bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P575: Impaired Distal Perfusion Predicts In-Hospital Outcome in Patients With Symptomatic Middle Cerebral Artery Stenosis
Authors: Yaghi Shadi , De Havenon Adam H , Honda Tristan , Hinman Jason D , Raychev Radoslav I , Sharma Latisha K , Feldmann Edward , Romano Jose G , Prabhakaran Shyam , Liebeskind David S
Published: March 2021

Background:
Perfusion imaging is increasingly used to risk stratify patients with symptomatic intracranial stenosis. Length of hospital stay (LOS) in patients with ischemic stroke is a surrogate marker of increased morbidity. We aim to determine the association between perfusion delay on T max (< 4 sec, 4-6 sec, and > 6 sec) on perfusion weighted imaging and LOS in patients with symptomatic middle cerebral artery (MCA) stenosis.

Methods:
We included consecutive patients with left MCA stenosis admitted with ischemic stroke or TIA <7 days from onset who underwent perfusion imaging (CT or MR perfusion) processed with RAPID software. We excluded patients with core infarct ≥ 30 mL. Perfusion mismatch was divided into three groups: mismatch volume ≥ 15 mL based on T max > 6 sec delay, mismatch volume ≥ 15 mL based on T max 4-6 sec delay, and neither of the above mismatch patterns. The primary outcome was LOS, both as a continuous variable and categorical (≥ 7 days (prolonged LOS) vs. <7 days).

Results:
179 out of 194 patients met the inclusion criteria; mean age was 70.2 ± 15.4 years, 53.1% were women, median (IQR) NIHSS was 4 (1-9); 83.2% underwent MR perfusion; 38.5% had a mismatch volume ≥ 15 mL based on T max > 6 sec and 31.3% had a mismatch volume ≥ 15 mL based on T max 4-6 sec and the median (IQR) LOS was 4 days (2-8). After adjusting for age and NIHSS, T max > 6 sec mismatch definition was associated with prolonged LOS (OR 2.90 95% CI 1.06-8.18; p=0.039) but T max 4-6 sec definition was not (OR 1.45 95% CI 0.46-4.58, p=0.528), without any interaction based on perfusion imaging modality (p interaction = 0.568). We found similar associations when LOS was considered as a continuous variable for T max > 6 sec (β coefficient=2.01, 95% CI 0.05-3.97, p=0.044) and T max 4-6 sec (β coefficient=1.24, 95% CI -0.85-3.34, p=0.244). In receiver operating curves, the optimal mismatch volume for T max > 6 sec was 10 mL (sensitivity 0.61 and specificity 0.63) whereas for T max 4-6 sec it was 39 mL (sensitivity 0.61 specificity 0.56).

Conclusion:
In patients with recently symptomatic MCA stenosis, the T max > 6 sec definition for mismatch, but not T max 4-6 sec, is associated with prolonged LOS. Prospective studies are needed to validate our findings and define the optimal mismatch threshold in patients with symptomatic MCA stenosis.
Abstract P58: Motor Recovery After Chronic Stroke Correlates With Diffusion Tensor Measures of Ipsilesional Cerebral and Cerebellar White Matter Integrity
Authors: Chiang Sarah N , Rana Siddharth , Humphries Joseph B , Leuthardt Eric C
Published: March 2021

Introduction:
We aimed to determine whether white matter (WM) tract integrity improved after a brain-computer interface (BCI) rehabilitation program for chronic stroke patients with upper extremity weakness. Mean diffusivity (MD) was calculated from diffusion tensor imaging (DTI) and is an indication of the integrity of axons and myelination in WM. MD is a biomarker in subacute stroke for post-stroke motor deficits and recovery.

Methods:
DTI scans were performed with 9 chronic hemiplegic stroke patients within 2 weeks of initiation and completion of a 12-week BCI rehabilitation program. All patients were a minimum of 6 months post-stroke. MD was then calculated using DSI-Studio for WM tracts in each patient at both pre- and post-therapy time points. Motor function was evaluated at these time points using the upper extremity portion of the Fugl-Meyer Assessment (UEFM).

Voxelwise statistical analysis comparing pre- and post-intervention MD values was carried out using tract-based spatial statistics (TBSS). Relationships between MD measures in regions of interest and changes in motor function were estimated with Spearman correlations.

Results:
Voxelwise analysis using TBSS showed no significant group-level change in MD of WM tracts throughout the brain after completing BCI rehabilitation.

However, the change in MD in ipsilesional cerebral WM was positively correlated with UEFM change (Spearman’s rho = 0.75, p = 0.02) as was the pre-BCI MD in the ipsilesional cerebellar WM (rho = 0.78, p = 0.01). The correlations between contralesional MD measures and UEFM change were not statistically significant.

Conclusion:
Correlation between changes in mean diffusivity of ipsilesional cerebral white matter and motor improvement in chronic stroke supports the literature that recovery may be mediated by axonal remyelination and regeneration. Furthermore, we find that pre-therapy, ipsilesional cerebellar white matter MD correlates with motor recovery and as such may serve as a predictive measure of the effectiveness of BCI therapy for patients.
Abstract P581: Neonatal Stroke is Not Associated With Birth Trauma
Authors: Dunbar Mary , Norris Abbey , Craig Brandon T , Mohammad Khorshid , Esser Michael , Carlson Helen , Kirton Adam
Published: March 2021

Acute neonatal stroke causes cerebral palsy, lifelong morbidity and mortality. Neonatal arterial ischemic stroke (NAIS) and hemorrhagic stroke (NHS) are most common. Pathophysiology is poorly understood and causation is often attributed to observed obstetrical factors such as instrumentation (forceps or vacuum) or operative delivery despite no empiric evidence supporting an association. We explored the relationship between birth trauma and neonatal stroke via population-based, prospectively collected registries in Southern Alberta, Canada. Consecutive cases of NAIS (n=59), NHS (n=20), and neonatal hypoxic-ischemic encephalopathy HIE with MRI-confirmed injury (HIE+, n=78)) were compared to neonates without injury (HIE-n=77). Cranial soft tissue swelling was objectively quantified as a trauma score from T1-weighted images using a semi-automatic segmentation method performed by two blinded investigators. Maternal, obstetrical, perinatal, and outcome variables were obtained from medical records. Multinomial regression modeling evaluated the relationship between diagnosis and birth trauma as measured by total soft tissue swelling score and diagnosis (HIE- as controls). Across the 234 infants studied, mean age at MRI (4.1+/-1.3 days) and sex (54% male) were comparable. Measurable scalp trauma was present in 93(40%), the proportion of which did not differ across groups. On univariate analysis, mean trauma scores did not differ between groups, were not associated with NHS or HIE+, and were lower for the NAIS group compared to HIE- (controls). Multinomial modeling revealed no relationship between scalp trauma and outcome. We conclude that the leading forms of acquired neonatal brain injury are not associated with objectively measured birth trauma. The term “birth trauma” should be removed from the perinatal stroke vernacular to help counsel traumatized parents and advance studies of genuine pathophysiology.
Abstract P582: Accuracy of Transcranial Doppler in Detection of Intracranial Stenosis in Patients With Sickle Cell Disease
Authors: Krementz Nastajjia , Gardener Hannah , Torres Luis F , Alkhalifah Moayd , Campo-Bustillo Iszet , Campo Nelly , Koch Sebastian , Rundek Tatjana , Alvarez Ofelia , Romano Jose G
Published: March 2021

Background:
Stroke is among the most devastating consequences of sickle cell disease (SCD). Most SCD strokes occur due to intracranial stenosis, that can be detected by increased flow velocities on Transcranial Doppler (TCD). However, increased velocities may also reflect anemia rather than arteriopathy and vessel stenosis. We aimed to assess the accuracy of TCD in detection of intracranial stenosis in SCD.

Methods:
Pediatric SCD patients with at least one TCD and MRA within one month apart were identified from a retrospectively collected database maintained at our institution from January 2000 to December 2016. Patient demographics, hemoglobin level, transfusion and hydroxyurea status were collected, along with mean flow velocities (mFV) and degree of stenosis from bilateral middle and anterior cerebral, and internal carotid arteries. A mFV of
>
200 cm/s and vessel stenosis
>
50% were considered abnormal. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were obtained to assess overall accuracy of TCD velocities in relation to vessel stenosis. Multivariate analysis was performed to identify independent factors associated with MRA stenosis.

Results:
A total of 164 patients were included in the database (median age 12 [IQR 8.9] years, 56% had ischemic strokes) and 64 of them had at least one TCD and MRA one month apart. Of these, 20% had ischemic strokes, 17% had MRA stenosis
>
50% and 10% had TCD velocity
>
200 cm/s. TCD mFV
>
200 cm/s had a high specificity (95%) and NPV (87%) but low sensitivity (29%) and PPV (55%) when compared to MRA stenosis
>
50%. As a continuous variable, TCD mFV 137.5 cm/s had the best balance between maximal specificity (77%) and sensitivity (72%). After adjustment for age, hemoglobin level, transfusion status, hydroxyurea, and vessel, for every increase in cm/sec on TCD, there was a 2% increase in the odds of
>
50% stenosis on MRA (OR=1.02, 95% CI 1.01-1.03, p<0.001).

Conclusion:
Our study reports that TCD mFV is a positive predictor of MRA stenosis in SCD, independent of patient characteristics, including hemoglobin. A mFV
>
200 cm/s is highly specific but less sensitive to detect stenosis
>
50%. Lower mFV cut points may need to be considered for early detection of intracranial stenosis and risk of stroke.
Abstract P583: Comparison of FAST-S to BEFAST-S for Pediatric Stroke: A Comprehensive Stroke Center Retrospective Analysis
Authors: O’Connor Kevin , Grewal Parneet , Campbell Margie l , Lightner Donita , Lee Jessica D
Published: March 2021

Objective:
To assess the demographic characteristics and presenting symptoms in a cohort of pediatric patients with ischemic stroke and develop a tool to improve recognition of ischemic stroke at the institution and in the community.

Methods:
We conducted a retrospective review of children aged 1 month to 18 years with radiologically confirmed ischemic stroke admitted to the University of Kentucky between January 2013 and June 2020. Characteristics such as age, sex, and diagnosis were recorded. The FAST (Face, Arms, Speech) and BEFAST (Balance, Eyes, Face, Arms, Speech) mnemonics were applied to all patients. We then applied the FAST-S tool and used the novel BEFAST-S. FAST-S adds new onset seizure to the previously validated tool.

Results:
For the study period, we identified 158 cases. Most patients were ≥ 3 years of age (n=113) and most were male (n=96). About one third (31%, n=50) of presentations concerning for stroke had diagnosed ischemic stroke at time of discharge; the majority were ≥ 3 years of age (n=31). Strokes were commonly associated with trauma (24%, n=12) and infection (22%, n=11). Common mimics for stroke included seizure in the absence of stroke (30%, n=33), migraine (18%, n=20), and conversion disorder (13%, n=14). FAST and BEFAST each identified the same 30 patients as having ischemic stroke (60%), with 26 patients being ≥ 3 years of age. Inclusion of new onset seizures (FAST-S/BEFAST-S) correctly identified one additional patient ≥ 3 years of age (87%, n=27) and nine additional patients under 3 (n=19, 78% versus n=4, 21%). New onset seizure reduced the number of missed strokes regardless of age from 40% (n=20) to 16% (n=8).

Conclusions:
Although BEFAST improves the sensitivity of identification of ischemic strokes in adults, it did not identify additional strokes beyond FAST in our pediatric population. Inclusion of new onset seizure in addition to either FAST or BEFAST, however, reduced the number of missed strokes by at least half, particularly in children < 3 years of age. Thus, education of FAST-S or BEFAST-S may be useful for providers and emergency services.
Abstract P584: Sleep in Pediatric Stroke Study (SleePSS): Neuroimaging and Neurocognitive Correlates of Sleep Health in Pediatric Stroke
Authors: Slim Mahmoud , Westmacott Robyn , Mumin Anissa , NARANG INDRA , Weiss Shelly , Moharir Mahendranath d , Pulcine Liza , MacGregor Daune , DEVEBER Gabrielle A , Dlamini Nomazulu
Published: March 2021

Introduction:
Pediatric arterial ischemic stroke (AIS) is a serious cause of lifelong neurological and cognitive disabilities. Although they are at increased risk of obstructive sleep apnea (OSA), children with AIS may have abnormal sleep indices even in the absence of OSA diagnosis. This can adversely affect their blood vessels health (impaired cerebrovascular reactivity, CVR) and can lead to neurocognitive impairments. Therefore, we aimed to investigate the association of cerebral blood vessels health with polysomnographic measures and cognitive function in children with AIS.

Hypothesis:
Quantitative measure of negative CVR, i.e. fractional negativity (fneg) and negative CVR correlate significantly with abnormal overnight oxygen and carbon dioxide levels in children with AIS, even in the absence of OSA.

Methods:
We conducted a single-centre cross-sectional study in children with AIS aged between 8 and 18 years old and who were not at risk of OSA (i.e., pediatric sleep questionnaire score<0.33). All children were evaluated using:

(1) Non-invasive Blood Oxygen Level Dependent magnetic resonance imaging to study CVR.

(2) An overnight polysomnography

(3) Comprehensive evaluation of intellectual abilities, attention and executive function.

Results:
Ten children with AIS (40% males; median age: 14.3 years) were included after a median of 8.8 years following stroke onset. None of the children was diagnosed with OSA. We found significant correlations between fneg and minimum oxygen saturation during REM sleep (r=0.81, r=0.68 and r=0.76 in grey matter, white matter and whole brain, respectively; p<0.05). The whole brain mean negative CVR correlated significantly with the visual spatial, fluid reasoning, and emotion regulation indices (r=-0.82, -0.8, and 0.75, respectively, p<0.05). Mean negative CVR in white matter correlated significantly with the indices of executive function (emotion regulation, cognitive regulation and global executive composite scores, r=0.72-0.76, p<0.05).

Conclusion:
Impaired CVR in children with AIS correlates with abnormal sleep indices even in the absence of OSA diagnosis. This can potentially result in cognitive difficulties, the majority of which remain not fully explained by stroke-related factors.
Abstract P585: Age- and Sex-Specific Temporal Trends in the Incidence of Pediatric Stroke in New York State From 2006-2016
Authors: Vanguru Husitha R , Anikpezie Nnabuchi , Albright Karen C , Latorre Julius G , Otite Fadar O
Published: March 2021

Objectives:
1. To estimate sex- and race-specific incidence of pediatric stroke by age group 2. To describe trends in pediatric stroke incidence in New York(NY) from 2006 to 2016

Methods:
International Classification of Disease codes were used to retrospectively to identify all acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral venous thrombosis (CVT) admissions in pediatric patients (0-19 years old [yo]) in the 2006-2016 NY State Inpatients Database (SID; total N=4,083). Incident counts were combined with annual US Census data to compute age- and sex-specific incidence. Joinpoint regression was used to evaluate trends in incidence over time.

Results:
Across the study period, 52% of all pediatric strokes were AIS, 23% ICH, 11% SAH, and 14% CVT. Total stroke incidence/100,000 population was 47.8 and the age-standardized incidence in >=1yo was 4.8. Incidence differed by age (1-4yo: 4.4, 5-9yo: 3.6, 10-14yo: 4.5, and 15-19yo: 6.7), but not by sex. Age-standardized incidence of strokes in >=1yo also differed by race (Blacks 5.9, Whites 4.0, Hispanics 3.3, Asians/Pacific Islanders 3.1). While there was no change in overall stroke, AIS, or SAH incidence, ICH (annualized percentage change [APC] 4.3%, 95%CI 1.7-6.9) and CVT (APC 4.1, 95%CI 1.22-6.25%) increased over time. When stratified by age, overall stroke incidence increased over time in 15-19 yo (APC 1.3%, 95%CI 0.27-2.35, p=0.019), but not in other age groups.

Conclusion:
We observed increasing incidence in pediatric ICH, CVT, and overall stroke in 15-19 yo in the state of NY. Pediatric stroke incidence in NY is disproportionately higher in blacks compared to other races. Further investigation is warranted to determine the association of these changes with risk factors, lifestyle and systems of care.
Abstract P587: A Standardized MRA Scanning Protocol Leading to Changes in Stroke Prevention Treatment Plan for Pediatric Sickle Cell Patients
Authors: Dhillon Parmpreet , Morrone Kerry , Hsu Kevin , Lax Daniel , Mitchell William
Published: March 2021

Background and Purpose:
Magnetic Resonance Angiography (MRA) is performed on pediatric patients with sickle cell disease (SCD) to classify degree of cerebrovascular stenosis, informing stroke risk and treatment plan for stroke prevention. Flow artifact intrinsic to MRA with technician dependent factors can lead to over-interpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol.

Methods:
A standardized MRA scanning protocol with an echo time (TE) of <5msec based on the SWiTCH (Stroke With Transfusions Changing to Hydroxyurea) study protocol for patients with SCD was implemented at Montefiore Medical Center, NY (MMC) in May 2016. This project included a retrospective chart review of patients at MMC ≤ 21 years of age with SCD who had one MRA head pre-May 2016 AND one MRA post-May 2016. Of the 81 patients that met inclusion criteria, 29 patients were found to have cerebral vasculopathy on pre-May 2016 imaging and included in the analysis. Level of arterial stenosis on MRA, TE, and treatment plans were documented both pre- and post-May 2016. McNemar analysis was used to determine the significance of change in treatment plans before and after implementation of the standardized MRA scanning protocol.

Results:
24/29 (83%) patients were on chronic transfusion therapy for cerebrovascular disease pre-May 2016 whereas 18/29 (62%) required chronic transfusion therapy post May 2016. Notably, 6 patients had a resolution of cerebral vasculopathy leading to discontinuation of chronic

transfusion therapy whereas 0 patients required escalation of therapy to chronic transfusions. McNemar analysis showed this difference to be statistically significant (p = 0.042).

Conclusion:
Implementing a standardized MRA scanning protocol allowed for chronic transfusion therapy, which has potentially significant side effects, to be discontinued in 6 out of 24 patients. Minimizing flow artifact with TE <5msec can improve accurate interpretation of true cerebrovascular disease and ensure appropriate treatment plans are in place for stroke prevention.
Abstract P588: A Rare RNF213 Variant is Associated With Moyamoya Disease in an African American Family
Authors: Sunmonu N. Abimbola , Thomas Matthew , Ulep Robin , Ambati Naveen A , Worrall Bradford B
Published: March 2021

Objective:
To investigate potential genetic susceptibility for moyamoya disease (MMD) in an African American family.

Methods:
A young girl with MMD (proband), her father and paternal half-brother underwent cerebrovascular imaging with MRI and MRA. Cerebral angiography was also performed on the girl and her father. Genetic analysis of the MMD susceptibility gene RNF213 was conducted on all three relatives, while ACTA2 gene was analysed in the proband only.

Results:
The proband presented with pseudobulbar affect and chorea, then subsequently had a right hemispheric ischaemic stroke and rapid, ultimately fatal clinical decline. Detailed family history raised suspicion for familial MMD and investigation of her relatives. Her father had a small haemorrhagic thalamic stroke without residual neurologic deficits; a clinically silent ischaemic infarct was incidentally discovered on neuroimaging. He remains clinically stable despite slowly progressive disease on imaging. Her brother is neurologically intact and has normal cerebrovascular imaging to date. They are all heterozygous for the rare Arg4131Cys variant in RNF213. They are the first Black people and only the 3rd, 4th and 5th people in the world known to harbour this variant. MMD was confirmed in the girl and her father with cerebral angiogram.

Conclusions:
This study illuminates the clinical and genetic complexity of familial MMD. It underscores the importance of genetic testing and surveillance cerebrovascular imaging even in asymptomatic relatives of probands with MMD. Although the clinical significance of Arg4131Cys remains unclear, modest variant-disease segregation in this family is consistent with a growing body of evidence supporting its probable pathogenicity. Furthermore, our study illustrates its wide phenotypic spectrum, from asymptomatic carrier to late presenting, mild disease to fulminant, rapidly fatal childhood disease. To our knowledge, this is also the first report of heritable MMD in a Black family. We demonstrate the value of considering diseases more predominant in one specific ancestry when evaluating patients from other ethnic backgrounds. Finally, we highlight the importance of racially and ethnically diverse participants in biomedical research.
Abstract P591: A Significant Dose-Response in Elevated Troponin Levels for Case-Fatality Among Patients With Acute Ischemic Stroke
Authors: Kleindorfer Dawn , Sucharew Heidi , Haverbusch Mary , Alwell Kathleen S , Rothenberg Florence , WASHKO DANIEL , Demel Stacie L , Merkler Alexander E , Jasne Adam , Slavin Sabreena , De Los Rios La Rosa Felipe , Woo Daniel , Mackey Jason , Mistry Eva , Coleman Elisheva R , Walsh Kyle B , Star Michael , Kissela Brett M
Published: March 2021

Introduction:
About 21% of acute ischemic stroke (AIS) patients present to medical attention with an elevated cardiac troponin (cTn). Previously, we described that elevated cTn is associated with an increased case-fatality at 1 year. However, it is not clear if there is a dose-dependent relationship between cTn and case-fatality, or if this effect is related to causes of death.

Methods:
Within a catchment area of 1.3 million we screened local hospital admissions using ICD-9/10 codes 430-436/I60-I68, G45-46 in 2014/2015, and ascertained all physician-confirmed AIS cases by retrospective chart review. Positive cTn was defined by the standard 99th percentile. To account for by hospital variance in cTn results in machine brands and normal ranges, cTn values were log-transformed and centered. Case fatality at 1 year and cause of death was obtained from the National Death Index database. Logistic regression evaluated the impact of cTn on case fatality, and included demographic and clinical risk factors in the model. The percentage with all-cause and cardiac/non-cardiac case-fatality was computed by quartiles of centered cTn levels and compared using the chi-square test.

Results:
In 2014/2015, there were 2989 AIS cases ascertained, which were 53% female, 30% black, with a mean age of 70 (SD 14). 441 patients with hypertropinemia were included in the analysis. See Table for case fatality at 1 year by quartile of centered cTn levels. There was no association between cTN and non-cardiac case-fatality. After adjustment for demographic and clinical characteristics, every 0.5 point increase in the centered cTn level increased the cardiac case-fatality by OR 1.19 (1.09, 1.31), p<0.01.

Discussion:
We found that the impact of hypertropinemia on case fatality after AIS appears to be a dose-dependent association: as cTn increases, so does the cardiac case-fatality. This suggests that the degree of cTn elevation is likely an important prognostic marker for cardiac death in AIS patients.
Abstract P592: Admission Hyperglycemia is Associated With Subsequent Ischemic Stroke After Transient Ischemic Attack or Minor Stroke: A Secondary Analysis of the POINT Trial
Authors: Mac Grory Brian C , Yaghi Shadi , Shah Shreyansh , Chhatbar Pratik Y , Graffagnino Carmelo , Le Scott , Kam Wayneho , El-Husseini Nada , Ehrlich Matthew , Schrag Matthew , Xian Ying , Johnston S Claiborne , Feng Wayne
Published: March 2021

Introduction:
Hyperglycemia is associated with increased lesion volume and worse functional outcome after acute ischemic stroke, however, it is not known whether it is associated with further cerebrovascular events. The aim of this study was to examine the association between admission hyperglycemia and subsequent ischemic stroke.

Methods:
This was an exploratory analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which compared combined clopidogrel/aspirin with aspirin alone with respect to the primary outcome of subsequent ischemic stroke, myocardial infarction, or vascular death. We dichotomized patients based on a serum glucose threshold of 180mg/dl (chosen
a priori
based on the upper boundary of the active control arm of SHINE). We calculated hazard ratios (HR) for subsequent ischemic stroke at 90 days via a Cox proportional hazards model adjusting for age, sex, study treatment assignment and vascular risk factors. We performed sensitivity analyses excluding patients with a known history of diabetes and in patients whose index event was a TIA vs. minor stroke.

Results:
Of 4,878 patients in this analysis (mean age 64.6 years), 594 (12.2%) were hyperglycemic on presentation and 267 (5.5%) had a subsequent ischemic stroke within 90 days. Admission hyperglycemia was associated with subsequent ischemic stroke (HR 1.88; 95% CI:1.39-2.53, p<0.01). This association persisted after adjustment for relevant covariates (aHR 1.86, 95% CI: 1.37-2.52, p<0.01), in non-diabetic patients (n=3,529, aHR 3.1, 95% CI:1.7-5.7, p<0.01), in patients with TIA (n=2,327, aHR 2.2, 95% CI: 1.2-4.1, p<0.01), and in patients with minor ischemic stroke (n=2,304, aHR = 1.5, 95% CI: 1.1-2.2, p=0.02).

Conclusions:
Hyperglycemia portends a higher risk of subsequent ischemic stroke after adjusting for known predictors of stroke recurrence. This study may provide further support to pursuing aggressive secondary prevention strategies in this population.
Abstract P594: Cardiac Natriuretic Peptides for Diagnosis of Covert AtrialFibrillation After Acute Ischemic Stroke: A Meta-Analysis of Diagnostic Accuracy Studies
Authors: Zhang Kejia , Kamtchum Tatuene Joseph , Li Mingxi , Jickling Glen C
Published: March 2021

Background and purpose:
Detection of atrial fibrillation (AF) after acute ischemic stroke is pivotal for the timely initiation of anticoagulation to prevent recurrence. Besides heart rhythm monitoring, various blood biomarkers have been suggested as complimentary diagnostic tools for AF. We aimed to summarize data on the performance of cardiac natriuretic peptides for the diagnosis of covert AF after acute ischemic stroke and to assess their potential clinical utility.

Methods:
We searched PubMed and Embase for prospective studies reporting the performance of B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the diagnosis of covert AF after acute ischemic stroke. Summary diagnostic performance measures were pooled using bivariate meta-analysis with random-effects model.

Results:
We included six studies focusing on BNP (n = 1930) and three studies focusing on NT-proBNP (n = 623). BNP had a sensitivity of 0.83 (95% CI: 0.64-0.93), a specificity of 0.74 (0.67-0.81), a positive likelihood ratio of 3.2 (2.6-4.0), and a negative likelihood ratio of 0.23 (0.11-0.49). NT-proBNP had a sensitivity of 0.91 (0.65-0.98), a specificity of 0.77 (0.52-0.91), a positive likelihood ratio of 3.9 (1.8-8.7), and a negative likelihood ratio of 0.12 (0.03-0.48). Considering a pre-test probability of 20%, BNP and NT-proBNP had post-test probabilities of 45% and 50%.

Conclusions:
NT-proBNP has a better performance than BNP for the diagnosis of covert AF after acute ischemic stroke. Both biomarkers have low post-test probabilities and may not be used as a stand-alone decision-making tool for the diagnosis of covert AF in patients with acute ischemic stroke. However, they may be useful for a screening strategy aiming to select patients for long-term monitoring of the heart rhythm.
Abstract P60: Xanthine Oxidase Mediates Cerebrovascular Dysfunction in Chronically Stressed Female Mice
Authors: Burrage Emily N , Coblentz Tyler , Childers Ryan , Price Christian , Bryner Randy , Frisbee Jefferson C , Chantler Paul D
Published: March 2021

Chronic stress is a risk factor for many cerebrovascular diseases including stroke and vascular dementia. Our lab has preciously shown that chronic stress in male mice and rats reduces cerebrovascular function, mediated by an increase in oxidative stress, potentially via the xanthine oxidase pathway. However, the role of xanthine oxidase on cerebrovascular function in female mice has yet to be explored. Here, we examined the effect of chronic stress on middle cerebral artery function and xanthine oxidase expression in female mice. At 18 weeks of age, mice underwent the unpredictable chronic mild stress (UCMS; 5days/week for 7hrs/day) paradigm to elicit a chronic stress phenotype. On week 26, mice were euthanized and the middle cerebral arteries (MCA) were removed and positioned in a pressurized myobath. To test for vessel health, the MCA was exposed to increasing concentrations of acetylcholine (Ach; 10-9M to 10-4M) in the presence or absence of febuxostat (10uM), a xanthine oxidase inhibitor as well as increasing doses of phenylephrine (PE; 10-9M to 10-4M) and sodium nitroprusside (SNP; 10-9M to 10-4M). Coronal sections of brain tissue were then stained for the xanthine oxidase enzyme, imaged using a Nikon Eclipse 800 and fluorescence intensity was analyzed via ImageJ. MCA dilation to Ach was impaired in female mice that underwent UCMS compared to control mice (9.5±1um vs 20±1um; p<0.05). Incubating the MCA with febuxostat had no effect on control mice but improved MCA dilation in the UCMS mice (9.5±1um to 17±0.5um; p<0.05). No differences were found between control vs UCMS groups in response to PE or SNP. To support this, preliminary data (n=3-4/group) shows a trend of increased fluorescence intensity of xanthine oxidase expression within the somatosensory cortex of the mice exposed to UCMS compared to controls (41,666±2,923AU vs 31,091±3,759AU, respectively; p=0.059). Together, these data suggest increased xanthine oxidase activity plays a role in cerebrovascular dysfunction in female mice.
Abstract P600: Social Network Structure and Function Are Associated With Blood Pressure Reduction in Stroke Survivors
Authors: Boden-Albala Bernadette , Roberts Eric T , Stern-Nezer Sara , Goldmann Emily , Parikh Nina , Appleton Noa , Drum Emily , O’Connor Joyce , Lakon Cynthia , Ryan Nessa , Parides Michael
Published: March 2021

Background:
The risk of recurrence of stroke has been found to be modifiable through changes in health behavior and reducing key risk factors such as hypertension. Evidence suggests social networks can influence health behaviors and health outcomes; however, there is a lack of literature on the relationship between stroke survivor’s social network and secondary prevention efforts. In this study, we assessed the association between social network structure and systolic blood pressure (SBP) reduction at one-year post stroke.

Methods:
Using data from the DESERVE (Discharge Educational Strategies for Reduction of Vascular Events) trial, we assessed the social networks of 552 participants who have had a mild/moderate stroke or transient ischemic attack (TIA). At baseline enrollment, participants were asked to identify up to 5 persons, or “alters,” with whom they discuss important matters, such as health. The data on the alters were then classified into structural and functional characteristics. The combination of the number of alters and the amount of alters that met the “optimal” level for each characteristic were used to determine the characteristics of the social network. We used linear regression models to quantify the SBP change on social network characteristics adjusting for age, gender, race-ethnicity, education, marital status, and prior stroke history.

Results:
Stronger social networks were associated with greater SBP reduction. The overall mean SBP reduction at 12-month follow-up was 5.6 (±24.5) mmHg. On fully adjusted models having 3-5 alters compared to none (mean SBP reduction of 11.4 mmHg, p = 0.01) and having a family and friend network compared to a family-only network (mean SBP reduction of 7.6 mmHg, p = 0.01) were significantly associated with a larger SBP reduction.

Conclusion:
Social networks may play an important role in blood pressure reduction in patients post stroke. Future interventions should involve social networks to help reduce vascular risk and enhance secondary prevention efforts.
Abstract P602: Stroke Risk Factors Among the Young Over Time in the GCNKSS
Authors: Madsen Tracy E , Khoury Jane C , Alwell Kathleen S , Adeoye Opeolu M , De Los Rios La Rosa Felipe , Coleman Elisheva R , Demel Stacie L , Ferioli Simona , Flaherty Matthew L , Jasne Adam , Haverbusch Mary , Khatri Pooja , Mackey Jason , Martini Sharyl R , Mistry Eva , Slavin Sabreena , Star Michael , Walsh Kyle B , Woo Daniel , Broderick Joseph P , Kissela Brett M , Kleindorfer Dawn
Published: March 2021

Background:
Data from the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) have demonstrated stable or increasing stroke incidence rates in young adults with differences by sex and race, suggesting the need for targeted approaches to stroke prevention in the young. We aimed to describe trends over time in prevalence of stroke risk factors among adults ages 20-54 with stroke by sex and race.

Methods:
Cases of incident stroke (IS, ICH, SAH) occurring in those 20-54 years old and living in a 5-county area of southern Ohio/northern Kentucky were ascertained during 5 study periods (1993-1994, 1999, 2005, 2010, 2015). All physician-adjudicated inpatient events and a sampling of outpatient events were included, excluding nursing home events. Data on risk factors (hypertension, diabetes, obesity (BMI≥30), and high cholesterol) diagnosed prior to stroke were abstracted from medical records, and prevalence of each risk factor was reported over time in race/sex groups. Trends over time were examined using the Cochran-Armitage test.

Results:
Over the 5 study periods, 1204 incident strokes were included; 49% were women, 33% were black, and mean age was 46 (SD 7) years. Premorbid hypertension increased over time in Black women (48% in 1993/4 to 76% in 2015, p=0.005) but not in any other race/sex group (all p>0.05). Premorbid high cholesterol increased significantly in all race/sex groups (Figure, all p<0.05) except for White men (p=0.06). There were no significant trends over time in pre-stroke diagnoses of diabetes or obesity in any of the race/sex groups (Figure).

Conclusions:
Among patients aged 20-54 with incident stroke in a large population-based study, the change in the prevalence of hypertension and high cholesterol differed by sex and race, while obesity and diabetes were stable over time in all race/sex groups. Future research is needed to address risk factor control at a population level and to understand the role of undiagnosed pre-stroke risk factors in the young.
Abstract P604: Incidentally-Discovered Asymptomatic Ischemic Lesions Identified Using Natural Language Processing Are Strong Risk Markers for Future Ischemic Stroke
Authors: Kent David M , Leung Lester Y , Zhou Yichen , Luetmer Patrick H , Kallmes David F , Fu Sunyang , Zheng Chengyi , Liu Hongfang , Chen Wansu
Published: March 2021

Background:
White matter disease (WMD) and silent brain infarction (SBI) are known to be risk markers for stroke. Nevertheless, the predictive value of these changes when seen incidentally on routinely-obtained neuroimages is unknown.

Methods:
In this retrospective cohort study, Kaiser Permanente-Southern California health plan enrollees aged ≥ 50 years old with a brain CT or MRI scan between 2009-2019 and without a prior history of ischemic stroke, transient ischemic attack, or dementia were identified. Natural language processing (NLP) was used to identify patients with SBI and WMD on the index neuroimaging report. We used Cox proportional hazards to estimate the risk of future ischemic stroke associated with the presence of SBI and of WMD, controlling for major stroke risk factors.

Results:
Among 262,875 individuals receiving brain neuroimaging, 13,154 (5.0%) and 78,330 (29.8%) had SBI and WMD, respectively. The Table below summarizes the crude stroke incidence rates. The crude hazard ratio (HR) was 3.40 (95% CI 3.25-3.56) for SBI and 2.63 (95% CI 2.54-2.71) for WMD. In the multivariable model controlling for all major stroke risk factors, the effect of SBI was found to be stronger in younger versus older patients and for MRI- versus CT-discovered lesions. With MRI, the average adjusted HR over time was 2.95 (95% CI 2.53-3.44) for those < age 65 and 2.15 (95% CI 1.91-2.41) for those ≥ age 65. With CT scan, the average adjusted HR over time was 2.48 (95%CI 2.19-2.81) for those < age 65 and 1.81 (95% CI 1.71-1.91) for those ≥ age 65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69-1.82) and was not modified by age or imaging modality. The effect of SBI decreased gradually over time, while the effect of WMD remained constant.

Conclusion:
Incidentally-discovered SBI and WMD are common in patients ≥ age 50 and are associated with substantial increases in the risk of subsequent symptomatic stroke. The findings may represent an opportunity for stroke prevention.
Abstract P605: Border-Zone Infarcts Predict Early Recurrence in Patients With Large Artery Atherosclerotic Subtype Despite Medical Treatment
Authors: Kvernland Alexandra , Prahbakaran Shyam , Khatri Pooja , De Havenon Adam H , Yeatts Sharon D , Scher Erica , Torres Jose L , Ishida Koto , Frontera Jennifer , Lord Aaron , Liebeskind David S , Yaghi Shadi
Published: March 2021

Objective:
We aim to investigate infarct patterns and 90-day recurrence in patients with symptomatic intracranial atherosclerotic disease.

Background:
Large artery atherosclerosis subtype carries a high risk of early recurrent stroke despite medical management. Predictors of recurrence remain poorly understood. We hypothesized that border-zone infarcts are associated with a higher risk of recurrence.

Design/Methods:
We included consecutive patients admitted to NYU Langone Health (Manhattan and Brooklyn campuses) over 32-months with a diagnosis of acute ischemic stroke secondary to symptomatic intracranial or tandem atherosclerosis. Patients with purely extracranial stenosis were excluded. The primary predictor was infarct pattern (border-zone vs. non-border-zone infarction), defined in accordance to previous studies. We used univariate and multivariable cox-regression models to determine associations between infarct pattern and recurrent cerebrovascular events (RCVE) at 90-days.

Results:
Ninety-nine patients met the inclusion criteria; 95 were intracranial and 4 were tandem lesions. The mean age was 70 years, 58.6% were men, 15.1% Black and 16.1% Asian. The median symptom onset to arrival time was 1 day, nearly 74.7% of patients were treated with dual antiplatelet therapy and 99% were treated with high intensity statin. Within 90 days of follow up, 19.2% (19/99) had RCVE. In univariate analyses, the only factor associated with RCVE was border-zone infarct pattern when compared to non-border-zone infarct pattern (30.2% vs. 10.7%, p=0.02). In cox regression models, after adjusting for age and sex, border-zone infarct pattern was associated with increased risk of RCVE (adjusted HR 3.21 95% CI 1.21-8.51, p=0.019). Sensitivity analyses excluding patients with tandem lesions (n = 4) did not meaningfully change our findings (adjusted HR 3.04 95% CI 1.11-8.31, p=0.031).

Conclusions:
In real world post-SAMMPRIS medically treated patients with ICAD, infarct pattern was predictive of 90-day RCVE. Border-zone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for this high-risk cohort.
Abstract P606: Hemodynamic Predictors of Multiple Recurrent Strokes in the Patients With Prior Lacunar Stroke
Authors: de Havenon Adam H , Kvernland Alexandra , Delic Alen , Wong Ka-ho , Sheibani Nazanin , Yaghi Shadi
Published: March 2021

Background:
Recurrent stroke has higher morbidity and mortality than incident stroke. We evaluated hemodynamic risk factors for multiple recurrent strokes.

Methods:
We included patients in the SPS3 trial. The primary predictor was the top tertile, compared to the bottom tertile, of the mean systolic blood pressure (mSBP) and blood pressure variability represented as standard deviation (sdSBP) using blood pressures from day 30 of the trial to the end of follow-up. We excluded blood pressures from the first 30 days to reduce confounding from the trial’s intervention. We fit a logistic regression model to ≥2 recurrent strokes from day 30 to the end of follow-up and, to accurately analyze the multiple failure-time data, we ordered the multiple failure events to the Prentice, Williams and Peterson extension of the Cox proportional-hazards model.

Results:
We included 2,882 patients, of which 223 had a recurrent stroke and 41/223 had ≥2 recurrent strokes for a total of 272 strokes. The mean (SD) number of blood pressure readings was 78.0 (37.4). The etiology of the 272 strokes was 161 (59.2%) lacunar, 22 (8.1%) intracranial atherosclerosis, 10 (3.7%) extracranial atherosclerosis, 24 (8.8%) cardioembolic, and 55 (20.2%) cryptogenic or other. In both unadjusted and adjusted logistic regression models and PWP Cox models, the top tertile of sdSBP was consistently predictive of multiple recurrent strokes, while mSBP was not (Tables 1/2).

Conclusions:
We found that in patients with an index lacunar stroke, higher SBP variability, but not mean SBP, was predictive of multiple recurrent strokes of varying mechanisms.
Abstract P609: Restarting Anticoagulant Therapy After Intracranial Hemorrhage With Atrial Fibrillation: A Nationwide Retrospective Cohort Study
Authors: Shin Dong Hoon , Jung Jaehun , Bae Gi Hwan
Published: March 2021

Background:
Atrial fibrillation (AF) should be treated with anticoagulants to prevent stroke and systemic embolism. Resuming anticoagulation after intracerebral hemorrhage (ICH) poses a clinical conundrum. The absence of evidence-based guidelines to address this issue has led to wide variations in restarting anticoagulation after ICH. This study aimed to evaluate the risks and benefits of anticoagulation therapy on all-cause mortality, severe thromboembolism, and severe hemorrhage and compare the effect of novel direct oral anticoagulants (NOACs) with warfarin on post-ICH mortality in patients with AF.

Methods:
This retrospective cohort study was performed using health insurance claim data obtained between 2002 and 2017 from individuals with newly developed ICH with comorbid AF. We excluded participants aged < 40 years and those with traumatic ICH, subdural hemorrhage, or subarachnoid hemorrhage. The primary endpoint was all-cause mortality, and the secondary endpoints were severe thrombotic and hemorrhagic events. Anticoagulants, antiplatelet agents, and non-users were analyzed for survival with propensity score matching.

Results:
Among 6735 participants, 1743 (25.9%) and 1690 (25.1%) used anticoagulants and antiplatelet agents, respectively. Anticoagulant (HR, 0.321; 95% CI, 0.264-0.390; P < 0.0001) or antiplatelet users (HR, 0.393; 95% CI, 0.330-0.468; P < 0.0001) had a lower risk of all-cause mortality than non-users. However, there was no difference between the two drug users (HR, 1.183; 95% CI, 0.94-1.487; P = 0.152; reference: anticoagulant). The risk of acute thrombotic events, although not hemorrhagic events, was significantly lower in anticoagulant users than in antiplatelet users. In addition, anticoagulation between 6 to 8 weeks post-ICH showed a tendency of the lowest risk of death. Further, NOACs were associated with a lower risk of all-cause mortality than warfarin.

Conclusions:
Our results showed that in patients with AF, resuming anticoagulants between 6 and 8 weeks after ICH improved all-cause mortality, severe thromboembolism, and severe hemorrhage. Further, compared with warfarin, NOAC had additional benefits.
Abstract P612: Iron Deficiency Anemia and Ischemic Stroke in Patients With Pulmonary Arteriovenous Fistulas
Authors: Topiwala Karan , Patel Smit , Pervez Mubashir , Shovlin Claire , Alberts Mark J
Published: March 2021

Introduction:
Pulmonary-arteriovenous-fistulas (PAVFs) are pathologic right-to-left shunts resulting in paradoxical embolism causing acute-ischemic-stroke (AIS). Recent single-center studies have identified that in patients with AIS associated with PAVF (AIS-P), traditional stroke risk-factors are not prominent and instead stroke-risk is associated with low serum iron. Single-centre studies have the risk of introducing a selection bias, while multicentre trials are challenging since PAVF still remains a rare and under-recognised entity. We thus seek epidemiological validation of such stroke predictors in patients with PAVF.

Methods:
We conducted a retrospective analysis of all AIS-admissions within the Nationwide-Inpatient-Sample (NIS) database (2005-2014). Baseline characteristics were compared across AIS populations [AIS-P (with PAVF) and R(routine)-AIS (without PAVF)]. We also compared morbidity, mortality and management trends of AIS in patients with and without PAVF.

Results:
Of 4,271,910 patients admitted with AIS, 822 (0.02%) were diagnosed with a PAVF. Over this decade the prevalence of PAVF per million AIS-admissions, rose from 197 to 368 (P
trend
=0.026). Patients with PAVF were younger with a median age (IQR) of 57.5 (42.2 -70.4) years
vs.
72.5 (60.8-82.1) years (p<0.001); but had comparable age-adjusted inpatient morbidity (χ
2
p=0.71) and all-cause mortality (χ
2
p=0.26). On multivariate analyses, the odds ratios (95% confidence-interval) favouring PAVF as the cause for AIS were 9.0 (6.79-11.94) for hypoxemia, 4.64 (3.84-5.60) for patent-foramen-ovale, 4.52 (3.42-5.97) for pulmonary hypertension, 4.07(2.23-7.44) for epistaxis, and 2.12 (1.60-2.82) for iron deficiency anaemia [all p-values <0.001].

Conclusion:
Pulmonary-arteriovenous-fistula related AIS represents a significantly younger demographic, which suffers inpatient morbidity and mortality comparable to routine ischemic-stroke. They carry a unique set of stroke-risk markers, including treatable conditions such as iron deficiency anemia. Further studies are needed to examine a causal role for such markers on ischemic-stroke risk in this cohort.