bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP163: Exome Array Analysis of Ischemic Stroke in a South Swedish Population
Authors: Söderholm Martin , Almgren Peter , Jood Katarina , Stanne Tara , Olsson Maja , Illinca Andrea , Andsberg Gunnar , Norrving Bo , Engström Gunnar , Melander Olle , Jern Christina , Lindgren Arne
Published: March 2022

Background:
Genome-wide association (GWA) studies have identified a few risk loci for ischemic stroke. Yet, these variants can explain only a small part of the genetic contribution to the disease. Coding variants associated with amino acid substitutions or premature termination of protein synthesis could have a large effect on disease risk. We performed an exome array analysis of rare coding variants for ischemic stroke.

Methods:
Patients with ischemic stroke (n=2,385) and control subjects (n=6,077) from three Swedish studies were genotyped with the Illumina HumanOmniExpressExome BeadChip. Single-variant association analysis was performed of non-synonymous variants with minor allele frequency <5% (n=33,130). A separate genome-wide association (GWA) analysis was also performed, based on 700,000 genotyped common markers and subsequent imputation according to 1000 Genomes.

Results:
No variant in the exome analysis was significantly associated with ischemic stroke after Bonferroni correction (all p>1.5x10-6). The two strongest associations were found for missense variants in the genes DNAH11 (odds ratio: 0.14 [95% confidence interval: 0.05-0.41], p=2.9x10-4), and ATF6 (odds ratio: 2.03 [1.38-2.98], p=3.6x10-4). The GWA analysis showed that the sample was homogenous (median genomic inflation factor=1.006). No genome-wide significant association with overall ischemic stroke risk was found (all p>5x10-8). However, previously reported associations for the PITX2 and ZFHX3 gene loci with the subtype cardioembolic stroke were replicated (p=7x10-15 and 6x10-3).

Conclusion:
None of the coding non-synonymous genetic variants reached the pre-defined significance level in this exome array analysis for ischemic stroke. Further studies on exome variation should be performed in even larger samples to identify novel genetic risk factors.
Abstract TP166: A Population-based Study of the Incidence of Primary and Secondary Spinal Cord Infarction
Authors: Afzal Mohammad Rauf , Chugtai Morad , Qureshi Mushtaq H , Suri M. Fareed K , Qureshi Adnan I
Published: March 2022

Background:
There is a paucity of reliable data regarding epidemiology of spinal cord infarction in population-based studies.

Objectives:
To determine the incidence of spinal cord infarction using a population-based design.

Methods:
Medical records and neuroimaging data of all patients with spinal cord infarction from Stearns and Benton Counties, Minnesota, between January 1st, 2010 and May 31st, 2014 were reviewed. Patients with a first-time diagnosis of spinal cord infarction were categorized as primary or secondary depending upon underlying etiology was identified. We calculated the incidences of primary and secondary spinal cord infarction adjusted for age and sex based on the 2010 US census. The severity of deficits at presentation were classified according to ASIA Impairment Scale (AIS).

Results:
A total of 8 spinal cord infarctions were identified among 136,654 resident populations, 5 were primary spinal cord infarctions in this population-based study. Three secondary spinal cord infarctions were observed secondary to aortic graft placement, embolic phenomenon and aortic arterial disease. The severity of deficits based on AIS were B(n=2), C(n=3) and D(n=3). The age- and sex-adjusted incidence of spinal cord infarction was 1.33 [95% confidence interval (CI) 0.6 -2.5] per 100, 000 person-years. The age- and sex-adjusted incidence of primary and secondary spinal cord infarction was 0.83 [95% confidence interval (CI) 0.3 - 1.8] and 0.49 [95% confidence interval (CI) 0.1 - 1.3 per 100, 000 person-years. The location of infarction was classified as cervical, (c7-t1 in 1, c7-t6 in 1 , c7-t2 in 1 ) thoracic (t8 in 1, t10-t11 in 1, t9 level to conus medullaris in 1, t10 level to conus medullaris in 1) and lumbar( L1 in 1.) patients respectively. No case fatality was observed at 1 month.

Conclusions:
We provide incidence rates for spinal cord infarction to assist in further studies and resource allocation.
Abstract TP169: Temporal Trends and Outcomes of Acute Ischemic Stroke in Patients With Human Immunodeficiency Virus Infection
Authors: Patel Urvish , Simpson David M , Dhamoon Mandip S
Published: March 2022

Introduction:
Human Immunodeficiency Virus (HIV) infection is associated with acute ischemic stroke (AIS) and HIV incidence is increasing yearly. Neurological complications (NC) are common in HIV and may increase stroke risk, but no large population based studies have studied NC in HIV and the HIV-AIS association.

Hypothesis:
We hypothesized that: HIV prevalence among AIS is increasing over time; HIV is associated with worse outcomes and greater cost in AIS; and NC increases risk of AIS.

Methods:
In the Nationwide Inpatient Sample database (years 2000-2011), adult hospitalizations for AIS, HIV and NC were identified by ICD-9-CM codes; the analytic cohort constituted all AIS hospitalizations. We performed weighted analysis using chi-square, t-test, Jonckheere trend test, and the Wilcoxon rank-sum test.

Results:
Among 5,224,074 AIS hospitalizations, 8277(0.16%) had HIV. Those with HIV, compared to without, were more often younger (median 49 vs. 72 years; p<0.001), male (69.0% vs. 45.5%; p <0.001) and Black (59.5% vs. 15.8%; p<0.001). AIS with HIV was associated with discharge to skilled nursing facilities and intermediate care facilities (48.7% vs. 43.3%; p<0.001), lower use of Medicare/Medicaid (69.1% vs. 74.6%; p<0.001), and increased length of stay (+3 days; p<0.001) and cost (+$6714; p<0.001). Among those with HIV and AIS, only 5.6% had concurrent NC (p<0.001), including CMV encephalitis (1.45%), neurosyphilis (1.30%), cryptococcal meningitis (0.99%), cerebral toxoplasmosis (0.14%), and primary CNS lymphoma (0.13%). On trend analysis, prevalence of concurrent AIS and HIV increased from 0.11% in 2000 to 0.17% in 2011 (p<0.001). Those with HIV in AIS, compared to those without HIV, had lower prevalence of hypertension (52.6% vs. 75.6%; p<0.001) and diabetes mellitus (19.7% vs. 32.2%; p<0.001), but higher prevalence of renal disease (31.6% vs. 24.6%; p<0.001), and psychosis and depression (31.4% vs. 12.1%; p<0.001).

Conclusions:
There was an increasing trend over time of HIV infection in AIS hospitalizations and increased discharge to long-term care facilities and high cost burden. Further research would clarify AIS risk factors in HIV patients to mitigate adverse outcomes, considering the lower prevalence of traditional AIS risk factors.
Abstract TP179: Ischemic Stroke Subtypes and Relationship With Migraine in the Atherosclerosis Risk in Communities Study
Authors: Androulakis X.M. , Rosamond Wayne , Yim Eunsil , Dennis Lauren C , Gottesman Rebecca , Sen Souvik
Published: March 2022

Introduction and Hypothesis:
Epidemiological studies have shown that migraine with aura (MA) is an independent risk factor for ischemic stroke. We assessed the hypothesis that migraine with aura is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk In Communities (ARIC) study.

Methods:
We included 12844 participants among this ongoing prospective cohort of ARIC. All participants completed an in-person headache questionnaire: headaches are classified as MA, migraine without aura, or non-migraine headaches. All stroke diagnoses are based on computer-derived diagnosis and physician medical record review, with differences adjudicated by a second physician reviewer. Classification required evidence of sudden or rapid onset of neurological symptoms lasting ≥24 hours. Strokes were further classified according to etiologic subtype as thrombotic brain infarction, lacunar infarction, and cardioembolic stroke.

Results:
At the third ARIC study visit, 12.7% (1633) of participants had migraine and 8.5% (1093) had non-migraine headaches. 29% (472) of participants among migraineurs had MA. A total of 817 ischemic strokes occurred from1987-1989 to 2012, of which 51% (417) were thrombotic, 27% (224) were cardioembolic, and 22% (176) were lacunar stroke. Participants with MA had an increased odd of ischemic stroke, compared with participants with migraine without aura (unadjusted OR 2.4, 95% CI 1.6-3.6, P<0.0001). MA had a stronger association with cardioembolic stroke (OR 3.3, 95% CI: 1.4-8.0, p=0.009), compared with thrombotic stroke (OR 2.0, 95% CI: 1.2-3.4, p=0.01). There was no significant association between MA and lacunar stroke.

Conclusions:
Results from this prospective cohort are consistent with previous studies demonstrating an association between MA and ischemic stroke. Further, we report a stronger and significant association with the cardioembolic stroke subtype, with a significant but smaller association with thrombotic strokes. Etiology of the observed association is currently being evaluated in this population.
Abstract TP186: Lack of Insurance is Associated with Increased Risk of Intracerebral Hemorrhage
Authors: Sevush-Garcy Jennifer L , Merkler Alexander E , Navi Babak B , Kamel Hooman
Published: March 2022

Introduction:
Effective management of hypertension is essential for the prevention of intracerebral hemorrhage (ICH), but disparities in access to healthcare create a barrier to achieving this aim.

Hypothesis:
Among patients presenting for emergency care of hypertension, lack of insurance is associated with a higher risk of subsequent ICH.

Methods:
We performed a retrospective cohort study using administrative data from all acute care hospitalizations and emergency department (ED) visits in California, Florida, and New York between the years of 2005 and 2011. Our cohort comprised patients discharged from the ED with a primary diagnosis of hypertension, defined as International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 401-405. Patients with a prior or concomitant diagnosis of cerebrovascular disease (ICD-9-CM codes 430-438) were excluded. Patients 65 years and older were excluded because these patients often have access to Medicare insurance. Our predictor variable was lack of insurance, as compared with Medicaid or commercial insurance. Patients were followed for the primary outcome of ICH, defined using previously validated ICD-9-CM codes. Survival statistics were used to calculate the cumulative rate of ICH and Cox proportional hazards analysis was used to assess the association between lack of insurance and development of ICH while adjusting for demographic characteristics and vascular risk factors.

Results:
Among 361,019 patients with 3.4 (+/- 1.8) years of follow-up, the cumulative rate of ICH in patients without insurance was 1.03% (95% confidence interval [CI], 0.90-1.18%) as compared to 0.88% (95% CI, 0.80-0.96) in patients with insurance. After adjusting for demographic variables and vascular risk factors, lack of insurance was associated with the development of ICH (hazard ratio, 1.20; 95% CI, 1.07-1.34).

Conclusion:
In a large, heterogeneous group of patients presenting for emergency care of hypertension, lack of insurance was associated with an increased risk of ICH after discharge. Further investigation is needed to address the impact of access to healthcare on rates of this disabling disease.
Abstract TP189: Hip Hop Stroke: Adapting a Facilitator-driven Evidence-based Multimedia Program into a Scalable Digital-only Version
Authors: Leighton-Herrmann Ellyn , Hecht Mindy , Hedmann Monique , Noble James , Williams Olajide
Published: March 2022

A major barrier to timely care for ischemic stroke is delayed hospital arrival, often due to failure to identify symptoms as those of a stroke or serious enough to seek immediate care. We developed a facilitator-driven multimedia stroke literacy intervention - Hip Hop Stroke (HHS) - to improve knowledge of risk factors, symptoms, urgent action, treatment and prevention. HHS uses Hip Hop music and child-centric media (e.g., cartoons) to engage 4th-6th graders and their parents in high-risk minority communities. We have previously published on the efficacy of our 3-day program to improve short and long-term knowledge of children and transmission of key principles to adults. In an effort to widely disseminate HHS in an effective, cost-efficient way, we developed a pilot study to test a self-guided digital adaptation of the program.

We conducted focus groups with fifth graders to inform the modification of the existing HHS curriculum into six 20-minute, self-guided computer modules. We pilot tested the digital program with 4th and 5th graders (N=55) and assessed the effect on stroke knowledge through pre/post surveys embedded into the first and last modules. Data were analyzed using Pearson χ2 and Fisher exact tests.

Stroke knowledge improved after the program to a degree consistent with data from our facilitator-driven program. The proportion of students able to correctly identify symptoms of stroke significantly increased from pre to post-test on all symptoms. At post-test, 96% identified that a stroke occurs in the brain, compared to 44% at baseline (p<.001). Every student (100%) correctly identified slurred speech at post-test, compared to 43% at baseline (p<.001). Identification of an appropriate urgent plan for a hypothetical stroke scenario - calling 911 - also increased significantly. Importantly, students found the program enjoyable and engaging, and 84% said they shared stroke information with a family member at home.

These results show promise for computer-based stroke literacy programming for elementary school children and may serve as a conduit for health messages into the home when child mediation techniques are incorporated. This method may represent a novel strategy for broad dissemination of stroke information or other chronic diseases.
Abstract TP193: Antihypertensive Therapy in Patients With Pre-morbid Hypertension Does not Modify Short-term Outcome in Acute Ischemic Stroke
Authors: Cyprich Janelle , Boehme Amelia K , Samai Alyana A , George Alexander , Ryan Matthew T , El Khoury Ramy , Martin-Schild Sheryl
Published: March 2022

Background:
Hypertension is a recognized risk factor for ischemic stroke. Recent studies have suggested that patients with acute hypertension on admission for acute ischemic stroke (AIS) have worse outcomes compared to patients who present with blood pressure values within normal range. We sought to determine whether patients who are medicated for chronic hypertension prior to admission have better outcomes following ischemic stroke compared to unmedicated patients.

Methods:
Patients who presented to our center with AIS between 07/2008-07/2014 were included if pertinent past medical history and medication status were available at admission. Logistic regression was used to assess differences in baseline, in-hospital, and outcome variables in patients with medicated hypertension (HTN+/M+) and unmedicated hypertension (HTN+/M-) as compared to those with no hypertension (HTN-). The primary outcome measure was poor functional outcome (modified Rankin Scale > 2) on discharge.

Results:
A total of 1,401 cases were analyzed; 305 patients (21.8%) in the HTN- group, 200 patients (14.3%) in the HTN+/M- group, and 896 patients (63.9%) in the HTN+/M+ group. After adjustment for age, NIHSS score at baseline, and tPA administration, patients in the HTN- group were significantly less likely to experience poor functional outcome than patients in the HTN+/M+ group (OR=0.63, 95% CI 0.45-0.88, p=0.0031). There was no significant difference in likelihood of poor functional outcome between HTN+/M- and HTN+/M+ patients (OR=0.87, 95% CI 0.64-1.19, p=0.2870).

Conclusions:
The absence of hypertension in the setting of AIS is associated with lower odds of poor functional outcome. However, patients who were medicated for hypertension compared to those who had untreated hypertension did not differ in functional outcome following ischemic stroke, suggesting that the presence of hypertension contributes to outcome and this exposure is not completely ameliorated by antihypertensive therapy.
Abstract TP197: Dyslipidemia Should be Associated With an Increased Risk of Hypertension in a Working-age Japanese Male Population
Authors: Nishiyama Yasuhiro , Otsuka Toshiaki , Ueda Masayuki , Kimura Kazumi
Published: March 2022

Introduction:
Hypertension is the single most important modifiable risk factor for ischemic stroke and also one of the main comorbidities associated with dyslipidemia.

Hypothesis:
This study aimed to examine the extent to which dyslipidemia increases the risk of developing hypertension in a Japanese working-age male population.

Methods:
We analyzed data from 14,215 non-hypertensive male workers (aged 38 ± 9 years) who underwent annual medical check-ups. Subjects were followed-up for a median of 4 years to determine new-onset hypertension, defined as blood pressure ≥140/90 mmHg or use of antihypertensive medication. The associations between serum lipid levels and the development of hypertension were examined.

Results:
During the follow-up period, 1,483 (10.4%) subjects developed hypertension. After adjusting for age, body mass index, impaired fasting glucose/diabetes, baseline blood pressure category, alcohol intake, smoking, exercise, and parental history of hypertension, subjects with a total cholesterol (TC) level ≥222 mg/dL were at a significantly increased risk of developing hypertension (hazard ratio 1.28, 95% CI 1.06–1.56) compared to subjects with a TC level ≤167 mg/dL. Similar results were observed for subjects with high low-density lipoprotein cholesterol (LDLC) and non-high-density lipoprotein cholesterol (HDLC) levels. Intriguingly, a clear U-shaped relationship was found between the HDLC level and the risk of developing hypertension; compared to the third quintile, the multi-adjusted hazard ratio was 1.22 (95% CI 1.03–1.43) in the lowest quintile and 1.34 (95% CI 1.12–1.60) in the highest quintile.

Conclusions:
Elevated serum levels of TC, LDLC, and non-HDLC were associated with an increased risk of hypertension in working-age Japanese men. Furthermore, for HDLC, the risk of developing hypertension was increased at both low and high levels.
Abstract TP2: Heparin Use Across Major Endovascular Trials
Authors: Kreitzer Natalie , Khatri Pooja , Adeoye Opeolu , Abruzzo Todd , Grossman Aaron , Ringer Andrew , Broderick Joseph
Published: March 2022

Introduction:
At present date, 14 randomized endovascular trials for acute ischemic stroke have been published with more recent trials demonstrating a benefit of endovascular therapy. Heparin use during the endovascular procedure is a potential confounder of patient outcome. We sought to describe and highlight differences in the heparin protocols of the major endovascular trials.

Hypothesis:
We hypothesized that heparin protocols would differ among endovascular stroke trials.

Methods:
We reviewed the heparin protocol from the methods section of 14 endovascular trials for acute ischemic stroke. In studies where the protocol was not included in the methods section or the appendix of a manuscript, the principal investigator of the trial was contacted to provide insight into the use of heparin during the study.

Results:
No two of the major endovascular stroke trials used the same heparin protocol. Table 1 details the variability in the protocols. In cases where heparin dosing was not discussed, we left the study “N/A” in the table.

Conclusion:
Although numerous endovascular ischemic stroke trials have been conducted, heparin use and its documentation during the procedure have varied greatly over the past 20 years. Heparin, an anticoagulant, could contribute to either increased bleeding or improved clot removal and maintenance of recanalization. Future studies of the role of adjunctive antithrombotic therapy during endovascular therapy are needed, and heparin use in these protocols should be specifically detailed and ideally standardized.
Abstract TP206: Clinical Predictors of Hemorrhagic Transformation in Non Lacunar Ischemic Stroke
Authors: Zurru Maria C , Alonzo Claudia , Brescacín Laura , Pigretti Santiago , Luzzi Ariel , Guido Bibiana , Camera Luis , Cristiano Edgardo , Waisman Gabriel
Published: March 2022

Introduction:
intracerebral hemorrhagic transformation (HT) is a multifactorial phenomenon in which ischemic brain tissue converts into a hemorrhagic lesion with blood vessel leakage, and can significantly contribute to additional brain injury after stroke. Understanding mechanisms and identifying predictors of HT may contribute to improve clinical outcomes in stroke patients.

Hypothesis:
to evaluate clinical predictors of HT in non-lacunar ischemic stroke patients.

Methods:
patients were prospectively included in a multidisciplinary secondary stroke prevention program. Pre-stroke vascular risk factor profile and control were obtained from electronic medical records. Acute SBP, DBP and PP were obtained in the emergency room and HT was evaluated with on-admission and one-week CT or MRI. Predictors of HT were identified by multivariate analysis. Exclusion criteria: TIA, lacunar stroke and patients without one-week CT or MRI.

Results:
747 patients with a non-lacunar ischemic stroke (mean age 77±11 years, 61% females) were included. HT was observed in 94 patients (13%); they were older (82±8 vs 77±11; p 0.0001), had higher prevalence of hypertension (94% vs 81%; p 0.003) and AF (45% vs 20%; p 0.0001), and lower e-GFR (56±29 vs 65±27 ml/min/1.73 m2; p 0.04). They also had higher on-admission SBP (168±30 vs 146±23 mmHg; p 0.0001), DBP (88±18 vs 81±13 mmHg; p 0.0001) and PP (78±23 vs 63±21 mmHg; p 0.0001); anticoagulant therapy was more frequent in this group (27% vs 12%; p 0.0001). After adjusting by age and vascular risk factors in the multivariable analysis: the age > 80 years, PP on admission > 60 mm de Hg, e-GFR < 60 ml /min/1,73 m2 and pre-stroke AF were associated with increase of risk of HT. (table)

Conclusion:
predictors for HT in our cohort were also related with severe vascular disease. Identification of these high risk patients is crucial in clinical decision making regarding thrombolytic treatment and optimal timing for antithrombotic therapy initiation.
Abstract TP213: Accuracy of Transcranial Color-coded Sonography for the Detection and Measurement of Intracranial Arterial Stenosis When Compared to CT Angiography in Patients With Acute Ischemic Stroke and Transient Ischemic Attack
Authors: Rocha Letícia J , Zotin Maria Clara Z , Santos Renata S , Libardi Milena C , Martins Filho Rui Kleber V , Barreira Clara M , Camilo Millene R , Alessio-Alves Frederico F , Dias Francisco A , Cougo-Pinto Pedro T , Abud Daniel G , Pontes-Neto Octávio M
Published: March 2022

Introduction:
Transcranial Color-Coded Sonography (TCCS) including B-mode imaging and color-coded Duplex is non-invasive, bedside and inexpensive tool for the assessment of the intracranial circulation. TCCS can be used to assess intracranial stenosis but its accuracy has not been systematically compared to CT angiography in acute stroke patients.

Hypothesis:
TCCS has high accuracy when compared to CT angiography for the detection and measurement of intracranial arterial stenosis in patients with acute ischemic stroke.

Methods:
In this prospective study 43 patients (67% male; mean age: 59.8 ± 11 years) with acute ischemic stroke or Transient Ischemic Accident (TIA) underwent examinations of the intracranial arteries by TCCS and CT angiography. Different examiners that were blinded to test results performed the exams. TCCS and CT angiography were performed during the hospital stay. All stenotic segments of intracranial vessels were classified into 4 groups: normal or mild (<50%), moderate (50%-70%), severe (≥70%) and subocclusion/occlusion.

Results:
580 of 645 arterial segments in 43 patients were evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of TCCD in comparison with CT angiography for the detection of moderate to severe intracranial stenosis (≥50%) were 81.5%, 100%, 100%, and 76% respectively. The Cohen’s kappa between TCCS and CT angiography was 0.76 (p<0.001).

Conclusions:
TCCS is a bedside non-invasive tool that can be used to evaluate intracranial arteries with high accuracy for moderate to severe stenosis when compared to CT angiography. Moderate agreement was found between TCCS and CT angiography for the evaluation of intracranial stenosis in patients with acute ischemic stroke or TIA.
Abstract TP220: Neutrophil Gelatinase-associated Lipocalin in Patients With Acute Ischemic Stroke
Authors: Kim Ji Hwa , Han Sang Won , Ahn Seong Hwan , Lee Kyung-Yul
Published: March 2022

Introduction:
Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker in diagnosis and prognosis in kidney and cardiovascular disease. However, the relationship between NGAL concentration and ischemic stroke is poorly understood.

Hypothesis:
We investigated plasma NGAL concentration in patients with acute ischemic stroke in relation to medical history, risk factors, hematologic and biochemical tests, stroke severity and subtype.

Methods:
Clinical data of 139 patients who admitted to a tertiary hospital with TIA (n=17) and ischemic stroke (n=122) were collected. We evaluated the following parameters: A) Medical history and risk factors of the patients; B) Hematologic and biochemical blood test at the time of admission; C) Stroke severity which was assessed using the National Institutes of Health Stroke Scale (NIHSS); D) Stroke subtype which was decided by the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification.

Results:
In our study (62% male, mean age 65 ± 14 years), median admission serum NGAL level was 75 ng/mL (interquartile range [IQR] 52-112 ng/mL). Serum NGAL level was elevated in 21 (15.1%) patients with the cutoff point of 150 ng/mL. High plasma NGAL concentrations were associated with age (
p
= 0.018) and previous history of coronary artery occlusive disease (
p
= 0.003). Mean NIHSS score in high NGAL group was higher than normal NGAL group (7.6 ±7.2
vs
4.4 ± 5.6,
p
= 0.021). We observed significant correlations between serum NGAL with C-reactive protein (spearman coefficient rho = 0.319,
p
< 0.001), erythrocyte sedimentation rate (r = 0.410,
p
< 0.001), creatinine (r = 0.237,
p
= 0.005), blood urea nitrogen (r = 0.353,
p
= 0.003), estimated glomerular filtration rate (r = -0.471,
p
< 0.001), fibrinogen (r = 0.327,
p
< 0.001) and homocysteine (r = 0.189,
p
= 0.032). There were no significant differences in mean serum NGAL level between TIA patients and stroke patients, and stroke subtypes by TOAST classification.

Conclusions:
Increased NGAL in acute ischemic stroke patients is associated with age, previous coronary artery occlusive disease history and stroke severity. Elevated plasma levels of NGAL appear to be correlated with some biomarkers associated with inflammation, coagulation and kidney dysfunction.
Abstract TP225: The Central Nervous System Varicella Zoster Virus (CNS-VZV) Vasculopathy in HIV Patients
Authors: Panichpisal Kessarin , Vongveeranonchai Nuttawan , Janjua Nazli , Plengsombat Wassana , Nugent Kenneth
Published: March 2022

Background:
Varicella zoster vasculopathy of the central nervous system (CNS-VZV) is rare. This topic has not been systemically analyzed in HIV patients.

Method:
We reviewed case reports/series in the literature from Pubmed using search term: varicella zoster, vasculopathy, stroke and HIV.

Results:
Forty-eight patients were identified. Eight patients (17%) had VZV vasculopathy after started on highly active antiretroviral therapy (HAART) consistent with central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS). The average time from starting HAART to a neurological deficit was approximately 3 weeks. Rash occurred in ∼67%, with a mean 12 month interval from rash to CNS symptom onset though in 18 (64%) it occurred just prior to symptom onset. Patients had CNS lesions in the following distributions: posterior circulation, n=22 (46%); anterior circulation, n=13 (27%); and spinal, n=10 (21%). Specific abnormalities included stenosis/occlusion in 15 (83%), saccular aneurysm in 4 (22%), fusiform aneurysm in 2 (18%), and arterial wall enhancement in 2 (11%). The vasculopathy involved large vessels in 21/47 patients (45%), small arteries in 19 (40%), and both large and small arteries in 7 (15%). CSF pleocytosis was found in 30/36 patients (83%) (mean: 101), and CSF protein was elevated in 25/34 patients (74%). CSF immunological analysis was available in 29 patients. Twenty-five patient (89%) had either CSF positive for VZV DNA by PCR or anti-VZV IgG. 17/23 (74%) patients had VZV DNA positive in their CSF, and 13/21 (62%) had anti-VZV IgG antibody. Of the 35 patients with available treatment data, acyclovir was used as initial treatment in 27 (77%) with good recovery in 23 (85%). Thirteen cases received acyclovir with corticosteroids, and 11 had a good recovery (84%). Fourteen cases received acyclovir alone; 8 had a good recovery (57%). The mortality rate was 49%. VZV vasculopathy secondary from CNS-IRIS had better prognosis with a mortality rate 13%.

Conclusion:
Prompt treatment with acyclovir while waiting for CSF immunology is critical when CNS-VZV vasculopathy is a possibility. Rash, abnormal angiography or CSF pleocytosis give clues for diagnosis but not rule it out if negative. Steroid seems to improve the outcome of these patients.
Abstract TP23: Endovascular Treatment versus Best Medical Treatment in Acute Ischemic Stroke Patients: a Meta-analysis of Randomized Controlled Trials Which Permitted Recruitment of Patients Aged > 85 Years
Authors: Ishfaq Muhammad F , Rahman Haseeb A , Thomas Abraham P , Qureshi Adnan I
Published: March 2022

Background:
There is controversy whether the benefit of endovascular treatment is applicable to acute ischemic stroke patients who are aged >85 years.

Objective:
To determine the effects of endovascular treatment on clinical and safety outcomes compared with best medical treatment in trials that permitted recruitment of patients aged>85 years. .

Methods:
Four randomized trials that compared endovascular treatment with best medical treatment in acute ischemic stroke patients met the inclusion criteria. We calculated pooled odds ratios and 95% CIs (confidence intervals) using random-effects models. The primary endpoint was a favorable outcome defined by a modified Rankin scale grade of 0 (no symptoms), 1 (no significant disability), or 2 (slight disability) at 90 days post-randomization.

Results:
Of the 1012 total subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to endovascular treatment compared with best medical treatment (1012 subjects analyzed, odds ratio 2.37, 95% CI 1.81-3.13, p< .001). Excellent outcome (modified Rankin scale grade of 0 or 1) was also significantly greater among those randomized to endovascular treatment (881 subjects analyzed, odds ratio 2.47, 95% CI 1.69-3.61, p< .001). Risk of symptomatic intracranial hemorrhage was similar between endovascular treatment and medical treatment (1012 subjects analyzed, odds ratio 1.33, 95% CI 0.73-2.26; p= 0.38). In two trials that provided a comparison of odds of favorable outcome between patients aged ≥ 80 years and < 80 years, the odds for favorable outcome were higher in patients aged <80 years ( 811 subjects analyzed, odds ratio 2.32, 95%CI 1.71-3.16, p< .001 ).

Conclusions:
Compared with best medical treatment, the odds of achieving a favorable outcome or excellent outcome at 3 months post-randomization is approximately 2 folds higher with endovascular treatment among patients including those aged > 85 years with acute ischemic stroke
Abstract TP232: Symptomatic Plaque with Low-grade Stenosis Which Retains Hyperintensity After an Ischemic Event may Indicate a High Risk of a Subsequent Ipsilateral Ischemic Event
Authors: Kurosaki Yoshitaka , Kinosada Masanori , Kawasaki Toshinari , Takata Megumu , Matsumoto Naoki , Fukuda Hitoshi , Handa Akira , Chin Masaki , Yamagata Sen
Published: March 2022

Introduction:
Intraplaque hemorrhage (IPH) has been reported to be a characteristic feature of a vulnerable plaque, indicated by an area of high signal intensity on carotid MRI. It has been reported that symptomatic low-grade stenosis with IPH is strongly associated with ischemic events, but there are limited data regarding the dynamics of the carotid plaque signal. The aim of this study was to assess the time-dependent change of carotid plaque in the symptomatic patient with low-grade stenosis.

Methods:
Thirty-eight symptomatic patients with carotid low-grade stenosis (0.31 between time points was considered significant. We then investigated changes in rSI and subsequent ipsilateral ischemic events.

Result:
Of the 38 patients, there were strong-positive and positive plaque at baseline in 22 and 12 patients, respectively. During a mean follow-up period of 42.5 months, 26 positive plaques (74%) at baseline kept an rSI of >1.25, and all of 4 negative plaques at baseline changed positive. Strong-positive plaques at baseline showed a lower tendency to be negative than positive plaque (p=0.08). Twenty-one of the 38 patients (55%) experienced a total of 26 recurrent ischemic events. In patients who experienced recurrent ischemic events, 19 plaques (73%) were strong-positive and 5 plaques (19%) were positive. Compared to the most recent carotid MRI, rSI at the event was stable in 18 patients (69%) and increased in 8 patients (31%).

Conclusions:
Most symptomatic plaque with low-grade stenosis retained its hyperintensity after ischemic events and had a high rate of subsequent ipsilateral ischemic events. A sustaining high signal intensity might be associated with an increased risk of subsequent ischemic events. Follow-up observation by carotid MRI has the potential to increase the accuracy of stroke risk stratification in the management of carotid low-grade stenosis.
Abstract TP235: Does a 24/7 Stroke Service Make a Difference in Hyperacute Stroke Care? Early Experience of a Public Hospital in Bogota DC, Colombia
Authors: Vicini-Parra Javier , Ospina Jenny , Correa Cristian , Gomez Natalia , Bohorquez Stephania , Arroyo Lorena , Echavarria Luisa , Ruiz Jorge , Casallas Adriana , Guerrero Alejandra , Espinosa-Jovel Camilo A , Ramos-Romero Martha L , Betancourt Andres , Barrios Gustavo , Hedmont Daniel , Sobrino-Mejia Fidel E
Published: March 2022

Introduction:
A prospective stroke database was implemented as part of a still-growing comprehensive stroke centre (CSC). This CSC is located within a referral public hospital (Hospital Occidente de Kennedy) in Bogota DC, Colombia , and serves 2.3 million people of mainly low economic income. During the first 7 months of the CSC (Period 1: August 1st 2014 - March 1st 2015), the neurology-lead stroke team was available from 6 am to 6 pm. Stroke patients who arrived at night were treated by emergency physicians. After period 1, the stroke team was available 24/7 (Period 2, March 2nd 2015 - July 31st 2015).

Hypothesis:
The presence of a stroke team 24/7, increases the monthly rate of thrombolysed patients and of activated stroke codes.

Methods:
Printed forms were filled for every patient who arrived with diagnosis of acute ischemic stroke (AIS) or transient ischemic attack (TIA). Data was transcribed to an electronic database (Numbers, Apple Inc.) and analyzed with SPSS Statistics version 23 (IBM Corporation).

Results:
During the entire year, 104 stroke codes were assessed and 39 patients were thrombolysed; 26.3% of these occurred during night shift and 73.7% in day shift. Figures are depicted in table 1. During period 2, the probability of thrombolysis during night shift increased 2.2 times and the number of non-activated stroke codes was reduced by 14.1%. Therefore, in period 2 only one patient who was a candidate for IV rtPA did not receive treatment, whereas in period 1 this happened in 4 patients.

Conclusions:
In our experience, the availability of a 24/7 stroke team lead by neurology doubled the amount of patients thrombolysed at night and reduced the number of stroke codes that were not activated by emergency physicians. Counterintuitively, neither the rate of monthly thrombolysis nor that of stroke codes were modified in our case. However, the evaluated periods were short and our stroke network is still in its beginnings.
Abstract TP247: Results of the New York City Stroke Task Force Emergency Medical Services Stroke Prenotification Survey
Authors: Kirchoff-Torres Kathryn F , McClellan Fabienne , Labovitz Daniel L , Johnson Samantha A , Leifer Dana
Published: March 2022

Introduction:
EMS stroke prenotification (S-PN) expedites and increases tPA use. In 1/15, the New York State Dept. of Health (NYS DOH) began tracking S-PN data; however the baseline S-PN frequency and stroke teams’ S-PN experiences and practices in New York City (NYC) and Long Island (LI) had not been established.

Hypothesis:
The American Heart Association American Stroke Association NYC Stroke Task Force (NYC STF), a panel of stroke clinicians from NYC and LI, sought to assess current regional S-PN experiences.

Methods:
Online survey by the NYC STF was opened to NYS DOH designated stroke centers in NYC and LI from 12/8/14-1/12/15. Hospitals were instructed to respond based on the previous 12 months, using data or best estimation. Results were analyzed with frequency distributions.

Results:
Response rate= 75.8% (47/62 hospitals). Respondents: Stroke Coordinators= 66.0%, Stroke Directors= 10.6%, other= 23.4%. Most hospitals received patients from Fire Dept., City of NY (n= 38) and other private/municipal EMS. Many (53.2%) reported receiving S-PN for eligible patients <50% of the time; 27.7% reported receiving S-PN 50-89% of the time; only 14.9% reported receiving S-PN 90-100% of the time. Hospital size did not affect S-PN rate. Only 37.0% reported documenting receipt of S-PN >50% of the time. ED nurses most often received initial S-PN (n= 36), followed by ED clerks (n= 17); 80.4% of hospitals gave stroke triage training to these personnel. Most hospitals (91.5%) used a single-call activation for stroke team/radiology; only 57.5% reported activating it >50% of the time before patient arrival. Contact information for kin/witness (n=37), patient name (n=27) and birthdate (n=25) were most desired to add to S-PN. Frequently perceived barriers: inconsistently receiving S-PN from EMS (n=39), incomplete S-PNs (n=24). Most hospitals (65.8%) perceived positive impact of S-PN; 34.2% perceived no impact/too early to tell.

Conclusions:
In 2014, stroke teams in NYC and LI perceived wide variations in the rate of S-PN. ED nurses, clerks and EMS personnel are prime recipients for stroke triage training. Hospitals desire contact/identifying information as part of S-PN. More consistent documentation and review of S-PN data is needed to improve its impact on stroke care.
Abstract TP257: Apoptotic Erythrocytes Attenuate Macrophages Proinflammatory Phenotype in Intracerebral Hemorrhage
Authors: Chang Che-Feng , Taylor Roslyn , Steinschneider Arthur , Ai Youxi , Sansing Lauren H
Published: March 2022

Introduction:
Inflammation contributes to both injury and recovery after intracerebral hemorrhage (ICH). Our previous studies showed that blood-derived CCR2
+
monocytes/macrophages infiltration induces brain injury in acute ICH, whereas these cells are also essential for hematoma clearance at later stage of ICH. However, the mechanism that educates macrophages (MΦ) to change from classical activation to assisting in recovery in the hemorrhagic brain is still missing. In wound healing, contact with apoptotic cells induces macrophage alternative activation.

Hypothesis:
Apoptotic erythrocytes activate phosphatidylserine (PtdSer) receptors on MΦ to decrease MΦ proinflammatory response and induce MΦ alternative activation to aid in hematoma clearance.

Methods:
Bone marrow-derived macrophages were treated with thrombin to induce MΦ proinflammatory activation and to mimic ICH
in vitro
. We used PHK-26 labeled-apoptotic erythrocytes and recombinant annexin V to competitively inhibit PtdSer-receptor interactions to study the effect of apoptotic erythrocytes on MΦ phenotype and erythrophagocytosis ability. RT-qPCR and immunofluorescence were performed to detect MΦ polarization genes expression and the engulfment of erythrocytes.

Results:
Exposure to apoptotic erythrocytes decreased proinflammatory genes TNF-alpha (∼50%) and CD86 (∼30%) up-regulation induced by thrombin (10 U/ml) treatment for 12 hour (Figure). Recombinant annexin V (10μg) abolishes the benefit from apoptotic erythrocytes and reduces MΦ erythrophagocytosis.

Conclusions:
Macrophage alternative activation and erythrophagocytosis is induced by exposure to apoptotic erythrocytes in a PtdSer-dependent manner. Targeting PtdSer sensing receptor on MΦ could be a potential therapeutic strategy to promote MΦ alternative activation and subsequently to enhance hematoma clearance in ICH.
Abstract TP259: Surrogate MRI Signatures for Contrast Enhanced Imaging That Predict Acute Blood-brain Barrier Damage in Ischemia-reperfusion
Authors: Nagaraja Tavarekere N , Keenan Kelly A , Ewing James R , Knight Robert A
Published: March 2022

Background and Purpose:
Contrast-enhanced magnetic resonance imaging (CE-MRI) is used to measure blood-brain barrier (BBB) damage after stroke, but is contra-indicated in patients with compromised kidney function. Thus, there is a need for non-contrast MRI techniques that portend BBB damage. We examined the relationships between CE-MRI and non-contrast MRI measures to test whether the latter serve as surrogate biomarkers of BBB damage in acute stroke.

Methods:
Male Wistar rats (∼300 g; N=22) were subjected to focal cerebral ischemia-reperfusion using a middle cerebral artery suture occlusion model. They were imaged in a 7 Tesla Bruker MRI system. The parameters measured were: cerebral blood flow (CBF), T
2
, T
1
and T
1
-under-off resonance-saturation (T
1sat
). All data except CBF were expressed as ipsilateral-to-contralateral ratios (I-C). Post-reperfusion BBB damage was measured by CE-MRI via blood-to-brain forward volumetric transfer constant (K
trans
) maps. CBF, T
2
, T
1
and T
1sat
were compared to K
trans
from the same region of interest (ROI). Scatterplots with Pearson correlation coefficients (r) were used to compare the data and significances inferred at
p
<0.05.

Results:
Preoptic area (PoA) and striatum (Str) were found ischemic in nearly all rats, with neocortical areas lesser affected. During occlusion, CBF in PoA and Str were 26±15 and 42±18 ml/100g/min (20-25% of contralateral side), respectively. After reperfusion, CBF was 78±27 and 99±50 ml/100g/min in PoA and Str, respectively. Contrast enhancement or BBB damage was observed in the PoA in all 22 rats and in 17 in Str. The I-C values of T
2
, T
1
and T
1sat
elevated between occlusion and reperfusion periods and were associated with increased K
trans
values (
p
=0.05). The extent of CBF reduction during occlusion was significant and correlated inversely with increased K
trans
(r=-0.5;
p
=0.03), but this relationship was lost after reperfusion (r=0.3;
p
=0.3).

Conclusions:
The data suggest that reduction in CBF during occlusion and post-reperfusion elevation of T
2
, T
1
, and T
1sat
(i.e. vasogenic edema) are reliable predictors of impending BBB damage in acute stroke. With further confirmation, non-contrast based MRI evaluation of the BBB in acute stroke may be utilized in cases where CE-MRI is not possible.
Abstract TP260: Efficacy of Laropiprant in Ameliorating Hyperglycemia-mediated Intracerebral Hemorrhage
Authors: Mendes Monique , Ali Sherry , Dore Sylvain , Ahmad Abdullah
Published: March 2022

Introduction:
The respective importance of PGD2 and its receptor DP1 in the vasculature, the blood, and the brain warrants further examination of their role in hyperglycemia-mediated intracerebral hemorrhage (ICH).

Hypothesis:
In this study, we tested whether deletion of the DP1 receptor or its blockade by the selective antagonist Laropiprant improves functional and anatomical outcomes following ICH in hyperglycemic mice.

Methods:
Wildtype (WT) and DP1-/- C57BL/6 mice were given 2g/kg glucose; blood glucose levels and c-peptide levels were monitored over 4h. In the second cohort, WT and DP1-/- mice treated with saline or the DP1 receptor antagonist were given 2g/kg glucose and ICH was induced at 1h by giving a single dose of collagenase in the striatum. Neurologic deficits, brain injury volume, and edema volume were calculated at 72h. Further, the brain sections from these groups were subjected to Perls’ staining and Iba1 and GFAP immunoreactivity to determine the effect of Laropiprant on the modulation of iron levels and gliosis.

Results:
Acute injection of glucose led to a significant increase in the glucose level in WT and DP1-/- mice. DP1-/- mice exhibited faster clearance of glucose overload compared with the WT mice. Similarly, WT mice treated with Laropiprant also exhibited faster clearance of glucose. Similar patterns were observed in c-peptide levels of these groups. The injury volume in DP1-/- mice compared with WT was significantly lower (8.3±1.8 vs 19.3±5.6mm3; p<0.01). Furthermore, WT mice treated with Laropiprant also exhibited significantly lower brain lesion volume (9.1±3.2 vs 19.3±5.6mm3; p<0.01). Interestingly, a significant decrease in Iba1 immunoreactivity and Perls’-labelled iron content was observed in hyperglycemic DP1-/- compared with the hyperglycemic WT mice.

Conclusion:
Together, the data suggest that inhibition of the DP1 receptor improves glucose tolerance/clearance and attenuates functional and anatomical deficits following hyperglycemia-mediated ICH. Additional studies are underway to investigate further mechanisms.

[This work was supported by NIH R01 NS046400 (to S.D.).]
Abstract TP263: Whole Brain Screening of Cellular and Molecular Changes After Stroke
Authors: Aswendt Markus , Hsueh Brian , Ishizaka Shunsuke , Sun Guohua , Cheng Michelle , Deisseroth Karl , Steinberg Gary K
Published: March 2022

Objective:
Recovery can occur after stroke in both human and animals, and this is attributed in part by rewiring of neural connections in areas adjacent to or remotely connected to the infarct. As stroke can cause brain-wide network changes, it is important to interrogate regenerative processes in the whole brain after stroke. In this study we use a high resolution 3D whole brain imaging technique called CLARITY to visualize the cellular and structural changes in stroke mice during recovery.

Hypothesis:
We hypothesize that the CLARITY procedure will provide a more detailed and complete visualization of post-stroke regenerative processes in the whole brain.

Material/Methods:
We used C57Bl6 WT mice with 10-12 weeks of age. Ischemic stroke was induced by transient middle cerebral artery occlusion using an intraluminal suture. Mice were sacrificed at different time points (Post-stroke day 1, 7, 14 and 28) and brains were processed with the CLARITY protocol. Brains were immunostained repeatedly with antibodies for neurons, glia, oligodendrocytes, microglia/macrophages and blood vessels.

Results:
Stroke brains collected at different post-stroke timepoints became optically transparent after the CLARITY process. Interestingly, the ischemic area turned transparent for all timepoints except post-stroke day 7 and 28. At this time point the ischemic area remains opaque after CLARITY process, suggesting that the cellular composition at this timepoint is resistant to the CLARITY treatment. Immunostaining with MAP2 demonstrates labeling of neuronal processes in the whole brain. Current studies investigate other cell types and cellular processes, such as glial scarring (GFAP), microglia/macrophage accumulation (CD68) and angiogenesis (Collagen IV) to map the reorganization at the cellular level with high resolution in 3D whole brain.

Conclusion:
Stroke brains can be made optically transparent after the CLARITY process. This allows high resolution whole brain 3D imaging to probe for the cellular and molecular mechanisms during stroke recovery.