bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 187: Electrocardiographic Heart Rate-corrected Qt Interval And Risk Of Stroke In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study
Authors: Soliman Elsayed Z , Howard George , Howard George , Cushman Mary , Kissela Brett , Kleindorfer Dawn O , Le Anh , Judd Suzanne E , McClure Leslie A , Howard Virginia J
Published: July 2021

Background:
Prolongation of heart rate-corrected QT interval (QTc) is a well established predictor of cardiovascular morbidity and mortality. Little is known, however, about the relationship between this simple electrocardiographic (ECG) marker and risk of stroke.

Methods:
A total of 27,411 participants aged > 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during an up to 7 years of follow-up (median 2.7 years). Cox proportional hazards analysis was used to estimate the hazard ratios for incident stroke associated with prolonged QTcFram interval (vs. normal) and per 1 standard deviation (SD) increase, separately, in a series of incremental models.

Results:
The risk of incident stroke in the study participants with baseline prolonged QTcFram was almost 3 times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for age, race, sex, antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease, QRS duration, warfarin use, and QT-prolonging drugs (full model), the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0060)], and was consistent across several subgroups of REGARDS participants. When the risk of stroke was estimated per 1 SD increase in QTcFram, a 24% increased risk was observed [HR (95% CI): 1.24 (1.16, 1.33), p<0.0001)]. This risk remained significant in the fully adjusted model [HR (95% CI): 1.12 (1.03, 1.21), p=0.0055]. Similar results were obtained when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used.

Conclusions:
QTc prolongation is associated with a significantly increased risk of incident stroke independently from known stroke risk factors. In light of our results, examining the risk of stroke associated with QT-prolonging drugs may be warranted.
Abstract 19: Resolving Post-Stroke Depression is associated with Post-Stroke Functional Recovery
Authors: El Husseini Nada , Goldstein Larry B , Peterson Eric D , Zhao Xin , Pan Wenqin , Olson DaiWai M , Zimmer Louise O , Williams John W , Bushnell Cheryl , Laskowitz Daniel T
Published: July 2021

Background/rationale:
Depression is common after stroke and is associated with poor functional outcome, but its relationship with the change in functional status after adjustment for other factors remains uncertain. We investigated the independent relationship between depression and post-stroke functional recovery.

Methods:
Data were obtained as part of the multicenter Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) registry in which depression assessed by a self-reported depressive symptoms scale (the Patient Health Questionnaire-8; PHQ-8≥10), and modified Rankin scale (mRS) were prospectively assessed 3 and 12 months following hospitalization for ischemic stroke. Univariate logistic analysis followed by multivariable logistic modeling adjusted for race, gender, age and post-hospital rehabilitation, was performed to evaluate the association between depression at each time-point and the change in mRS between 3 and 12 months.

Results:
Data was available for 1444 patients (55.7% men, 82.6% White) from 97 hospitals in the United States. Relative to 3 months, the 12 month mRS was stable or improved in 692 (75.8%) and worse in 349 (24.2%) patients. Overall, 134 patients were persistently depressed, 126 had resolving depression by 12 months and 104 patients had incident depression at 12 months. Older age, lack of rehabilitation, and 3 and 12 months depression status were associated with worse disability (increasing mRS) between 3 and 12 months. After covariate adjustment, both depression status at 3 and 12 months (p= 0.010) and older age (OR= 1.02, 95% CI 1.01-1.03 per 10-years, p<0.001) remained associated with worsening mRS. Compared with those who were not depressed at either time point, those who had resolving depression (PHQ-8≥10 at 3 but not 12 months) were less likely to have a worsening mRS (OR=0.49, 95%CI 0.29-0.83) whereas the association between incident depression at 12 month and worsening mRS was marginal (OR=1.48, 95% CI 0.95-2.30). Being depressed at both time points was not associated with a worsening in mRS between 3 and 12 months (OR=0.85, 95% CI 0.53-1.34).

Conclusion:
The change in depressive status between 3 and 12 months following hospitalization for stroke was associated with incremental changes in functional outcome. Patients who had resolving post-stroke depression were less likely to have worsening disability. A reciprocal relationship and a confounding effect between depression and mRS cannot be excluded.
Abstract 1911: Recanalization of Proximal Arterial Occlusion in the SENTIS Trial
Authors: Liebeskind David S , Shuaib Ashfaq , Köhrmann Martin , Dillon William P , Liu Songling , Nogueira Raul G , Schellinger Peter D
Published: July 2021

Background:
Collateral circulation may enhance recanalization in acute ischemic stroke. Augmentation of collaterals with partial aortic occlusion may promote recanalization and thereby influence outcomes in the SENTIS randomized controlled trial of the NeuroFlo device. We conducted a post hoc analysis of angiography acquired in SENTIS to evaluate potential differences in recanalization rates between NeuroFlo-treated and non-treated arms, accounting for site of arterial occlusion.

Methods:
Blinded imaging expert review of baseline and 6-hour follow-up angiography (CTA, MRA, or DSA) from the core lab was conducted for evaluation of recanalization. Recanalization was defined as TIMI 2-3 in the arterial segment distal to baseline occlusion. Baseline demographics, stroke presentation characteristics, and medical history variables were analyzed with respect to recanalization in univariate and subsequent multivariable logistic regression models after adjusting by treatment arm.

Results:
Serial angiography was available in 109/515 SENTIS subjects, including 56 in the treatment arm and 53 in the non-treated arm. Baseline demographics, stroke presentation characteristics, and medical history variables did not differ statistically between arms. Across all sites of arterial occlusion, recanalization occurred in 25.7% of cases, with similar rates between device (25.0%) and medical therapy (26.4%) arms. Age and baseline stroke severity (NIHSS score) were significant predictors of recanalization in univariate analyses. Multivariable logistic regression analyses confirmed that baseline NIHSS score was the sole predictor of recanalization (OR 0.90, p=0.0458) per one unit increase, with decreased recanalization in more severe strokes. Device treatment was not associated with significant increases in recanalization rates (p=NS). Recanalization of terminal internal carotid artery (12.5%), proximal MCA or M1 (17.9%) and M2 (46.7%) occlusions was not different between arms (all p=NS). Recanalization of proximal arterial occlusion in acute ischemic stroke cases enrolled in SENTIS was more frequent in M2 occlusions.

Conclusions:
More severe strokes at baseline were less likely to recanalize and device therapy did not increase recanalization rates. Treatment with the NeuroFlo device may invoke mechanisms of collateral perfusion distinct from direct arterial recanalization.
Abstract 202: Sex Differences In Ischemic Stroke: The Role Of Genetic Sex
Authors: MANWANI BHARTI , Venna Venugopal Reddy , Arnold Arthur P , Tarabishy Sami , McCullough Louise D
Published: July 2021

Background/Purpose—
Ischemic stroke is now recognized as a sexually dimorphic disease with women enjoying lower stroke incidence relative to men until an advanced age. This has largely been attributed to the neuroprotective effects of estrogen in females. However, recent failure of estrogen supplementation clinical trials and in vitro studies showing differences in ischemic sensitivity in sex steroid depleted media, suggest that factors other than hormones may shape this dichotomy. Since the sex chromosomal complement differs in men (XY) and women (XX), this may contribute to the underlying etiology of sex differences. The objective of this study was to investigate the
genetic sex contributions to the etiology of sex differences in cerebral ischemia.
Since it is extremely difficult to dissect the effects of sex chromosomes from hormones, we used a four core genotype (FCG) mouse model in this study where, Sry, the testis determining gene is deleted from the Y chromosome and inserted on an autosome in XY
-
SryMale(XYM). The four different genotypes, XXM(XX male), XYM(XY male), XXF(XX female) and XYF(XY female) derived by a cross between XXF and XYM can be compared to study the influence of sex chromosome(XX/XY) or sex(Sry/hormones) in stroke sensitivity.

Methods—
Stroke was induced by 90 minutes MCAO in FCG mice. Histological assessment was performed at 24 and 72 hours after stroke using cresyl violet staining. Sry PCR was done on brain samples from these mice.

Results—
At 24 hrs after MCAO, XXF’s(18.7±1.6%) and XYF’s(15.6±4%) had significantly smaller total hemispheric infarcts compared to either XYM’s(35±6.8%) or XXM’s(28±6.5%). ANOVA revealed a main effect of sex,
F(1,12)=4.9,p<0.05.
Hemispheric infarcts at 72 hours post stroke show a similar trend, with XXF’s(22±3.2%) and XYF’s(21±1%) having smaller hemispheric infarcts vs. XYM’s(35±7%) or XXM’s(30±2%). Sry mRNA expression was seen in brains of XXM’s and XYM’s.

Conclusions-
We found a sex effect in this study as all mice with Sry gene(XXM, XYM) had higher injury. It remains possible that these effects were secondary to the protective effects of estrogen (in XXF and XYF). However, this is unlikely as our preliminary studies have shown that XYF’s have very low estrogen levels (equivalent to males). Thus, we conclude that these differences may be due to the detrimental effects of Sry gene in the male brain. It is speculated that Sry may be the missing piece of puzzle that mediates sex specific cell death after stroke. Studies in gonadectomized FCG mice to further dissociate hormonal effects from direct effects of Sry are ongoing.
Abstract 208: Detailed Analysis of the 30-day Outcomes in the Stenting Arm of the SAMMPRIS Trial
Authors: Derdeyn Colin , Fiorella David , Lynn Michael , Levy Elad , Hoh Brian , Barnwell Stanley , Pride Lee , Zaidat Ossama , Cloft Harry , McDougall Cameron , Klucznik Richard , Lane Bethany , Turan Tanya , Janis Scott , Chimowitz Marc
Published: July 2021

Background:
Enrollment in first multicenter, randomized trial of Stenting and Aggressive Medical Management for Prevention of Recurrent Ischemic Stroke (SAMMPRIS) was stopped early owing to an excess 30-day event rate in the stenting group relative to the medical arm and a futility analysis. The purpose of this study was to carefully examine the peri-procedural events that occurred in the trial and to correlate them with any baseline or procedural factors that might be associated with an increased risk for an adverse outcome.

Methods:
224 of 451 patients were randomized to the stent arm. 33 suffered an independently-adjudicated endpoint event (stroke or death) within 30 days. The present analysis was limited to patients that underwent the complete per-protocol stenting procedure (n=209). 30 total endpoint events occurred in these 209 patients. Two asymptomatic hemorrhages also occurred and were included in the analysis of peri-procedural complications. Study records, including case report forms, procedural reports, and baseline and procedural imaging for these 32 patients were reviewed. 30-day events were further categorized as wire perforation, reperfusion hemorrhage, and thrombo-embolic ischemic stroke. The ischemic strokes were further categorized as perforator or embolic, based on imaging findings. Baseline and procedural factors in these patients were compared to the remaining 177 patients for predictors of the 30-day events.

Results:
There were seven wire perforations, six resulting in an endpoint. Five were subarachnoid hemorrhages (SAH). One was treated with nBCA and resulted in an ischemic stroke. One additional asymptomatic SAH occurred as a result of a wire perforation. Six intra-parenchymal hemorrhages (IPH) occurred. Five of the six were definitely delayed hours or days after a successful revascularization procedure, likely representing reperfusion hemorrhage. One was asymptomatic. The remaining 19 30-day endpoints were ischemic strokes. 12 were perforator strokes and seven were distal embolic. Two of these were related to delayed stent thrombosis days after the procedure. No correlation between operator experience or volume in the trial and 30-day events was found. Baseline risk factors and procedural factors were also not correlated with the risk for a procedural complication.

Conclusions:
The 30-day events in the SAMMPRIS trial were multi-factorial, with no single factor accounting for the majority of events. Further research on angioplasty and stenting for intracranial stenosis will need to address several different mechanisms for this procedure to be proven effective.
Abstract 2225: Vertebral Artery Stenting for the Treatment of Bow Hunter Syndrome: a report of four cases.
Authors: Darkhabani M Ziad , Thompson Matthew , Lazzaro Marc A , Taqi Asif , Zaidat Osama O
Published: July 2021

Background:
Bow Hunter syndrome is a rare condition that results from vertebrobasilar insufficiency secondary to mechanical occlusion or stenosis of the vertebral artery due to head rotation. Traditionally, surgical intervention with C1-C2 fusion or decompression of the vertebral artery was the mainstay of therapy. Endovascular intervention was rarely described for the treatment of bow hunter syndrome.

Methods:
The neurointerventional database between July 2005 and October 2010 was reviewed for identification of all cases of bow hunter syndrome that were treated with vertebral artery stenting. We report clinical, technical and outcome data on four patients with bow hunter syndrome who were treated with vertebral artery stenting.

Results:
Vertebral artery stenting was performed in the V2 segment (C2-C6) of the vertebral arteries in all four patients without significant technical difficulties. All patients reported symptomatic relief with minor or no residual stenosis on dynamic digital subtraction angiography.

Conclusion:
Vertebral artery stenting for the treatment of Bow Hunter syndrome is feasible, safe, and clinically effective. Endovascular techniques might offer an alternative and a minimally invasive therapy for the treatment of bow hunter syndrome.
Figure 1
. Case #1. (A) Selective left subclavian angiogram showing the left vertebral artery with head in neutral position. (B) Narrowing of the V2 segment with head turned to the left. (C) Post-stenting of the V1 (origin) and V2 segments with head turned to the left.
Abstract 2268: Trends In Reasons For Non-eligibility For tPA
Authors: Tong Xin , George Mary G
Published: July 2021

Background:
Use of IV tPA has increased over time, as has the adherence to the NQF endorsed performance measure for receipt of IV tPA within 3 hours. Little is known about trends in the reasons for patient ineligibility for IV tPA. This study examines trends in reasons for not providing IV tPA over time and by race and gender among acute ischemic stroke patients in the Paul Coverdell National Acute Stroke Registry (PCNASR), a quality improvement program for acute stroke implemented by state health departments.

Methods:
There were 13,164 PCNASR patients enrolled from 2008- 2010 with a clinical diagnosis of acute ischemic stroke with documentation of LKW and who arrived within 2 hours of LKW. Cochran-Armitage tests were used to test for trend on accepted reasons for not providing IV tPA within 3 hours of time last known well (LKW). Chi-square tests were used to test for differences among reasons between men and women and between non-Hispanic whites and minorities. Multiple reasons for not giving tPA could be selected.

Results:
Among 13,164 acute ischemic patients admitted between 2008 and 2010 with documentation of LKW and who arrived within 2 hours of LKW, 3781 (28.7%) received IV tPA, 7284 (55.3%) had documented reasons for not receiving IV tPA, and 2099 (16.0%) did not receive IV tPA. Contraindications to IV tPA, advanced age, rapid improvement and inability to determine eligibility increased over time. Mild stroke decreased over time. Conditions with warning, advanced age, limited life expectancy and family refusal were more common in women; mild stroke and rapid improvement were more common in men. Contraindications were more common in minorities; advanced age, mild stroke and rapid improvement, and family refusal were more common in non-Hispanic whites. When advanced age was selected, 46.6% of patients were over age 90 and 3.4% were under age 80. When stroke too mild was selected, 44.8% of patients had missing NIHSS scores, 42.1% of scores were 0-4, 8.8% were 5-9, and 4.3% were ≥ 10. The three most common reasons for not providing tPA were rapid improvement (40.9%), mild stroke (33.0%), and contraindications (29.2%) in 2010.

Conclusions:
More than half of ischemic stroke patients arriving within 2 hours of LKW were ineligible to receive IV tPA. There was little use of advanced age for patients under age 80. Documentation of stroke too mild was not substantiated by an NIHSS score in nearly half of patients. Better documentation of NIHSS score should be provided.
Abstract 2276: Microhemorrhage Burden Increases the Risk of Hematoma Growth in Patients with Intracerebral Hemorrhage
Authors: Martí-Fàbregas Joan , Morenas Estrella , Delgado-Mederos Raquel , Dinia Lavinia , Granell Esther , Marín Juan , Pérez de la Ossa Natalia , Sanahuja Jordi , Arce Ana María , Alonso de Leciñana María , RENEVAS
Published: July 2021

Introduction
Microhemorrhages (MH) are lesions detected on radiological studies resulting from an underlying small-vessel angiopathy. We assesed the hypothesis that the presence of MH increases the risk of hematoma growth (HG) in patients with acute Intracerebral Hemorrhage (ICH).

Methods
We evaluated a series of patients in a prospective and multicentre study. We included patients with a spontaneous supratentorial ICH within the first 6 hours after symptom onset, that also had a follow-up CT 24-72 hours later and a MRI performed after a variable time after ICH. HG was defined as an increase >33% in the volume of hematoma on the follow-up CT, in comparison with the admission CT. The volume was calculated using the formula AxBxC/2. On MR scans we assessed the presence, number and distribution of MH. After differential diagnosis with other radiological lesions, MH were evaluated on echo-gradient sequences and defined as hypointense rounded lesions with a diameter <10mm. Statistical analysis: Bivariate tests with the whole sample and with the subgroup of patients with less than 3 hours from symptom onset.

Results
We studied 46 patients, whose mean age was 68.8±11.2 y and 68% were men. Mean baseline volume was 19.1±27.3 cc. We detected MH in 7/15 patients with HG and in 18/31 patients without HG (46.7% vs 58.1%, p=0.53). In the subgroup of patients with 10 MH, the risk of HG was higher than in patients with 0-10 MH (75% vs 28.6%, p=0.067), and this difference was significant when considering only patients with a <3 hours evolution (100% vs 31%, p=0.044). We did not observe any association between risk of HG and distribution of MH. Age and time to CT were equivalent in the two groups (with and without HG), either in the <6 or <3 hours subgroups.

Conclusions
In conclusion, in patients with hyperacute ICH, the presence of more than 10 MH increases the risk of HG. This is probably an indirect marker of a more severe underlying angiopathy.
Abstract 2284: Reliability and Validity of the MGHS Dysphagia Screening Tool for Stroke Patients
Authors: Stebelton Jeanette , Savolainen Diane , Carli Margo , Filizetti Roxanne , Massey Barb
Published: July 2021

Background
Dysphagia occurs in approximately 55% of acute stroke patients and is associated with aspiration pneumonia. Clinical practice guidelines recommend that all patients who are admitted with the diagnosis of stroke or suspected stroke should be screened for dysphagia utilizing a validated screening tool prior to receiving any food, fluid, or medication by mouth.

Purpose
The purpose of the study is to determine the reliability and validity of the Marquette General Health Systems Dysphagia Screen for identifying patients at risk for aspiration.

Method
This non-randomized study utilized a collaborative tracking tool that compared results of the Nursing Dysphagia Screen (NDS) to the Speech Language Pathologist Swallow Evaluation (SLPSE). Two Registered Nurses rated each patient utilizing the NDS and then the patient was rated on the SLPSE. The NDS includes10 items: and the Speech Language Pathologist portion of the tool consisted of 8 items.

Results
One hundred subjects ranged in age from 20-94 (M=70.31, SD=14.6). There were more males (n=58) than females (n=42). The majority were admitted to the medical unit (64%), followed by cardiac (14%), ICU (12%) and CCU (10%). Length of stay ranged from 1-15 days (M=3.73, SD=2.8). NIH scores ranged from 0-20 (M=6.8, SD=7.4). Kappa was calculated to determine inter-rater reliability. For 63 pairs of ratings between two staff nurses, Kappa=.81 indicates strong reliability. Scores on the Nursing Dysphagia Screen were compared to 86 Speech Language Pathologist Swallow Evaluations. The Phi Coefficient was not significant indicating that the nurses’ and speech therapists ratings’ were similar. In addition, when there were differences it was false positives by nurses.

Conclusion
The MGHS NDS is a quick screening tool used by nursing in an effort to prevent aspiration. Prior to implementing the use of the tool, it was important to establish the reliability and validity of the tool. Results indicate that there is strong inter-rater reliability. Validity was established given that there were no significant difference in ratings between the nurses and speech therapists. It appears that the MGHS NDS is an effective early screening tool for dysphagia.
Abstract 2291: Enhanced Carotid Plaque On Contrast-enhanced Ultrasound Is Associated With Plaque Instability And Rupture
Authors: Matsumoto Noriko , Kimura Kazumi , Uno Masaaki , Sakai Kenichoro , Sadahira Yoshito , Nishimura Hirotake
Published: July 2021

Background:
Ischemic stroke is one of causes of atherosclerotic diseases, and is closely associated with vulnerable plaque at the origin of the internal carotid artery. Several studies have shown that neovascularization in atheromatous plaque serves as a reliable maker of plaque vulnerability.Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of carotid intraplaque neovascularization. The aim of the present study was to investigate the histopathologic findings of enhanced carotid plaque on CEUS.

Methods:
We studied consecutive 18 patients (16 men, mean age 69.4 ± 6.7 years) who underwent carotid endarterectomy. Enhanced plaque was classified into two subgroups: a spotty pattern as moving bright spots within plaque (
Figure 1
A, Panel A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque (
Figure 1
B, Panel A). Sonazoid (Daiich-Sankyo, Tokyo, Japan), perflurobutane microbubbles, was used as the contrast agent. A bolus intravenous injection of Sonazoid (0.015 mL/kg body weight (0.12 μ L perflurobutane microbubble /kg body weight)) was performed via the peripheral venous line followed by a flush with 10 mL of normal saline. We investigated the association between enhanced plaque on CEUS and histopathologic findings.

Results:
CEUS revealed enhanced plaque in 11 (61.1%) of 18 patients. Only a spotty pattern (spotty subgroup) was observed in 5 patients, whereas both a spotty and linear pattern (linear subgroup) was observed in 6. The amount of neovascularization was larger in enhanced than in non-enhanced plaque (6.79 ± 5.17/2.5 mm
2
vs. 1.12 ± 0.90/2.5 mm
2
, P=0.001). Furthermore, the enhanced group had more macrophage aggregation (7.76 ± 3.70% vs. 4.23 ± 1.63%, P=0.030) and intraplaque hemorrhage (18.84 ± 14.88% vs. 5.52 ± 9.68%, P=0.013) compared with the non-enhanced group. Thin fibrous cap (<200 μ m) was more frequent in enhanced than non-enhanced plaque (100% vs. 28.6%, P=0.002). All of the enhanced plaques with a linear pattern had fibrous cap rupture, but this was observed in only 20% of those with a spotty pattern (P=0.015,
Figure 1
B, Panel B).

Conclusions:
Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque.
Abstract 2303: Therapeutic Intensity and Functional Gains of Stroke Patients during Inpatient Rehabilitation.
Authors: Wang Hua , Camicia Michelle , Terdiman Joseph , Mannava Murali K , Sandel M E
Published: July 2021

Objectives:
To study the effects of therapeutic intensity on functional gains of stroke patients in inpatient rehabilitation.

Design:
A retrospective cohort study.

Setting:
An inpatient rehabilitation hospital (IRH) in northern California.

Participants:
Three hundred and sixty stroke patients discharged from the IRH in 2007.

Interventions:
Average number of minutes of rehabilitation therapy per day, including physical therapy (PT), occupation therapy (OT), speech language therapy (SLT), and total treatment.

Main Outcome Measures:
Functional gain measured by the Functional Independence Measure

(FIM
TM
), including activities of daily living (ADL), mobility, cognition, and total FIM
TM
scores.

Results:
The study sample had a mean age of 64.8 years (SD=13.8), and was 57.4% male, and 61.4% White. About three quarter of the patients had an ischemic stroke; 61.4% had one or more significant comorbid conditions. Median IRH length-of-stay (LOS) was 20 days. The mean total therapy time was 190.3 minutes per day (PT 114.0, OT 42.8, and SLT 33.8). The mean total functional gain was 26.0 (ADL 9.1, mobility 11.4, and cognition 6.2). A longer therapeutic duration per day was significantly associated with functional improvement (r=0.20, p<.001). However, patients who received total therapy time of less than 3 hours per day showed significantly lower total functional gain than those treated 3 hours or longer. There was no significant difference in total functional gain between patients treated 3-3.5 hours and over 3.5 hours per day. Intensity of PT, OT, and SLT in hours per day of treatment time was also significantly associated with corresponding sub-scale functional improvements. Figure 1 presents age and gender adjusted therapeutic intensity and FIM
TM
Gain. Multiple linear regression analyses showed that young age, hemorrhagic stroke, earlier admission to IRH, and longer IRH stay were independent predictors of functional improvement.

Conclusions:
The study demonstrated a significant relationship between therapeutic intensity and functional gain during IRH stay and provides evidence of treatment intensity thresholds for optimal functional outcomes for stroke patients in inpatient rehabilitation.
Key Words:
Stroke, rehabilitation therapy, intensity, functional outcomes.
Abstract 2311: Hospitalization Costs of Stroke among Adults 18-64 Years in the United States
Authors: Wang Guijing , Zhang Zefeng , Ayala Carma , Dunet Diane , Fang Jing , George Mary
Published: July 2021

Background and purpose:
The average cost of stroke, a leading cause of death and serious long-term disability, has been estimated to range from $468 to $146,149 worldwide, and varies 20-fold in the United States. A robust cost estimate is needed for policy makers, public health researchers and practitioners to use as a reference in making resource allocation decisions and assessing cost-effectiveness of intervention programs. This study examined the hospitalization costs of stroke using a large administrative data.

Methods:
We identified 97,374 hospitalizations with a primary or secondary diagnosis of stroke from pooling 2006-2008 MarketScan inpatient datasets. We investigated the costs by stratifying the hospitalizations by stroke types (hemorrhagic ICD-9 430-432, ischemic ICD-9 433-434, ill-defined ICD-9 436-437, and late-effects ICD-9 438) and diagnosis status (primary and secondary). For hospitalizations with stroke as the primary diagnosis, we identified those with a secondary diagnosis of hypertension, ischemic heart disease (IHD), and diabetes. We used multiple regression models to estimate the impact of stroke types and diagnosis status on the costs controlling age, sex, geographic region, and Charlson Comorbidity Index (CCI).

Results:
Of the 97,374 hospitalizations (average cost $20,396 ±23,256), the number of hospitalizations with hemorrhagic, ischemic, ill-defined, and late-effects of stroke was 16,331, 62,637, 38,312, and 14,221 with an average cost of $32,035 ±32,046, $18,963 ±21,454, $19,430 ±22,159, and $18,946±19,891, respectively. Over 61% of the hospitalizations listed stroke as a secondary diagnosis only. Regression results showed that the costs increased by at least $962 per CCI unit increase (p<0.001). Hemorrhagic stroke cost $14,499 more than ischemic stroke (p<0.001). For hospitalizations with the primary diagnosis of stroke, those with a secondary diagnosis of IHD had higher costs than those without IHD, especially among those of ischemic stroke ($9835 higher, p<0.001), while hypertension and diabetes as a secondary diagnosis lowered the costs. Hospitalizations with a primary diagnosis of ischemic stroke had $3195 lower cost than those listed as secondary diagnosis, but hospitalizations with a primary diagnosis of hemorrhagic stroke had $8001 higher cost than those listed as a secondary diagnosis.

Conclusions:
The costs of stroke hospitalizations were high and varied greatly by stroke types, diagnosis status, and comorbidities. Stroke types and their comorbidities should be considered when developing cost-effective strategies for stroke prevention.
Abstract 2334: Consumer Survey Indicates Aspirin Use Remains Less Than Optimal in Stroke Survivors
Authors: Fort John G , Baer Lorraine R
Published: July 2021

Background:
Low-dose aspirin is recommended for the secondary prevention of ischemic stroke or TIA. With the availability of aspirin (ASA) over-the-counter, actual ASA use and regimens are difficult to determine using insurance claims databases. Likewise physician involvement in ASA therapy is not captured. In the recent Agency for Healthcare Research and Quality (AHRQ) survey, ASA use among stroke survivors was reported, but there were no data on ASA dosing regimens or provider recommendations.

Methods:
In December 2009, an internet-based questionnaire was completed using a consumer internet panel of 23,139 US households (HHs) with an individual/caretaker of an individual who had suffered stroke and/or myocardial infarction (MI). After confirming that the HH had someone who met the diagnostic criteria, random sampling was performed to obtain 500 individuals with either previous stroke only or stroke + MI and 500 individuals with previous MI only who were currently taking ASA as a result of their condition.

Results:
A random sample of 1579 HHs were screened, yielding 842 total stroke and 737 MI only HHs. Aspirin was not used for stroke or MI in 411 of these HHs (342 total stroke and 69 MI only). The remaining 500 stroke HHs and 500 of the 668 MI only HHs (168 HHs terminated when MI only quota filled) were included in the analysis. Use of ASA for secondary prevention of was 59% (500/842) for total stroke sufferers compared with 83% (650/785) for total MI sufferers. At least 91% of stroke (445/488) or MI (466/496) survivors reported taking ASA precisely as recommended by their physician. The most common dosing regimen was ASA 81 mg once daily, followed by 325 mg once daily.

Conclusions:
Aspirin use among patients with previous stroke was <60% in this 2009 internet-based survey, which is similar to the results of the recent AHRQ survey (57% ASA use among US stroke survivors over the 7-year period of 2000-2006.) Stroke patients identified cardiologists and GPs as their primary healthcare provider, and these two physician groups are the most frequent recommenders of ASA therapy to this patient population. Taken together, these findings suggest that continued effort is needed to optimize the use of ASA therapy in secondary stroke prevention as recommended by current guidelines.
Abstract 2337: Apparent Diffusion Coefficient (ADC) Signal Maturation: Rates Of ADC Decline Depend On Severity Of Perfusion Deficit During Hyperacute Ischemic Stroke
Authors: An Hongyu , Ford Andria L , Eldeniz Cihat , Chen Yasheng , Vo Katie D , Derdeyn Colin P , Powers William J , Lee Jin-Moo , Lin Weili
Published: July 2021

Background:
While it is known that a reduction of blood flow leads to a decrease in apparent diffusion coefficient (ADC), how ADC evolves as a function of time from ischemia onset is unclear. We evaluated ADC signal change in brain tissue with temporally stable hypoperfusion, examining the relationship between severity of hypoperfusion and the rate of ADC decline during acute ischemia.

Methods:
Ischemic stroke patients were sequentially imaged with diffusion-perfusion weighted imaging at <4.5hr (tp1) and at 6hr (tp2) after stroke onset, to directly assess the temporal evolution of ADC. One month FLAIR provided the final infarct region. Registration aligned all images for each patient. Dynamic susceptibility contrast method allowed calculation of mean transit time (MTT). Hypoperfusion was defined as tissue with MTT > 4sec + the contralateral median MTT. In tissue with stable hypoperfusion on tp1 and tp2, ADC regions of interest (ROIs) with normal or moderate reduction on tp1 were evaluated. To avoid capturing tp1 ADC voxels that had already maximally declined (floor effect, <30 ×10
-5
mm
2
/s), ADC values < 60 were excluded. To assess how ADC declined with varying degrees of hypoperfusion, tissue was divided into 6 MTT ranges: 3-6 (ROI1), 6-9 (ROI2), 9-12 (ROI3), 12-15 (ROI4), 15-18 (ROI5) and >18 (ROI6) seconds. Paired t-tests compared tp1 and tp2 ROIs for each patient. Infarct probability based on tp3 FLAIR was computed for each ROI.

Results:
43 patients were imaged at 2.9 (tp1) and 6.4 hrs (tp2) after stroke onset, of which 37 returned for 1 month FLAIR. The 6 ROIs with increasing MTT severity were found in 41, 27, 19, 12, 6, and 10 patients for ROI’s 1-6, respectively. ADC values for all ROIs were similar at tp1 (near normal), despite different tp1 MTT. For ROI1-3, ADC values did not decline between tp1 and tp2 or decreased mildly (ROI3, P=0.079). For severe hypoperfusion, ADC decreased significantly: ROI4 (p=0.006), ROI5 (P=0.038), and ROI6 (P=0.0001). Using linear regression to approximate the ADC decline, the slopes were significantly different from zero with ADC decay rates of -1.87×10
-5
mm
2
/s/hr (R=0.58), -2.86×10
-5
mm
2
/s/hr (R=0.65) and -4.51×10
-5
mm
2
/s /hr (R=0.82) for ROI4-6, respectively (
Figure
). The median infarct probabilities for the 6 ROI’s increased with increasing MTT severity: 16%, 53%, 57%, 87%, 100%, and 90% for ROI1-6, respectively.

Conclusions:
ADC remained normal after ischemic stroke in regions with stable, moderate hypoperfusion. In contrast, with stable, severe hypoperfusion (MTT>12s), ADC decreased from 3-6 hours and the rate of decline was highly dependent on the degree of hypoperfusion.
Abstract 2344: Video-EEG Reveals Subclinical Ischemic Seizures And Limited Efficacy Of Phenobarbital In Neonatal Mice
Authors: Kadam Shilpa D , Kang Seok Kyu , Kim Shin Tae , Johnston Michael V
Published: July 2021

Ischemia in the immature brain is an important cause of neonatal seizures. The exact timing of neonatal stroke onset is usually unclear and the diagnosis delayed until presentation with seizures a few to several hours later. Optimal seizure treatment in neonates remains uncharacterized and the widely used drug phenobarbital has limited clinical efficacy. Developmental profiles of chloride co-transporter expression and function in immature brains have been proposed to dictate the age dependent anti-seizure efficacy of GABA-agonists and this switch is known to occur in P8-9 mouse pups. To investigate the anti-seizure efficacy of the first line anticonvulsant and GABA
A
-agonist phenobarbital (PB) and NKCC1 antagonist bumetanide (BTN) as adjunct treatment on neonatal ischemic-seizures, we utilized synchronous video-EEG and unilateral carotid-ligation to produce acute ischemic-seizures in postnatal day 7 and 10 CD1 mice. Quantitative analyses of pre- and post-treatment EEGs were done using Pinnacle (Pinnacle technology Inc., KS) seizure scoring and Insight software (Persyst development corp., AZ) for evaluation of seizure grades (clinical vs. subclinical or electrographic) and treatment efficacy. Severity of acute ischemic seizures and incidence of subclinical seizures was higher at P7 and a gender-specific susceptibility was detected in males that correlated with a lag in KCC2 expression levels in naïve males compared to age-matched females, not detected at P10. However, the P7 brains were comparatively more resistant to infarcts unlike at P10 when they occurred frequently. PB showed a better efficacy at P10. BTN treatment 1h following PB however failed to act as an efficacious adjunct therapy and aggravated subclinical seizures in P10 females. At P7, both PB and add-on BTN treatment failed to stop seizures. EEG power (0.5-32 Hz) was lowered after PB treatment at both ages. Post-ischemic down-regulation of KCC2 expression was detected at both ages tested compared to age-matched naïve brains. This study showed that 1. Quantification of subclinical ictal events better evaluate anti-seizure efficacy of treatments and 2. The down-regulation of KCC2 in ischemia may further decrease the efficacy of drug actions that are dependent on a hyperpolarizing chloride gradient for their anticonvulsant action. This decrease in efficacy failed to be rescued by blocking the immature chloride co-transporter NKCC1.
Abstract 2346: Traditional Cardiovascular Risk Factors Explain Only Small Proportion of the Variation in Carotid Plaque
Authors: Kuo Frank , Gardener Hannah , Dong Chuanhui , Cabral Digna , Della-Morte David , Santiago Maria , Elkind Mitchell S , Sacco Ralph L , Blanton Susan H , Rundek Tanja
Published: July 2021

Background and Objectives:
Subclinical atherosclerotic plaque is an important marker of increased vascular risk. Traditional risk factors explain less than 50% of the variance in atherosclerotic carotid plaque (ACP). Identifying factors underlying unexplained ACP, either deleterious or protective, may help targeting preventive strategies with significant scientific impact and health relevance. We aimed to identify individuals with unexplained subclinical ACP or unexplained protection against ACP using 2-D high-resolution B-mode carotid ultrasound.

Methods:
As a part of the NINDS carotid imaging project of the Northern Manhattan Study, 1,790 stroke-free individuals (mean age 69±9; 60% women; 61% Hispanic, 19% black, 18% white) were assessed for total ACP burden (TACP), the sum of plaque areas in all carotid arteries (mm
2
) within an individual and transformed using a cube root function (x
1/3
) for normality. Multiple linear regression models were conducted: (1) including pre-specified traditional risk factors (age, sex, LDL-cholesterol, diabetes, pack-years of smoking, blood pressure (BP), and treatment for BP); and (2) the best-fit model with addition of socioeconomic and less traditional factors including inflammation biomarkers and homocysteine. The standardized TACP residual scores were constructed from the best-fit regression model to select individuals with unexplained TACP.

Results:
Prevalence of carotid plaque was 58%. Mean TACP was 12.1±mm
2
before the x
1/3
transformation. Traditional model (model 1) explained 21% of the variance in TACP (

R
2
=

0.21). Age (15%), smoking (3%), systolic BP (1.2%), and diabetes (1%) were most contributing factors. The best-fit model (model 2) explained 23% of TACP, with most contribution by age (14%), smoking (3%), systolic BP (1%), fasting glucose (1%), LDL:HDL ratio (1%), diastolic BP (1%), homocysteine (1%) and white blood cell count (1%).

Conclusion:
Variation in subclinical carotid plaque is largely unexplained by traditional and novel risk cardiovascular risk factors. Identification of genetic and environmental factors underlying unexplained subclinical atherosclerosis is of utmost importance for successful prevention of cardiovascular disease and stroke.
Abstract 2365: Impact of Socioeconomic Level on Cardiovascular Risk in Ischemic Stroke Patients: The OPTIC Registry
Authors: Amarenco Pierre , Abboud Halim , Labreuche Julien , Arauz Antonio , Bryer Alan , Lavados Pablo G , Massaro Ayrton , Munoz Collazos Mario , Steg Philippe Gabriel , Yamout Bassem I , Vicaut Eric ,   OPTIC Registry Investigators
Published: July 2021

Background :
The impact of socioeconomic factors (SEF) on the risk of future vascular events in stroke patients has been understudied. The Outcomes in Patients with TIA and Cerebrovascular disease (OPTIC) registry included patients in secondary prevention of stroke.

Objective :
to stratify the risk of vascular event recurrence in patients with cerebral infarction according to presence of PAD, ankle-brachial index (ABI), known coronary artery disease (CAD), involvement of several arterial beds, geographic variations and SEF.

Method :
Between January 2007 and December 2008, 3635 patients aged 45 years or older were enrolled in the OPTIC registry from 245 sites in 17 countries in the following regions: Latin America (1543 patients), Middle East (1041 patients), North Africa (834 patients), and South Africa (217 patients). PAD was present in 7.8%, ABI in 22%, CAD in 12.8%, and 31.1% were unemployed, 26.2% had less than 2 school years, 23% of patients had no health insurance, 12.8% lived in rural area, 8.4% lived alone, 7.5% did not live in a house/flat. Primary endpoint included vascular death (VD), myocardial infarction (MI) and stroke.

Results :
During median follow-up of 731 days, 524 patients had at least 1 primary event; 190 patients had VD, 88 nonfatal MI, and 296 nonfatal stroke. The estimated risk of primary endpoint was 15.6% (95%CI, 14.4-17.0%) at 2-year. The risk increased with the number of vascular beds involved from 13.1% to 30.7% (p for trend<0.001). Using patients from Latin America as reference, age-sex-adjusted HR was 1.29 (95%CI, 1.04-1.60) for Middle East, 1.31 (95%CI, 0.90-1.89) for South Africa, and 1.64 (95%CI, 1.32-2.04) for North Africa. The absolute additional risk of having a primary endpoint ranged between, 4.7% for unemployed patients to 17.5% for patients not living in a house/flat. In multivariate analysis, living in rural area, not living in a house/flat, unemployment status, no health insurance cover, and less than 2-years school were associated with an increased cardiovascular risk (all adjusted p<0.004). There was a stepwise increase in the primary endpoint with the number of low SEF ranging from 13% to 62% (adjusted p-value for trend<0.001).

Conclusions :
vascular risk in stroke patients in North and South Africa, Middle East and Latin America varies not only with the number of arterial beds involved but also with socio-economic variables, particularly poor health insurance cover, not living in a house/flat and low education level
Abstract 2373: Childhood Stroke Impairs Functional Behavior
Authors: Lo Warren , Mackay Mark , Hajek Christine , Greenham Mardee , Gomes Alison , Gordon Anne , Anderson Vicki , Yeates Keith O
Published: July 2021

BACKGROUND:
Stroke can affect children with long-term impairment of intellectual ability and increased risk of attention deficits and psychiatric disorders. Although limited studies in the literature suggest that stroke can chronically impair functional behavior and social adaptation, these functional outcomes have received little attention. We performed a pilot case-control study to examine the hypothesis that pediatric stroke impairs adaptive behavior, and we addressed the secondary hypotheses that stroke volume and location predict impaired functional behavior.

METHODS:
Children ages 6-15 years who had neonatal or childhood onset arterial ischemic stroke were identified by chart review at the Nationwide Children’s (Columbus, OH, USA) and Royal Children’s Hospital (Melbourne, Australia). Subjects were included if they could complete the test battery. Age- and gender-matched children who had asthma were selected as controls. Stroke cases were assessed with the Pediatric Stroke Outcome Measure and had an MRI brain scan after the acute phase of stroke. Cases and controls underwent functional assessments at least one year after the incident stroke. The battery of tests and ratings included the Wechsler Abbreviated Scales of Intelligence, WISC-IV Processing Speed Index, Child Behavior Checklist, Adaptive Behavior Assessment System, and Child & Adolescent Scale of Participation. Infarct volumes were measured by manual segmentation.

RESULTS:
The sample included 10 children with perinatal stroke, 26 with acquired childhood stroke, and 15 controls. Median age at assessment was 8.7 yrs (IQR 6.9-11.9) and median time after presentation was 5.1 yrs (IQR 2.8-7.4). The median PSOM for stroke cases was 1 (range 0-8.0) and for controls was 0 (range 0-1). Stroke was significantly associated with lower levels of multiple daily living skills (p range 0.001-0.025), functional academics (p=0.048), and self-care (p=0.020), as well as a trend toward impaired school participation (p=0.064), but was not associated with impaired intellectual functioning or behavioral adjustment. Larger Infarcts showed a trend association with higher PSOM total scores (p=0.091). Infarcts that involved both cortex and subcortical parenchyma were associated with poorer daily living skills (p range 0.005-0.052) and a trend toward impaired home community participation (p=0.079). Age of stroke onset was not associated with impairments.

Conclusions:
Stroke causes deficits that may not be appreciated by standard IQ screening or report of overt behavior disorders. These deficits can affect daily living skills and result in impaired adaptive behavior. Strokes involving both cortex and subcortex, as a proxy for more extensive strokes, may be particularly associated with impaired adaptive behavior. These results are “best case” estimates because our study excluded mentally retarded or grossly impaired children.