggins John , Zaharchuk Greg , Straka Matus , Kemp Stephanie , Bammer Roland , Lansberg Maarten G , Albers Gregory W ,   The DEFUSE 2 Investigators
Published: March 2022

Background:
It is hypothesized that early DWI lesions accurately estimate the size of the irreversibly injured ischemic core and that appropriately thresholded PWI lesions (Tmax > 6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and post-treatment PWI is hypothesized to predict infarct volume.

Methods:
This is a substudy of DEFUSE 2; all patients who had technically adequate MRI scans at 3 time points were included: just prior to endovascular therapy, within 12 hours post-therapy, and at 5 days. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program and manually adjusted by the DEFUSE 2 core lab if needed. Final infarct volumes were assessed on the Day 5 FLAIR and corrected for edema. Reperfusion was defined based on the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.

Results:
Seventy-eight patients were eligible; the 28 patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r = 0.81, p < 0.001) with a slope of 0.95. Twelve patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 sec) volume and final infarct volume with a slope of 1.17 (r = 0.93, p < 0.001). Using all 78 patients, the union of baseline DWI with early follow-up PWI is highly correlated with final volume (r = 0.86, p < 0.001) with a slope of 1.01. The median absolute difference between observed and predicted final volume is 15 ml (IQR, 4.8-32.8).

Conclusions:
Early DWI and PWI (Tmax > 6 sec) volumes provide a reasonable approximation of final infarct volume following endovascular therapy.
Abstract 42: Cerebrovascular Reactivity (CVRx) and Intracranial Pressure Reactivity (PRx) Assessment of Impaired Cerebrovascular Autoregulation in Intracranial Hypertension
Authors: Bragin Denis E , Statom Gloria , Nemoto Edwin M
Published: March 2022

Introduction:
We previously showed that the decrease in critical cerebral perfusion pressure (CPP) to 30 mmHg obtained by cerebral blood flow (CBF) autoregulation curve with increasing intracranial pressure (ICP), compared to 60 mmHg when CPP is reduced by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP. We concluded that determination of the critical CPP by the CBF autoregulation curve is not applicable to brains at high ICP. We hypothesized that dynamic ICP (PRx) and cerebrovascular (CVRx) reactivity would better detect impaired autoregulation.

Methods:
In vivo 2-photon laser scanning microscopy (2PLSM) over the rat parietal cortex was used to measure microvascular (MV) flow velocity, NADH fluorescence (hypoxia) and blood brain barrier (BBB) integrity (fluorescein dye extravasation). Doppler flow, temperatures, ICP, arterial pressure and blood gases were monitored. CPP was reduced stepwise from 70 to 50 and 30 mmHg by increasing ICP. At each CPP, a transient 10 mmHg rise in mean arterial pressure (MAP) was induced by i.v. dopamine bolus. PRx is a ratio of the ICP change in response to MAP increase (PRx=ΔICP/ΔMAP). CVRx is a ratio of the change in CBF with MAP change (CVRx=ΔCBF/ΔMAP).

Results:
CBF autoregulation curves indicated a critical CPP of 30 mmHg at high ICP. However, our 2PLSM data show that reduction of CPP to 50 mmHg by increasing ICP caused a transition from capillary to microvascular shunt flow associated with brain edema, hypoxia and BBB opening. At a normal CPP (70 mmHg) blood pressure challenge caused no change in ICP (PRx=-0.03±0.07, n=5), i.e., intact pressure reactivity. When CPP was decreased to 50 and 30 mmHg by ICP elevation, PRx increased to 0.09±0.16 and 0.26±0.14, respectively (n=7, p<0.05). Similarly at a normal CPP MAP challenge showed a CVRx of -0.02±0.05, reflecting intact cerebral autoregulation. When CPP was decreased to 50 and 30 mmHg by ICP, CVRx increased to 0.11±0.13 and 0.26±0.14, respectively, reflecting impaired autoregulation (p<0.05).

Conclusions:
As determined by PRx and CVRx at high ICP the critical CPP is 50 mmHg where MV shunting, brain edema, hypoxia and BBB leakage begin to occur which is higher than the 30 mmHg determined by static autoregulation.
Abstract 47: ICONS: Identifying Continence OptioNs after Stroke: Findings From a Randomised Trial
Authors: Thomas Lois H , French Beverley , Sutton Christopher J , Forshaw Denise , Cheater Francine , Roe Brenda , Leathley Michael J , Burton Christopher , McColl Elaine , Booth Jo , Brittain Katie , Carter Bernie , Rodgers Helen , Walker Andrew , Barrett James ,   ICONS Patient, Public and Carer Involvement Groups, Watkins Caroline L
Published: March 2022

Introduction:
Urinary incontinence following acute stroke is common, affecting between 40%-60% of people in hospital after a stroke. Despite the availability of clinical guidelines for urinary incontinence and urinary incontinence after stroke, national audit data suggest incontinence is often poorly managed. Conservative interventions (e.g. bladder training, pelvic floor muscle training and prompted voiding) have been shown to have some effect with participants in Cochrane systematic reviews, but have not had their effectiveness demonstrated with stroke patients.

Methods:
A cluster randomised controlled pilot trial designed to assess the feasibility of a full-scale cluster randomised trial and to provide preliminary evidence of the effectiveness and cost-effectiveness of a systematic voiding programme for the management of continence after stroke. Stroke services were randomised to receive the systematic voiding programme, the systematic voiding programme plus supported implementation (using facilitation as a means of enabling and supporting staff to change their practice), or usual care. The trial aimed to recruit 500 participants in 12 stroke services (4 services per arm). The primary outcome was presence/absence of urinary incontinence. Secondary outcomes included frequency and severity of urinary incontinence, quality of life and cost-utility. Outcomes were measured at six weeks, twelve weeks and twelve months after stroke. Process data included rates of recruitment and retention and fidelity of intervention delivery. An integrated qualitative evaluation was conducted in order to describe implementation and assist in explaining potential mediators and modifiers of the process.

Results:
Recruitment ended on July 31
st
2012. In total 413 participants were recruited; 164 received the systematic voiding programme, 125 the systematic voiding programme plus supported implementation and 124 usual care. Findings from the six and twelve week primary and secondary effectiveness outcomes will be presented.

Conclusion:
Not yet available.
Abstract 51: Strict Blood Pressure Control with Intravenous Nicardipine is Associated with Lower Risk of Acute Re-bleeding after Aneurysmal Subarachnoid Hemorrhage.
Authors: Shirani Peyman , Fukuda Keiko , Tieu Lynn , Higashida Randall , Lawton Michael , Smith Wade , Ko Nerissa
Published: March 2022

Background:
Re-bleeding from ruptured intracranial aneurysm is a major cause of death and disability. Although the risk has been significantly decreased with the practice of early aneurysm treatment within 72 hours, re-bleeding is still reported as 4-13% in the first 24 hours. American Heart Association guidelines recommend decreasing the systolic blood pressure (SBP) to less than 160 mmHg to decrease the risk of re-bleeding and neurologic decline. We examined the rate of re-bleeding prior to aneurysm treatment in our SAH population by targeting a strict SBP goal of less than 140 mmHg using IV nicardipine infusion.

Method:
All patients with aneurysmal SAH admitted between August 2003 and March 2012 were included in the study. Re-bleeding was defined by clinical neurological deterioration and radiographic evidence of new blood on CT prior to aneurysm treatment. In addition to presence of re-bleeding, patient demographics, clinical and radiographic grade on admission, aneurysm location, treatment modality, and complications such as hydrocephalus, hyponatremia, and cerebral vasospasm were abstracted from patient charts. Our blood pressure management protocol is used to keep SBP < 140 mmHg for all SAH patients before aneurysm treatment with labetalol IV 5-10mg every 15 minutes and nicardipine IV infusion starting at 5mg/hour. Patients with evidence of vasospasm or elevated intracranial pressure were excluded from our blood pressure protocol.

Result:
Of 1357 patients admitted with aneurismal SAH, re-bleeding occurred in 17 cases (1.32%) prior to aneurysm treatment. Ten patients (59%) with early re-bleed died before hospital discharge. We found three patients with side effects from nicardipine infusion , two with phlebitis, and one with tachycardia.

Conclusion:
Our study showed lower re-bleeding rates compared to other studies of aneurysmal SAH. We attribute the lower rates in part to aggressive blood pressure lowering with early use of nicardipine infusion to keep SBP 140 mmHg. The use of nicardipine infusion appears to be safe and may decrease morbidity and mortality associated with early re-bleeding.
Abstract 52: Early Elevation of Plasma Plasminogen Activator Inhibitor-1 is Associated with Vasospasm following Subarachnoid Hemorrhage
Authors: Chou Sherry H , Orzell Susannah C , Suh Sarah , Henderson Galen , Sorond Farzaneh , Du Rose , Feske Steven K , Lo Eng H , Ning MingMing
Published: March 2022

Background:
While the mechanism of early brain injury following subarachnoid hemorrhage (SAH) remains unclear, animal studies suggest that SAH is associated with significant changes in the fibrinolytic cascade. Human data shows that SAH-related brain ischemia is associated with the polymorphism in plasminogen activator inhibitor 1 (PAI-1) promotor linked to higher plasma PAI-1 levels. However, human plasma PAI-1 has not been previously studied in SAH. We hypothesize that elevated plasma PAI-1 is associated with VSP and poor outcome in SAH.

Methods:
In a prospective cohort of 61 SAH subjects, we compared plasma PAI-1 levels by ELISA (R&D Systems) on post-SAH days 1, 5, 7 and 14 with respect to angiographic VSP and to functional outcome at 3- and 6-months. Angiographic VSP was defined as >50% reduction in vessel caliber on post-SAH day 6-8 angiography. Poor functional outcome was defined as a modified Rankin score >2. Biomarker levels were compared using Wilcoxon rank sum test. Bonferroni correction was applied for multiple comparisons.

Results:
Subjects with (n=25) and without VSP (n=36) were comparable in gender, Fisher and Hunt and Hess (HH) grade distribution, aneurysm treatment modality, and incidence of hydrocephalus. Subjects with VSP had lower mean age (50 vs. 56). Elevated plasma PAI-1 on post-SAH day 1 was strongly association with VSP (3.28 vs. 1.82 ng/mL; p=.0058) and showed a trend towards association with VSP on post-SAH day 5 (2.65 vs 1.83 ng/mL, p=0.05). Plasma PAI-1 levels were not associated with functional outcome at 3 or 6 months. Elevated plasma PAI-1 on post-SAH day 1 remained significantly associated with VSP (p=0.0155) after adjustment for age and HH and Fisher grades by logistic regression.

Conclusion:
Early elevation of plasma PAI-1 on post-SAH day 1 is strongly and independently associated with angiographic VSP in this small prospective SAH cohort and may be a candidate biomarker for VSP. Future mechanistic studies with simultaneous measurements of tissue plasminogen activator (tPA) and tPA-PAI complex and larger clinical studies are necessary to understand the utility of PAI-1 as potential biomarker in SAH.
Abstract 54: A Novel Technique in Controlling for Severity of Subarachnoid Hemorrhage and Measuring Outcomes in the Analysis of the Nationwide Inpatient Sample: The NIS-SAH Severity Score and NIS-SAH Outcome Measure
Authors: Washington Chad W , Derdeyn Colin P , Dacey Ralph G , Dhar Raj , Zipfel Gregory J
Published: March 2022

Introduction:
The Nationwide Inpatient Sample (NIS) is the largest publicly available inpatient care database. Its use in subarachnoid hemorrhage (SAH) outcome studies, has been limited by an inability to control for SAH severity, and unverified outcome measures. To address this, we developed the NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM).

Methods:
Three patient populations were used. Pop-I (N=148,958) and -II (N=147,395) were derived from the 1998-2009 NIS. Pop-III (N = 716) was derived from our institution. Using Pop-I, diagnosis codes likely to predict poor outcome were used to create the NIS-SOM. To create the NIS-SSS, diagnoses likely to predict SAH severity were entered into a regression model assessing poor outcome; model coefficients of significant factors were summed to generate the NIS-SSS. NIS-SOM was validated in Pop-III against modified Rankin Score (mRS) using inter-rater reliability; NIS-SSS was validated against Hunt-Hess (HH) grade using ANOVA; and the ability of NIS-SSS to predict poor outcome by mRS was analyzed using logistic regression. Using Pop-II, the ability of NIS-SSS to predict poor outcome was compared to other common measures of disease severity (APR-DRG, APS-DRG, and DRG).

Results:
A strong correlation between NIS-SOM and mRS was found, with agreement and Kappa statistic of 85% and 0.63 when poor outcome was defined by mRS > 2 and 95% and 0.84 when poor outcome was defined by mRS > 3. The NIS-SSS significantly correlated to HH grade (Fig. 1A) and strongly predicted poor outcome (Fig. 1B).

When compared to APR-DRG, APS-DRG, and DRG, NIS-SSS was more accurate in predicting SAH outcome (AUC = 0.69, 0.71, 0.71, and 0.79, respectively).

Conclusion:
Our results indicate that: NIS-SOM is a valid measure for SAH outcome, NIS-SSS is a valid measure for SAH severity, and NIS-SSS outperforms other measures of disease severity in predicting SAH outcome. We believe NIS-SOM and NIS-SSS should be included in future NIS analyses.
Abstract 56: Association between Increased Plasma Catecholamine Levels and Neurogenic Pulmonary Edema in Patients with Subarachnoid Hemorrhage
Authors: Inamasu Joji , Sugimoto Keiko , Kato Yoko , Hirose Yuichi
Published: March 2022

Background:
Neurogenic pulmonary edema (NPE) occurs relatively frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been indicated as its principal cause. The objective of this study is to evaluate the relative contribution of each catecholamine in pathogenesis of NPE.

Methods:
Records of 77 SAH patients (23 men/54 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were retrospectively analyzed.

Results:
Eight patients (10%) were diagnosed with NPE. Plasma epinephrine (366.9±347.4 vs. 130.3±167.4 pg/mL,
p
=0.001) and norepinephrine (3481.1±1678.9 vs. 835.5±688.9 pg/mL,
p
<0.001) levels were significantly higher in the NPE+ group than NPE- group. Demographic comparison revealed that the severity of SAH and cardiac damage/dysfunction was significantly more profound in the NPE+ group. Multivariate logistic regression analysis revealed that increased norepinephrine levels were predictive of NPE (OR, 1.002; 95% CI, 1.001-1.004), but epinephrine levels were not. Linear regression analysis showed that plasma epinephrine and norepinephrine levels were positively correlated. Receiver operating characteristic (ROC) curves showed that threshold values predictive of NPE existed for both catecholamines, and sensitivity/specificity was higher for norepinephrine. After quadrichotomization of patients based on the results of ROC curves, patients whose plasma epinephrine/norepinephrine levels exceeded the threshold values were significantly more likely to experience NPE.

Conclusions:
Norepinephrine rather than epinephrine appears to play a more active role in pathogenesis of SAH-induced NPE, although both catecholamines may be involved. Since the number of SAH patients complicated by NPE is relatively small, a multi-center study may be required to clarify the issue.
Abstract 59: Predictors of Intracranial Hemorrhage in SWIFT
Authors: Raychev Radoslav , Jahan Reza , Liebeskind David , Saver Jeffrey
Published: March 2022

Introduction:
The main aim of this study is to investigate the mechanistic and clinical factors contributing to the beneficial effect of Solitaire over Merci in lowering symptomatic intracranial hemorrhage (SICH) in the SWIFT trial. We also sought to determine which radiographic ICH subtype affects clinical outcome.

Methods:
The SWIFT trial database was analyzed for incidence of different ICH subtypes in all 144 enrolled patients. Each ICH subtype was correlated with baseline clinical and imaging characteristics, procedural factors, and clinical outcome. Multivariate logistic regression model was used to identify the most significant predictors of the individual ICH subtypes.

Results:
Table Among all analyzed clinical and procedural factors for each ICH subtype, rescue therapy with TPA was the most common ICH predictor and occurred more frequently in the Merci group, although this difference was not statistically significant (10.9% vs. 3.4%; p = 0.085). Basal ganglia ICH was the only radiographic subtype associated with worsened outcome at 90 days (OR 3.33; p = 0.025). SICH was associated with higher mortality (OR 5.73; p = 0.048), mRS shift (OR 2.41; p = 0.011), and high NIHSS (ME 22.35 points; p = 0.004) at 90 days.

Conclusions:

The higher rate of ICH in the Merci arm was mainly due to increased occurrence of SAH, and to a lesser degree of IVH, PH2, and cortical ICH. Each one of these ICH subtypes was strongly associated with TPA rescue therapy. In comparison to Merci device, Solitaire likely offsets SICH due to lower incidence of vascular injury and decreased need for additional TPA administration.

Other predictors of PH2, SAH, and SICH were high baseline INR, ASPECTS, and NIHSS, respectively, none of which differed between the two treatment arms.

Basal ganglia ICH was the only radiographic subtype affecting clinical outcome. This type of hemorrhage was associated with higher reperfusion, prolonged time to treatment, and was also influenced by rescue therapy with TPA.
Abstract 6: Preventable Readmission Rates among Medicare Beneficiaries with Ischemic Stroke
Authors: Lichtman Judith H , Leifheit-Limson Erica , Wang Yun , Goldstein Larry
Published: March 2022

Background:
Hospital readmissions are being used to assess quality of care for several conditions. Recent studies, however, find that only a small proportion of readmissions after MI are preventable, casting doubt on the merits of using all-cause readmissions to compare hospital performance. Data related to preventable readmissions after stroke are limited. We determined rates of all-cause and potentially preventable readmissions within 30 days of discharge after ischemic stroke using national Medicare data, and identified patient-level factors associated with preventable readmissions.

Methods:
The cohort included all fee-for-service Medicare beneficiaries ≥65 yrs discharged alive with a primary diagnosis of ischemic stroke (ICD-9 433, 434, 436) in 2006. Only the first readmission was used if there were multiple readmissions within 30 days. Preventable readmissions were identified using Agency for Healthcare Research and Quality methodology. Overall, hospital, and regional preventable readmission rates were assessed. A random effect Cox proportional hazards model was used to identify patient-level factors associated with preventable readmissions.

Results:
Among 302,565 ischemic stroke hospital discharges, 39,057 (14.8%) patients were readmitted within 30 days. Of these, 13.6% (n=5,322) were potentially preventable. The median hospital-level rate was 14% (Inter quartile range [IQR] 11.6-16.8%) for all-cause and 1.6% (IQR 0.7-2.3%) for preventable readmissions. Preventable readmission rates were higher in the Southeast and Mid-Atlantic and lower in the Mountain and Pacific regions. In risk-adjusted analysis, older age, previous MI, CHF, and diabetes were strong predictors of preventable readmissions.

Conclusion:
Almost 15% of elderly stroke patients were readmitted within 30 days, but only 2% with a readmission that was potentially preventable. National programs aimed at reducing 30-day post-stroke readmissions may have limited impact unless they focus on the small subset of potentially preventable readmissions. Identifying patients at greatest risk is an important step for developing post-discharge interventions to minimize preventable readmissions.
Abstract 61: Limited Eligibility for Trials of Endovascular Therapy for Acute Ischemic Stroke in the US: A Population-Based Assessment
Authors: Khatri Pooja , Khoury Jane , Alwell Kathleen A , Moomaw Charles J , Kissela Brett M , Adeoye Opeolu , Woo Daniel , Flaherty Matthew L , Ferioli Simona , Kleindorfer Dawn
Published: March 2022

BACKGROUND:
Definitive evidence of the effectiveness of mechanical embolectomy for acute ischemic strokes (AIS) is lacking. In light of the recently futile Interventional Management of Stroke (IMS) III Trial, several Phase III trials are underway or being designed to test combined IV/intra-arterial (IA) therapies in novel subgroups. With the concern that more trials are being undertaken than can be feasibly completed in a timely manner, we estimate the number of AIS patients eligible for IA trials in the US annually.

METHODS:
We ascertained all AIS in 2005 seen in an ED among our 1.3 million Greater Cincinnati/Northern Kentucky (GCNK) population. Relevant data, including age, last known well (LKW) times, and NINDS/ECASS3 eligibility criteria for IV rtPA, were abstracted from patient charts. We assumed that patients <18 or >85 years, with NIHSS<8 or with prior disability (modified Rankin >2) would not be enrolled in IA trials. We also assumed that door to randomization would typically be 60 minutes and randomization to IA therapy would be 60 minutes; thus LKW needed to be <6 hours to initiate IA therapy at <8 hours (per FDA clearance). Regional IA-trial eligibility rates were then age/race/sex-adjusted to the 2010 US census data to estimate national rates.

RESULTS:
In 2005,1842 AIS had ED encounters among GCNK residents, and 434 (24%) were NIHSS≥8. After overlapping exclusions of age (23%), baseline disability (46%), and time (38% >6 hrs, 20% undocumented), 86 AIS met potential eligibility for IA trials. Among these, 77 (90%) arrived within 3.5 hours, including 57 IV rtPA-eligible. After adjustment, we estimate 410,000 AIS presentations to a US ED annually, and 16,663 (4.1%) eligible for IV/IA trials (19,500 for all IA trials).

CONCLUSIONS:
Our estimate of 16,663 (4.1%) AIS that might qualify for IV/IA trials annually will be reduced dramatically by additional patient selection criteria (thrombus, core, higher NIHSS), availability/participation of recruiting centers, transport delays, and non-consent by subjects/surrogates; literature-based projections will be provided at the presentation. The stroke field will need to minimize trials, collaborate internationally, and/or pool trial data to complete a definitive, Phase III trial in a timely (5-year) manner.
Abstract 69: Can Patient or Arterial Characteristics Guide the Choice between Carotid Angioplasty and Carotid Endarterectomy? The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)
Authors: Moore Wesley S , Roubin Gary S , Rosenfield Kenneth , Altafullah Irfan , Ansel Gary M , Voeks Jenifer H , Meschia James F , Lal Brajesh K , Howard George , Brott Thomas G
Published: March 2022

Background:
We have previously reported that carotid artery stenting (CAS) carries a higher stroke risk than carotid endarterectomy (CEA) in patients over the age of 70. The question arises if advanced age is a surrogate for other factors? If so, can those factors be separately identified such that advanced chronological age alone would not be considered a contra-indication for CAS? Here we consider whether the CAS/CEA choice could be guided by other factors known in the clinical center at the time of patient evaluation, independent of age, in order to provide optimal 4-year outcomes.

Methods:
Demographic factors (age, sex and race), symptomatic status, patient risk factors (hypertension, diabetes, dyslipidemia, smoking), and arterial characteristics (percent stenosis) were available on 2,502 patients. Additional detailed arterial characteristics (ulcerated plaque, distal tortuosity, sequential lesions, circumferential calcification) were available on 1141 CAS and 438 CEA patients. Potential differential treatment efficacy was assessed by the addition of factor-by-treatment interaction terms to a proportional hazard model containing established predictors of outcome (treatment, symptomatic status, sex, age and age-by-treatment interaction).

Results:
No other factor was found to mitigate advanced age with evidence of additional treatment effect modification of 4-year outcome (p > 0.10).

Discussion:
Beyond the previously described differential treatment efficacy by age, there were no other patient or arterial characteristic detected to identify patient subgroups that would differentially benefit from the choice of CAS versus CEA. Our inability to identify factors to guide treatment choices could be due to the low number of stroke and death events, incomplete information regarding arterial characteristics in the CEA population, or the potential exclusion of “high risk” groups (such as those with severe arterial tortuosity) from the study.
Abstract 77: Posterior Circulation Stroke in Children Due to Cervical Spine Abnormalities
Authors: Fox Christine K , Stout Charles E , Gupta Nalin , Lawton Michael T , Dowd Christopher F , Fullerton Heather J
Published: March 2022

Background:
Vertebral artery dissection due to dynamic compression by abnormal C1-C2 anatomy is under-recognized in childhood stroke. Our aim was to describe underlying pathologic variants of C1-C2 soft tissue or bone in children with vertebral artery dissection and posterior circulation strokes.

Methods:
A series of five children diagnosed with vertebral artery dissection from compression by C1-C2 soft tissue or bone were identified at a single pediatric stroke center. Diagnostic evaluation, anatomic cause of dissection, and treatment were abstracted from medical records.

Results:
Five children (all boys, ages 6 - 14) were identified with a diagnosis of posterior circulation embolic strokes due to focal vertebral artery dissection and presumed compression against adjacent C1-C2 abnormalities. Four had recurrent events, including basilar artery thrombosis, before the cervical abnormality was identified. Vertebral artery dissections were caused by bony (congenital arcuate foramen, post-traumatic os odontoideum) and soft tissue pathology (ruptured atlantoaxial bursa, anomalous C1-C2 connective tissue bands) (Table). Vertebral artery compression at dissection sites during head rotation was confirmed by angiography with head in neutral and rotated in children with soft tissue anomalies. No other etiology for stroke or dissection was found in any of the cases. For secondary stroke prevention, four children underwent direct surgical decompression of the vertebral artery or spinal fusion; one opted for activity restriction and aspirin. None had further recurrences after treatment with a median follow-up of 9 months (range 1 to 61).

Conclusions:
In children with recurrent vertebral artery dissection and strokes, C1-C2 bone imaging and dynamic angiogram with neck rotation can identify cervical pathology that may otherwise be missed. Cervical stabilization or resection of the compressive pathology should be considered to prevent stroke recurrence.
Abstract 81: Circulating Interleukin-6 Levels Associate With Risk Of First-ever Cerebrovascular Events In Patients With Cardiovascular Risk Factors
Authors: Miwa Kaori , Tanaka Makiko , Okazaki Shuhei , Furukado Shigetaka , Sakaguchi Manabu , Mochizuki Hideki , Kitagawa Kazuo
Published: March 2022

Background and objective:
Relations between inflammatory marker levels and future stroke have been recently shown, but it remains unclear how these measurements could be combined with established surrogate-markers for stroke, carotid intima-media thickness (IMT) and silent lacunar infarction (SLI) for prediction. The purpose of this study is to clarify whether inflammatory marker levels are associated with cerebrovascular events (CVEs) independent of IMT and SLI

Methods:
We enrolled 464 outpatients who had cardiovascular risk factors without any preexisting cardiovascular disease (CVD). We examined the presence of SLI by MRI; evaluated IMT by ultrasound; and measured high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and IL-18 at baseline and assessed their associations with CVEs using Cox proportional hazards models. We further calculated measures of reclassification and discrimination.

Results:
During 4.8±2.6 years of follow-up, CVEs occurred in 25 patients. In age- and sex-adjusted analysis, IL-6, but neither hsCRP nor IL-18, was associated with CVEs. The association remained significant after adjustment for conventional risk factors, IMT, and SLI (hazard ratios (HR):1.80, [95% CI: 1.06-3.08], per 1-SD increase in log IL-6, p=0.03). Compared to the patients with below median IL-6 without SLI, those with above median IL-6 and SLI had a higher risk of CVEs (HR: 4.14, [1.31-15.73], p=0.0014). The combination of IL-6 and SLI resulted in the net reclassification improvement of 14.3% (p=0.04), and the integrated discrimination improvement gain of 2.1% (p=0.05).

Conclusion:
IL-6 levels improved CVEs risk stratification in patients with cardiovascular risk factors without prior CVD. Further large investigations will be needed to assess whether risk refinements measuring IL-6 levels lead to a meaningful change in clinical cerebrovascular events.
Abstract 86: Expanding The Lacunar Infarct: Molecular Reorganization Of Axons Adjacent To Human White Matter Stroke
Authors: Hinman Jason D , Tung Spencer , Vinters Harry V , Carmichael S. Thomas
Published: March 2022

White matter stroke compromises approximately 25% of all strokes and accounts for significant disability by directly damaging myelin and axons. Patients presenting with white matter stroke often worsen clinically during the acute presentation. MRI studies demonstrate that white matter stroke lesions often expand in size over time. In part, this may be due to progressive expansion of infarcts through functional disruption of adjacent axons. The function of myelinated axons is dependent on molecular clustering of voltage-gated sodium channels at nodes of Ranvier. This clustering is partly dependent on the interaction with myelinating oligodendrocytes at axonal regions adjacent to nodes, termed paranodes. Here, we examined 10 autopsy cases of patients with lacunar infarcts and 3 controls for the molecular integrity of axonal microdomains adjacent to stroke. Lacunar infarcts were identified using clinical history and H&E sections. Serial sections were labeled for immunofluorescent markers of nodes and paranodes as well as neurofilaments and myelin basic protein. Compared to controls, there is lengthening of paranodes adjacent to white matter stroke consistent with disrupted axon-oligodendrocyte molecular interactions. In addition, immunolabeling for both voltage-gated sodium channels and their cytoskeletal anchors are disrupted in peri-infarct tissue. These abnormalities of axonal microdomains are present in a region larger than the infarct size as measured by H&E. These results indicate that white matter stroke produces functional disorganization of axons adjacent to the traditional lacune. A white matter stroke peri-infarct marked by molecularly disorganized axons provides a new therapeutic target for the treatment of white matter stroke.
Abstract 95: Remote Postconditioning Protects Ischemic Brain by nNOS and p-ERK Activation
Authors: PIGNATARO GIUSEPPE
Published: March 2022

Objective:
It has recently been hypothesized that a sub-lethal ischemic insult induced in one organ is able to protect from a harmful ischemia occurring in a different and anatomically distant organ. Objective of this study is to characterize remote ischemic femoral postconditioning as a new method to induce post-ischemic brain neuroprotection

Methods and Results:
Remote ischemic postconditioning was induced in adult rats by 100 minutes of middle cerebral artery occlusion (tMCAO) followed by several cycles of femoral artery occlusion-reperfusion. One hundred minutes of tMCAO followed, 10 minutes later, by 20 minutes of femoral artery occlusion effectively reduced cerebral infarct volume by 50%.Importantly, this protection was still present 7 days after remote postconditioning. Furthermore, the use of in vivo silencing strategy allowed to demonstrate that NO production through nNOS mediates part of the neuroprotection induced by remote ischemic postconditioning. Indeed, whereas CNS nNOS expression was up-regulated by remote postconditioning, the pharmacological inhibition of nNOS or its silencing-mediated knocking-down partially reverted this neuroprotective effect. This nNOS overexpression and activity seemed to be p-ERK dependent. In fact, p-ERK expression increased in brain cortex after remote postconditioning, and its pharmacological inhibition prevented both nNOS overexpression and remote postconditioning-mediated neuroprotection. Interestingly, neuroprotection induced by remote postconditioning was partially reverted when ganglion transmission was pharmacologically interrupted by hexamethonium, thus showing that neural factors are involved in this phenomenon.

Interpretation:
Collectively, the results of the present study demonstrate that remote postconditioning induces a marked neuroprotection through p-ERK/nNOS, neuronally-mediated activation, and may represent a new clinically feasible therapeutic approach to treat ischemic stroke.
Abstract 98: Post-ischemic Intra-arterial Infusion of Liposome-encapsulated Hemoglobin Can Reduce Ischemic Reperfusion Injury
Authors: Shimbo Daisuke , Abumiya Takeo , Shichinohe Hideo , Nakayama Naoki , Kazumata Ken , Houkin Kiyohiro , Ishizuka Takanobu
Published: March 2022

Background:
We sometimes encounter severe brain edema and hemorrhagic transformation due to ischemic reperfusion (I/R) injury after thrombolysis and/or thromboectomy. The mechanism of I/R injury is thought to depend on blood-brain barrier disruption mediated by matrix metalloproteinase-9 (MMP-9) mainly produced by circulating neutrophils. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an efficient oxygen carrier without blood cells including neutrophils, can reduce I/R injury through reducing the effect of neutrophil MMP-9 in the rat transient middle cerebral artery occlusion (MCAO) model.

Methods:
Male Sprague-Dawley rats were subjected to transient MCAO for 2 hours and then were divided into three groups: 1) LEH group infused with LEH (10ml/kg/h) through the recanalized internal carotid artery for 2 hours, 2) vehicle group infused with saline, and 3) control group subjected to recanalization only. After 24-hour reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, MMP-9 expression, MMP-9 activity and reactive oxygen species (ROS) production.

Results:
Compared with the control group, the LEH group showed significantly better neurological score (p<0.05), smaller infarct and edema size (p<0.01, p<0.05 respectively). MMP-9 expression, activity and ROS production in the LEH group were lower than those in the control group (p<0.001, p<0.01 and p<0.05, respectively). There was no significant difference between the results in the vehicle group and those in the control group.

Conclusion:
The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of neutrophil MMP-9. LEH may be a promising candidate to prevent I/R injury.
Abstract NS13: YOU CALL - WE CALL Trial: Impact of a Multimodal Support Intervention After a “Mild” Stroke
Authors: Rochette Annie , Korner-Bitensky Nicol , White Carole , Bravo Gina , Côté Robert , Green Teresa , Lanthier Sylvain , Wood-Dauphinee Sharon ,   You call - We call TRIAL team
Published: March 2022

purpose:
To assess the impact of a post-discharge multimodal support intervention - “WE CALL” versus a passive “YOU CALL” intervention (providing telephone contact information of a resource person) in individuals with first mild stroke. Primary outcomes were unplanned use of health services for negative events and quality of life. Secondary outcomes included planned use of health services, participation and mood.

Methods:
Single-blind RCT stratified on level of co-morbidity. WE CALL participants were phoned 13 times over the six month period (weekly to monthly) by a trained healthcare professional to discuss any new or ongoing issues. Blind assessments were done at baseline and at 6 and 12 months. Use of health services was collected through participant diaries. We used a mixed model approach for statistical analysis on an intention-to-treat basis where the group factor was intervention type and occasion factor time, with a significance level of 0.01.

Results:
We enrolled 186 patients (We = 92; You = 94) with a mean age 62.5 ± 12.5 and 41% female. There were no baseline differences between groups on the primary (Euroquol-EQ5D, Quality of Life Index) or secondary outcomes (Assessment of Life-Habits (LIFE-H), and Beck Depression Inventory II). At six months, 92% (137/149) had visited a physician while less than 20% a rehabilitation specialist. No significant differences were seen between groups at six months on any outcomes with both groups improving from baseline on all measures (effect sizes ranged from 0.2 to 0.8). The only significant change from 6 months to one year (n=139) was in the social domains (relationships, work and recreation) of the LIFE-H (increment in score=0.4/9±1.3 [95%CI=0.1-0.7]; ES=0.3). Qualitatively the WE Call intervention was perceived as reassuring, increased insight and problem solving while decreasing anxiety. In contrast, only 6/94 (6.4%) of YOU Call participant availed themselves of intervention.

Conclusion:
While the two groups improved equally over time, some of the WE CALL intervention key features, which will be described, were reported to be very helpful.

Clinical Trial Registration:
http://www.controlled-trials.com unique identifier:
ISRCTN95662526

Funding:
Canadian Stroke Network/CIHR
Abstract NS17: REM Sleep is Moderately Associated With Off-line Motor Skill Learning in Individuals with Chronic Stroke
Authors: Siengsukon Catherine , Al-Sharman Alham , Stevens Suzanne
Published: March 2022

Background:
Sleep enhances motor skill learning in individuals with chronic stroke. However, the mechanisms underlying over-night (or
off-line)
motor skill enhancement remains unknown. Stage 2 non-REM and REM sleep have been associated with off-line motor skill learning in young adults. Therefore, we hypothesize that off-line motor skill learning in individuals with stroke will be positively correlated with time spent in stage 2 non-REM and REM sleep.

Purpose:
The purpose of this study was to assess which sleep parameters are associated with off-line motor skill learning in individuals with chronic (> 6 months) stroke.

Methods:
Eighteen individuals with chronic stroke underwent polysomnographic recording for three consecutive nights and practiced a continuous tracking (CT) task. The first night served as an acclimation night, and the second night served as a baseline night. The morning after the baseline night, participants practiced a CT task. Participants returned in the evening for polysomnographic recording. The following morning, participants performed a retention test of the CT task. Paired t-tests were used to assess improvement in tracking performance from the last practice block to the retention block. Pearson correlations were used to assess relationships between off-line motor skill learning and time spent in stage 2 non-REM and REM sleep.

Results:
Participants demonstrated an improvement in performance on the tracking task following a night of sleep as demonstrated by a significant reduction in tracking error from the last practice block to retention (t(17)=2.674, p=.016). Off-line learning was only weakly correlated with amount of time spent in stage 2 non-REM sleep (r= .123), but was moderately correlated with amount of time spent in REM sleep (r= .368).

Conclusion:
This study is the first to find that off-line motor skill learning is weakly associated with time spent in stage 2 non-REM sleep, but is moderately related to time spent in REM sleep for individuals with chronic stroke. In conclusion, sleep is a factor that should be considered when treating individuals following stroke. Future studies should determine if enhancing REM sleep pharmacologically would improve motor skill learning and potentially impact recovery following stroke.