bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP42: Coherent Neural Oscillations Inform Early Stroke Motor Recovery
Authors: Cassidy Jessica M , Wodeyar Anirudh , Srinivasan Ramesh , Cramer Steven C
Published: June 2021

Introduction:
Neural oscillations may contain valuable information for stroke rehabilitation. The objective of this study was to examine the predictive performance of neural oscillations in early stroke motor recovery using dense array electroencephalography (EEG). Since past work theorizes that neural oscillations underlie behavior, we hypothesized that coherent oscillations with ipsilesional primary motor cortex (M1) across a 1-30 Hz band would significantly predict early motor recovery post-stroke.

Methods:
Individuals with stroke admitted to an inpatient rehabilitation facility (IRF) completed a three-minute resting EEG recording and structural MRI around the time of IRF admission and motor testing (Functional Independence Measurement motor subscale (FIM-motor)) at IRF admission and discharge. We examined how well FIM-Motor change was predicted using EEG power and coherence with ipsilesional M1 across delta (1-3 Hz), theta (4-7 Hz), alpha (8-12 Hz), low beta (13-19 Hz), and high beta (20-30 Hz) frequency bands, along with corticospinal tract (CST) injury, in a lasso regression with K-fold cross-validation for deviance estimation.

Results:
Twenty-seven subjects (20 males, 58.3±14.6 years, 8-17 days post-stroke) with predominantly mild-moderate motor impairment participated. EEG ipsilesional M1 coherence with 16 leads overlying both hemispheres predicted 61.8% of FIM-motor change from IRF admission to discharge, with higher frequencies (alpha, high beta) positively relating to motor recovery. Lower frequencies overlying contralesional parietal (theta) and frontal (delta) regions inversely and positively related to motor recovery respectively. Coherence outperformed EEG power and CST injury measurements. Ipsilesional M1 coherence also predicted 55.2% of the variance in residuals derived from a predictive model containing only CST injury, suggesting that EEG coherence and CST injury contain unique information for motor recovery prediction.

Conclusions:
Early after stroke, coherence of neural oscillations with ipsilesional M1 across the entire brain through a wide frequency spectrum is best at predicting functional gains from inpatient rehabilitation and may be feasible as a bedside biomarker of motor recovery.
Abstract TMP43: Differential Cortical Effect Modulated by Anodal, Cathodal and Bihemispheric Transcranial Direct Current Stimulation (tDCS) in Patients With Ischemic Stroke
Authors: Chhatbar Pratik Y , DeVries William , Grattan Emily , Kautz Steven A , Feng Wuwei
Published: June 2021

Introduction:
The differential brain modulatory effects across hemispheres from different montages in stroke patients is not well established. We aimed to investigate the cortical excitability on lesional and contra-lesional hemisphere modulated by anodal, cathodal and bihemispheric montage at 4 mA tDCS strengths.

Hypothesis:
Bihemispheric tDCS montage induces more cortical excitability on the lesional hemisphere.

Methods:
Eighteen aging stroke patients with unilateral ischemic stroke of 6 or more months and inducible motor evoked potentials (MEP) underwent 3 sessions of 30 minutes 4 mA tDCS combined with occupational therapy. Each session was at least 2 days apart and consisted of one of the 3 different montages: anodal (Anode: lesional C3/C4, Cathode: non-lesional FP1/FP2), cathodal (Anode: lesional FP1/FP2, Cathode: non-lesional C3/C4), or bihemispheric (Anode: lesional C3/C4, Cathode: non-lesional C3/C4). We collected MEP size, short intracortical inhibition (SICI, 3 ms) and intracortical facilitation (ICF, 15 ms) on bilateral abductor pollicis brevis (APB) muscles using single or paired pulse TMS at 5 timepoints (baseline and four post-tDCS 12 minutes apart sessions).

Results:
All 18 subjects had comparable resting motor threshold (rMT) across 3 montages (see A). Bihemispheric tDCS montage offered significantly larger peak-to-peak MEP responses on the lesioned cortex (ANOVA, F=8.97, P<0.01) but not on the non-lesioned cortex (ANOVA, F=0.86, P=0.42). These differences were apparent in single pulse, SICI and ICF (see B).

Conclusion:
Our findings support that bihemispheric montage is better suited in post-stroke motor recovery tDCS applications.
Abstract TMP55: Understanding Cultural and Knowledge Barriers to Acute Stroke Care in the Filipino American Community
Authors: Moya Antonio L , Grospe Vincent , Brock Julia , Nhat-Doan Vo Linh , Cheng Eric , Heilemann MarySue
Published: June 2021

Introduction:
Filipino Americans (FilAms) in Los Angeles make up the largest Filipino community outside of the Philippines and 2nd largest Asian subgroup in L.A. County. FilAms also have higher rates of stroke, high blood pressure, and diabetes not only compared to other Asian subgroups but also to African American and Latino communities. Little is known about FilAm knowledge and cultural barriers in accessing acute stroke care.

Methods:
Using a qualitative descriptive design, we studied knowledge, attitudes, and health behaviors of the L.A. FilAm community with regard to acute stroke care by conducting 5 focus groups of 5-7 people each and 6 semi-structured interviews with key community leaders. Participants were recruited through L.A. FilAm community organizations. Focus groups were organized as follows: 1st: elderly community members at high stroke risk; 2
nd
: spouses of those at high stroke risk; 3
rd
: paid caregivers of those with stroke risk; 4
th
: unpaid caregivers of those with stroke risk; 5
th
: young FilAms with family members with stroke risk. Six individual interviews were with elderly FilAms identified as exceptionally healthy by community leaders. We conducted thematic analysis, coding for themes on barriers to acute stroke care.

Results:
Two key themes have emerged: 1) spiritualistic fatalism and the belief that God is in control of all outcomes despite an individual’s will and 2) fear of calling 911, specifically linked to shame in being perceived as unhealthy by neighbors, fear of deportation among undocumented FilAms, and fear of high ambulance cost. Elderly participants perceived social media as one of the most effective ways to widely engage FilAms on stroke.

Conclusion:
Beliefs related to spiritualistic fatalism as well as fear of calling 911 are powerful barriers to acute stroke care among FilAms. The results can inform a culturally-relevant intervention for the community using social media, the Internet, and Filipino television programs to encourage FilAms to obtain acute stroke care. Data collected is currently being integrated into a FilAm stroke media tool. Lessons learned from this project will also be used to create stroke education for other U.S. Asian Pacific Islander communities.
Abstract TMP59: Metabolomic Profiles Are Associated With Incident Ischemic Stroke in Women
Authors: Rexrode Kathryn M , Hu Jie , Li Jun , Balasubramanian Raji
Published: June 2021

Introduction:
Although metabolomic profiling has identified metabolites associated with coronary heart disease, few studies have examined the association with incident ischemic stroke.

Hypothesis:
Metabolomic profiles will differ in women who develop incident ischemic stroke from those who don’t.

Methods:
We applied a liquid chromatography-tandem mass spectrometry metabolomics platform to measure 540 known plasma metabolites (Broad Institute) in a set of 1074 women in the Nurses’ Health Study with baseline blood samples (537 incident ischemic stroke cases, 537 controls). Cases were matched 1:1 by age, race, hormone therapy use, smoking status, history of coronary heart disease and cancer, and fasting status. All strokes were confirmed with medical record review by a physician. Conditional logistic regression models were performed with log-transformed, standardized metabolites and adjusted for (A) matching factors only, (B) body mass index, hormone therapy and aspirin use, physical activity, alcohol, and histories of hypertension, diabetes and elevated cholesterol. Adjustment for multiple testing was based on Storey’s q value procedure to control the false discovery rate (FDR), with FDR <0.05 required for model A and an unadjusted p value < 0.05 for model B. A metabolite score was estimated as a linear combination LASSO of the subset of metabolites that met the threshold for statistical significance after controlling FDR at 0.05.

Results:
The mean age was 65 years, and the mean time to ischemic stroke was 5.4 years. Twenty-three metabolites were significantly different among those who developed ischemic stroke after adjustment for matching and stroke risk factors (model B); these included 10 lipid metabolites, 5 amino acid derivatives, 3 purine/pyrimidine derivatives and 3 other metabolites. Several metabolites were related to tRNA and mitochondrial dysfunction. A stroke metabolite score (SMS) of 19 of these metabolites selected by LASSO was strongly associated with stroke risk: multivariable odds ratio of 4.00 (95% CI: 2.64 - 6.08) for ischemic stroke comparing women in the highest to lowest quartile of SMS.

Conclusions:
These data suggest that novel metabolites are associated with incident ischemic stroke in women.
Abstract TMP68: Mortality in Stroke Patients Transferred for Higher Levels of Care
Authors: Lyerly Michael J , Albright Karen , Howard George , Donnelly John
Published: June 2021

Introduction:
We previously reported that age and race disparities exist in transfer for a higher level of care among acute ischemic stroke (AIS) patients. This study examined the association of transfer with in-hospital mortality stratified by age and race.

Methods:
In this cross-sectional analysis, we extracted AIS patient characteristics and transfer status from State Emergency Department Databases and State Inpatient Databases of 7 states between 1/1/2010-12/29/2010. We used stabilized inverse probability of treatment weights and fit generalized linear models with a flexible restricted cubic spline term for age, reporting risk differences (RDs) and risk ratios (RRs) with 95% confidence intervals (CIs). Because of potential unmeasured confounders, we reported E-values, which represent the minimum confounder-outcome and exposure-confounder RRs that could shift the associations to the null or the CI limits to include 1.

Results:
We identified 82,487 AIS discharges of whom 5.4% were transferred. After adjusting for age, race, gender, hospital type, minority-serving status, and Elixhauser comorbidities through weighting, transferred white patients, particularly age <65, had higher in-hospital mortality compared to those not transferred (Figure). Although young black patients also had higher mortality, this was not seen among black patients aged ≥65. E-values suggest that a strong unmeasured confounder would be required to shift the associations to the null (RRs>2.0), but a weaker confounder could shift the CIs (RRs>1.5). The NIHSS has been reported to have E-values as high as 1.8.

Conclusions:
In our geographically diverse sample, we found that AIS transfer is associated with higher in-hospital mortality among white patients and younger black patients. Our data suggests that a strong unmeasured confounder could explain the association. Further work is needed to identify factors leading to higher mortality in transferred AIS patients.
Abstract TMP71: Marked Circadian Variation in Number and Type of Hyperacute Strokes During the 24 Hour Day-Night Cycle
Authors: Khorramian Eeman , Starkman Sidney , Sanossian Nerses , Liebeskind David , Avila Gilda , Stratton Samuel , Eckstein Mark , Pratt Franklin , Sharma Latisha , Restrepo Lucas , Valdes-Sueiras Miguel , Kim-Tenser May , Villablanca Pablo , Conwit Robin , Hamilton Scott , Saver Jeffrey
Published: June 2021

Background:
Circadian variations in stroke onset provide critical information for allocation of prehospital and hospital resources in clinical care and clinical trials. Studies of stroke circadian timing have had conflicting findings, and understanding would benefit from analysis confined to patients with defined onset in waking and clearly distinguished ischemic and hemorrhagic stroke subtypes.

Methods:
We analyzed all patients enrolled in the NIH FAST-MAG phase 3 trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of onset (last known well). Onset times were analyzed in 1h time blocks throughout the 24h day-night cycle. Patient demographic and clinical features, medical history, imaging characteristics, and stroke deficit severity were evaluated for association with onset times.

Results:
Among 1632 patients, final diagnoses were acute cerebral ischemia in 76.2% and intracranial hemorrhage in 23.7%. Hourly circadian variation in onset is shown in the Figure. Acute cerebral ischemia (ACI) had a unimodal distribution with peak onset at midday (12:00-12:59); intracerebral hemorrhage (ICH) a bimodal distribution with peaks at mid-morning (08:00-08:59) and early evening (18:00-18:59). Events were markedly reduced in early morning, with only 3.4% starting in the 25% of the day between 00:00-05:59. The proportion of events that were hemorrhagic was higher in the first 8h of the day (00:00-07:59) than the remaining 16h, 33.3% vs 22.5%, p=0.006. Both among ACI and ICH patients, vascular risk factors, presenting deficit severity, and initial brain imaging findings were fairly homogenous throughout all day-night time periods.

Conclusion:
There is marked, more than 10-fold, circadian variation in onset of acute cerebrovascular disease, and circadian variation in the ratio of ischemic to hemorrhagic neurovascular events. These findings can inform resource planning for regional systems of acute stroke care.
Abstract TMP77: Predictors of Readmission After Stroke in a Cohort of Privately Insured Patients
Authors: Hussein Haitham M , Chrenka Ella , Herrmann Amanda , Droegemueller Carol
Published: June 2021

Introduction:
Reducing readmission rate is a healthcare priority. The aim of this project is to examine factors associated with readmission after stroke in a privately insured cohort.

Methods:
Our organization is a health insurance provider as well as a healthcare provider. We retrospectively identified members of our insurance plan who discharged from one of our family of hospitals (one comprehensive stroke center, one primary stroke center, and two stroke ready hospitals) 2014-2018 with a stroke diagnosis. Using insurance claims, we captured all readmissions and ER visits in the 30 days after discharge. Using the same data, we were also able to identify primary care visits in the year preceding and the month following the index stroke. The impact of primary care was examined in a univariate analysis and a multivariate analysis adjusting for age, sex, race, stroke type, and length of stay (LOS).

Results:
We identified 1177 patients after excluding those who were not members of our insurance plan and those who had a planned admission such as to inpatient rehab (mean age 71±15 years; 53% women; 17% non-white). Stroke types were 72% ischemic stroke; 12% TIA; 7% ICH; 4% SAH. Most common discharge destination was home 68% followed by skilled nursing facility 27%. Overall 30-day all-cause readmission rate was 31% (21% inpatient admission, 8% ER visit, and 2% both). In an unadjusted model, there was a significant association between number of primary care visits and probability of readmission (OR 0.60 [95% CI 0.50-0.72]; p<0.0001). This association remained significant in the multivariate analysis (OR 0.73 [95% CI 0.58-0.91]; p=0.005). Other variables independently associated with readmission include age, LOS, and ischemic type of stroke. There was no association between readmission and sex or race and no interaction between primary care and sex nor between primary care and race.

Conclusion:
Established primary care is protective from stroke readmission. In high risk patients (older age with ischemic stroke and prolonged length of stay), efforts should be made to arrange for primary care sooner than later.
Abstract TMP94: Frequencies of Hereditary Cerebral Small Vessel Diseases Among Patients With Adult-Onset Leukoencephalopathy
Authors: Uemura Masahiro , Nozaki Hiroaki , Sakai Naoko , Ando Shouichirou , Kanazawa Masato , Kondo Hajime , Iwanaga Akira , Murota Hiroyuki , Ikeuchi Takeshi , Mizuta Ikuko , Mizuno Toshiki , Onodera Osamu
Published: June 2021

Introduction:
Recently, various causative genes have been identified in adult-onset white matter disorders. Some of these genes cause cerebral small vessel disease (CSVD). However, the frequency of genetic CSVD is unknown in the group of adult-onset white matter disorders (leukoencephalopathy). The purpose of this study is to clarify the frequency of genetic CSVD in adult-onset leukoencephalopathy patients and to examine their clinical features.

Methods:
One hundred patients in the Japanese cohort were included. All patients had neurological symptoms/signs and white matter lesions of grade 3/III classified by Fazekas grade on magnetic resonance imaging. Initially, genetic tests for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL),
high-temperature requirement A serine peptidase 1 (HTRA1)-
related CSVD and retinovasculopathy with cerebral leukoencephalopathy (RVCL) were performed by Sanger method. For the remaining samples, we preformed whole exome sequencing. Patients were divided into groups according to the age at onset of neurological signs/symptoms and family history.

Results:
In 40 of 100 patients with leukoencephalopathy, we identified genetic mutations that cause CSVD: twenty-five patients with CADASIL,10 patients with
HTRA1
-related CSVD, 3 patients with pseudoxanthoma elasticum (PXE), 1 patient with RVCL, and 1 patient with a mutation in
COL4A1
. More than 85% patients have mutations in
NOTCH3
or
HTRA1
. In addition, we identified 3 patients with vanishing white matter disease, and 1 patient with X-linked adrenoleukodystrophy. The hereditary CSVDs other than CADASIL or
HTRA1
-related CSVD were identified in the groups of age at onset ≤ 40 years-old irrespective of family history or age at onset ≤ 55 years-old with family history.

Conclusions:
The frequencies of genetic CSVDs were quite high among patients with leukoencephalopathy with neurological signs/symptoms. Although the genetic tests for CADASIL and
HTRA1-
related CSVD are sufficient for the most patients, we should consider the other genetic diseases especially for the patients with younger age onset of neurological signs/symptoms or positive family history.
Abstract TMP96: Automated Segmentation of White Matter Hyperintensities and Enlarged Perivascular Spaces in a Cohort of Patients With Acute Ischemic Stroke or Transient Ischemic Attack
Authors: Powell Kimerly A , Gallagher Katie M , Hannawi Yousef
Published: June 2021

Introduction:
Cerebral Small Vessel Disease (CSVD) is a major cause of acute ischemic stroke (AIS), intracerebral hemorrhage and cognitive impairment. Methods to quantify the disease burden have been largely limited to white matter hyperintensities (WMH) as the disease surrogate and focused mainly on MRI sequences acquired for research purposes. We develop here novel methods to quantify WMH and enlarged perivascular spaces (EPVs) based on clinically acquired MRI sequences in patients with transient ischemic attack (TIA) or AIS.

Methods:
Subjects presenting with TIA or AIS and had brain MRI within 24 hour of hospital admission were selected for this study. Preprocessing pipeline was developed locally that included bias correction, image rescaling, rigid body registration to the Montreal Neurological Institute (MNI) space, skull stripping and intensity normalization. WMH segmentation was performed using a combination of global thresholding of FLAIR sequences that was spatially restricted to the white matter regions which were defined using a population-based atlas of age matched controls. EPVs in the basal ganglia were segmented on T2 sequences using adaptive thresholding of basal ganglia mask that was created from the ICBM template image and age-matched population average atlas. Segmented objects less than 3 mm in diameter were labelled as EPVs. Validation of the accuracy of EPVs segmentation was performed by expert counting of EPVs and WMH was validated using volume similarity against expert manual segmentation of WMH.

Results:
41 patients (age 61.2±16.1, 65% males, 19.5% had TIAs, and 79.5% had AIS) were included. WMH volume was (manual: 21.34±20.48 mls vs automated: 15.74±14.56 mls) achieving a volume similarity of 0.92±0.01. EPVs in the basal ganglia counts were 16.32±5.4 using the automated method. Validation through comparison with manual segmentation of the axial slice with the highest EPVs (Doubal Method) showed significant correlation (Spearman’s rho=0.53, P = 0.0004).

Conclusions:
We describe successful segmentation of WMH and EPVs on clinically acquired MRI sequences in patients with TIA or AIS. This method will have applications to quantify CSVD burden in large clinical trials and clinical practice.
Abstract TMP97: Autonomic Nervous System Dysfunction Correlates With Increased Blood Pressure Variability After Acute Ischemic, But Not Hemorrhagic, Stroke
Authors: de Havenon Adam H , Cortez Melissa , Peterson Cecilia , Tuuhetaufa Fa , Petersen Nils , Wong Ka-Ho
Published: June 2021

Background:
Elevated blood pressure variability (BPV) in the days after acute stroke onset is associated with worse outcome. However, the mechanism of increased BPV remains unknown, but may be due to dysfunction of the autonomic nervous system, which can be measured by pupil response to a light stimulus.

Methods:
This is a retrospective study of 109 patients in a neurocritical care unit: 45 with acute ischemic stroke (AIS), 44 with intracerebral hemorrhage (ICH), and 20 with subarachnoid hemorrhage (SAH). The primary outcome is BPV, measured as standard deviation of SBP (SD), using all blood pressures from admission to 72 hours later. The primary predictors are pupillary light reflexes (PLR) from the same period, measured with a bedside pupilometer, the NPi-200. We used linear regression to evaluate the association between PLRs and BPV, and adjusted for patient age and gender.

Results:
The mean (SD) age was 60.7 (16.4) and 58.7% were male. The mean (SD) number of blood pressure and PLR measurements were 30.0 (9.0) and 10.4 (7.3). We found that parasympathetically mediated PLR measures were associated with BPV in AIS patients (Table 1), but no consistent pattern emerged in ICH or SAH patients (all p>0.05). The relationships between BPV and PLR for AIS patients were linear in nature (Figure 1), and were consistent with parasympathetic hypofunction in patients with the greatest BPV.

Conclusions:
Elevated BPV is associated with parasympathetic hypofunction, as measured by pupillary response to light, after acute ischemic, but not hemorrhagic, stroke. Further research is needed to better understand this relationship as it may represent a therapeutic target for BPV reduction.
Abstract TP107: Midline Shift Predicts Functional Outcomes in Porcine Ischemic Stroke Model
Authors: Spellicy Samantha , Kaiser Erin , Bowler Michael , Jurgielewicz Brian , Webb Robin , West Franklin , Stice Steven
Published: June 2021

In this study, we sought to identify acute MRI parameters which are predictive of long-term functional outcomes as well as assess the effects of a neural stem cell extracellular vesicle (NSC EV) therapeutic in a large animal model of ischemic stroke. In this randomized study, stroke was induced through a permanent right-sided middle cerebral artery occlusion (MCAO) on 16 male landrace pigs, which were divided into either treatment or control group. NSC EVs or PBS was administered at 2, 14, and 24 hours, and MRI was conducted at day 1 and 84 post-stroke. Data on 65 gait and 25 behavior parameters were collected pre-stroke and at multiple timepoints over 84 days following MCAO. Of all 15 measured MRI parameters, axial and coronal midline shift (MLS), at day 1 post stroke, had the highest total number of significant correlations (52 parameters at p<0.05) to acute and chronic functional measurements in control animals such as step time in the left front limb (p=0.0322) and cycle time in the right hind limb (p=0.0011) respectively. This suggests MLS is the best overall predictor of specific functional deficits at both acute and chronic timepoints, which to our knowledge has never been shown in an animal model. Additionally, the parameters found to be correlated to MLS in control animals were not correlated in NSC EV-treated animals, suggesting NSC EV treatment disrupts this natural correlation between degree of MLS and functional outcomes. NSC EVs and control pigs were binned into either high or low MLS groups and their survival and recovery was assessed by the modified Rankin Scale (mRS). While there was a significant difference in mRS scores of control animals with high and low MLS at day 6 post-MCAO (p=0.0008), there was not in NSC EV-treated animals (p=0.6754). Further, there was a significant difference in survival of control animals with high and low axial MLS (p=0.0401), but not in the NSC EV group (p=0.4142). Additionally, mRNA expression of GFAP was significantly correlated with increasing MLS in non-treated but not NSC EV-treated animals. These findings show although NSC EV treatment does not significantly alter the degree of MLS 1-day post-MCAO, it does alter gene expression, increase survival, and improve functional recovery following large MLS alterations.
Abstract TP113: Delayed (21 Days) Post Stroke Treatment With RPh201, A Botany-Derived Compound, Improves Neurological Functional Recovery in a Rat Model of Embolic Stroke
Authors: Wang Chunyang , Chopp Michael , Huang Rui , Zhang Yi , Golembieski William , Li Chao , Lu Mei , Zhang Zheng Gang , Zhang Li
Published: June 2021

Introduction:
Despite the recent advances in the acute stroke care, treatment options for long-term disability are limited. RPh201 is a botany-derived bioactive compound that has been shown to exert beneficial effects in various experimental models of neural injury. However, the effect of RPh201 on stroke recovery has not been investigated. The present study evaluated the effect of RPh201 on functional recovery after stroke.

Methods:
Young adult Wistar rats subjected to embolic middle cerebral artery occlusion (MCAO) were randomized into the following experimental groups stratified by sex (n=20/group): 1) RPh201 treatment, and 2) vehicle (cottonseed oil). RPh201 (20 μl) or vehicle were subcutaneously administered twice a week for 16 consecutive weeks starting at 21 days after MCAO. An array of behavioral tests were performed during 120 days after treatment initiation.

Results:
Male, but not female, ischemic rats treated with RPh201 exhibited significant (p<0.05) improvement of neurological function measured by adhesive removal test, foot-fault test, and modified neurological severity score at 90 and 120 days after initiation of treatment. Immunohistochemistry analysis showed that RPh201 treatment robustly increased neurofilament heavy chain positive axons and myelin basic protein densities in the peri-infarct area by 61% and 31% in the male rats, respectively, when compared to the vehicle treatment, which were further confirmed by Western blot analysis. The RPh201 treatment did not reduce infarct volume in both male and female rats.

Conclusions:
Our data demonstrated that RPh201 has a therapeutic effect on improvement of functional recovery in male ischemic rats even when the treatment was initiated 21 days post stroke. Enhanced axonal and myelination densities by RPh201 in ischemic brain may contribute to improved stroke recovery.
Abstract TP118: Activation of Alpha-7 Nicotinic Acetylcholine Receptor Improved Long-Term Cognitive Function of Mice With Long-Bone Fracture and Stroke
Authors: Hou Kang , Wei Meng , Zhang Meng , Wang Zhanqiang , Shaligram Sonali , Huang Jinhao , Barbosa Do Prado Leandro , Wong Julia , Carion Rose , Sun Tuanpeng , Zhan Lei , SU Hua
Published: June 2021

Introduction:
Tibia fracture (BF) enhances stroke injury and when occurring 6 hrs before stroke (BF6+Stroke) causes long-lasting cognitive dysfunction in mouse. Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) reduced neuroinflammation, neuronal injury and sensorimotor dysfunction in mice with BF one day after stroke (Stroke+1BF).

Hypothesis:
Activation of α-7 nAchR improves long-term cognitive function of BF6+Stroke mice.

Methods:
BF6+Stroke mice were randomly assigned to saline, PHA-568487 (α-7 nAchR agonist) and MLA (α-7 nAchR antagonist) treatment groups. The sensorimotor function were tested by adhesive removal and corner tests at 3 days, the cognitive function was tested by Y-maze weekly for 8 weeks and Novel Objective Recognition (NOR) at 8 weeks post-injuries. The neuronal damage, neuroinflammaiton, neurogenesis were analyzed 3 and/or 8 weeks post-injuries.

Results:
Similar to Stroke+1BF mice, PHA reduced and MLA enhanced neuronal injury, neuroinflammation, and sensorimotor dysfunction of BF6+Stroke mice. Further, PHA reduced and MLA enhanced their long-term cognitive dysfunction. In Y maze test, all mice made fewer alternations 1-week post-surgeries than baseline; PHA group recovered to baseline at week 5 post-surgeries; saline and MLA groups continuously made fewer alternations throughout the 8-weeks. In NOR test, PHA group spent more time, MLA group spent less time than saline group on novel objects. Injection of BrdU in the 2
nd
week post-surgeries labeled more neurons in the contralateral than in the ipsilateral dentate gyrus in all groups; PHA group had the most, MLA group had the least BrdU
+
neurons. Injection BrdU in the 7th week post-surgeries did not labeled any neuron.

Conclusion:
Activation of α-7 nAchR decreased neuronal damage and neuroinflammation, increased neurogenesis at the dentate gyrus of BF6+Stroke mice; and improved their sensorimotor and long-term cognitive function.
Abstract TP131: Carotid Stenosis and Polyvascular Disease
Authors: Chaturvedi Seemant , Meschia James F , Lal Brajesh K , Howard George , Roubin Gary S , Turan Tanya N , Teal Philip , Brown Robert D , Barrett Kevin M , Chimowitz Marc I , Demaerschalk Bart M , Howard Virginia J , Huston John , Lazar Ronald M , Moore Wesley S , Moy Claudia S , Voeks Jenifer H , Brott Thomas G
Published: June 2021

Background:
Presence of atherosclerotic disease in more than one vascular bed (polyvascular disease) is associated with an increased risk of long-term vascular events. In the setting of asymptomatic carotid stenosis, the predictors of disease in other vascular beds is not well delineated.

Objective:
To identify the frequency and predictors of disease in other vascular beds the CREST 2 randomized trial population with hemodynamically significant stenosis.

Methods:
Recorded baseline characteristics among CREST 2 participants included: demographics, past medical history, lifestyle factors, and laboratory studies. Each variable was tested against three potential definitions of disease in other beds (cardiac, peripheral arterial disease (PAD) or disease in cardiac + PAD). Statistical analysis was done with Chi square and t tests as appropriate.

Results:
Data from 1447 patients were available for analysis. In these subjects with carotid disease, 51% also had cardiac disease, 24% also had PAD, and 16% had disease in in both cardiac and PAD. There was no relationship between age or race and presence of disease in other beds. Those with cardiac disease were more likely to be male. Diabetes, hypertension, hypercholesterolemia, and former history of smoking were all more common in those with either cardiac and PAD (TABLE). Elevated triglyceride and low HDL levels were also associated with all three definitions of disease in other beds. Those with either PAD or cardiac + PAD were more likely to be current smokers.

Conclusions:
Among CREST 2 participants, several medical conditions and lifestyle factors were associated with an increased frequency of disease in other vascular beds. Smoking, in particular, appears to be more common in those with PAD. Future analyses will address whether those with disease in other beds have higher rates of stroke or death.
Abstract TP138: Chronic Kidney Disease in Heart Failure Patients is Associated with Increased Prevalence of Atrial Fibrillation or Atrial Flutter as well as CVA/TIA
Authors: Lu Christopher , Chan Jack , Yu Zejia , Anzenberg Paula , Torosoff Mikhail
Published: June 2021

Background:
The CHADS-VASC score does not incorporate renal dysfunction in stroke risk assessment in patients with atrial fibrillation and the prevalence of atrial fibrillation, atrial flutter, and cerebrovascular accidents (CVA) in patients with concurrent CHF and CKD is not well investigated.

Objective:
Evaluate the prevalence of history of stroke, atrial fibrillation, atrial flutter in patients with CHF and CKD.

Methods:
Data from the single institution Get With The Guidelines- Heart Failure (GWG-HF) cohort of 2938 consecutive inpatients with known GFR was utilized. CHADS-VASC score was calculated from the GWG-HF variables. Chronic kidney disease (CKD) was defined as GFR <60 ml/min.

Results:
An overwhelming majority (95%) of GWG-HF patients had elevated >1 CHADS-VASC score, which was also significantly more common in patients with CKD (97.6% vs. 91.7% in patients without CKD, p<0.0001). Average CHADS-VASC score was also significantly increased in patients with CKD (4+/-1.3 vs. 3.3+/-1.4, p<0.0001). Furthermore, CKD was associated with increased prevalence of atrial fibrillation and/or flutter (45.6% vs. 35.3%, p<0.0001) and stroke history (17.5% vs. 12.3%, p=0.002). When stroke and TIA histories were removed from the CHADS-VASC score ("CHAD-VASC score"), the remaining variables were strongly predictive of stroke or TIA (14.2% vs. 3.8%, p<0.0001). In multivariate logistic regression analysis, both CHAD-VASC score (OR 2.6, 95%CI 1.3-5.4, p=0.009) and CKD (OR 1.5, 95%CI 1.2-1.8, p=0.001) were associated significantly increased odds of prior stroke or TIA.

Conclusions:
In patients admitted with heart failure, CKD is associated with increased prevalence of atrial fibrillation or atrial flutter as well as increased prevalence of CVA/TIA. Further prospective studies are warranted to examine whether CKD history should be included in stroke risk assessment in patients with atrial fibrillation or atrial flutter, in conjunction with existing risk assessment frameworks.
Abstract TP139: Utilization and Outcomes of Extracranial-Intracranial Bypass Surgery in Adult Moyamoya Population
Authors: Patel Smit D , Lima Jussie , Patel Neel , Taboada Susan , Rane Schweta , Saini Vasu , Mittal Sanjay
Published: June 2021

Introduction:
The Extracranial-Intracranial bypass (EC-IC) surgery is performed to restore blood flow to the brain and prevent both hemorrhagic and ischemic strokes in Moyamoya disease (MMD) patients. There is a lack of contemporary data regarding EC-IC utilization, racial disparities, related mortality, and disability in the US.

Method:
Using ICD 9-CM codes 437.5 and 39.28, MMD and EC-IC procedures were extracted from National Inpatient Sample 2005-2015. The weighted discharge was used to generate national estimates. Predictors of revascularization utilization were evaluated using multivariable logistic regression analysis to avoid confounding effect. Disability was defined as non-home discharges, after excluding mortality.

Results:
Of total 24,484 admissions for MMD, 3,965 (16.2%) underwent revascularization. The mean age of revascularization patients was (SE) ~42 (0.52) years and F: M ratio of 3:1. After multivariable logistic model analysis, higher utilization rates were found in 40-59 year age group (48.3%, OR:1.29; P=0.02), who had ischemic strokes (9.2%, OR:1.38; P=0.03), and conventional cerebral angiography (30.2%, OR:1.80; P=0.001). Lower utilization rates were found in African Americans (14.9%, OR: 0.66; P=0.004), Hispanics (5.7%, OR: 0.60; P=0.03), Medicare recipients (13.6%, OR: 0.55; P=0.009), Northeast (11.5%, OR: 0.47; P= 0.003), Midwest (22.7%, OR: 0.55; P= 0.02), and South (24.8%, OR: 0.46; P=0.0002) compared to the West region. There is no utilization difference in gender female (72.4%, OR: 0.89; P=0.36). After EC-IC surgery, 79% were discharged home, 21% discharged to assistive facilities, and 0.6% died. After adjusting for hospital characteristics and associated comorbidities, lower disability (OR: 0.75; P=0.04) and the mortality rate was reported (OR: 0.80; P=0.71) among revascularization.

Conclusions:
This nationally representative date within the US suggests that though there is no gender disparity in utilization of EC-IC bypass surgery, there is a significant racial and regional disparity in the utilization of the procedure. Patients undergoing revascularization had better functional outcomes. Further research is needed to identify potential predictors for underutilization in these cohorts.
Abstract TP141: Can the Human Eye Match a Computer Algorithm in Identifying Hypoperfusion in Asymptomatic Carotid Artery Stenosis?
Authors: Marshall Randolph S , Lazar Ronald M , Meschia James F , Meyers Philip M , Connolly E Sander , Gutierrez Jose , Lal Brajesh K , Lehman Vance T , Lindell Edward P , Siegel Jason L , Lin Michelle P , Honda Tristan , Edwards Lloyd J , Howard George , Huston John , Brott Thomas G , Liebeskind David S
Published: June 2021

Background:
Perfusion weighted imaging on MRI (MRP) and computerized tomography perfusion (CTP) are increasingly required to manage large vessel disease. Computerized algorithms can quantify perfusion data, but the programs are expensive and not widely used outside acute stroke evaluation. We aimed to determine how well human observers can identify asymmetries in cerebral perfusion images compared with an automated computer algorithm.

Methods:
Ten clinicians experienced in treating carotid artery disease (4 vascular neurologists, 3 neuroradiologists, 1 vascular surgeon, 1 neurosurgeon, 1 interventional radiologist) were given 28 post-processed, color-coded, axial-slice MRP scans from patients in the Carotid Revascularization Endovascular versus Stenting Trial - Hemodynamics (CREST-H) study. All patients had >70%, unilateral, asymptomatic carotid artery stenosis and had varying degrees of time-to-peak (TTP) delay on the side of stenosis, ranging from 0 to 2 secs, quantified by a semi-automated system that computes quantitative perfusion maps, using deconvolution of tissue and arterial signals (Olea, Cambridge, MA). A minimum volume of 10cc was required for a given TTP delay. Clinicians were asked to determine asymmetry (y/n) and side of occlusion for each case. Number of correct responses that matched the computer output were tallied.

Results:
We averaged correct responses by the 10 clinicians for cases at each increment of TTP delay; (Figure). At TTP delays ≥1.5 seconds, accuracy was ≥80%. At 1.25 sec accuracy fell to 60%, and at ≤ 1 sec, accuracy was ≤50%. For TTP=0 (no asymmetry), accuracy was 71%.

Conclusions:
Visual impression of hemodynamic asymmetry among experienced clinicians was reasonably accurate for TTP delays ≥1.5 seconds, but declined with more subtle asymmetries. Depending on the clinical impact of TTP delays (for CREST-H: correlation with cognitive decline), experienced clinicians may perform as well as an automated algorithm.
Abstract TP15: A Multicenter Study Comparing Solumbra to Standard Aspiration and Stent Retriever Thrombectomy
Authors: McCarthy David J , Saini Vasu , Chen Stephanie , Luther Evan , Sheinberg Dallas , Arthur Adam , Kim Joon-Tae , De Leacy Reade , Maier Ilko , Psychogios Marios , Rai Ansaar , Keyrouz Salah , Fargen Kyle , Dumont Travis , Kan Peter , Alawieh Ali , Eyad Almallouhi , Spiotta Alejandro , Starke Robert
Published: June 2021

Background:
Standard mechanical thrombectomy (MT) techniques utilized include aspiration thrombectomy (ADAPT), stent retriever (SR), and a combination of both (Solumbra). Many studies compare outcomes between ADAPT and SR; however, there has yet to be a large multicenter investigation comparing ADAPT and SR to Solumbra.

Methods:
All patients from the participating STAR collaboration who underwent MT from 2015-2019 were included. Patients were analyzed by first MT technique utilized (ADAPT, SR, or Solumbra). Univariable and multivariable linear regression was utilized to analyze the MT technique association to number of thrombectomy attempts and procedure time. Univariable and multivariable logistic regression was utilized to determine the association between MT technique and the following outcomes: recanalization, symptomatic hemorrhage, 90-day functional independence, or 90-day mortality. P value less than 0.5 was considered significant.

Results:
A total of 2515 MT for stroke were identified: 1155 (46%) ADAPT, 735 (29%) SR, 625 (25%) Solumbra. Patients who received Solumbra MT were older (p<0.001), had higher IV-tPA administration rates (p<0.01), and lower onset-groin times (p<0.01). Separate multivariable linear regression analyses revealed that Solumbra technique had significantly high procedure times (OR 10.2, p<0.001) but less thrombectomy attempts (OR -0.8, p<0.001) compared to other MT techniques. There was no difference in recanalization success between techniques (ADAPT 85%, SR 84%, Solumbra 86%). Compared to Solumbra, ADAPT and SR thrombectomy had significantly lower incidence of symptomatic hemorrhage (ADAPT OR 0.32, p=0.009; SR OR 0.39, p=0.039) and ADAPT had a significantly lower likelihood of mortality (OR 0.50, p<0.001). There was no difference in 90-day functional independence (mRS≤2) rates between MT techniques.

Conclusion:
Compared to standard ADAPT and SR thrombectomy, the Solumbra technique for MT is a longer procedure that results in an increased likelihood of hemorrhage and 90-day mortality.
Abstract TP154: Arcuate Fasciculus Integrity and Outcome of Post-stroke Aphasia: A 6-month Follow-up DTI Study
Authors: Bae Chorong , Na Yoonhye , Cho Minjae , Hwang Yu Mi , Tae Woo-Suk , Pyun Sung-Bom
Published: June 2021

Objectives:
We evaluated the changes of arcuate fasciculus (AF), an important connecting pathway for language function, using DTI at 1-month and 6-month after stroke and investigated the relationship between structural changes of AF and improvement of post-stroke aphasia.

Methods:
We collected data from the STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Twenty-six patients with aphasia (PWA) who had first-ever stroke, presence of aphasia evaluated by Western Aphasia Battery (WAB) and no previous neurological or psychiatric diagnosis. The WAB and DTI data within 1 month (initial) and 6 months after (follow-up) stroke onset were used for analysis. And fractional anisotropy (FA), mean diffusivity (MD), fiber number (FN) and differences (Δ) at two time points of these parameters were obtained in bilateral AF in diffusion tensor tractography (DTT). Three types (I: not reconstructed, II: disrupted, discontinued or shallow, III: preserved) of classification according to integrity of AF was also included.

Results:
DTT parameters of bilateral AF showed statistically significant decrease in FA and increase in MD. Types of AF were changed in 6 patients (23%): 3 patients from type III to type II, 2 patients from type II to type I, and 1 patient from type II to type III. In Pearson’s correlation analysis, significant correlation was observed between 6-mon aphasia quotient (AQ) and parameters of left AF; positive correlation with FA (r=0.707, p<0.001), and negative correlation with MD (r=-.540, p<0.001). However, there was no correlation between 6-mon AQ score and FN of left AF, and all parameters of right AF. In addition, ΔDTT parameters were not correlated with either 6-mon AQ or ΔAQ.

Conclusions:
The AF changes over time not only in dominant but also in nondominant hemispheres in patients with aphasia after stroke. But amount of changes (Δ) in AF parameters were not associated with language recovery.

Acknowledgement:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2019R1A2C2003020).
Abstract TP158: Direct Path Functional Connectivity Changes in Stroke Survivors’ Brain Motor Areas Using a Brain Computer Interface Intervention for Upper Extremity Recovery
Authors: Remsik Alex , Bjorklund Erik , Williams Leroy , Gjini Klevest , Mazrooyisebdani Mohson , Nair Veena , Prabhakaran Vivek
Published: June 2021

Objective:
This research seeks to identify changes in frequency specific directional flow of information transmission (functional connectivity) as a result of BCI intervention. Direct path functional connectivity (isolated effective coherence (iCOH)) changes between motor-related brain areas (Brodmann areas (BA) 1-7) are thought to relate to electrophysiological signatures of motor learning.

Methods:
N=16 right hemisphere stroke survivors participated in 9-15 sessions with the BCI. Participants executed hand movements prompted by visual cues on a monitor concordantly with the corresponding audio instructions (e.g., Left, Right, Rest). The ‘screening’ sessions (i.e. pre and post BCI intervention) contained two runs, each consisting of 15 trials for rest, left hand, and right hand movements (i.e., 5 trials for each of the three conditions, the order of trials in a run was random). iCOH is based on formulating a multivariate autoregressive model from time series measurements, and calculating the corresponding partial coherences after setting all irrelevant connections to zero, according to Pascual-Marqui et al. 2014. From the spectral density matrix (including Mu[8-12 Hz] and Beta[18-26 Hz] ranges) obtained from estimated signals in the selected ROI, the partial coherences between any pair of nodes can be calculated. The t-statistics was performed for iCOH values between post and pre of the impaired (left) hand movement trials and thresholded at p=0.05( t=2.13, uncorrected).

Results:
In the Mu band, iCOH decreased pre to post from contralesional BA 4 to ipsilesional BA 5 and increased from ipsilesional BA 4 to ipsilesional BA 6. In Beta band, iCOH decreased pre to post from ipsilesional BA 5 to contralesional BA 7 and increased from ipsilesional BA 4 and & contralesional BA 7 to ipsilesional BA 6 and also from ipsilesional BA 1,2,3 to contralesional BA 4.

Conclusion:
There is a consistent change in the direction of information flow, as measured by iCOH, toward the ipsilesional motor and pre-motor areas (BA 4,6). Significant iCOH increases are observed in both Mu and Beta from ipsilesional BA 4 to ipsilesional BA 6 suggesting an increase in participation of motor brain areas associated with motor planning and execution with participation in BCI intervention.