bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP17: Impact Of Cigarette Smoking And Its Interaction With Hypertension And Diabetes On Cognitive Function
Authors: Restifo Daniel , Zhao Chen , Kamel Hooman , Iadecola Costantino , Parikh Neal S
Published: February 2022

Introduction:
We evaluated the association of a cigarette-smoking biomarker with cognitive function, and tested whether smoking acts synergistically with hypertension and diabetes to influence cognition.

Methods:
We performed a cross-sectional analysis of nationally representative data from the US National Health and Nutrition Examination Survey. From 2011-2014, participants ≥60 years old were given 4 standardized cognitive tests by trained examiners: immediate word recall, delayed word recall, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST) - a multidomain cognitive test. Participants also had 3 consecutive standardized blood pressure measurements and hemoglobin A1c and serum cotinine tests, the latter an accurate biomarker of cigarette smoking/exposure. We used linear regression to evaluate the association of cotinine with cognitive performance. Where an association was found, interaction term testing evaluated effect modification by systolic blood pressure and hemoglobin A1c as continuous measures, and hypertension and diabetes as categorical variables. Models were adjusted for demographics, socioeconomic factors, education, cardiovascular risk factors/disease, alcohol use, and depression.

Results:
The mean age of 3,244 participants was 69 years and 54% were women. Self-reported current smoking was present in 23%, 77% had hypertension, and 24% had diabetes. In adjusted linear regression models, higher serum cotinine levels were associated with worse performance on the DSST (β, -0.02; 95% CI, -0.03, -0.01; P=0.001), and non-significantly on the AFT (β, -0.003; 95% CI, -0.006, 0.0003; P=0.07), but not immediate or delayed recall. For the DSST, effect modification by systolic blood pressure (P=0.14) and hemoglobin A1c (P=0.39) was not observed. There was also no evidence of effect modification when testing interactions for hypertension and diabetes.

Conclusions:
Higher levels of a smoking biomarker were associated with worse performance on a multidomain cognitive test at the population level, regardless of hypertension or diabetes. These data demonstrate the detrimental impact of smoking on cognition and underscore the broad importance of promoting smoking cessation to preserve cognitive health.
Abstract WP183: Pregnancy-related Factors Associated With Stroke In Mothers And Newborns: Data From The International Maternal Newborn Stroke Registry
Authors: Gulati Asish K , Castri Paola , Deveber Gabrielle A , Menon Bijoy K , Majersik Jennifer J , Clark Erin , AARON SANJITH , Christudass Christhunesa , Railean Anastasia , MacKay Mark T , Fink Matthew E , Bushnell Cheryl
Published: February 2022

Background:
Maternal and newborn stroke occur during the same period when physiological and anatomic connections between mother and infant may provide a rationale for common pathogenetic mechanisms. The similarities and differences between maternal and newborn stroke remain poorly understood. We created the International Maternal Newborn Stroke Registry - the first database to explore these relationships.

Methods:
Eleven international sites participated; 9 enrolled cases for this analysis. Eligible cases were newborns (from 28 weeks gestation to 28 postnatal days) or mothers (peripartum or within 6 weeks postpartum) diagnosed with stroke (ischemic, hemorrhagic, cerebral sinovenous thrombosis). Preterm infants (< 28 weeks gestation) and neonates with germinal matrix/intraventricular hemorrhage were excluded. Descriptive statistics were performed to compare stroke sub-types, demographic and pregnancy-related risk factors.

Results:
We enrolled 103 cases, 69 newborn and 34 maternal. Median maternal age was 29 years (IQR 25-36) for the maternal group and 32 years (IQR 30-36) for the neonatal group. Women with maternal strokes were more likely to have pre-eclampsia (15%) and migraine (44%). Compared to maternal strokes, newborn strokes occurred more often in women from urban locations, were ischemic, and were less likely to be associated with alcohol use and pre-eclampsia during pregnancy (Table).

Conclusion:
In this novel registry, we describe factors that impact both maternal and newborn stroke. Urban area of residence and maternal age > 30 were associated with newborn strokes, while migraine and pre-eclampsia were strongly associated with maternal strokes. Differing mechanisms and stroke subtypes may explain these differences. In addition, lack of access to healthcare in certain geographical locations may lead to under-identification. Further research is needed to determine if these results are consistent when applied to a larger sample size.
Abstract WP187: Longitudinal Discrimination Modifies The Efficacy Of Skills-based Intervention In Stroke Survivors
Authors: Wing Jeffrey J , Meier Helen , Drum Emily , Boden-Albala Bernadette
Published: February 2022

Introduction:
Racial discrimination has existed for centuries in the US and contributes to disparities in stroke and stroke outcomes. Measures of structural racism have been used to quantify these disparities. Our objective was to determine if the efficacy of a skills-based intervention on blood pressure reduction in a cohort of mild/moderate strokes varied by historic redlining, the US Federal government’s sanctioned discrimination in mortgage risk assessment.

Methods:
The Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) intervention randomized 552 participants to a skills-based intervention or usual care. Participants addresses were geocoded and linked to federally sponsored Home Owners’ Loan Corporation (HOLC) color-coded maps from the 1930s. Participants residing in graded locations (n=279) were given weighted historic redlining scores (HRS) calculated using the proportion of 1930s HOLC residential security grades contained within 2010 census tract boundaries and a discrimination score based current lending practices. The change in systolic blood pressure was modeled linearly with generalized estimating equations used to account for clustering by site.

Results:
Participants were 34% Hispanic, 31% non-Hispanic Black, 28% non-Hispanic white, and 7% other race. The intervention was most efficacious in areas of persistent (Δ=6.05 mmHg reduction; p=0.003) and declining discrimination (Δ=11.08 mmHg reduction; p=0.007) versus usual care. In areas that were gentrifying, the intervention was least efficacious (Δ=7.33mmHg increase; p=0.022) and minimal in areas of no discrimination (Δ=0.054 mmHg reduction; p=0.903).

Conclusions:
Historic redlining practices are a form of structural racism that established geographic systems of disadvantage. The efficacy of interventions are impacted by underlying systems of disadvantage such that contextual factors beyond race must be considered when designing trials.
Abstract WP206: Temporal Trends In Stroke Patients Who Had Prior Transient Ischemic Attack And Did Not Present To The Emergency Room: A Population Study
Authors: Aziz Yasmin N , Kandregula Krishna , Sucharew Heidi , Demel Stacie , Alwell Kathleen , Woo Daniel , Ferioli Simona , Khatri Pooja , Adeoye Opeolu M , Flaherty Matthew L , Mackey Jason , Martini Sharyl R , Mistry Eva , Coleman Elisheva R , Jasne Adam , Slavin Sabreena , Walsh Kyle B , Star Michael , Haverbusch Mary , Kissela Brett , Kleindorfer Dawn O
Published: February 2022

Background:
Acute ischemic stroke (AIS) is a leading cause of disability worldwide, with up to 30% of cases preceded by transient ischemic attack (TIA). Urgent evaluation of TIA symptoms is recommended to reduce risk of stroke, but not all patients with TIA symptoms seek evaluation. Our goal was to assess temporal trends in the demographics of such patients.

Methods:
Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) for years 2005, 2010, and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥18yrs of age presenting to the ED. We identified patients who had a preceding TIA based on symptoms within 60 days of presentation, as judged by an adjudicating physician. Demographics, histories, and proportion of patients with TIA were compared across study years using Wilcoxon rank sum test or chi-square test.

Results:
We identified 5977 patients presenting with AIS across three epochs. Of these 207 (3%) had prior suspected TIA and did not seek immediate medical attention; 56/1790 (3%) in 2005, 62/1993 (3%) in 2010, and 70/2194 (3%) in 2015 (p-value=0.99). Patients with suspected TIA had increasing rates of previously diagnosed HLD and DM over the three time periods. No other risk factors or demographics showed a change over time. Known HTN was consistently prevalent across epochs (Table 2).

Conclusion:
Over the three epochs, 3% of AIS patients consistently did not seek emergent medical attention for a recent preceding TIA. A substantial proportion of these patients were increasingly already diagnosed with DM and HLD over the study periods, and the majority were persistently diagnosed with HTN. This is an opportune cohort for future targeted outreach.
Abstract WP208: Post-stroke Cognitive Impairment And The Risk Of Recurrent Stroke And Death: A Systematic Review
Authors: Dowling N. Maritza , Singh Ruben , Power Melinda C , Nadareishvili Zurab
Published: February 2022

Post-stroke cognitive impairment (PSCI) occurs in 20%-40% of stroke patients and was reported to be a risk factor of recurrent stroke and death. However, to date, no systematic review and meta-analysis exists to precisely estimate the associated risk. The goal of the current study was to conduct a systematic review of published literature on the association between PSCI and risk of recurrent stroke and death. We searched Ovid MEDLINE and Scopus for studies published from 1992 to 2019, combining the following keywords: post-stroke cognitive impairment, risk of stroke recurrence, mortality, post-stroke dementia. Of the 929 references, we identified 23 studies (n=28,305 patients) that met eligibility criteria. The time of PSCI diagnosis ranged from 7 days to 6 months, and 3-month after stroke was the most common time point of neuropsychological testing. The majority (65%, 15/23) of these studies evaluated PSCI mortality endpoint (n = 23,554), while 35% (8/23) looked at combined endpoint of recurrent stroke and death (n= 4,751). In mortality studies, 86% (13/15) showed significantly higher risk of death in PSCI patients compared to those without it (OR/HR/RR range from 1.42 to 7.42). In the two largest studies (n=8,822 and n=6,504), the adjusted HR were 1.42 (1.34-1.50) and RR 2.0 (1.3-3.2) respectively. Only 14% (2/15) of the studies showed negative results. However, one negative study [HR: 1.00 (0.79-1.86)] included a large cohort (n=3,948). In recurrence studies, 75% (6/8) reported higher risk with OR/HR/RR ranging from 1.48 to 4.86. Subgroup analyses in the two largest recurrence clinical trial studies (n=1,528 and n=1,240) reported HR 1.48 (1.04-2.09) and OR 2.32 (1.10-4.89). No association between PSCI and recurrent stroke was found in 25% (2/8) of recurrence studies including those with n=458 [HR 1.74 (0.89-3.39)] and n=202 patients [RR 1.25 (0.47-3.33)].This systematic review revealed about a 0.5 to 7 times increased risk of recurrent stroke and death in patients with PSCI suggesting that PSCI might be a marker predicting recurrent events in secondary stroke prevention. A meta-analysis is warranted to increase the precision and validity of risk estimates of PSCI and study the bases for differences across studies.
Abstract WP216: Breast Cancer Susceptibility Genes And Cerebral Small Vessel Disease
Authors: Pope Brandon , Wolcott Zoe , de Havenon Adam H , Goldstein Eric
Published: February 2022

Introduction:
Aside from being implicated in breast and ovarian cancer, breast cancer susceptibility genes (BRCA) growing evidence suggests an additional intersection between BRCA mutations and hypercholesterolemia, endothelial damage, hyperglycemia and an increased non-neoplastic mortality. With the influence of BRCA on typical cerebrovascular risk factors, we aimed to identify if BRCA mutations increased the prevalence of cerebral small vessel disease (CSVD).

Methods:
We performed a retrospective cross-sectional chart review of adults with confirmed BRCA1 or BRCA2 mutations compared against BRCA wild-type individuals with breast and/or ovarian cancer. Demographic and medical history were recorded. Brain MRI was interpreted for markers of CSVD. Statistical significance (p < 0.05) was tested via the Chi-squared or Fisher’s, Wilcoxon rank-sum and the Student’s t-test analyses for binary, ordinal or interval variables, respectively. Adjusted logistic regression models were fit to calculate odds ratio. All models were tested for multicollinearity by variance inflation factor calculation and for goodness-of-fit (GOF) via the Hosmer-Lemeshow GOF test.

Results:
One hundred forty individuals were included, with 47% (66/140) being BRCA mutant. Demographic and cerebrovascular risk factors were similar amongst the cohort. Estrogen antagonist therapy was more common in the BRCA wild-type group [25% (16/64) vs 44.6% (33/74), p = 0.016]. Lacunar infarcts, Fazekas grading and perivascular spaces were not significantly different across the cohort. Cerebral microbleeds (CMBs) were more prevalent in those with BRCA mutation: [36.4% (24/66) vs 18.9% (14/74), p = 0.021]. This finding persisted despite adjustment for cerebrovascular risk factors (OR 2.71, 95%CI 1.20 - 6.14, p = 0.017) yielding a predicted probability of 18.2% (95%CI 3.7 - 32.8).

Conclusion:
For those with BRCA mutation, we identified a nearly 3 fold increase in CMB prevalence despite adjustment for cerebrovascular risk factors. The mechanism underlying is presently unknown, though likely related to endothelial dysregulation. Further studies are needed to confirm our findings on a larger scale and investigate intraparenchymal hemorrhage risk amongst those with BRCA mutations.
Abstract WP22: Cognitive Decline Among Older Adults With Stroke And Hospital-acquired Infections: The Cardiovascular Health Study
Authors: Cole Kyril , Boehme Amelia , Tounkara Mamadou , Longstreth Will , Brown Bruce , Gale Shawn , Hedges Dawson , Kunzelman jacqueline , Elkind Mitchell S
Published: February 2022

Introduction:
Hospital-Acquired Infections (HAIs) are contracted during hospitalization for another disorder. We hypothesized that older adults with incident stroke and HAI experience faster subsequent cognitive decline than those having stroke without HAI and those without stroke.

Methods:
The Cardiovascular Health Study (CHS) is a cohort of Medicare-eligible participants aged ≥ 65 years. Incident ischemic stroke was ascertained from medical records. HAIs were assessed by hospital discharge ICD-9 codes. Global cognitive function was measured annually by modified mini-mental state examination (3MSE) and executive function by digit symbol substitution test (DSST). We used linear mixed models to estimate decline in mean 3MSE and DSST scores over a mean of seven years by incident stroke and HAI status among participants free of stroke at baseline.

Results:
In the 3MSE analysis, 393 participants had incident stroke and HAI, 766 had stroke only, and 4,284 had no stroke. With no stroke (
Fig 1A,
black line), cognitive decline accelerated with age: mean declines of 0.27 points/year at age 70, 1.10 points/year at age 80, and 2.47 points/year at age 90. After stroke with HAI (red line), mean decline was 0.29 points/year faster than with no stroke (95% CI: 0.17, 0.40; p < 0.001). In contrast, after stroke without HAI (blue line), mean decline was similar to that with no stroke (0.09 points/year faster; 95% CI: -0.13, 0.32; p = 0.410). Mean decline was 0.19 points/year faster after stroke with HAI than after stroke without HAI, though these differences were not statistically significant (95% CI: -0.05, 0.44; p = 0.123). Mean decline in DSST score (
Fig 1B
) after stroke with HAI was similar to stroke without HAI (0.09 points/year faster decline after stroke with HAI; 95% CI: -0.08, 0.27; p = 0.297).

Conclusions:
Mean cognitive decline after stroke with HAI was faster than with no stroke but may be similar to that after stroke without HAI. As a limitation, we did not have data on stroke severity.
Abstract WP227: Is Obesity Driving The Increase In Young Stroke?
Authors: Solomonow Jonathan , Yarbrough Karen L , Chaturvedi Seemant , Mehndiratta Prachi
Published: February 2022

Background:
Obesity is a known risk factor for acute ischemic stroke (AIS) in both the adult and young (<50 years) population. Prior studies suggest that this association is mediated through risk factors such as diabetes and hypertension; however, the extent of this association has not been reported. Our aim was to identify the association of obesity with young AIS, and the burden of lifestyle-related risk factors based on different body-mass-index (BMI) categories in patients with young AIS.

Methods:
All patients with AIS, younger than 50 years, admitted to the University of Maryland Medical System hospitals between Jan 2017 and December 2020, were included. Patients were categorized into 3 BMI categories - 1) Normal (18.5-24.9), 2) Overweight (25-29) and 3) Obese (≥30). Lifestyle-related risk factor (HTN, DM, DLD, and sleep apnea) burden and distribution was analyzed across the three groups using Chi-squared tests of association. One-way Welch’s ANOVA was utilized to test mean differences in number of risk factors across BMI categories.

Results:
We identified 1272 patients with young stroke. A total of 797/1272 (63%) of our young stroke patients were obese and 23.1% (n=294) were in the overweight category. In the obese category: mean age was 41.4 years (SD +/- 6.75), 49.4% were women and 53.4% were Black. Risk factor burden was significantly higher in the obese vs. the overweight and normal weight categories (Table 1)(p = <0.001). The proportion of patients with HTN, DM, DLD and sleep apnea was significantly higher in the obese category.

Conclusions:
A majority of young stroke patients were obese, and the obese and overweight patients were predominantly African American. Obese patients had the highest proportion of all medical risk factors, as well as a risk factor burden nearly twice as high as those with normal BMI. Efforts to reduce obesity hold promise in mitigating the burden of stroke in young adults.
Abstract WP234: Age And Type 2 Diabetes Reduce The Coherence Of Theta And Gamma Oscillations Between Brain Networks
Authors: Rabiller Gratianne , sato yoshimichi , Wong SuWai , Ip Zachary , Yazdan-shahmorad Azadeh , Liu Jialing
Published: February 2022

Introduction:
The integrity of the functional connectivity across networks relies on synchronous activation of neurons, which reduces with age. Type 2 diabetes (T2DM) is a major risk factor for stroke and cognitive decline and also a precocious aging, yet the electrophysiological changes in T2DM and its interaction with aging is not well understood. The current study sought to delineate the age and diabetic effect on the resting state field potential in regions crucial for cognition.

Methods:
Local field potential was recorded under urethane anesthesia with multichannel electrodes spanning the cortex and hippocampus (HPC) in control (db/+) and diabetic (db/db) mice, at 200 or 400 days of age. Brain state and neural activity in signal power of δ, θ, γ waves and sharp-wave associated ripples (SWRs) were determined. Coherence and phase-amplitude coupling (PAC) within the HPC or between cortex and HPC were computed to reflect the level of functional communication across brain networks.

Results:
Our results show that age decreased the θ/δ amplitude (T/D) ratio and the signal power of the theta, gamma and high gamma in the cortex and the HPC. Both age and diabetes prolonged the average duration of SWR clusters and inter-ripple intervals. The greatest SWR signal power was detected in db/db mice at 200 ds of age compared to the other 3 groups, so were the γ power in the cortex and HPC during SWRs. Both age and diabetes reduced θ coherence between cortex and HPC. Age also reduced γ coherence within the hippocampus. Interestingly, while age reduced the coherence of high γ band between hippocampus and CTX, diabetes significantly increased it. To the contrary, age increased coherence in δ within the hippocampal layers. Diabetes decreased the θ-low γ PAC between CA1 and cortex and within CA1. However, diabetes increased δ-γ PAC within the slm, while both age and diabetes increased the δ-γ PAC between the hippocampus and the cortex.

Conclusion:
The neural activity and synchrony in brain regions crucial for cognitive function is impaired by age and further confounded by T2DM. The perturbation of resting state field potential signal power and coherence may underlie age and diabetes induced loss of functional connectivity and cognitive decline.
Abstract WP241: Transcriptome Analysis Of The Liver Reveals Novel Mechanisms By Which Prenatal Alcohol Exposure Contributes To Worse Stoke Outcome
Authors: Pinson Marisa , Bake Shameena , Sohrabji Farida , Miranda Rajesh
Published: February 2022

Introduction:
Susceptibility to adult-onset disease has been linked to early life adversity. In this study, we assessed the impact of a common early adverse experience, prenatal alcohol exposure (PAE), on neurobehavioral outcomes following cerebrovascular ischemic stroke. We also assessed impact of PAE and stroke on the transcriptome of intermediary organs of the gut-brain axis. Specifically, mesenteric adipose and liver, which are supplied by portal circulation from the gut are hypothesized to mediate inflammatory and neuroprotective adaptations to stroke.

Methods:
Pregnant Sprague Dawley rats were exposed to either vaporized ethanol or room air from gestation day 8 to 19. At 5 months, progeny were subjected to unilateral endothelin-1 induced occlusion of the middle cerebral artery and outcomes evaluated after 2 days. Stroke induced disabilities were assessed from behavioral assays (adhesive removal, Vibrissae evoked fore-limb placement and circling) and infarct size. The liver transcriptome was assessed by sequencing, from age-matched stroke-exposed and naïve offspring.

Results:
PAE rats had worse neurological scores 2 days post stroke compared to control (p<0.05). We observed that the liver was substantially more transcriptionally responsive to PAE status than adipose tissue. Moreover, PAE offspring exhibited a 1.6-fold increase in upregulated genes and a 2.4-fold increase in down-regulated liver gene transcripts following stroke, compared to control offspring. Only 448 differentially expressed genes (DEGs) were common between the control and PAE groups. DEGs unique to PAE contribute to triglyceride metabolism, steroid metabolism, and cholesterol biosynthesis pathways. Weighted correlation network analysis identified 24 gene network modules, one of which, a liver proinflammatory network, was strongly correlated with post stroke neurological function (Pearson's r=-0.63, p<0.01).

Conclusion:
The present study shows that PAE predisposes middle-aged rat offspring for worse outcomes following cerebrovascular ischemic stroke. This effect is associated with persistent reprogramming of the liver transcriptome and an exacerbated proinflammatory response.
Abstract WP246: Intraventricular Administration Of Stanniocalcin-2 Promotes Post-stroke Functional Recovery In A Translational Rodent Model
Authors: Azadian Matine , Santhanam Sruthi , McConnell Kelly W , George Paul M
Published: February 2022

Enhancing an endogenous stem cell response is a promising approach to improve stroke recovery. We have previously shown that a conductive polymer cannula system for human stem cell delivery and electrical stimulation of the post-stroke environment increases endogenous stem cell production and improves functional recovery in a rodent model of distal middle cerebral artery occlusion (dMCAO). Transcriptomic analyses coupled with lentiviral manipulation identified stanniocalcin 2 (STC-2) as one key mediator of this functional improvement. To further investigate the role of STC-2, we intraventricularly administered recombinant STC-2 one week post-dMCAO and assessed functional recovery via vibrissae-forepaw (WP) test at 5 weeks. Our results indicate that intraventricular injection of STC-2 alone post-stroke improves functional recovery in comparison to a control and intraventricular saline group (n=10 per group, p=<0.001, see Figure 1A). Histological analyses revealed an increase in endogenous stem cells that express immature neuronal markers (doublecortin, colocalized with bromodeoxyuridine) between the subventricular zone and peri-infarct region of the STC2-treated group (n=5 per group; p=0.019, see Figure 1B). Additional studies are necessary in order to further elucidate the causative molecular mechanisms involved; however, we believe this study yields great translational potential as our results may help enable a route to augment endogenous responses in the post-stroke environment.
Abstract WP249: Effect Of Acute Hyperglycemia On Stroke Outcome And Immune Response
Authors: Chen Hansen , Chiang Terrance , Kim Anika , Bliss Tonya , Cheng Michelle Y , Steinberg Gary
Published: February 2022

Background:
Acute hyperglycemia occurs in over 40% of ischemic stroke patients, increases hemorrhagic transformation (HT) and worsens stroke outcome. Previous rodent studies reported deleterious effects of hyperglycemia on stroke outcome during acute stroke (within hours to days), however, its impact during subacute stroke period (days to weeks) remains unclear. Moreover, the mechanisms underlying hyperglycemia’s worsening of stroke outcomes remains elusive. In this study, we investigated the effect of acute hyperglycemia on immune responses and stroke outcome in acute and subacute phases.

Method:
Male C57/BL6 mice were subjected to middle cerebral artery occlusion (MCAO) for 30 min, followed by reperfusion to mimic ischemic stroke. Acute hyperglycemia was induced by glucose injection 10 min before MCAO. For the acute phase study, mice were sacrificed at 4.5 hrs to assess blood-brain barrier leakage (Evans blue) and brain immune cell populations (flow cytometry), and at 24 hrs to evaluate brain infarct, swelling and HT. In the sub-acute phase, mice were allowed to survive 14 days after stroke to evaluate mortality rate, neurological deficit, and motor-sensory dysfunction using a rotating beam test.

Result:
In the acute phase, hyperglycemia rapidly increased BBB leakage by 4.5 hrs after stroke, when compared to the normoglycemia group (p<0.0001). At this early timepoint, hyperglycemic mice brains showed more Ly6C
hi
microglia and infiltrating myeloid cells, including neutrophils and Ly6C
hi
monocytes, than normoglycemic mice. By 24 hrs after stroke, hyperglycemic mice showed increased HT and larger brain edema; brain infarct volume however, was not affected. In the subacute-phase, hyperglycemic mice exhibited a higher mortality rate than normoglycemic mice (100% VS 25%, p=0.0008), with greater body weight loss, and worsened neurological deficit and rotating beam performance.

Conclusion:
Acute hyperglycemia adversely impacts stroke outcomes in acute and subacute phases, with HT and brain edema as the key pathological events associated with higher mortality, as well as more severe neurological and motor-sensory deficits. Rapid modulation of immune responses may play an important role in mediating the detrimental effect of hyperglycemia.
Abstract WP253: Increased Hydrogen Sulfide As A New Mechanism For Hyperglycemic Worsening Of Stroke Outcome
Authors: Derry Paul J , Liopo Anton , McKelvey Ann , Vo Anh , Gnanasekaran Aswini , McHugh Emily , Tour James M , Olson Kenneth R , Kent Thomas
Published: February 2022

Introduction:
Hyperglycemia at stroke onset worsens outcome and reduces the effectiveness of reperfusion therapies. Increased oxidative and mitochondrial injury likely contribute. To treat this mechanism, we synthesized (PEG)-ylated carbon nanoparticles (CNPs) from acid oxidation of activated charcoal (OAC) generating 3 nm discs, catalytic superoxide dismutase mimetics that protect mitochondrial complexes. Cellular uptake is rapid and delayed I.V. PEG-CNPs are highly protective in reversible MCAO in hyperglycemic rats. Hydrogen sulfide (H
2
S) is an essential gaseous transmitter with a narrow therapeutic index associated with many disorders e.g., diabetes. Its synthesis is influenced by radicals. Excess H
2
S is toxic to mitochondrial complex IV. H
2
S is endogenously oxidized to polysulfides (PS), potent antioxidants also needed for protein persulfidation. We hypothesized that OAC’s favorable redox potential will catalyze H
2
S oxidization to PS, acute hyperglycemia will increase H
2
S and PEG-OACs will blunt the increase.

Methods:
b.End3 brain endothelial and HEK293 cultured cells were employed. SSP4 fluorescence measured PS levels with increasing concentrations of PEG-OACs. AzMC fluorescence detected H
2
S levels in cells incubated in 100 mg/dL glucose media followed by glucose 500 mg/dL with or without PEG-OACs, first in normoxia followed by anoxia/normoxia.

Results:
PEG-OACs dose dependently increased cellular PS levels (Fig 1a). High glucose increased H
2
S levels especially during anoxia/normoxia (Fig 1b). PEG-OACs completely eliminated the glucose-induced increase in H
2
S (Fig 1c).

Conclusions:
Acute hyperglycemia increased H
2
S production especially under conditions mimicking ischemia/reperfusion, an effect eliminated by PEG-OACs. Because of mitochondrial toxicity, an H
2
S increase may contribute to worsened outcome in hyperglycemic stroke. These results suggest a new therapeutic target for this important cause of poor stroke outcome.
Abstract WP256: Favorable Outcome In Intracerebral Hemorrhage Is Associated With With Higher 15-lox-1 Expression
Authors: Iwuchukwu Ifeanyi O , Asatrian Aram , Nguyen Doan , Bazan Nicolas G
Published: February 2022

Background:
In previous studies, we identified a higher abundance of the docosanoid, Neuroprotectin D1 (NPD1), a lipid anti-inflammatory mediator, in intracerebral hemorrhage (ICH) patients with favorable outcome. In this study, we hypothesized that favorable outcome is due to increased expression of 15-LOX-1, a critical enzyme in the endogenous synthesis of NPD1 compared with patients with unfavorable outcome.

Methods:
After informed consent, whole blood were collected in PaxGene blood RNA tubes from consecutive patients with acute spontaneous ICH within 48 hours of admission. Total RNA was used for real-time PCR using Taqman probe for 15-LOX-1. The PCR cycle threshold (Ct) of 15-LOX-1 was normalized to the endogenous control GAPDH and fold change determined. Demographic and clinical data were collected. Outcome measures included 90-day modified Rankin score. In this study favorable outcome is defined as MRS 0-3 (n=11) and unfavorable outcome as MRS 4-6 (n=25).

Results:
Thirty-six patients were included in the study with a mean age of 61.9 years (SD 13.1). In patients with favorable outcome, the mean normalized Ct for 15-LOX-1 was 3.5 (SD 1.8) while in unfavorable was 8.9 (SD 3.8), and for normal healthy was 1.4 (SD 0.4). Expression of 15-LOX-1 was 43-fold higher in patients with favorable outcome.

Conclusion:
The increased expression of 15-LOX-1 suggests a significant synthesis and abundance of NPD1 in patients with MRS 0-3 compared with patients with MRS 4-6 and suggests that early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology
Abstract WP263: Effective Combination Therapy For Experimental Stroke: Synergistic Neuroprotection By Lau-0901 And At-npd1
Authors: Belayev Ludmila , Mukherjee Pranab , Reid Madigan , Obenaus Andre , Khoutorova Larissa , Roque Cassia R , Simons Tyler , Park Bohyung Katie , Oria Reinaldo , Bazan Nicolas G
Published: February 2022

Objective:
Cerebral ischemia causes irreversible brain damage, which involves oxidative stress, the release of endogenous substances and inflammation. We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAF-R) plus administering a selected docosanoid after middle cerebral artery occlusion (MCAo) would lead to neurological recovery. Following small bioactive molecules were investigated: LAU-0901 (LAU), PAF-R antagonist that blocks pro-inflammatory signaling, and aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways, and their combination that exerts potent anti-inflammatory activity in the brain. This study investigated the dose-response and therapeutic window in a model of focal cerebral ischemia.

Methods:
Male SD rats were subjected to 2h of MCAo, behavior was evaluated on days 1-7, and an
ex vivo
MRI was conducted on day 7. In Dose-response, rats were treated with LAU (45 and 60mg/kg, IP, at 3h), AT-NPD1 (111, 222, and 333μg/kg, IV, at 3.15 h after onset of stroke), LAU+AT-NPD1 or vehicle (n=5-6 per group). In Therapeutic window, LAU (60mg/kg, IP), AT-NPD1 (222μg/kg, IV), LAU+AT-NPD1 were administered at 3, 4, 5, and 6 h after onset of MCAo.

Results:
Treatments with LAU (45 and 60 mg/kg) alone improved behavior on days 1-7 by 32-38%; AT-NPD1 (all doses) by 20-30% compared to vehicle groups. The neuroprotective effect was enhanced using the LAU+AT-NPD1, which resulted in improved behavior up to 35-40% on days 1-7. Total lesion volumes, which were computed using T2WI, were significantly reduced with LAU-0901 (45 and 60mg/kg) by 76-85% and AT-NPD1 (all doses) alone by 62-77% compared to the vehicle group. Ischemic core, penumbra, and total lesion volumes were dramatically reduced with LAU+AT-NPD1 by 92-94% compared to the vehicle. LAU and AT-NPD1 alone, improved behavior on day 7 by 35 and 28%. In contrast, LAU+AT-NPD1 improved behavior by 46% when administered at 3h, by 52% at 4h, 34% at 5h, and 19% at 6h.

Conclusion:
LAU-0901 and AT-NPD1 alone provide high-grade neuroprotection. Combination therapy with LAU-0901 and AT-NPD1 is more effective than the single therapy, affording synergistic neuroprotection with improved behavior when administered up to 6 h after MCAo in rats.
Abstract WP27: Sars-cov-2 And Stroke Characteristics: A Report From A Regional Medical Center Serving Three Counties In South Carolina
Authors: West Abbie , Davis Sherry , Hughes Sheri , Kamboj Gurinder , Trivedi Tushar
Published: February 2022

Introduction:
Recent studies have shown patients with coronavirus disease 2019 (COVID-19) develop significant coagulopathy with thromboembolic complications including ischemic stroke. However, data are sparse regarding the clinical characteristics, stroke mechanism, and patient outcomes.

Methods:
We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 2020 and June 2021, within at a Regional Medical Center serving three large counties in South Carolina. We further investigated clinical and demographic characteristics, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS), and stroke subtype as measured by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria among patients with COVID-19 who also suffered from an acute ischemic stroke.

Results:
During the study period, out of 1087 hospitalized patients with a diagnosis of COVID-19 infection, 18 patients (1.6%) had an imaging-proven ischemic stroke. Of these 18 patients, 10 (56%) were men, 16 were African-Americans (89%), 2 (11.1%) patients were <55 years of age. All patients had at least one known vascular risk factor. Cryptogenic stroke was more common in patients with COVID-19 (83%). The median time (days) from COVID-19 symptom onset to stroke symptom onset was 11 (IQR 10-28), while the median time from being tested positive for COVID-19 to stroke diagnosis was 10 (IQR 2-24). Our study sample had a median admission NIHSS score of 5 (IQR 3-11) and a median peak D-dimer level of 2101 (IQR 1349 - 3213). Interestingly, 38% of these patients were already on therapeutic anticoagulation before the diagnosis of stroke. Patients with COVID-19 and stroke had an inpatient mortality rate of 11%. None of these patients met the criteria for IV-tPA treatment or thrombectomy.

Conclusion:
We observed a modest rate of ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly secondary to coagulopathy associated with COVID-19 infection. Further studies are needed to guide management for stroke prevention in patients with COVID-19.
Abstract WP45: Multiply-Encountered And Multiply-Thrombolysed Telestroke Patients - A Unique Patient Population
Authors: Morton Johanna L , Boyd Kristina L , Anderson Eric , Hallock Jason
Published: February 2022

Background:
Many hospitals utilize telestroke services for the remote diagnosis and treatment of acute stroke. Through this practice, an unusual subset of patients with multiple presentations having received thrombolysis numerous times has emerged. This study describes the largest known sample of this multiple encounter population within a single teleneurology practice spanning 39 states over 7 years.

Methods:
A retrospective observational study of the experience of a single teleneurology practice serving over 400 hospitals from July 2014 to July 2021 was performed. The patient database was queried to identify patients with multiple thrombolysis encounters. Clinical data was abstracted and compared to a random sample of matched singly-thrombolysed case controls.

Results:
A total of 181 patients received thrombolysis more than once, with 165 having received thrombolysis twice and 16 having received thrombolysis three or more times. Nine patients received care in multiple states. The maximum number of encounters was 25. The multiply-thrombolysed group were more likely to be male than the singly-thrombolysed (84.0% vs 45.3%, P<0.0001). The multiply-thrombolysed group was younger (58.8±15.2 vs 62.8±17.5, P=0.02) and had higher initial NIHSS (6.5±4.3 vs 3.2±5.8, P<0.0001). The multiply-thrombolysed group had lower rates of gaze deviation, dysarthria, extinction, facial droop, abnormal LOC answers. The multiply-thrombolysed group had lower rates of antiplatelet use (21.0% vs 53.5%, P<0.0001). TLSW-to-door time was shorter in the multiply-thrombolysed group (84.6 vs 182.7 minutes, P<0.01). There were no differences in door-to-consult or door-to-needle times between the groups, but the consult length was longer in the multiply-thrombolysed group (61.8 vs 46.4 min, P<0.01). The thrombolysis rate in the multiply-thrombolysed group was 46.7%.

Conclusion:
The observed phenomena of recurrent telestroke encounters with repeated thrombolysis administration is not well-described nor understood. Given the inherent risk and resource utilization associated with thrombolysis, further analysis including outcomes of this patient population is warranted.
Abstract WP54: Patient Location Impacts Accuracy Of Inpatient Stroke Alerts
Authors: Davis Nicolle W , Singh Amita , Bailey Meghan , Khanna Anna , Wilson Christina A
Published: February 2022

Background:
Strokes that occur during inpatient hospitalization require rapid identification and stroke-alert activation from hospital staff in heterogeneous settings, often resulting in overutilization of stroke team resources on stroke mimics. An understanding of the factors that impact accuracy of identification of inpatient strokes would assist in improving care in this population.

Methods:
This was a retrospective analysis from a single Joint-Commission certified Comprehensive Stroke Center. All patients for whom an inpatient stroke alert was called between 2/1/2019 - 4/30/2021 were included. Metrics captured in our local stroke-alert registry were analyzed, with comparisons made between patients who were determined to have a true stroke versus stroke mimic.

Results:
Of 705 inpatient alerts, mean patient age was 66 years, 50% were male, 62% occurred in the daytime, and mean NIHSS was 12. The majority of alerts were stroke mimics (76%); most common non-stroke diagnoses were encephalopathy, medical decompensation, and seizure. Among patients with true stroke, 86% were ischemic, with 13 patients receiving thrombolytics and 21 patients undergoing mechanical thrombectomy. One stroke mimic received thrombolytics. Although most alerts originated from medicine units (38%) and floor beds (49%), true stroke was most often diagnosed on cardiology (39%) and hematology/oncology (38%) units, and in the ICU or intermediate care setting (54%). Logistic regression adjusted for age and time of day showed true strokes were significantly associated with male sex, location (stratified by specialty), shorter time to CT completion, and higher initial NIHSS (p<0.05).

Conclusions:
A majority of inpatient alerts are stroke mimics, particularly on medicine floors. Stroke education could be tailored to staff to incorporate these findings to ensure that stroke patients are not missed, while stroke team resources are not overutilized on mimics.
Abstract WP65: Evaluation Of Visitation Restrictions On Stroke Caregiver Preparedness During Inpatient Rehabilitation
Authors: Camicia Michelle E , Lutz Barbara J , Stram Douglas , Tucker Lue-Yen , Ray Cristine , Theodore Brian
Published: February 2022

Introduction:
Family caregivers (CG) are an essential component of stroke care transitions. Restrictions in family visitation in inpatient rehabilitations units due to COVID-19 has limited training opportunities for CGs. In this study, visitation to the inpatient rehabilitation unit was restricted by policy to one day of CG training as a result of the COVID-19 pandemic. Caregivers were assessed using the 25-item self-reported Preparedness Assessment for the Transition Home (PATH) instrument.

Methods:
The study cohort was stratified into 2 study groups: pre- (discharge [D/C] from the IRU before 3/16/2020; n=136) and post- (D/C after 3/16/2020; n=142) visitation policy change We calculated proportions of categorical clinical and demographic variables (age, income, gender, race, marital status, CG gender, relationship) and compared them between 2 study groups using Chi-squared tests. Means (standard deviations) for the overall PATH score and for each PATH domain were calculated and compared between study groups using independent samples t-tests.

Results and Conclusions:
No statistically significant differences in characteristics between groups were found, nor in the overall PATH score. However, the difference between the pre- and post- policy change groups in the domain of prognosis and insight was significant (P=0.04). The items in this domain are listed below. Providers must find innovative ways to communicate information about recovery, the impact of stroke, required preparations, and care needs during times of restricted visitation to improve caregiver preparedness during inpatient rehabilitation.
Abstract WP66: Acute Stroke Screening For Cognitive Disorders And Depression
Authors: Barrett A M , Convoy-Hellmann Janice , Loring David , Saurman Jessica , Benameur Karima , Goldstein Felicia C , Krishnan Shilpa , Nahab Fadi B
Published: February 2022

Introduction:
As stroke survivors transition from acute to post-acute care, and finally to community settings, the Centers for Disease Control reports ~65% receive NO rehabilitation. Even more receive rehabilitation too late, after critical brain changes for recovery are complete. Stroke survivors with invisible disabilities of cognition and depression are especially vulnerable to experience poor recovery. We launched a dedicated process to identify invisible disabilities. Our long-term objective is to make acute and post-acute, evidence-based intervention accessible.

Hypothesis:
>50% of acute stroke patients have cognitive deficits, or depression.

Methods:
Our comprehensive stroke center completes bedside psychometric assessment with standardized instruments for aphasia (Language Screening Test, LAST), spatial neglect (Catherine Bergego Scale, CBS), memory/global cognition (Montreal Cognitive Assessment, MoCA), delirium (3-Minute Diagnostic Interview for the Confusion Assessment Method, 3D-CAM) and depression (Patient health questionnaire, PHQ-8). Patients unable to respond to questions are assessed for spatial neglect and delirium (standardized observations).

Results:
105 ischemic stroke survivors were assessed in the first quarter of program launch (April-July, 2021). Of that group, patients met screening criteria for spatial neglect (47%), aphasia (40%), delirium (19%) and depression (31%). Over 90% had memory / global cognitive impairment (MoCA<26/30).

Conclusions:
Our initiative, which includes systematic acute stroke unit spatial neglect screening, confirmed the previously reported high rate of cognitive disorders and depression (Champod, Eskes, Barrett, 2020). Our current step implements uniform recommendations for patients with deficits, and will examine post-acute outcomes, number receiving rehabilitation and medical follow-up, and treatment disparities (right/left stroke, under-represented groups).
Abstract WP70: Racial-ethnic Differences In Reintegrating To Normal Living Among Stroke Survivors
Authors: Rebello Vida , Wing Jeffrey J , Drum Emily , Boden-Albala Bernadette
Published: February 2022

Background:
In the continuum of care for stroke survivors, racial-ethnic disparities are most prominent during post-stroke rehabilitation. This includes reintegration of stroke survivors to normal living, an important component in stroke rehabilitation and predicts stroke survivors’ participation in typical daily activities and post-stroke depression. We assessed the association between racial-ethnic factors and ability of survivors to reintegrate to normal living at one-year post stroke.

Methods:
Using data from the DESERVE (Discharge Educational Strategies for Reduction of Vascular Events) trial, we assessed reintegration to normal living (RNL) using the RNL index of 335 participants with acute stroke. Race and ethnicity were asked at baseline and the survivors’ RNL index was assessed at one-year follow-up. The RNL index was calculated from 11 questions rating survivor’s reintegration from 0-10 (no to complete integration). We used linear regression to assess variations in race-ethnicity on RNL index adjusting for intervention, age, sex, education, living arrangement, stroke history, and severity of recent stroke.

Results:
At baseline, 27.8% identified as Non-Hispanic (NH) white, 31.6% identified as NH black, 34.9% identified as Hispanic and 5.7% identified as NH other. Crude mean RNL index was greater in the intervention arm than the usual care arm for Hispanics and NH blacks (Figure). In adjusted models, NH whites (5.88, CI: -2.9,14.8) and NH Blacks (6.63, CI: -1.1,14.3) had higher RNL index compared to Hispanics.

Conclusion:
Racial-ethnic differences may play a clinically important role in reintegrating stroke survivors to normal living. Future interventions must be aimed at understanding fundamental causes of disparities that may lead to inequities in stroke survivors’ rehabilitation to better implement preventative strategies well before stroke incidence.