bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP119: Alterations Of Inflammatory Cytokines In Super-acute Stroke Patients And The Potential Pathogenesis
Authors: Li Fangfang , Zhao Haiping , Xia Mingrong , Zang Weizhou , Zhang Jiewen , Luo Yumin
Published: February 2022

Background:
Sufficient understanding of the systemic inflammatory response after stroke will make the therapeutic strategy targeting inflammation more feasible. Here, we aimed to identify the globally alterations of circulating cytokines in super-acute ischemic stroke (AIS).

Methods:
A broad panel of 65 cytokines was measured in the plasma of twenty-eight AIS patients within 6 hours after stroke onset (
n
=28), cerebral hemorrhagic patients (
n
=28) and healthy controls (
n
=18). The diagnostic power of the candidate cytokines and their relationship with the number of lymphocytes and neutrophils were analyzed by receiver operating characteristic (ROC) and spearman rank correlation respectively.

Results:
The expression level of plasma IL-1beta, IL-2, IL-2R, IL-5, IL-10, CD40L, HGF, MIP-3alpha and MMP-1 were obviously up-regulated, while IL-16 was down-regulated in AIS patients compared to healthy controls. Among them, IL-2R, IL-10, IL-16, MIP-3alpha, and MMP-1 were specially altered in AIS patients, while IL-1beta, IL-2, IL-5, CD40L and HGF were elevated simultaneously in AIS patients and hemorrhagic stroke patients. Interestingly, IL-6 and TNF-beta were found to be key cytokines among the 65 inflammatory factors to distinguish cerebral hemorrhage from ischemia. Furthermore, plasma IL-1beta, IL-16, CD40L and HGF were obviously correlated with the number of lymphocytes, and IL-1beta and IL-16 were significantly associated with the number of neutrophils in AIS patients. These results suggest that lymphocytes and neutrophils associated inflammation may play a pivotal role in AIS.

Conclusions:
These significantly changed inflammatory mediators could serve as biomarkers for AIS diagnosis. More importantly, except for some mutual pathological processes, AIS and hemorrhage had their own distinctive pathogenesis, and transformation of this knowledge to further research may provide novel treatment strategy for AIS.
Abstract TMP20: Cerebrovascular Injury Associated With COVID-19 And Non-COVID-19 Acute Respiratory Distress Syndrome
Authors: Shoskes Aaron , Huang Merry , Hassett Catherine , gedansky aron , Buletko Andrew B , Duggal Abhijit , Uchino Ken , Cho Sung-Min
Published: February 2022

Background:
Neurologic complications of Coronavirus Disease 2019 (COVID-19) may be associated with neurotropism of the virus or secondary brain injury from systemic inflammation. Acute respiratory distress syndrome (ARDS) is associated with cerebrovascular injury, including both ischemia and hemorrhage. We aimed to compare brain MRI findings of COVID-19 associated ARDS with non-COVID-19 ARDS.

Methods:
A registry of patients with COVID-19 from March 2020 through July 2021 from a hospital network was reviewed. Patients who met criteria for ARDS by Berlin definition and underwent MRI during their hospitalization were included. These patients were matched 1:1 by age and sex with patients who underwent MRI from another registry of patients of ARDS in the same hospital between 2010 and 2018. Cerebrovascular injury was classified as either acute cerebral ischemia (ischemic infarct or hypoxic ischemic brain injury) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs).

Results:
Of 13,319 patients with COVID-19 infection, 26 patients had ARDS and MRI. Sixty-six of 678 non-COVID-19 ARDS patients had an MRI and were matched 1:1 by age and sex resulting in 23 matched pairs. The median age was 66 and 59% of patients were male. Patients with COVID-19 ARDS were more likely to have hypertension and chronic kidney disease but otherwise baseline medical characteristics were similar. ARDS severity as determined by PaO2/FiO2 ratio at ICU admission was similar between both groups. No difference was seen in the prevalence of cerebrovascular injury (52% vs 61%, p=0.8), cerebral ischemia (35% vs 43%, p=0.8), ICH (43% vs 48%, p=1.0), or CMBs (43% vs 39% p=1.0) on MRI between the COVID-19 and non-COVID-19 cohorts. However, two unique patterns of injury were seen only among COVID-19 patients: hemorrhagic leukoencephalitis (3 patients, 12%) and bilateral cerebral peduncular ischemia with microhemorrhage (2 patients, 8%).

Conclusion:
Cerebrovascular injury was common in both COVID-19 and non-COVID-19 ARDS without significant frequency difference. However, COVID-19 ARDS had unique neuroimaging patterns that may indicate distinct patterns of brain injury of COVID-19.
Abstract TMP22: Genetic Predisposition To Cardiovascular Disease Is Associated With Higher Risk Of Stroke In Persons With COVID-19
Authors: Both Cameron , Abdelhakim Safa , Acosta Julian , Szejko Natalia , Leasure Audrey C , Jasne Adam , Sharma Richa , Sheth Kevin N , Falcone Guido J
Published: February 2022

Background and Purpose:
Stroke is a serious complication of COVID-19. However, the risk factors for this complication are poorly understood. We hypothesize that genetic predisposition to cardio- and cerebrovascular disease (CVD) leads to an increased risk of stroke in patients with COVID-19 infection.

Methods:
We evaluated data from a nested cohort study conducted within the UK Biobank focused on persons with documented COVID-19. Incident strokes (ischemic and hemorrhagic) were identified by combining inpatient data (including critical care and discharge diagnostic codes) and primary care data, the latter entered by providers within 30 days of a positive COVID-19 test. Genetic predisposition to CVD was evaluated through a polygenic risk score that integrated genomic information on 2,176 independent genetic risk variants for stroke, coronary artery disease and cardiometabolic risk factors. This score was divided into low (0-20
th
percentile), intermediate (20
th
-80
th
percentile), and high (80
th
-100
th
percentile) genetic risk.

Results:
A total of 11,882 study participants (mean age 65.8, SD [8.6], female sex 6,306 [53.1%]) with documented COVID-19 infection were included in this study, including 99 (0.8%) persons that sustained a stroke during the infection. Compared to persons with low genetic predisposition to CVD, those with intermediate and high genetic risk had 35% (OR 1.35, 95%CI 1.14-1.55) and 2.4-fold (OR 2.38, 95% CI 1.71-3.05) higher risk of stroke (test for trend p=0.004). Sub-scoring analyses evaluating one polygenic risk score per CVD trait of interest indicated that genetic predisposition to hypertension (p=0.017) and smoking (p=0.03) were the most important genetic risk factors.

Conclusions:
Genetic predisposition to CVD is associated with a higher risk of stroke in persons with acute COVID-19 infection. Genetic risk factors for hypertension and smoking appear to mediate a significant portion of this association. Genetic information should be considered in the multiple ongoing efforts to create risk-stratification strategies to identify COVID-19 patients at high risk of stroke.
Abstract TMP23: Impact Of Covid-19 On Number Of Acute Stroke Patients In Japan: A Nationwide Survey In Primary Stroke Centers
Authors: Yamagami Hiroshi , Ohara Nobuyuki , IMAMURA HIROTOSHI , Sakai Nobuyuki , Hirano Teruyuki , Hashimoto Yoichiro , Ogasawara Kuniaki , Miyamoto Susumu
Published: February 2022

Background and Purpose:
We sought to investigate the impact of COVID-19 pandemic on number of acute stroke patients admitted to Japanese primary stroke centers (PSCs).

Methods:
The Japan Stroke Society and the MHLW registry of mechanical thrombectomy for acute ischemic stroke conducted a national annual survey of hospitalization volumes for acute ischemic stroke, intracranial cerebral hemorrhage, and subarachnoid hemorrhage in PSCs. Number of acute stroke patients was defined as sum of three stroke subtypes admitted within 7 days after the onset. Monthly acute stroke volumes were compared between 2019 and 2020, among COVID-19 waves, and regional infectious rates.

Results:
The stroke volume data was completed in 530 PSCs. The annual acute stroke volume was declined 2.5% from 179,893 in 2019 to 174,385 in 2020. Number of acute stoke patients was declined during COVID-19 expanding periods (1
st
wave, Mar-May; 2
nd
wave Jul-Aug; 3
rd
wave Nov-Dec), whereas it was increased in the other months. The mean decline rate of stroke volumes from 2019 to 2020 was greater in 125 PSCs located in prefectures with high estimated SARS-CoV 2 infected rate (more than 2,300 per million people) than in 405 PSCs of the other regions (-4.6±15.4% vs -0.1±20.0%, P=0.008), especially during COVID-19 expanding periods (-8.2±17.9% vs -3.1±21.3%, P=0.009).

Conclusions:
Acute stroke volumes were declined in 2020 from 2019 in Japanese PSCs, especially during COVID-19 expanding periods and in highly infected regions. The overwhelmed health care system and infection control practices may have associated with decline of number of acute stroke patients during COVID-19 pandemic.
Abstract TMP41: Local Epidemiology And Diagnostic Results Of Truly Occult Emboli In Patients With ESUS
Authors: Siegler James E , Thau Lauren , Hester Taryn , Yeager Terri , Vigilante Nicholas , Kamen Scott E , Heslin Mark , Shannon Ryan , Zhang Linda E , Butler Miriam , Higham Christopher , Oak Solomon , Wolfe Jared , Patel Parth , Thon Jesse M
Published: February 2022

Introduction:
Ipsilateral nonstenotic (<50%) internal carotid artery (ICA) plaque, cardiac atriopathy, and patent foramen ovale (PFO) may account for a substantial proportion of embolic stroke of undetermined source (ESUS).

Methods:
Consecutive stroke patients at our center (2019-2021) with unilateral, anterior ESUS were categorized into the following mutually exclusive etiologies: (1) nonstenotic ipsilateral ICA plaque (≥3mm), (2) atriopathy (sex-adjusted mod-to-severe atrial enlargement) & (3) PFO. Clinical and diagnostic results were compared between patients in each group, and against those with “true ESUS” (who failed to meet criteria for these 3 groups).

Results:
Of 133 included patients, there was minimal overlap between the mutually exclusive ESUS etiologies (2 having nonstenotic plaque + atriopathy, and 1 having atriopathy + PFO). Older patients more frequently had atriopathy, while patients with PFO had fewer vascular risk factors when compared to the other groups (padj≤0.1; Table). Patients with nonstenotic plaque had more frequent tobacco use (p=0.06), more severe white matter disease (p=0.07), and greater ipsilateral v. contralateral plaque (p<0.01). Twice as many patients with atriopathy presented with an ICA/M1/basilar occlusion (54%) when compared to other groups (p=0.03). Atriopathy was independently associated with older age (ORadj 1.09/year, 95%CI 1.02-1.17) and proximal occlusion (ORadj 16.47, 95%CI 2.86-94.65), with tobacco use associated with a non-atriopathic origin (ORadj 5.56/year, 95%CI 1.07-29.01). Five of 8 patients with atriopathy (63%) monitored with outpatient telemetry had atrial fibrillation, while 3/30 (10%) “true ESUS” and 0/12 (0%) nonstenotic plaque patients had atrial fibrillation.

Conclusions:
Certain clinical and radiographic features may be useful in predicting the proximal source of occult cerebral emboli, and can be used for cost-effective outpatient diagnostic testing.
Abstract TMP42: Prevalence, Awareness, Treatment And Associated Factors Of Depression Among Community-dwelling Stroke Survivors In Korea
Authors: Lee Eungjoon , Kwon Oh Deog , Kim Seung Jae
Published: February 2022

Background and Purpose:
Post-stroke depression (PSD), a prevalent complication of stroke, causes poor outcomes. However, little is known about its prevalence and management among community-dwelling stroke survivors. Thus, we investigated the prevalence, awareness, treatment, and associated factors of PSD in a community setting.

Methods:
A cross-sectional study was performed using representative data from the Korea National Health and Nutrition Surveys 2014, 2016, and 2018. A total of 11,122 participants aged ≥ 40 years were categorized, including 343 stroke survivors and 10,779 non-stroke survivors. We then calculated and compared the prevalence, awareness, and treatment of depression between the two groups. Depression was defined as a score ≥10 in the nine-item Patient Health Questionnaire (PHQ-9). Multivariate logistic regression analyses were performed to examine the predictors of the prevalence, awareness, and treatment of PSD.

Results:
Depression was significantly more prevalent among stroke survivors than in non-stroke survivors (22.2% vs. 8.5%, respectively), while the differences in the awareness and treatment rates were insignificant. Female sex (adjusted odds ratio [aOR], 4.95; 95% confidence interval [CI], 2.17-11.28), lower-income (aOR 0.66, 95% CI 0.44-0.97), poorer self-rated health status (aOR 0.41, 95% CI 0.21-0.80), and limitation in daily activities (aOR 6.40, 95% CI 3.08-13.31) were independent predictors of PSD (Table 1). However, only 46.8% of patients with PSD were aware of their condition, and only 20.5% were receiving treatment. This trend was generally not affected by patients’ characteristics.

Conclusions:
Clinicians should more actively screen for and treat depression among stroke survivors.
Abstract TMP44: The Novel Predictors Of Poor Functional Outcome In Acute Lacunar Infarction By Using Hierarchical Cluster Analysis Of Clinical Variables
Authors: Takahashi Junichiro , Sakai Kenichiro , Okumura Motohiro , Kida Hiroyuki , Maku Takahiro , Nakada Ryoji , Kitagawa Tomomichi , Sato Takeo , Takatsu Hiroki , Komatsu Teppei , Sakuta Kenichi , Mitsumura Hidetaka , Iguchi Yasuyuki
Published: February 2022

Background:
Lacunar infarct (LI) is a heterogeneous disorder of cerebral small vessel. Hierarchical clustering (HC) is useful for exploring potential underlying clinical phenotype in heterogeneous disease. Our aim is to identify the predictive factors of poor functional outcome in LI to classify the subjects into distinct subgroups using HC and compare the clinical variables including clinical outcome among groups.

Methods:
From October 2012 to April 2020, LI patients within 24 hours from the onset were enrolled. We used a HC k-means clustering algorithm on patients’ baseline data. We also compared clinical outcome among each cluster groups.

Results:
Among 187 patients (144 male, median age 66 years old, median NIHSS score2), three clusters were identified. Cluster1(58%), mostly comprised of younger patients (p<0.01), had fewer past history of ischemic stroke (p=0.007). The severity of deep subcortical white matter hyperintensity (DSWMH) and periventricular hyperintensity (PVH) were mild, and small number of cerebral microbleeds (MBs) are detected (p<0.001 for each). Cluster2(15%), mostly comprised of older patients (p<0.001), had the highest NIHSS score on admission (p=0.021). Serum D-dimer and Cr levels were relatively higher (p<0.001, p=0.003, respectively). Cluster3(28%), mostly comprised of men, represented the highest number of MBs (p<0.001) and increase of mean IMT (p =0.003). Poor functional outcome defined as mRS at 3 months > 2-6 was 4% of cluster1, 100% of cluster 2 and 12% of cluster 3 (p=0.001). In multivariate logistic regression analysis, the phenotype of cluster was the strongest predictor of poor functional outcome (OR 16.1, 95% CI 6.04-42.9, p<0.001, Figure).

Conclusion:
Three clusters with different clinical outcome were identified. The phenotype of cluster was the strongest predictive factor of poor functional outcome. Further study to identify whether management of these components provide different clinical outcome was warranted.
Abstract TMP48: Effects Of Telestroke On Endovascular Therapy Timeliness And Outcomes
Authors: Yan Zhiyu , Viswanathan Anand , Estrada Juan J , Singhal Aneesh , Etherton Mark R , Schwamm Lee H , Zachrison Kori S
Published: February 2022

Backgrounds:
Telestroke is associated with improved reperfusion and improved outcomes for stroke patients. Our objective was to examine the effect of telestroke on procedural timeliness and outcomes among patients transferred for endovascular therapy (EVT).

Methods:
We identified all EVT encounters at our urban, telestroke-enabled, academic comprehensive stroke center (CSC) from 1/1/2017 to 12/31/2020 in our institutional Get With The Guidelines-Stroke registry linked with our telestroke consultation records. EVT encounters were categorized based on mode of arrival: i) transferred via the telestroke network (Tx+TS), ii) transferred without telestroke (Tx-TS), or iii) directly presenting to the CSC (DP). The three groups were then compared on efficacy and safety measurements including first-pass rate, successful reperfusion (TICI 2b/3) and post-procedure complications, as well as mortality and functional independence (mRS ≤ 2) outcomes both at discharge and 90-day post discharge using multi-group testing.

Results:
After excluding 29 encounters with unknown arrival mode, our sample of 287 EVT encounters included 168 Tx+TS cases, 35 Tx-TS cases, and 84 DP cases. Patients’ demographics and baseline characteristics (NIHSS at admission and prior comorbidities) were balanced across the groups (Table). Compared to both Tx-TS and DP, Tx+TS has significantly shorter door to puncture time (Tx+TS: 30 mins vs. Tx-TS: 62 mins vs. DP: 92 mins, p < 0.001). Procedural efficacy and safety, in-hospital outcomes and post discharge outcomes were similar across groups.

Conclusion:
Our study demonstrates that telestroke plays an important role among patients transferred for EVT with improved procedural timeliness, and outcomes similar to those of directly presenting patients.
Abstract TMP54: Race-ethnic Disparities In Inpatient Insertable Cardiac Monitor Placement After Ischemic Stroke
Authors: Yaghi Shadi , Furie Karen L , Wechsler Lawrence R , Mullen Michael T , Stretz Christoph , Burton Tina , de Havenon Adam H
Published: February 2022

Background and Purpose:
Cryptogenic stroke accounts for 30% of ischemic stroke and in such patients, cardiac monitoring leads to increased detection of AF, increased utilization of anticoagulation, and decreased risk of recurrent stroke. We aim to identify differences in inpatient utilization of implantable cardiac monitors (ICMs) in patients with ischemic stroke.

Methods:
This is an analysis of the National Inpatient Sample. We included all ischemic stroke hospitalizations nation-wide between Jan 1
st
2016 and Dec 31
st
2018. We excluded patients with history of atrial fibrillation or atrial flutter. We compared survey weighted baseline demographics and characteristics between patients who received an inpatient ICM versus those who didn’t using logistic regression models.

Results:
We identified a weighted total 1,069,395 patients who met the inclusion criteria; 2.2% received an inpatient ICM. In multivariable analyses, factors associated with decreased odds of inpatient ICM placement including Black race (OR 0.76 95% CI 0.68 - 0.84, p < 0.001), residence in a micropolitan area (OR 0.79 95% CI 0.67 - 0.94, p = 0.008), hospital region [Midwest (OR 0.74 95% CI 0.61 - 0.90, p = 0.002), South (OR 0.68 95% CI 0.57 - 0.81, p < 0.001), and West (OR 0.37 95% CI 0.29 - 0.45, p < 0.001)], hospital bed size [small (OR 0.38 95% CI 0.39-0.46, p < 0.001) and medium hospital bed size (OR 0.73 95% CI 0.63 - 0.84, p < 0.001)], insurance status [Medicaid (OR 0.86 95% CI 0.76 - 0.98, p = 0.02) and self-pay (OR 0.51 95% CI 0.41 - 0.62, p < 0.001)], and non-teaching hospital (OR 0.52 95% CI 0.47 - 0.60, p < 0.001).

Conclusions:
There are important differences in inpatient ICM placement in patients with ischemic stroke highlighting disparities in inpatient care for patients hospitalized with ischemic stroke. More studies are needed to validate our findings.
Abstract TMP8: The Feasibility Of Machine Learning In Predicting Intracranial Aneurysm Rupture Risk
Authors: Yang Runlin , Kebria Parham Mohsenzadeh , Ren Yifan , Hall Jonathan , Michelle Foo , Zhou Kevin , Maingard Julian , Kok Hong , Khosravi Abbas , Asadi Hamed
Published: February 2022

Background:
Intracranial aneurysm (IA) is one of the most common causes of subarachnoid hemorrhage which is associated with high mortality and morbidity. Predicting aneurysms’ rupture risk has been an ongoing challenge clinically. The objective of this study is to utilize machine learning algorithms to predict IA’s rupture status based on simple parameters that can be measured in the daily clinical setting.

Methods:
A total of 448 IA cases with known rupture status (228 unruptured and 220 ruptured) were collected across three tertiary hospitals between November 2017 and November 2020. Twelve demographic and morphological parameters were obtained from all cases. Six machine learning models, namely Naive Bayes, Support Vector Machine, K-Nearest Neighbours, Gradient Boosting, Decision tree and Random Forest algorithms were applied to the dataset. Sensitivity, specificity and accuracy of each model was calculated along with Area Under the Curve (AUC) and F1 score. Furthermore, the relevant importance of all 12 variables was assessed.

Results:
Gradient Boosting and Random Forest algorithms were the ML algorithms with the highest AUC of 0.69, followed by Naive Bayes (AUC=0.66). Overall, Random Forest algorithm was the best-formed model with 67% sensitivity and 63% specificity. Support Vector Machine model gave the lowest favorable AUC of 0.45 with 45% sensitivity and 48% specificity. The most significant variable was the aneurysm neck width, followed by the parent artery diameter.

Conclusions:
Machine learning has the potential to assist with the IA’s rupture prediction by using simple variables that can be easily obtained in clinical practice. Further research, especially a larger sample size is required to improve diagnostic accuracy before its clinical translation.
Abstract TMP99: Genetics Of Stroke Of Undetermined Source: Overlap With Known Stroke Etiologies And Associations With Modifiable Risk Factors
Authors: Georgakis Marios K , Parodi Livia , Frerich Simon , Mayerhofer Ernst , Malik Rainer , Dichgans Martin ,   NINDS Stroke Genetics Network (SiGN), Rosand Jonathan , Anderson Chris D
Published: February 2022

Introduction:
Stroke etiology remains unknown in 30% of cases, hindering secondary prevention efforts. We leveraged human genetic data in order to identify evidence of overlap between stroke of undetermined source and defined stroke etiologies as well as causal relationships with modifiable risk factors.

Methods:
We analyzed genome-wide data from 16,851 ischemic stroke cases and 32,473 controls from the NINDS Stroke Genetics Network with TOAST- and CCS-defined subtypes. Using genetic risk scores for large artery, cardioembolic, and small vessel stroke (LAS, CES, SVS) we assessed the degree of overlap with stroke of undetermined source and used pairwise GWAS to search for shared loci. We then applied Mendelian randomization (MR) to identify causal risk factors for stroke of undetermined source.

Results:
There was significant overlap between stroke of undetermined source and all defined stroke subtypes at a genome-wide and locus level (19 shared loci with LAS, 2 with CES, 5 with SVS). Shared loci pointed to altered gene expression in arterial tissue and blood and atherosclerosis-related mechanisms. Further, genetically predicted carotid intima media thickness was associated with stroke of undetermined source. While genetic liability to atrial fibrillation also showed a significant association, this was attenuated in analyses excluding cases with incomplete diagnostic workup. MR analyses showed significant associations in blood pressure, diabetes, waist-to-hip ratio, inflammatory pathways (IL-6 signaling, MCP-1 levels), and elevated factor XI levels with stroke of undetermined source (Figure).

Conclusion:
These analyses suggest that stroke of undetermined source shares genetic and modifiable risk factors with defined stroke subtypes. Together, they raise the hypothesis that refinement of current subtyping approaches can reduce the proportion of cases classified as undetermined and optimize secondary prevention strategies.
Abstract TP100: Frequency, Spatial Distribution And Associations To Clinical Characteristics Of Multiple Lesions In A Large Multi-center Dataset Of Acute Ischemic Stroke Patients
Authors: Bonkhoff Anna K , Hong Sungmin , Bretzner Martin , Schirmer Markus D , Giese Anne-Katrin , Donahue Kathleen , Nardin Marco , Etherton Mark R , Regenhardt Robert , Wu Ona , Jern Christina , Lindgren Arne , Maguire Jane , Ullberg Teresa , Frid Petrea , Rost Natalia S , Wasselius Johan ,   on behalf of the MRI-GENIE and GISCOME Investigators and International Stroke Genetics Consortium
Published: February 2022

Introduction:
About ~10% of acute ischemic stroke (AIS) patients experience multiple acute lesions (MAL). However, the spatial distribution and clinical implications of such MAL are incompletely understood. Here, we scrutinized MAL in a large, radiologically deep-phenotyped cohort of AIS patients.

Methods:
We analyzed imaging and clinical data of 2.485 AIS patients [age: 63.3±14.8, 39%women] of the multi-site MRI-GENIE study. We computed occurrences of (i) MAL within one and, (ii) MAL in several vascular supply territories (with single or multiple lesions within single territories). We furthermore evaluated associations between the presence of MAL in multiple territories and stroke severity, white matter hyperintensity (WMH) and stroke lesion volumes, etiology, age and sex.

Results:
Half of all patients, i.e., 49.7%, presented with a single lesion. Another 37.3% experienced MAL in a single vascular territory, while 13% featured lesions in multiple vascular territories. For most vascular territories (anterior, middle and posterior cerebral artery, cerebellum) the ratio between single to multiple lesions in that territory equaled ~52%, only the brainstem region comprised fewer multiple compared to single lesions (19%). Combinations of anterior and posterior circulation lesions occurred in 5.6% of all patients, bilateral stroke in the anterior circulation in 3.4%. When comparing patients with lesions in only one compared to in more than one territory, there were no significant differences in WMH or lesion volume, stroke severity, age or sex (

p
FDR-corrected

>0.05). Patients with lesions in multiple territories had a significantly lower frequency of small vessel occlusions, but a significantly higher frequency of stroke of undetermined etiology. Differences in cardioembolic stroke frequency were only significant before correction for multiple comparisons (

p
uncorrected

=0.025). Frequencies of large vessel occlusions did not differ between the groups.

Conclusions:
Multiple lesions, especially those within one vascular territory, occurred frequently. Overall, there were no significant associations between MAL and stroke severity or cardioembolic stroke. Future studies are warranted to explore these findings in greater detail.
Abstract TP11: G-quadruplexes Regulate The Senescence Factor Cysteine-rich Angiogenic Inducer-61 In Primary Cerebral Endothelial Cells
Authors: Moruno-manchon Jose F , Noh Brian , McCullough Louise
Published: February 2022

Senescence in the cerebral endothelium has been proposed as a mechanism that can drive dysfunction of the cerebral vasculature, which precedes vascular dementia. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) is a matricellular protein secreted by cerebral endothelial cells (CEC). CCN1 induces senescence in fibroblasts. Whether CCN1 contributes to senescence of CEC and how it is regulated require further study. Aging has been associated with the formation of four-stranded Guanine-quadruplexes (G4s) in G-rich motifs of DNA and RNA. G4 stabilization regulates transcription and translation either by upregulation or downregulation depending on the gene target. Previously, we showed that aged mice treated with a G4-stabilizing compound had enhanced senescence-associated (SA) phenotypes in their brains, and exhibited cognitive deficits. The expression of human
CCN1
can be upregulated via the stabilization of G4s. A sequence in the 3’- untranslated region (UTR) of the
CCN1
mRNA has the ability to fold in to G4
in vitro
. Thus,
we hypothesize
that CCN1 is upregulated with aging and induces senescence, and that G4 stabilization upregulates CCN1 in cultured primary CEC.
We used
whole brain lysates, cerebral vessel fractions, and cultured primary CEC from young (4-months old, mo) and aged (18-mo) female mice to determine the CCN1 levels. SA phenotypes were determined by high-resolution fluorescence microscopy in cultured primary CEC, and we used Thioflavin T to recognize RNA G4s for fluorescence spectra.
We found
that CCN1 levels were increased in the brains of aging mice (p=0.0314, n=5), in cerebral vessel fractions (p=0.001, n=5), and in cultured primary CEC derived from aged mice (p=0.012, n=3), compared with those derived from young mice. In cultured CEC, a recombinant CCN1 protein induced SA phenotypes, such as SA beta-galactosidase activity (p=0.003, n=3), and double-strand DNA damage (p=0.016, n=3). Furthermore, CCN1 levels were upregulated by a G4 ligand (p=0.0103, n=3), and a G-rich motif in the 3’-UTR of the
Ccn1
mRNA folded into a G4 (p=0.008, n=4).
In conclusion
, we demonstrate that CCN1 induces senescence in cultured primary CEC, and we propose G4 stabilization as a novel mechanism that regulates the SASP component CCN1.
Abstract TP112: Racial Differences In Palliative Care Utilization And Impact On Inpatient Mortality Length Stay And Costs Among Patients With Ischemic Stroke
Authors: Chaudhry Mohammad Rauf , Kherani Danish , Fadah Kahtan , Chaudhry Saqib A , Singh Baljinder , Kausar Naila , Moreno Jorge , Ghatali Mohammad , Vellipuram Anantha Ramana , Maud Alberto , Piriyawat Paisith , Sheriff Faheem , Rodriguez Gustavo , Cruz-Flores Salvador
Published: February 2022

Background and Purpose:
Palliative is increasingly used in critically ill patients which has lead to shorter length of stays, higher inpatient mortality and lower utilization of aggressive treatment. We performed analysis to evaluate trends in utilization of palliative care among patients with Ischemic Stroke and its effect on in-hospital outcomes over a 10-year period.

Methods:
We obtained data for patients admitted to hospitals in the United States from 2009 to 2018 with a primary diagnosis of Ischemic stroke (IS) using a large national database. We determined the overall and among different races, rate of utilization of palliative care in patients with IS and associated in-hospital outcomes consisting of mean hospital charges, mean length of stay and in-hospital mortality.

Results:
Out of 5525248 patients admitted with primary diagnosis of IS, palliative care was used in 150301 (2.72%). There was a 1.05-fold utilization of PC (1.69% in 2009 vs 1.78% in 2018; p<0.001) from 2009 till 2018. Similarly, there were 1.003, 1.4, 1.04 and 1.05-folds increase in utilization of PC among different races: whites, blacks, hispanics and others respectively, p<0.001. Overall rates of PC utilization among different races: whites, blacks, hispanics and others were: 3.0%, 1.6%, 2.03% and 2.69%, p<0.001 respectively. The length of hospitalization remained significantly higher (6.0±7.4 versus 3.8±5.2, p<0.001) in patients undergoing PC compared those who did not. The cost of hospitalization remained significantly higher ($55068 ± 84630 versus $ 40148 ± 53479, p<0.001) in patients undergoing PC compared with those who did not. Patients with PC utilization had significantly higher (42.9% versus 1.56%, p<0.001) in-hospital mortality compared ones with out.

Conclusions:
Between 2009 and 2018, there has been a significant increase in utilization of PC among patients with IS along with longer length of stay and higher hospital charges. Patients with PC had significantly in-hospital morality. The findings in this IS population are paradoxical to what has been seen in other critical illnesses which may be related to differences in natural history.
Abstract TP114: High Prevalence Of Acute Cerebrovascular Injury On Brain Magnetic Resonance Imaging In Acute Respiratory Distress Syndrome
Authors: Huang Merry , gedansky aron , Hassett Catherine , Shoskes Aaron , Duggal Abhijit , Uchino Ken , Cho Sung-min C , Buletko Andrew B
Published: February 2022

Background:
Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory respiratory failure condition that may be associated with secondary cerebrovascular injury. We aimed to describe the prevalence and types of cerebrovascular injuries detected by brain MRI among ARDS patients.

Methods:
We reviewed a single-center ARDS registry data from a tertiary medical center from January 2010 to October 2018. Patients who underwent brain MRI during their index hospitalization were identified. MRIs were reviewed by two independent reviewers. Acute cerebrovascular injuries were classified as acute cerebral ischemia (ischemic infarct and hypoxic ischemic brain injury [HIBI]) or intracranial hemorrhage (ICH) including intraparenchymal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and cerebral microbleeds (CMBs). Descriptive statistics were conducted.

Results:
Of the 678 ARDS patients, 66 (9.7%) underwent brain MRI during their ARDS illness. The median time from hospital admission to MRI was 10 days (interquartile range 4-17). Of 66, 31 (47%) had MRI evidence of acute cerebrovascular injuries including acute cerebral ischemia in 33% (22/66) and ICH in 21% (14/66). Among those with cerebral ischemia, common findings were bilateral globus pallidus infarcts (n=7), multifocal ischemic infarcts (n=5), and HIBI (n=3). Twelve (86%) with CMBs constituted the most common type of ICH, followed by intraparenchymal hemorrhage (14%). Patient demographics, Charlson Comorbidity Index, or disease severity as measured by the presence of sepsis/sepsis shock, cardiac arrest, extracorporeal membrane oxygenation use, admission Acute Physiology and Chronic Health Evaluation III Score, Sequential Organ Failure Assessment Score, or admission PaO
2
/FiO
2
ratio did not differ among patients with and without cerebrovascular injury including cerebral ischemia or ICH. In-hospital mortality was significantly greater in ARDS patients with acute cerebral ischemia compared to those without ischemia (55% vs 27%, p=0.03).

Conclusion:
Among selected patients with ARDS who underwent brain MRI, a half had secondary cerebrovascular injury including acute cerebral ischemia and CMBs.
Abstract TP115: Variability Of Transcranial Doppler Criteria In The Determination Of Cerebral Circulatory Arrest
Authors: Darwish Sonja , Pereira Benedict , Schlick Konrad
Published: February 2022

Introduction:
Transcranial Doppler (TCD) is a commonly used testing modality in the diagnosis of cerebral circulatory arrest (CCA). There is currently no consensus in the United States for which vessels must be insonated to establish a CCA diagnosis. We evaluated TCD-CCA studies using four categories of vessel selection to determine which set of criteria would be most restrictive.

Methods:
We reviewed all TCD studies from our center that were performed for the evaluation of CCA. For each study, two readers determined whether the bilateral middle cerebral arteries (MCA) and the basilar artery demonstrated a pattern typical of CCA. In cases where one or more of these three primary vessels could not be located, specific proximal vessels were evaluated and used as a surrogate. Surrogate vessels for the MCAs included the ipsilateral carotid siphon and the terminal internal carotid artery. Surrogate vessels for the basilar artery required the evaluation of both intracranial vertebral arteries. A diagnosis of CCA was given according to four different criteria: absent diastolic flow in [1] bilateral MCAs and the basilar artery, [2] bilateral MCAs only, [3] the three primary vessels or a surrogate vessel when a primary vessel could not be located, and [4] bilateral MCAs or a surrogate vessel when either MCA could not be located.

Results:
Fifty-five TCD studies were included in this analysis. Of these, 17 studies were not able to insonate one of the three primary vessels. Seven of these incomplete studies included surrogate vessels for the absent primary vessel. When all three primary vessels were insonated, 17 studies were consistent with CCA. Twenty-four studies met CCA criteria when only the MCAs were evaluated, 19 studies met criteria when the primary vessels or a surrogate vessel were evaluated, and 26 studies met criteria when only the MCAs or their surrogate vessels were evaluated.

Conclusion:
The results of this analysis suggest that when different criteria for CCA are applied, the rates of CCA diagnosis change considerably. Since CCA is often a critical part of establishing death by neurologic criteria, it is important that national standards for a TCD protocol are established.
Abstract TP12: Biological Age For Prediction Of First-ever Intracerebral Hemorrhage And Cerebral Infarction In Advanced Age
Authors: Waziry Reem , Hofman Albert , Ghanbari Mohsen , Tiemeier Henning , Ikram Mohammad A , Viswanathan Anand , Klap Jaco , Ikram Kamran , Goudsmit Jaap
Published: February 2022

Introduction:
Successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease.

Methods:
The predictive value of biological age (BA) was assessed as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age. BA was also compared with commonly used biomarkers including tau and Aβ40 and Aβ42. The study included Individuals who consented for blood draw and follow-up in the Rotterdam Study. Biological age was computed using structural equation modelling. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel’s C and Area under the receiver operating characteristic curve.

Results:
The sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HR
BA-ICH:
2.30, 95% CI: 1.20, 4.30; HR
CA-ICH:
1.40, 95% CI: 0.76, 2.53) and higher precision with CI (HR
BA-CI:
1.30, 95% CI: 1.01,1.75; HR
CA-CI:
1.90, 95% CI: 1.48, 2.66). BA outperformed CA for prediction of ICH (AUC: 0.68 vs 0.53; Harrel’s C: 0.72 vs 0.53) and for CI (AUC:0.63 vs 0.62; Harrel’s C: 0.68 vs 0.67).

Conclusion:
Biological aging based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age. Wider applicability requires extension of such findings from the general population to the clinical and primary care settings.
Abstract TP120: The Impact Of Stroke On Cost And Length Of Stay After Cardiac Surgery.
Authors: Messe Steven R , Kasner Scott E , Mullen Michael T , Cummings Stephanie , Leibowitz Lee , Weimer James , Desai Nimesh , Acker Michael A
Published: February 2022

Introduction:
Stroke after cardiac surgery is associated with poor outcome but there are limited data on the impact on cost and length of stay (LOS).

Methods:
We performed a retrospective matched cohort study of patients who underwent cardiothoracic surgery at our tertiary referral center, identifying 44 strokes and 568 non-stroke controls matched by procedure and age (within 5 years of the max and min of stroke patients). Stroke severity was assessed by NIHSS.

Results:
The cohorts were well-matched, 34% of the stroke patients were female, compared to 37% of controls without stroke, p=0.71. Patients with stroke were younger than patients without stroke, median 68 vs 74 years, p=0.008. Strokes were severe, median NIHSS was 18 (interquartile range [IQR] 9 - 29). Patients with stroke had a higher risk of in-hospital mortality, 25% vs 9.5%%, OR 3.2, 95% CI 1.5 - 6.6, p=0.002 and were less likely to be discharged home 11% vs 63%, OR 0.06, 05% CI 0.02 - 0.016, p<0.0001. Mortality was associated with higher stroke severity, with median NIHSS 30 for patients who died compared to 16 for survivors, p=0.005. Stroke was associated with large increases in direct and indirect costs, as well as LOS (Table). Excluding patients who died (which may shorten LOS), stroke severity was associated with both total and ICU LOS in univariable linear regression: Every 1-point increase in NIHSS was associated with 1.1 additional hospital days (95%CI 0.1 - 2.1 days), p=0.03, including 0.8 days (95%CI 0.2 - 1.5 days) in the ICU, p=0.01.

Conclusions:
Stroke complicating cardiac surgery is associated with enormous increases in cost and length of stay, which is related to stroke severity.
Abstract TP127: Hypertension Provokes Development Of Cerebral Microhemorrhages In A Mouse Model
Authors: Fang Chuo , Lau Wei Ling , Vallejo Adrian , Liu Jihua , Liu Han , Paganini-Hill Annlia , Cribbs David H , Fisher Mark
Published: February 2022

Introduction:
Cerebral microhemorrhages (CMH) are the pathological substrate for cerebral microbleeds, represent focal hemosiderin deposits on MRI, and are associated with increased risk of cognitive impairment and ischemic and hemorrhagic stroke. Aging and hypertension are the most common risk factors for cerebral microbleeds. In this study, we analyzed the effect of hypertension on the development of CMH in a mouse model of aging.

Methods:
Hypertension was induced in aged (17 months old) female and male C57BL/6J mice, via infusion of angiotensin II (ATII) at 1000 ng/kg/min via Alzet pump over four weeks. We further examined underlying mechanism by inhibiting ATII type 1 receptor (AT1R) with telmisartan, via drinking water for 4 weeks. We collected mouse brains and performed standard histology using Prussian blue staining to detect CMH formation at 20x magnification. We also examined correlations between CMH burden and systolic (SBP) and diastolic (DPB) blood pressures.

Results:
ATII infusion induced significant increases in SBP (121±4 mmHg to 159±6 mmHg; p<0.001) and DBP (94±4 mmHg to 129±7 mmHg; p<0.001). Telmisartan completely blocked ATII-induced blood pressure elevation. Hypertension increased the number of CMH (p=0.01) in male and female mice. In animals with ATII infusion, number of CMH were positively correlated with SBP (r=0.45, p=0.02) and DBP (r=0.47, p=0.01). Telmisartan reduced by 55% the number of ATII-induced CMH, but compared to controls, CMH number remained elevated (p=0.03) in telmisartan-treated animals.

Conclusions:
ATII-induced hypertension promotes the development of CMH in aged mice in a manner that appears dependent on the extent of hypertension. However, in the presence of ATII with ATIR blockade, CMH develops even in the absence of hypertension. These findings emphasize the importance of presence and extent of hypertension in development of CMH in aging, as well as the significance of non-AT1R-mediated pathways independent of hypertension in ATII-induced CMH.
Abstract TP13: Beneficial Effects Of Exercise On Functional Outcome After Ischemic Stroke: A New Insight On Astrocytes Activation And Cellular Crosstalk
Authors: Li Fengwu , Bai Shangying , Geng Xiaokun , Ding Yuchuan
Published: February 2022

Introduction:
It has been recognized that astrocytes potentially affect the recruitment and function of neurons, and the interactions among astrocytes, microglia and neurons modulate neuroplasticity and neural circuit function. The present study attempted to explore whether astrocytes activation and cellular crosstalk were involved in neuroplasticity and neurorehabilitation.

Methods:
Sprague-Dawley adult rats were subjected to 2 h middle cerebral artery occlusion followed by reperfusion. Treadmill exercise (15m/min) was initiated 24 h after reperfusion for up to 21 days. Rats were assigned to groups entailing post-stroke rest or exercise for 30 min. Motor and cognitive functions were tracked. Western blotting was used to assess the proteins expression for neuroplasticity, including GAP-43, PSD-95 and BDNF. Immunofluorescence was used to assess astrocyte proliferation. Primary cells co-cultivation were used to determine the interaction of astrocyte and microglia by IL-33/ST2 interplays, and interaction of microglia and neuron by BDNF/TrkB interplays. The interactions affected by exercise were detected by Co-IP in ischemic rats. Besides, D-serine release by ELISA and NMDAR receptor expression were used to assess astrocyte-neuron direct communication.

Results:
Physical exercise significantly induce neuroplasticity and functional outcomes in ischemic rats, in association with astrocyte proliferation. Exercise induced IL-33/ST2 and BDNF/TrkB interplays in rats, suggesting the increasing astrocyte-microglia and microglia-neuron crosstalk. Exercise significantly increase astrocyte D-serine release and neural NMDAR expression, indicating the direct crosstalk in astrocyte and neuron. Primary cells co-cultivation further demonstrated the IL-33/ST2 interplays showing astrocyte-microglia crosstalk and BDNF/TrkB interplays showing microglia-neuron communication.

Conclusion:
These findings indicated beneficial effects of long-term treadmill exercise on neuroplasticity and functional outcome. Importantly, the results showed astrocyte activation and interaction with microglia and neuron in the biochemical processes underlying the exercise-induced post-stroke neuroplasticity and neurorehabilitation.
Abstract TP134: Association Of Neutrophil-lymphocyte Ratio With Functional Outcome In Spontaneous Intracerebral Hemorrhage
Authors: Atillasoy Jem , Leasure Audrey C , Schwartz Anna , Reznik Michael E , Moody Scott , Bevers Matthew B , Matouk Charles , Falcone Guido J , Sansing Lauren H , Kimberly W Taylor T , Sheth Kevin N
Published: February 2022

Introduction:
Neutrophil-to-lymphocyte ratio (NLR) is a marker of acute inflammation after brain injury. We sought to evaluate the relationship between NLR at admission and 3-month outcome in patients with spontaneous intracerebral hemorrhage (ICH).

Methods:
We pooled individual level data from 2 prospective ICH cohorts, the Acute Brain Injury Biorepository at Yale and Brown ICH registry. We included patients with ICH who had available NLR at admission (exposure of interest) and 3-month modified Rankin Scale (mRS). The primary endpoint was poor outcome at 3-months, defined as mRS 4-6. In each cohort, we fit multivariable logistic regression models to test for association between NLR (natural log transformed and quartiles) and 3-month mRS. Multivariable models were adjusted for sex and components of the ICH score. We then pooled study-specific results using a random-effects (with inverse variance-weighting) meta-analysis.

Results:
592 patients from Brown (69 years [SD 14], 47% female), and 107 patients from Yale (67 years [SD 14], 49% female) were included in the analysis. In the Brown cohort, average ICH volume was 9 cc and 64% of patients had lobar ICH. In the Yale cohort, ICH volume was 10.7 cc and 51% of patients had a lobar ICH. The NLR at admission was 8.21 [SD 9.39] in the Brown cohort and 6.98 [SD 11.35] in the Yale cohort (p=0.230). In the Brown cohort, NLR was associated with poor 3-month outcome in unadjusted (OR 1.28, 95% CI 1.06-1.54, p = 0.01) and adjusted analyses (OR 1.27, 95% CI 1.03-1.57, p = 0.03). In the Yale cohort, NLR yielded similar results in unadjusted (OR 1.80, 95% CI 1.11-2.92, p = 0.02) and adjusted analyses, although not statistically significant (OR 1.90, 95% 0.64-5.63, p = 0.24). Random effect models showed a consistent association in both unadjusted (OR 1.41; 95% CI, 1.04-1.90; p = 0.025; heterogeneity I
2
=40%; Q=1.67, p=0.2) and adjusted analyses (OR 1.29; 95% CI, 1.05-1.59; p=0.016; heterogeneity I
2
=68%; Q=0.49, p=0.48). Compared to the lowest quartile, the highest quartile of NLR had a 20% increase in the odds of having a poor outcome at 3 months (p=0.03).

Conclusions:
In a pooled study of two prospective cohorts, NLR was associated with poor functional outcome at 3 months. Future studies are needed to further evaluate NLR as a prognostic marker.