bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP66: Cerebrovascular Hemodynamics of Mechanical Circulatory Support Device Patients
Authors: Melmed Kara R , Shlick Konrad H , Rinsky Brenda , Song Shlee S , Lyden Patrick D
Published: June 2021

Background:
Multiple types of mechanical circulatory support (MCS) devices are commonly used in heart failure patients. These devices carry risk for neurologic complications, specifically cardioembolic stroke. Alterations in blood flow play a role in the pathophysiology, however there is limited data regarding cerebrovascular hemodynamics in MCS patients. We used transcranial Doppler (TCD) to define hemodynamics of commonly used MCS devices.

Methods:
We retrospectively examined charts from 2/2013 through 6/2016 for patients with MCS who underwent TCD, and obtained the following: peak systolic,end-diastolic velocities, mean flow velocities, pulsatility indices (PI) and number of high-intensity transient signals (HITS). Waveform morphologies were compared between devices.

Results:
Of 1,796 TCDs studies screened, 62 TCD studies were from 32 MCS patients. Of these, 21 were on extracorporeal membrane oxygenation (ECMO), 15 had a left ventricular assist device (LVAD), 18 had total artificial heart (TAH), and 2 had intra-aortic balloon pumps (IABP). Waveforms in patients supported by ECMO demonstrated continuous flow without clear systolic peaks. The averaged mean MCA velocity was 57.57 (SD= 21.00) cm/sec and mean PI is 0.35 (0.17). LVAD averaged mean MCA velocity was 57.57 (14.38) cm/sec and mean PI of 0.45 (0.28). PIs were low in patients with continuous-flow LVADs. Impella patients had morphologically distinct pulsatile waveforms compared to other types of VADs. IABP had averaged mean velocity of 56.21 (14.78) cm/sec and mean PI of 0.77 (0.15). These waveforms demonstrated pronounced diastolic upstrokes not present in other devices. In TAH patients, mean MCA velocity was 73.69 (33.00) cm/sec and PI of 0.86 (0.40). Emboli detection was performed in 46 studies, and HITS were detected in 29 (63%). Of these 15 (51%) were administered 100% oxygen which suppressed >50% HITS in 10 (67%) patients.

Conclusion:
Patients supported by MCS devices produce unique and characteristic waveforms on TCD studies. Further studies will describe normative values in this special population. HITS were not universally present and intermittently suppressible by oxygen, suggesting some may be gaseous in nature. Risk of stroke in patients with MCS and HITS is under study.
Abstract WMP74: Sex Differences in T Cell Immune Responses and Outcome After Stroke in Aged Mice
Authors: Ahnstedt Hilda , Patrizz Anthony , Bravo-Alegria Javiera , Sphychala Monica , Roy-O’Reilly Meaghan , Chauhan Anjali , McCullough Louise D
Published: June 2021

Introduction:
Sex differences are increasingly recognized in stroke. Stroke incidence is higher in men than in women until an advanced age and women have higher mortality and morbidity. Inflammatory responses are key determinants of outcome but have not been well studies in aged animals.

Hypothesis:
We hypothesize that there are important sex differences in inflammation in aged male and female mice.

Results:
We quantified T cells and T regulatory cells, as well as functional outcome after stroke in aged mice. Male and female C57BL/6 mice (20-21 months) were subjected to 60 min middle cerebral artery occlusion (n=16) by the filament model, or sham surgery (n=7). Immune responses in brain, blood and spleen were investigated 15 days post-stroke by flow cytometry. Functional outcomes were assessed at day 3, 7 and 14. Mortality was 25% in females and occurred at day 1, while in males 50% mortality was seen between day 3 and 9. Hemorrhagic transformation was seen in 53% of the males that died (5/8) and in none of the females (0/4). Flow cytometry analysis at day 15 showed significantly higher levels of CD8
+
T cells in the blood after stroke in males compared to females (73±5% of CD3
+
T cells vs 52±3%, P<0.001). CD8
+
T cells were found in brains from males and females after stroke but levels were not different from sham (Male Stroke: 64±7%, Female Stroke: 58±5%). Independent of the type of surgery (stroke or sham), we observed higher levels of splenic CD8
+
T cells in males (P<0.01). T regulatory cells were significantly increased in the brain after stroke in males compared to sham (P<0.01), but not in females. Open-field testing showed a decrease in center visits after stroke in both sexes at 3 days, however males spent more time immobile (P<0.01) indicating decreased locomotor activity and/or anxiety. This difference equalized at 7 and 14 days post-stroke.

Conclusion:
Higher mortality and hemorrhagic transformation rates were seen in aged males than in females after stroke. This may be associated with the elevated levels of CD8
+
T cells in blood and possible unfavorable effects on blood brain barrier permeability.
Abstract WMP76: Clots are Potent Triggers of Inflammatory Cell Gene Expression - Indications for Timely Fibrinolysis in Stroke
Authors: Campbell Robert A , Smith Tammy , Vieira-de-Abreu Adriana , Franks Zechriah G , Rowley Jesse W , Rondina Matthew T , Kraiss Larry W , Zimmerman Guy A , Weyrich Andrew S
Published: June 2021

Rationale:
Blood vessel wall damage often results in the formation of a fibrin clot that traps inflammatory cells, including monocytes. The effect of clot formation and subsequent lysis on the expression of monocyte-derived genes involved in the development and progression of ischemic stroke and other vascular diseases, however, is unknown.

Objective:
Determine if clot formation and lysis regulate the expression of human monocyte-derived genes that modulate vascular diseases.

Methods and Results:
We performed Next Generation RNA sequencing on monocytes extracted from whole blood clots. Thousands of mRNAs were significantly differentially expressed by monocytes from clotted versus unclotted whole blood (p>0.05), including upregulation of many inflammatory cytokines such as interleukin 8 (IL-8), IL-1β, tumor necrosis factor alpha, and monocyte chemoattractant protein-1 (MCP-1). Clotted plasma also increased expression of IL-8 and MCP-1, which far exceeded responses observed in LPS-stimulated monocytes. Upregulation of IL-8 and MCP-1 occurred in a thrombin-independent, but fibrin-dependent, manner. Fibrinolysis initiated shortly after plasma clot formation (i.e., 1-2 hours) reduced the global inflammatory response based on RNA-seq analysis and significantly reduced the synthesis of IL-8 and MCP-1 (p>0.05). Delayed fibrinolysis was far less effective in reducing inflammation. Consistent with these
in vitro
models, monocytes embedded in unresolved thrombi from patients undergoing thrombectomy stained positively for IL-8 and MCP-1.

Conclusion:
These findings demonstrate that clots are potent inducers of monocyte gene expression, and that timely fibrinolysis attenuates inflammatory responses. Dampening of inflammatory gene expression by timely clot lysis may contribute to the clinically-proven efficacy of fibrinolytic drug treatment within hours of stroke onset.
Abstract WMP83: Extracellular Vimentin Contributes to Von Willebrand Factor (VWF) String Formation in the Cerebrovasculature Following Endothelial Activation
Authors: Hong Sung-Ha , Ishola Titilope , Da Qi , Cruz Miguel A , Marrelli Sean P
Published: June 2021

Introduction:
VWF strings can form within the vascular lumen following endothelial activation and have been implicated in platelet adhesion and worsened outcome following stroke. However, the molecular interactions facilitating VWF string anchorage to the endothelial surface are currently unknown. Here we examined the novel role of endothelial vimentin in mediating the anchorage of VWF strings within the cerebrovasculature. We hypothesize that VWF released from activated endothelium remains anchored at the luminal surface (i.e. VWF strings) through direct interaction with extracellular vimentin.

Methods:
Cultured endothelial cell (EC) experiments were performed with human umbilical vein EC (HUVECs) and human brain microvascular EC (HBMVECs). EC were stimulated with histamine (10 uM) under flow conditions. Specific protein interactions were probed with recombinant vimentin and A2 domain of VWF. Mouse middle cerebral and superior cerebellar arteries from WT and vimentin KO mice were set up in a pressurized artery chamber, stimulated with histamine, and then processed for VWF immunofluorescence to quantify VWF strings. VWF string formation was further evaluated by cranial window preparation using labeled platelets to detect real-time
in vivo
string formation.

Results:
In cultured EC, histamine stimulation promoted the production of long VWF strings that were significantly attenuated in the presence of recombinant vimentin or A2 domain of VWF. In pressurized cerebral arteries, histamine stimulation promoted VWF strings that aligned along the luminal endothelial surface. VWF string formation was reduced 2.9 fold in arteries from vimentin knockout mice (P=0.02). Histamine stimulation in the cranial window produced platelet-adherent strings in the pial microvasculature.

Conclusions:
These studies provide
in vitro
and
in vivo
evidence for a novel interaction between vimentin and the A2 domain of VWF at the endothelial surface which contributes to the anchorage of VWF strings in the microvasculature. This vimentin/VWF interaction critically regulates VWF-mediated platelet adhesion at the surface of activated endothelium and could thus provide a novel therapeutic target in the treatment of acute ischemic stroke.
Abstract WP1: Thrombectomy Outcomes in Acute Ischemic Stroke due to Middle Cerebral Artery M2 Occlusion with Stent-Retriever, Aspiration, MERCI: Multi-Center Experience
Authors: Atchaneeyasakul Kunakorn , Malik Amer M , Yavagal Dileep R , Bouslama Mehdi , Haussen Diogo C , Kenmuir Cynthia L , Jadhav Ashutosh P , Jovin Tudor G , Nogueira Raul G
Published: June 2021

Introduction:
Recent trials demonstrated that mechanical thrombectomy improve functional outcome in anterior circulation acute ischemic stroke (AIS) due to emergent large vessel occlusion (ELVO) of the middle cerebral artery (MCA) M1 segment. However, such data regarding AIS due to MCA M2 segment ELVO is limited. Analysis of the STAR, SWIFT, and SWIFT-PRIME trials found thrombectomy in MCA M2 occlusion to be feasible in achieving successful reperfusion. The most optimal technique and/or device used for such reperfusion is not clearly defined. We aim to compare the outcome for the contemporary techniques and devices used for thrombectomy of AIS patients due to MCA M2 ELVO.

Methods:
A retrospective review of AIS patients with MCA M2 ELVO receiving thrombectomy from three tertiary care academic medical centers was conducted. Thrombectomy technique and thrombectomy device utilized were recorded. Outcomes were successful angiographic reperfusion (TICI ≥2b), favorable modified Rankin Scale (mRS≤2) at discharge and at 90 days, and rate of symptomatic intracerebral hemorrhage (sICH).

Results:
From October 1999 through June 2016, 253 AIS patients underwent thrombectomy for MCA M2 ELVO. Thrombectomy methods utilized were Stent-retriever (n=118), Aspiration only [manual or Penumbra device] (n=83), and MERCI retriever (n=52). Table 1 shows rate of outcomes measured. There was no difference in baseline NIHSS or in stroke onset to groin puncture time. Stent-retriever group showed a significantly higher recanalization rate, lower sICH rate, and favorable 90-day mRS versus Aspiration group or MERCI group, respectively. No significant difference was seen in discharge mRS between the groups.

Conclusions:
Thrombectomy for AIS patients with MCA M2 ELVO with Stent-retriever appears to be feasible with a significantly higher rate of recanalization, lower sICH rate, and favorable 90-day mRS when compared to Aspiration and MERCI.
Abstract WP103: ABCA1/HDL Signaling Pathway Mediates White Matter Remodeling and Improves Functional Outcome After Stroke
Authors: Li Rongwen , Chopp Michael , Chen Jieli , Zacharek Alex , Wang fengjie , Landshoot-Ward Julie , Cui Xu
Published: June 2021

The ATP-binding cassette transporter A1 (ABCA1) plays a critical role in the formation of brain HDL cholesterol, mainly from astrocytes. Specific brain ABCA1 deficient (ABCA1
-B/-B
) mice exhibit reduced HDL levels in brain tissue and cerebrospinal fluid, as well as increases in white matter (WM) damage and neurological deficits after stroke. We tested the hypothesis, that treatment of stroke in ABCA1
-B/-B
mice with intraventricularly infused HDL increases WM remodeling in the ischemic brain and attenuates ABCA1
-B/-B
induced deficits after stroke.

Method:
Adult male ABCA1
-B/-B
mice were subjected to permanent right distal middle cerebral artery occlusion (dMCAo), and were intraventricularly infused with PBS or recombinant human HDL3 (rhHDL3, 25μg in 100μl PBS) by transplanting a micro-osmotic pump (D1002, 0.25 μl/h for 14 days, Alzet) into the right lateral ventricle starting 24h after dMCAo. Animals were sacrificed 21 days after dMCAo. In vitro primary cortical neuron (PCN) culture derived from C57BL/6 and ABCA1
-B/-B
embryos and axonal outgrowth measurements were also employed.

Results:
1) There were no ischemic lesion volume changes between the two groups. 2) rhHDL3-infused ABCA1
-B/-B
stroke mice exhibited significantly increased WM-remodeling identified by increased level of myelin basic protein, increased densities of myelin and axons, increased number of oligodendrocytes and oligodendrocyte progenitor cells in the ischemic boundary zone, as well as improved functional outcome compared with PBS-infused ABCA1
-B/-B
stroke mice (p<0.05, n=8/group). 3) HDL (40 or 80μg/ml) treatment in ABCA1
-B/-B
-PCNs significantly increased axonal outgrowth compared to non-treatment control. Treatment of C57BL/6-PCNs with astrocyte-conditioned media derived from ABCA1
-B/-B
embryos significantly decreased axonal outgrowth compared to treatment with astrocyte-conditioned media derived from ABCA1 floxed-control embryos. However, ABCA1
-B/-B
-astrocyte-conditioned media combination with HDL treatment significantly increased C57BL/6-PCN axonal outgrowth compared to treatment with ABCA1
-B/-B
-astrocyte-conditioned media alone.

Conclusion:
ABCA1/HDL pathway may contribute to WM-remodeling as well as functional recovery after stroke.
Abstract WP108: Astrocyte-specific rAAV-mediated Insulin-like Growth Factor-1 Expression in Aging Female Rats Alters Stroke-induced Brain Immune Profile and Reduces Motor Impairment
Authors: Okoreeh Andre K , Bake Shameena , Sohrabji Farida
Published: June 2021

Introduction:
Middle-aged female rats sustain larger strokes than younger female rats. This may be due to age-related loss of circulating and parenchymal brain levels of insulin like growth factor-1 (IGF-1). With age, IGF-1 synthesis is decreased in astrocytes, a critical cell type for post-stroke recovery. Here we tested the hypothesis that replenishing IGF-1 in aging astrocytes will improve stroke outcomes by influencing the type and extent of immune cells infiltration into the brain post-stroke.

Methods:
Middle-aged (10-12 mo old, acyclic) female rats were injected into the striatum and cortex with adeno-associated virus serotype 5 (rAAV5) packaged with the coding sequence of the hIGF-1 gene downstream of an astrocyte-specific promoter (GFAP). The rAAV-control consisted of an identical shuttle vector construct without the hIGF-1 gene. Three to four weeks later, animals underwent 90 minute transient middle cerebral artery occlusion via intraluminal suture. At 2d post stroke, flow cytometry was used to determine the type and extent of peripheral immune cells trafficked into the brain. In parallel studies, animals were tested for performance on sensory motor tasks at 2d and 5 days after MCAo.

Results:
rAAV-mediated IGF-1 expression was confirmed in astrocytes with RT-PCR. Flow cytometry analysis of immune cells in the brain at 24h post-stroke found that proportion of Treg cells was greater in animals with rAAV-IGF-1 as compared to rAAV-controls. Additionally, while there was no difference in the proportion of M2 microglia, rAAV-IGF-1 enhanced M2 infiltrating macrophages. At 2d and 5d post stroke, stroke-induced sensory motor impairment was reduced in animals with rAAV-IGF-1 as compared to rAAV-controls.

Conclusion:
Targeted enhancement of IGF-1 in astrocytes of middle-aged females improved stroke-induced behavioral impairment concomitant with recruitment of anti-inflammatory cell types to the ischemic brain.
Abstract WP112: Residual Damage is Reduced Following Human Umbilical Tissue Derived Cell Infusion in a Non-human Primate Model of Cortical Injury
Authors: Orczykowski Mary E , Shobin Eli , Calderazzo Samantha M , Kramer Brian C , Mortazavi Farzad , Rosene Douglas L , Moore Tara L
Published: June 2021

Introduction:
Stroke is the leading cause of long-term disability in the United States due to impairments that endure after brain injury. While studies in rodent models have evaluated numerous neurorestorative treatments following stroke, none have received FDA approval. We evaluated a therapy using human umbilical tissue-derived cells (hUTC) as a potential neurorestorative treatment in our non-human primate model of cortical injury limited to the hand area of primary motor cortex. Given treatment 24 hours after injury, hUTC treated monkeys showed a significantly greater degree of recovery of fine motor function compared to vehicle treated controls (Moore et al., 2013). To explore the effect of hUTC, histopathological markers of inflammation and oxidative stress were assessed.

Hypothesis:
Treatment with hUTC will enhance the recruitment of glia to the injury and reduce the cascade of inflammation and oxidative stress.

Methods:
Using immunohistochemistry, activated microglia (LN3), reactive astrocytes (GFAP), oxidative damage (4HNE), and accumulated hemosiderin (Perls’ Prussian Blue) were quantified in ipsilesional primary motor cortex and underlying white matter. Microglia were counted using unbiased stereology. A Sholl Analysis was performed on traced perilesional astrocytes. The area of oxidative damage and hemosiderin was assessed using densitometry.

Results:
Compared to vehicle controls, density of activated microglia in the hUTC treated group approached a significant increase in the perilesional gray and white matter (p=0.070; p=0.092). Astrocytes exhibited more complex processes in treated monkeys (p=0.042). Staining for 4HNE was significantly reduced in white matter underlying the lesion in treated monkeys (p=0.033). Lastly, both the area and intensity of Perls’ staining for hemosiderin was significantly reduced in the perilesional area of treated monkeys (p=0.045; p=0.001).

Conclusions:
Treatment with hUTC resulted in increased activation of microglia and complexity of reactive astrocyte processes as well as reduced post-lesion oxidative damage and hemosiderin deposition. This suggests the hUTC treatment enhanced recovery, in part, by recruitment of glial cells that limited the damage following cortical injury.
Abstract WP113: Induced Pluripotent Stem Cells Derived Neurons Ideally Serve as a Human Stroke Model of Neuronal Damage and Neuroprotective Intervention
Authors: Khan Mushfiquddin , Dhammu Tajinder S , Baarine Mauhamad , Singh Avtar K , Singh Inderjit
Published: June 2021

Background:
Basic science research on stroke is lagging. Results from both animal and animal-derived neural cell models are, more often than not, less valid for human stroke. To address this lack of models for human stroke mechanisms, we developed induced pluripotent stem cell (iPSC)-derived human neurons and subjected them to excitotoxicity and oxygen-glucose deprivation (OGD) conditions. These conditions produced a disturbed nitric oxide (NO) metabolome similar to human stroke. A therapeutic intervention, the NO-based neuroprotective agent S-nitrosoglutathione (GSNO), was investigated for neuroprotection against excitotoxicity as well as OGD-induced neuronal nitric oxide synthase (nNOS) activation and the deleterious nNOS/peroxynitrite/calpain neurodegenerative system.

Methods:
The iPSC were generated using skin fibroblasts from normal adult human subjects. Neural precursor cells (NPC) were prepared using embryonic body and NPC were differentiated into neurons.

Results:
The differentiated iPSC neurons were positive for NeuN and β-tubulin (neuronal markers), and they responded to glutamate/NMDA-induced Ca
2+
influx. The majority of iPSC neurons (~90%) were nNOS-positive, supporting them as a suitable model for NO metabolome studies. To examine this model’s nNOS/peroxynitrite/calpain system under stroke conditions, nNOS activation (pnNOS)-dependent toxicity in the iPSC-derived neurons was observed. High expression levels were found for pnNOS Ser
1412
, 3-NT, and p25 fragment in glutamate/NMDA- and OGD-treated cells. GSNO treatment reversibly blocked glutamate/NMDA- and OGD-induced pnNOS and 3-NT expression levels. Calpain activity was also blocked.

Conclusions:
This study of iPSC-derived human neurons is the first of its kind to investigate excitotoxicity or OGD-mediated neurodegeneration mechanisms and therapeutic interventions under stroke conditions. The data provide evidence that the deleterious nNOS/peroxynitrite/calpain system in iPSC neurons is similar to human stroke and that GSNO treatment down regulates this deleterious system. These observations support that iPSC human neurons are a suitable model for studies on stroke-associated neurodegenerative mechanisms as well as therapeutic interventions.
Abstract WP120: MicroRNA Expression in Patients With Acute Ischemic Stroke
Authors: Modak Janhavi M , Roy-O’Reilly Meaghan A , Conway Sarah E , Zhu Liang , McCullough Louise D
Published: June 2021

Background and Purpose:
MicroRNAs (miRNAs) are a class of endogenous small non-coding ribonucleic acids that regulate gene expression and can impact cellular function by suppressing or activating downstream mRNA targets. Pre-clinical studies in animal models of stroke have demonstrated specific changes in miRNA expression profiles after ischemic stroke.

Methods:
Patients admitted to Hartford Hospital from January 2011 - March 2014 were considered for this study. Blood samples were collected within 24 hours of stroke presentation. miRNA profiles from peripheral blood samples of ischemic stroke patients were compared to controls. Patients with acute middle cerebral artery (MCA) cardioembolic strokes (based on TOAST criteria) were included (n=16). Blood collected from patients with no acute neurological deficits in an outpatient setting served as controls (n=8). Individuals with a history of active cancer, neoplastic brain lesions or traumatic brain injury were excluded. Based on literature review, 173 miRNAs were selected to assess for differential expression between cases and controls. miRNA profiling was conducted at Exiqon Services, Denmark, using miRCURY LNA™ microRNA Array. Statistical analysis was performed using SAS.

Results:
In patients with acute ischemic strokes, a statistically significant differential expression was observed in 14 miRNAs as compared to controls. MicroRNAs miR-1273e, miR-5187-3p were found to be downregulated in stroke patients (p=0.01). Other miRNAs showing a significant downregulation included let 7e-5p (p=0.03); miR-4709-3p, miR-4756-3p, miR-5584-3p, miR-647 (p=0.02); miR-4742-3p (p=0.03); miR-4764-5p, miR-4531 and miR-2116-5p (p=0.04). MicroRNAs miR-664a-3p (p=0.02), miR-943 (p=0.04) and miR-145-5p (p=0.03) were significantly upregulated. Differential expression in males and females was not observed.

Conclusion:
Ischemic stroke patients show a differential microRNA expression profile as compared to controls. Further studies can help identify microRNA signatures as well as the downstream targets involved in the ischemic stroke molecular cascade.
Abstract WP155: Is Erectile Dysfunction More Frequent Among Men with History of Stroke: Analysis of National Health and Nutrition Examination Surveys 2001 to 2004
Authors: Qureshi Adnan I , Afgan Sher , Saleem Muhammad A
Published: June 2021

Background:
A common question among men who are stroke survivors is whether stroke occurrence will interfere with sexual performance. The question continues to have major significance in resumption of normal activities and reintegration into society for stroke survivors.

Methods:
Using a standard questionnaire, we examined trends and prevalence of erectile dysfunction in regards to moderate (sometimes) to severe (always) disability to get and keep an erection adequate for satisfactory intercourse in a nationally representative sample of the United States population. We analyzed data from 4929 men who participated in National Health and Nutrition Examination Survey (NHANES) 2001 to 2004. Stroke was defined based on self-report of physician diagnosis.

Results:
Moderate to severe disability to get and keep an erection adequate for satisfactory intercourse was reported by 13 (6.4%) men with history of stroke and 276 (5.8%) without stroke, respectively (p=0.65). After adjustment for differences in age, men with history of stroke did not have any increase in risk of moderate to severe disability to get and keep an erection adequate for satisfactory intercourse (odds ratio [OR] 0.8; 95% confidence interval [CI] 0.4 to1.7).

Conclusions:
Erectile dysfunction was relatively infrequent among men with history of stroke and no higher than in men without stroke.
Abstract WP159: Effects of Gender on Sleep Alterations After Stroke
Authors: Griesbach Grace S , Finley Sarah K , Williams Jennifer , Harrington David
Published: June 2021

Introduction:
Stroke in women tends to lead to greater disabilities and increased likelihood of institutionalization compared to men. We explored if sleep disturbances following stroke are influenced by gender. We also evaluated if levels of thyroid hormone (TSH, T3, T4), which are associated to functional outcome are influenced by gender.

Methods:
Sleep was evaluated via polysomnography in stroke 33 patients (men: n=20; women: n=13; M age = 54). Functional outcome was assessed with the Supervision Rating Rating Scale (SRS) and the Mayo-Portland Adaptability Inventory 4 (MPAI). Patients were also evaluated for hormonal alterations. Sleep values were also compared with age-matched published normative data from uninjured adults.

Results:
Women performed worse on the MPAI Ability Index and Adjustment index compared to men (p<0.05). Women also showed more disability according the SRS (p<0.05). Ability Index and sleep efficiency was correlated for all (p<0.01). Both male and female stroke patients had a higher percent time in Stage 2 (M: 61.5 and 66.7, respectively) compared to normative data (45.7). Moreover, 88% of stroke survivors did not did not reach Stage 3. Women showed lower sleep efficiency, spent less percent of time in REM and had a higher percent wake after sleep onset compared to normative data. Women also had lower T3 levels compared to men (p<0.01). Incidence of apnea was higher in men compared to women (p<0.05). Men tended to have more central apnea (p=0.08). Men had more spontaneous arousals during sleep and reported more daytime sleepiness compared to women (p<0.05). Accordingly, Epworth scores were correlated with low levels of participation in the MPAI for men (p<0.03). Comparisons to normative data showed that men have a shorter sleep-latency (M: 8.3 vs 15.8).

Conclusions:
Whereas apnea is more predominant in men, alterations in sleep architecture appear to be more marked in women. Women also have lower levels of T3. Sleep alterations after stroke are associated with functional deficits. These findings have implications for cognitive processing, as Stage III and REM are important for memory consolidation.
Abstract WP17: Association of Blood Glucose and Clinical Outcome After Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Gordon Weston R , Behera Anit , Chibnall John , Alshekhlee Amer , Callison Richard C , Edgell Randall C
Published: June 2021

Background:
Elevated blood glucose (BG) levels at admission following acute ischemic stroke (AIS) have been associated with adverse clinical outcomes in thrombolytic and non-thrombolytic treated patients. This association has been inconsistent and has not been studied after mechanical thrombectomy (MT). The current study looks at multiple BG parameters and their association with outcome following MT in AIS.

Methods:
AIS patients undergoing MT with a retrievable stent between 2012 and 2016 at two stroke centers were studied. Favorable clinical outcome was defined as having a modified Rankin Scale score (mRS) of 0-2 at three months. Admission BG, maximum BG during the hospital stay, and serial measurements every 4-6 hours in the first 24 hours were recorded. The following demographic and clinical data was also collected: age, sex, baseline NIHSS score, onset-to-reperfusion times, HgA1c, and stroke mechanism.

Results:
Seventy-nine patients were identified (mean age 69, 49% male, SEM= 1.56); thirty-three patients had a favorable clinical outcome at three months and 46 had unfavorable outcomes. In univariate analysis, BG variability (standard deviation of BG, SD) in the first 24 hours following admission and maximum BG during hospital stay was associated with unfavorable outcomes (Table 1). The association between admission BG and favorable outcome was not statistically significant. In multivariate logistic regression analysis the SD of BG (OR= 1.08, 95% CI= 1.02-1.13, P= .005) had the highest predictive value for favorable outcome.

Conclusions:
Greater BG variability is associated with worse clinical outcome in patients with AIS undergoing MT. Using SD and/or serial measurements of BG appear better than single BG measurements at predicting clinical outcome in this population.
Abstract WP178: Combining Novel with Traditional Risk Factors Improves Stroke Prediction in Older Americans: A Systematic Review
Authors: Mlabasati Jack , Singer Jonathan , Conigliaro Alyssa , Selvan Prad , Levine Steven
Published: June 2021

Background:
The Framingham Risk Score, one validated model for predicting stroke risk in middle age does not perform as well in older cohorts who may have different/novel stroke risk factors.

Methods:
Two independent raters systematically reviewed (through July 31, 2016) PubMed and Embase, identifying studies including peer-reviewed, original, clinical studies, randomized controlled trials and cited references to assess independent risk factors for first ischemic stroke in older, (> 65 years) Americans using PRISMA guidelines.

Results:
467 relevant studies were identified. We extracted data from 42 papers and categorized their aims into 6 sections: Serologic/Diagnostic, Traditional, Psychosocial, Genetic, Cognitive, and Miscellaneous risk factors. Some studies fell into more than one category. Serologic/Diagnostic (11 studies) demonstrated: levels of serum androgens, C-reactive protein, advanced glycation endproducts, thrombin generation and increased left ventricular mass were significant risk factors; adipokines and plasma free fatty acids were not. Traditional (11 studies) risk factors included: age, hypertension (both systolic and diastolic), atrial fibrillation, diabetes, peripheral vascular disease, waist/hip ratio in women, and BMI in men. Two studies showed that risk associated with hypertension and diabetes diminishes significantly over age 75. One study showed the protective effect of physical activity increased with age. Psychosocial (13 studies): 6 studies found depression strongly associated with stroke risk. Also, positive affect and purpose in life protected against stroke. Socioeconomic status did not influence risk in 3 studies. Genetic (5 studies) included: Apolipoprotein E, coagulation factor XII, and phosphodiesterase 4D polymorphisms – all with equivocal results. Cognitive (4 studies): Lower cognitive functioning, increased stroke rates. Miscellaneous (4 studies): Decreased level of functioning and increased cadmium exposure were risk factors.

Conclusion:
Some traditional and other more novel risk factors emerged as increasing stroke risk in older individuals. Only a few studies evaluated each risk factor. Further studies are warranted to investigate risk factors for stroke in older cohorts.
Abstract WP182: Trends in Acute Ischemic Stroke Hospitalizations and Risk Factors Among Young Adults: 12 Years of Nationally Representative Data
Authors: Patel Urvish K , Poojary Priti , Jani Vishal , Dhamoon Mandip S
Published: June 2021

Background:
There is limited recent population-based data of trends in acute ischemic stroke (AIS) hospitalization rates among young adults (YA). Rising prevalence of stroke risk factors may increase stroke rates in YA. We hypothesized that 1) stroke hospitalizations and mortality among YA are increasing over time (2000-2011), 2) besides traditional stroke risk factors, non-traditional factors are associated with stroke in YA, 3) stroke hospitalization among YA is associated with higher mortality, length of stay (LOS), and cost.

Methods:
In the Nationwide Inpatient Sample database (years 2000-2011), adult hospitalizations for AIS and concurrent diagnoses were identified by ICD-9-CM codes; the analytic cohort constituted all AIS hospitalizations. We performed weighted analysis using chi-square, t-test, and Jonckheere trend test. Multivariable survey regression models evaluated interactions between age group (18-45 vs. >45 years) and traditional and non-traditional risk factors, with outcomes including mortality, LOS, and cost. Models were adjusted for race, sex, Charlson’s Comorbidity Index, primary payer, location and teaching status of hospital, and admission day.

Results:
Among 5220960 AIS hospitalizations, 231858 (4.4%) were YA. On trend analysis, proportion of YA amongst AIS increased from 3.6% in 2000 to 4.7% in 2011 (p<0.0001) but mortality in YA decreased from 3.7% in 2000 to 2.6% in 2011, compared to 7.1% in 2000 to 4.6% in 2011 (p<0.0001) among older adults. Non-traditional, especially behavioral, risk factors were more common among YA, and LOS and cost were higher (Table).

Conclusion:
There was a trend for higher proportion of YA among AIS hospitalizations, though there was a decreasing mortality trend over 10 years. Behavioral risk factors were more common among YA, and there was an increased length of stay and cost. AIS in YA may require different preventive approaches compared to AIS among older adults.
Abstract WP186: Pregnancy Associated Hemorrhagic Strokes Differ in Mechanisms and Risk Factors Compared with Hemorrhagic Strokes in Non-pregnant Young Women and Men
Authors: Miller Eliza C , Sundheim Kathryn M , Willey Joshua Z , Boehme Amelia K , Marshall Randolph S
Published: June 2021

Background:
Pregnancy-associated hemorrhagic stroke (HS), while rare, is a significant cause of maternal mortality. Prior studies have suggested that the pathophysiology of HS may differ in pregnant/postpartum women when compared with HS in other young adults.

Methods:
We conducted a single-center retrospective analysis of a prospectively collected stroke registry, for patients aged 18-45, admitted with HS of any type from 01/2008-03/2015. We reviewed charts for study variables, including patient characteristics, risk factors, stroke mechanisms, and outcomes. Good outcome was defined as modified Rankin score of 0-2 at time of discharge. We compared study variables between three groups: pregnant/postpartum women, non-pregnant/postpartum women, and men.

Results:
Of 219 young adults with HS during the study period, 93 (42%) were men and 126 (58%) were women, of whom 19 (15.1%) were pregnant/postpartum. Among men, 58 (62.4%) had ICH and 41 (33.3%) had SAH, 31 (75.6%) of which were aneurysmal. Among non-pregnant women, 49 (45.8%) had ICH and 61 (57%) had SAH, 53 (87%) of which were aneurysmal. Among pregnant/postpartum women, 10 had ICH (52.6%) and 11 (57.9%) had SAH, 1 of which was aneurysmal. Compared with men and with non-pregnant women, pregnant/postpartum women had fewer vascular risk factors, were more likely to have history of migraine, and were more likely to have the reversible cerebral vasoconstriction syndrome as stroke mechanism (11/19, 57.9% versus 0/93 men and 2/107 non-pregnant women, p=0.0001). While there were no deaths in the pregnant/postpartum group, there were no significant differences between groups in good outcome (Table).

Conclusions:
In our analysis, pregnancy-associated hemorrhages were uniquely non-aneurysmal and associated with fewer cerebrovascular risk factors than age-matched men and non-pregnant women, suggesting there is a pregnancy-specific pathophysiology for HS that requires special consideration.
Abstract WP194: Physical Activity and Risk of Stroke: Is the Standard Too High?
Authors: Jeong Han-Gil , Kang Dong-Wan , Kim Do Yeon , Park Eun Sun , Lee Seung-Hoon
Published: June 2021

Introduction:
The current stroke guideline recommends moderate- to vigorous- intensity physical activity (PA) at least 40 min/d 3 to 4d/wk. But recent evidences suggest low-level PA can also reduce cardiovascular mortality. We assessed the benefits of a range of PA to prevent incident stroke in a Korean population.

Methods:
From a prospective cohort data of National Health Insurance in Korea, we included 352896 individuals who received general health examination at 2009 and 2010. We excluded participants (1) with previous stroke (N=5917), (2) with incomplete data on PA (N=5155) and (3) disqualified due to death or emigration at the same year of examination (N=5498). Level of PA was assessed using questionnaire for frequencies of weekly PA in each of three intensity categories; light (≥30min/d; eg, walking), moderate (≥30min/d; eg, brisk walking) or vigorous (≥20min/d; eg, running). Moderate- to vigorous- intensity PA (MVPA) was classified into 4 categories; none, 1-2 times, 3-4 times, ≥5 times per wk. Cox proportional hazard regression was performed to assess the influence of each categories of MVPA on the risk of incident stroke.

Results:
In 336326 individuals (171681 men and 164645 women) with an average follow-up of 3.6 years, 2213 incident stroke cases occurred (1866 ischemic stroke and 347 intracerebral hemorrhage). MVPA was none in 50%, 1-2 times/wk in 20%, 3-4 times/wk in 13%, and ≥5 times/wk in 18% of the cohort. Multivariable analysis (adjusted for age, sex, income, alcohol, smoking, light intensity PA, hypertension, diabetes and hyperlipidemia) showed even individuals in MVPA 1-2 times/wk group had a 16% reduced risk of incident stroke (HR: 0.84, 95% CI: 0.73-0.96) compared with those in none MVPA group. MVPAs 3-4 and ≥5 times/wk were also associated with lower risk of incident stroke (0.79, 0.68-0.91 in 3-4 times/wk; 0.79, 0.70-0.89 in ≥5 times/wk). Similar results were observed in ischemic stroke, but not in intracerebral hemorrhage.

Conclusions:
Even 1-2 times a week of MVPA might be beneficial to prevent first-ever stroke in general population. From a public health perspective we need to encourage inactive people to do exercise with more achievable goal, considering 50% of individuals in this cohort were still physically inactive.
Abstract WP221: Predictors of Stroke in a Sample of Patients With Infective Endocarditis
Authors: Valenzuela Ives A , Klein Bradley , Dunn Lauren , Sorabella Robert , Han Sang Myung , Willey Joshua , George Isaac , Gutierrez Jose
Published: June 2021

Background:
Infective endocarditis (IE) affects up to 20,000 people per year in the United States. Stroke is a feared complication of IE and is associated with high morbidity and mortality. We aim to identify predictors of stroke in a large sample of patients treated at a tertiary care center.

Methods:
A retrospective chart review was carried out using ICD9 codes for IE and cerebrovascular events in patients admitted to the New York Presbyterian Hospital/Columbia University Medical Center from 2000 to 2015. Incident stroke was ascertained if imaging demonstrated an acute infarction during the hospital visit in which endocarditis was diagnosed using Duke’s criteria. Demographics, vascular risks and ancillary data were obtained by chart review. Generalized linear models were used to obtain the risk ratio (RR) and their 95% confidence intervals (95%CI) adjusting for age, sex, ethnicity, hypertension, diabetes, dyslipidemia, smoking, congestive heart failure (CHF), presence of cardiac vegetations, valvular abscesses, positive blood culture, and immunosuppression.

Results:
The sample included 727 IE subjects (mean age 61±18, range 18-101, 62% men, 62% non-white). Twelve percent of the sample were immunosuppressed. The majority of the patient had vegetations (61%) and positive blood cultures (87%, MRSA 13%) while valvular abscess were less frequent (13%). Of the 727 patients, 13% had an acute pre-surgical stroke (10% ischemic and 3% hemorrhagic). Meanwhile, of the 314 patient who underwent surgical intervention, only 0.5% had post-surgical strokes. The risk of pre-operative ischemic stroke was higher among patients with diabetes (RR 1.7, 1.1-2.8), cardiac vegetations (RR 2.8, 1.6-5.0), and history of prior stroke (RR 1.8, 1.8-2.9) while the risk of pre-surgical hemorrhagic stroke was higher among patients with history of prior stroke (RR 4.5, 1.7-11.9).

Conclusions:
Prior stroke was a risk factor for ischemic and hemorrhagic stroke, which suggests baseline brain vulnerability that may influence the risk of stroke in the setting of IE. Additionally, diabetes and the presence of vegetations increased the risk of ischemic stroke. Early identification of sub-populations with IE at risk of stroke may help stratify risk and test preventive interventions.
Abstract WP235: Rates of Diagnostic Testing for Embolic Sources in a Nationally Representative Cohort of Patients With Ischemic Stroke
Authors: Gupta Ajay , Navi Babak B , Yaghi Shadi , Kamel Hooman
Published: June 2021

Introduction:
Many strokes arise from a distant embolic source such as the heart or large arteries. It has recently been proposed that a minimum evaluation to identify such sources should include imaging of the intracranial and extracranial arteries, an echocardiogram, and continuous heart-rhythm monitoring for ≥24 hours. We sought to evaluate the utilization rates of these tests in a nationally representative cohort of U.S. patients with ischemic stroke.

Methods:
We analyzed inpatient and outpatient claims data from 2009-2014 in a 5% sample of Medicare beneficiaries ≥66 years of age. Using validated
ICD-9-CM
codes, we identified all patients with inpatient admission for ischemic stroke. Our outcomes were the following recommended diagnostic evaluations: intracranial arterial imaging (CTA, MRA, or TCD), extracranial imaging (CTA, MRA, or Doppler ultrasound), echocardiography (transthoracic or transesophageal), and heart-rhythm monitoring (Holter or loop recorder). We used
CPT
codes to identify whether these tests were performed within 3 months prior to and 6 months after the stroke.

Results:
We identified 23,475 patients with ischemic stroke. Extracranial vascular imaging was performed in 20,600 patients (87.8%; 95% confidence interval [CI], 87.3-88.2%), intracranial vascular imaging in 11,726 patients (50.0%; 95% CI, 49.3-50.6%), echocardiography in 19,278 patients (82.1%; 95% CI, 81.6-82.6%), and heart-rhythm monitoring in 2,063 patients (8.8%; 95% CI, 8.4-9.2%). Only 49 (0.2%) underwent the complete recommended diagnostic battery for the detection of embolic sources. These rates were not substantially different even after excluding patients with known atrial fibrillation, the most common source of embolic stroke.

Limitations:
We could not capture inpatient cardiac telemetry that was not formally interpreted by a physician.

Conclusions:
Among Medicare beneficiaries with acute ischemic stroke, the majority did not receive a full diagnostic evaluation for potential embolic sources of stroke. Promoting the widespread adoption of a more systematic interrogation of potential etiologies of stroke may allow for the implementation of more personalized secondary stroke prevention strategies.
Abstract WP236: Left Atrial Enlargement and Cryptogenic Stroke
Authors: Tadi Prasanna , MontalvoPerero Mayra , Reddy Pranav M , Yaghi Shadi
Published: June 2021

Introduction:
Despite extensive evaluation, no definite cause is identified in 30-40% of ischemic stroke patients. Biomarkers of atrial dysfunction or “cardiopathy” have been shown to be associated with ischemic stroke risk, a relationship independent of atrial fibrillation. Our aim was to determine the association between left atrial enlargement (LAE) and cryptogenic stroke.

Methods:
This was a single center retrospective study using the stoke registry of a comprehensive stroke center. The study was approved by the institution board review. We reviewed medical records of patients admitted with acute ischemic stroke between December 1
st
, 2013 and August 31
st
, 2015 for demographic data (age and sex) and risk factors (hypertension, hyperlipidemia, coronary artery disease, prior stroke, congestive heart failure, and current smoking status). A vascular neurologist determined stroke subtype and cryptogenic stroke was defined based on the embolic stroke of unknown source (ESUS) criteria. Patients with cardioembolic stroke were excluded and the control group included small vessel disease, large vessel disease and other causes including hypercoagulable states, dissection and drug use. The primary predictor was left atrial (LA) size from 2D echocardiography and LA size was categorized as normal, mild LAE, moderate LAE, and severe LAE using the American Society of Echocardiography Recommendations for chamber quantification.

Results:
We identified 236 patients with ischemic stroke; 85 cryptogenic stroke and 151 non-cryptogenic stroke. For the entirety of the group, the mean age was 67 years with 45% males. Patients with cryptogenic stroke were more likely to have moderate to severe LAE when compared to patients with known non-cardioembolic etiology (12.8% vs. 3.2%, p = 0.0061).

Conclusion:
Moderate to severe left atrial enlargement, a biomarker of atrial cardiopathy or dysfunction, is more prevalent in patients with cryptogenic stroke than non-cardioembolic strokes of known etiology. Clinical trials are needed to study anticoagulation vs. antiplatelet therapy in patients with cryptogenic stroke and evidence of moderate to severe LAE.
Abstract WP237: Novel Probe Attached to the Cervix Can Evaluate Right-to-left Shunt More Precisely Than Transcranial Doppler
Authors: Mitsumura Hidetaka , Arai Ayumi , Komatsu Teppei , Sakuta Kenichi , Sakai Kenichiro , Terasawa Yuka , Kubota Jun , Iguchi Yasuyuki
Published: June 2021

Introduction:
While the examination for the evaluation of right-to-left shunt (RLS) using contrast transcranial Doppler (TCD) is useful, insufficient temporal bone window interrupts the adequate TCD examination for precise diagnosis of RLS. Thus, we developed a novel probe (paste-able soft ultrasound probe; PSUP) attached to the cervix for RLS diagnosis.

Hypothesis:
Monitoring at carotid artery using PSUP can detect greater number of contrast microembolic signals (cMES) than that of TCD.

Methods:
Subjects were patients with ischemic stroke or transient ischemic attack who had one and more cMES in middle cerebral artery detected by screening test of TCD on admission. PSUP was a 2.0-MHz center frequency and had an equal property with TCD transducer. The shape was thin, soft, and square modified for adequate attachment to the neck. We monitored blood flow of unilateral middle cerebral artery by TCD and ipsilateral common carotid artery by PSUP simultaneously. After injection of saline agitated with air in the right antecubital vein, we performed single test without Valsalva maneuver (VM) and triple tests with VM. And then, we compared the number of cMES between PSUP and TCD among each patient.

Results:
We performed 48 simultaneous PSUP and TCD examination (12 studies without VM, and 36 studies with VM) on 12 patients (11 male, median age of 49 years) without any complication. The number of cMES on PSUP was significantly larger than that of TCD in all of 48 examination (345 vs. 206, p<0.001), in 12 studies without VM (72 vs. 37, p=0.017), and in 36 studies with VM (273 vs. 169, p<0.001).

Conclusions:
In order to evaluate the RLS, PSUP examination at common carotid artery is a powerful approach in comparison with TCD. For patients without sufficient temporal bone window, PSUP should play an important role of RLS diagnosis.