bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract W MP109: Childhood Cerebral Sinovenous Thrombosis (CSVT): Long-Term Neuropsychological Outcomes
Authors: Aziz Aly , Westmacott Robyn , Pontigon Ann-Marie , deVeber Gabrielle , MacGregor Daune , Askalan Rand , Yau Ivanna , Moharir Mahendranath
Published: July 2021

Background:
Outcome from childhood CSVT particularly in infants is poor. Most studies report “general” neurological outcomes; few describe neuropsychological outcomes specifically.

Objectives:
To study the spectrum of neuropsychological deficits following childhood CSVT.

Methods:
Retrospective review of clinical data [incl pediatric stroke outcome measure (PSOM)] & neuropsychological testing (NPT) from 1995-2011 was conducted. NPT included IQ [Wechsler Intelligence Score for Children (WISC-IV), Wechsler Preschool & Primary Scale of intelligence (WPPSI-III)], executive function [Behaviour Rating Inventory of Executive Function (BRIEF)] & attention [Test of everyday attention for children (Tea-Ch)]. Full scale IQ (FSIQ) included verbal comprehension (VCI), perceptual reasoning (PRI), working memory (WMI) & processing speed (PSI) index.

Results:
NPT was performed in 48/206 subjects. 41 (34 males) were analyzed [excl: cavernous sinus thrombosis (5), prematurity (1), concurrent arterial stroke (1)]. Mean age at NPT: 5.4-y (neonatal CSVT) and 8.5-y (non-neonatal CSVT; mean time from CSVT to NPT 2.4-y). NPT was abnormal (atleast 1SD below mean) in 87% patients in one (29%) or multiple (58%) tests. FSIQ was abnormal in 64% [VCI-69%, PRI-80%, WMI-71%, PSI-79%). Compared to normative population, patients scored significantly lower on FSIQ (p=0.026), VCI (p=0.608), PRI (p= 0.032), WMI (0.124) and PSI (p=0.007). No significant difference was seen in FSIQ between groups [neonates/non-neonates (p=0.827), single/multiple sinus (p=0.2), present/absent parenchymal lesions (p=0.991)]. However males scored significantly lower on FSIQ (p=0.006), PRI (p=0.004), WMI (p=0.002)& PSI (p=0.002)] but not on VCI (0.69)]. BRIEF [metacognition (p=0.061) & executive composite (p=0.095)] & Tea-Ch (p=0.046) scores were also poorer in males. Mean cognitive/behaviour sphere score (max 2.0) of PSOM (assessed closest to NPT) was worse in males (0.41) than females (0.14).

Conclusions:
Majority of childhood CSVT survivors (males > females) have detectable cognitive deficits on detailed NPT on long term follow-up. NPT is useful in accurate assessment of CSVT outcome & could guide academic interventions. Larger studies are needed to replicate these findings.
Abstract W MP27: Time to Peak Troponin T Levels Following Subarachnoid Hemorrhage
Authors: Duello Katherine , Nagel Jay P , Freeman William D , Blackshear Joseph L , Miller David A
Published: July 2021

Introduction:
Elevations of troponin after subarachnoid hemorrhage (SAH) frequently occur and are associated with cardiopulmonary complications. The time to peak elevation remains poorly described in terms of the natural history after SAH. Our two objectives were to define the temporal profile of troponin T elevation after SAH and correlate levels of troponin T with baseline neurological status. We hypothesized that troponin T would peak early after initial presentation.

Methods:
We reviewed the medical records of all aneurysmal and non-traumatic SAH patients from March 2011-December 2012. Troponin T from patients with ≥ 2 values was recorded with respect to SAH symptom onset. Patients with ≥ 1 Troponin T value were stratified according to admission Glasgow Coma Scale (GCS). GCS was dichotomized to > 8 or ≤ 8. Fisher’s exact test was performed comparing elevated peak troponin T (≥0.01 ng/ml) versus normal against GCS status cutoffs > 8 or 8 or less.

Results:
We identified 124 patients who had both troponin T and GCS reported, and 30 patients had ≥2 troponin T measurements within the first 40 hours of hospitalization. The median time to peak troponin T in these patients was 11.2 hours with a standard deviation of 6.2 hours (Range: 4.9-35.0 hours). Elevated troponin T was seen in 52 of 124. GCS of ≤ 8 was present in 43 of 124. Patients with elevated levels of troponin T had a greater chance of lower GCS [Odds ratio = 4.8 (95% CI: 2.2 to 10.7)] (P= <0.0001).

Conclusions:
The median time to peak troponin T after SAH injury was 11 hours. There was a statistically significant association between troponin T elevation and worse neurologic status at presentation (GCS ≤ 8). Although our small sample size found large variation in time to peak troponin, it supports the hypothesis that troponin peaks early after the initial presentation. Future studies using troponin elevation as a biomarker should focus on sample acquisition at the time of admission and in the first 1-2 days.
Abstract W MP42: Early Treatment With Minocycline Promotes Neurovascular Remodeling of Tight Junctions Facilitating Recovery After Stroke in Rat Brain
Authors: Yang Yi R , Salayandia Victor M , Estrata Eduardo Y , Thompson Jeffrey F , Rosenberg Gary A , Yang Yi
Published: July 2021

Minocycline (Mino) reduces reperfusion injury and inflammation after stroke in animals and humans, but the late effects on remodeling of the neurovascular unit are less well studied. Previously, we showed that tight junction proteins (TJPs) disappeared from microvessels after reperfusion injury, reappearing in newly formed vessels in peri-infarct regions (peri-I) at 3 weeks, and that MMPs are involved in BBB restoration during recovery. Prior studies of Mino investigated short-term neuroprotective effects with or without tPA. We hypothesized that early treatment with Mino would improve neurovascular remodeling during recovery. To test the hypothesis, we monitored the time course of neurovascular remodeling after spontaneous and Mino-induced stroke recovery. Adult spontaneously hypertensive rats had a 90 min transient MCAO with reperfusion. At the onset of reperfusion they received a single dose of Mino (3 mg/kg, i.v.) or vehicle. They were studied at multiple times up to 4 weeks with MRI, immunohistochemistry, and biochemistry. A single dose of Mino significantly reduced the infarct size and tissue loss in the ischemic hemispheres compared to vehicle-treated rats from 2 to 4 weeks as measured with anatomical T2 MRI and ADC. FA measured at 4 weeks showed improved white matter recovery. ASL showed that Mino improved cerebral blood flow in peri-I by 7 days after reperfusion. BBB permeability in peri-I was reduced with Mino at 4 weeks using dynamic contrast-enhanced MRI. By 4 weeks, Mino induced higher levels of TJPs (occludin, ZO-1, and claudin-5), and MMP-3. We found that active microglia/macrophages, surrounding and within the peri-I, expressed both pro-inflammatory factors (TNF-α and IL-1β) and anti-inflammatory factors (TGF-β and IL-10) at 4 weeks. Western blot analysis showed that treatment with Mino significantly reduced levels of TNF-α and IL-1β, and increased levels of TGF-β and IL-10. Our results suggest that the early treatment with Mino significantly promotes later neurovascular remodeling during stroke recovery by: 1) reducing brain tissue loss; 2) enhancing TJP formation in newly formed vessels; and 3) accelerating functional alteration of microglia activation from pro-inflammatory stage to anti-inflammatory stage.
Abstract W MP47: Mitochondrial P53 Inhibition Abolishes Detrimental Effect of Post-Stroke Isolation on Ischemic Injury
Authors: venna Venugopal R , O'Keefe Lena M , Xu Yan , Verma Rajkumar , Patrizz Anthony , Friedler Brett , McCullough Louise D
Published: July 2021

Background:
Social isolation is an important contributing risk factor for increased stroke injury and delayed functional recovery. Although previous studies strongly suggest that isolation prior to stroke increase injury in experimental models, little is known regarding the effects of SI after injury. Most patients do not seek medical attention until after the injury occurs; the ability to manipulate post-stroke housing environments has translational significance. In this study, we investigated the effects of post-stroke isolation.

Methods:
C57Bl6 mice were housed as pairs (PH), male with ovariectomized female for 2 weeks, then subjected to right middle cerebral artery occlusion and then assigned to single housing (SI) or continued PH. The effects of SI on infarct volumes and neurological deficit scores (NDS) at 72h were assessed. Brain lysates from a separate cohort at 6h post-stroke were used for mitochondrial p53, caspase3 and BCl2 protein levels by western blot. Using pifithrin-μ (PFT-μ), a mitochondrial p53inhibitor (2mg/kg given i.p. at 3h & 24h after stroke) we then explored the role of P53 on infarct in SI mice.

Results:
Post-stroke SI exacerbated infarct size compared to PH mice in males (Cortex: 61.6±4.8 vs 38.4±5.1; p<0.05); (Striatum: 79.2±6.1 vs 60.4±5.7; p<0.05); (Total: 58.1±4.6 vs 34.4±5.1; p<0.05). This effect is more pronounced in females (Cortex: 64.3±5.1 vs 37.1±3.1; p<0.01); (Striatum: 82.1±4.6 vs 56.5±4.6; p<0.01); (Total: 51.4±3.4 vs 30.3±3.8; p<0.01). PH mice displayed improved NDS compared to SI mice. The detrimental effects of SI are observed with an increase in mitochondrial p53 translocation (n=6/grp; p<0.05). Inhibition of mitochondrial p53 abolished the effects of SI and reduced TUNEL positive cells, suggesting that p53 plays a critical role in housing effects.

Conclusions:
We found that post-stroke SI leads to worse outcome in both males and females, along with increased mitochondrial p53 expression. P53 is a critical stress sensor activated in response to stress and ischemia. Inhibition of mitochondrial P53 by PFT-μ abolished the detrimental effects of SI on stroke volume and reduced apoptotic cell death. These findings suggest that mitochondrial P53 inhibition may minimize the detrimental effects of SI in stroke.
Abstract W MP53: Cerebrovascular Events Occurring after Hospital Discharge for Labor and Delivery
Authors: Sriram Nandita , Hovsepian Dominic A , Kamel Hooman , Navi Babak B
Published: July 2021

Introduction:
Stroke and other cerebrovascular events (CVE) are feared complications of pregnancy. Prior studies have reported an increased risk of CVE during the postpartum period, but these studies have not reported event rates after hospital discharge for labor and delivery.

Methods:
We performed a retrospective cohort study using the California State Inpatient and Emergency Department administrative databases to identify all pregnant women who went into labor at a non-federal, acute-care hospital from 2005 through 2011 and who were discharged without an ICD-9-CM diagnosis of cerebrovascular disease. The primary outcome was a CVE composite defined as any ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, cerebral sinus thrombosis, pituitary apoplexy, cerebral artery dissection, or hypertensive encephalopathy, occurring after hospital discharge and prior to 6 weeks after admission for labor and delivery. Descriptive statistics were used to calculate the incidence of postpartum CVE after hospital discharge and multivariate logistic regression was used to evaluate the association between several a priori selected clinical factors and postpartum CVE.

Results:
A total of 2,065,330 patients were included in this analysis. The rate of any CVE was 9.97 per 100,000 patients (95% CI 8.61-11.3). The mortality rate in patients with CVE was 7.8% (95% CI 4.1-11%). The mean age of patients with a CVE was 31.0 years as compared to 28.3 years in patients without a CVE (p<0.001). Risk factors for any CVE were eclampsia (OR 19.9, 95% CI 6.43-61.4), chronic kidney disease (OR 3.88, 95% CI 1.02-14.8), black race (OR 3.19, 95% CI 2.26-4.50), preeclampsia (OR 2.67, 95% CI 1.99-3.59), and age (OR 1.07 per year, 95% CI 1.05-1.09).

Conclusion:
The incidence of postpartum CVE after hospital discharge for labor and delivery is similar to rates reported for all postpartum events in prior publications. This suggests that a substantial proportion of postpartum cerebrovascular complications occur after hospital discharge. Therefore, clinicians should be aware that postpartum women remain at risk for stroke even if they have been discharged from their initial labor and delivery hospitalization without complication.
Abstract W MP54: Risk Factors for Nosocomial Infections after Intracerebral Hemorrhage and Their Impact on Outcome: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study
Authors: Lord Aaron S , Elkind Mitchell S , Langefeld Carl D , Moomaw Charles J , Badjatia Neeraj , Sekar Padmini , Vashkevich Anastasia , Rosand Jonathan , Kidwell Chelsea , Osborne Jennifer , Woo Daniel
Published: July 2021

Background:
Risk factors for nosocomial infections and their impact on ICH outcomes are unclear. We hypothesized that factors present on admission are associated with developing infection, and patients who develop infections have worse outcomes.

Methods:
We determined prevalence of infections among patients in ERICH, a multicenter, triethnic case-control study of ICH. Exclusion criteria specific to this analysis were incomplete CT data and death/withdrawal of care <72 hours after admission. Patients with infection <two weeks before ICH were excluded from risk factor analyses, but included for outcomes assessments. We compared prevalence of risk factors for infections using chi-square and non-parametric tests, and performed multivariate logistic regression for risk of infection.

Results:
We enrolled 1397 individuals, 144 of whom died/had withdrawal of care within 72 hours and 210 with incomplete CT data, leaving 1043 patients. Nosocomial infections occurred in 300 patients (29%). Factors associated with presence of infections included ICH volume (13mL vs. 7mL, p <0.0001), GCS on admission (13 vs. 15, p <0.0001), WBC > 10 (42% vs. 32%), and higher CRP levels (4.9 vs. 1.8, p=0.01). Blacks had higher infection rates versus whites and Hispanics (33% vs. 27% and 24%, p=0.06). Procedural factors associated with infection included ventriculostomy, intrathecal-tPA, and intubation, while major neurosurgical procedures were associated with a 10-fold increase in CNS infection (all p <0.001). Infections were associated with bowel-bladder dysfunction, CHF/pulmonary edema, decubiti, DVT, dysphagia requiring PEG, and MI. Patients with infection were more likely to have DNR/DNI orders or to be dead at discharge (12.3% vs. 6.5%, p=0.0017). In a multivariate model for factors associated with infection, ICH volume, HIV history, intubation, CHF/pulmonary edema, and dysphagia requiring PEG were all associated with infection.

Conclusion:
There are identifiable risk factors associated with nosocomial infection after ICH, and infections are associated with mortality. Identification of patients at risk for infections may improve outcomes after ICH.
Abstract W MP60: Atrial Fibrillation is Associated with Worse Collaterals in Acute Stroke: Angiography in the ENDOSTROKE Registry
Authors: Liebeskind David S , Nolte Christian H , Bohner Georg , Neumann-Haefelin Tobias , Hofmann Erich , Berkefeld Joachim , Singer Oliver C ,   for the ENDOSTROKE Study group
Published: July 2021

Background:
Risk factors for stroke may alter hemodynamics or invoke ischemic preconditioning, yet the impact of such factors on response to acute stroke treatment and the potential relationship with collateral circulation remains unknown.

Methods:
Consecutive cases enrolled in the International Multicenter Registry for Mechanical Recanalization Procedures in Acute Stroke (ENDOSTROKE) were analyzed with respect to collateral status on baseline angiography before endovascular therapy. ASITN/SIR collateral grade (0-1/2/3-4) was scored by the core lab, blind to all other data. Collateral grade was analyzed with respect to numerous baseline risk factors, demographics and outcomes after endovascular intervention.

Results:
109 patients (median age 69 years (25
th
, 75
th
percentiles: 56, 77); 51% women; median baseline NIHSS 15 (13, 18)) with complete (TICI 0) anterior circulation occlusions (M1, n=71; ICA, n=28; M2, n=10) at baseline were evaluated based on collateral grade (0-1, n=12; 2, n=41; 3-4, n=56). Worse collaterals were noted in patients with atrial fibrillation (ASITN grades 0-1/2/3-4: 21%/30%/49%) as compared to patients without atrial fibrillation (5%/42%/53%, p=0.024), yet cardioembolic stroke etiology was unrelated. Other baseline features such as age, gender, time to presentation, other co-morbidities and labs were unrelated to collateral grade. Post-procedure reperfusion (TICI 2b-3) was significantly associated with better collaterals (OR 2.58 (1.343-4.957, p=0.004). Similarly, final infarct size was significantly smaller in those with better collaterals. Good clinical outcomes (mRS 0-2 at day 90) were less frequent in those with poorer collaterals (OR 0.403 (0.199-0.813, p=0.011).

Conclusions:
Atrial fibrillation, but not cardioembolic stroke etiology, is associated with worse collaterals. Hemodynamic implications, such as diminished cardiac output due to atrial fibrillation, may result in less favorable outcomes after endovascular therapy for acute stroke.
Abstract W MP62: Plaque Heterogeneity of Carotid Artery Stenosis Measured by 3D Ultrasonography and the Gray Scale Median is Predictive of Cerebrovascular Events
Authors: Macharzina Roland-Richard , Helm Julia , Böhrsch Alexa , Grabs Anna , Sztajcel Roman , Vach Werner , Zeller Thomas , Neumann Franz-Josef
Published: July 2021

Background:
Risk of stroke was associated with ultrasonographic heterogeneity and echolucency of internal carotid artery stenosis (ICAS).

We intended to evaluate the prediction for cerebrovascular events in asymptomatic ICAS with a recently established plaque heterogeneity index (HI) determined with three-dimensional ultrasonography (3D-US) using the Gray Scale Median (GSM) in comparison to the GSM of single 2D gray scale sections alone. We hypothesized that an association between HI and ipsilateral neurologic events exists.

Patients and Methods:
In 245 patients informed consent was given after pre-screening examinations and gray scale 2D- and 3D-US was performed at 10 MHz to receive longitudinal sections through ICAS in a prospective fashion. Stenoses were graded according to NASCET criteria by duplex ultrasonography. In addition a majority received a baseline computer tomography (CT) angiography of ICAS to confirm stenosis grades in combination with a cerebral CT scan. HI was determined in a blinded fashion using the GSM of three parallel 3D-rendered longitudinal slices through the plaque by calculating the difference between the maximum and the minimum GSM divided by the mean. Neurologic assessment was scheduled every 6 months. The composite endpoint transient ischemic attack, stroke and amaurosis fugax ipsilateral to the ICAS was evaluated by a neurologist and cerebral CT or magnetic resonance scans were used to confirm diagnosis.

Results:
3D-US was performed in 160 asymptomatic ICAS at good quality to detemine GSM of whole plaque sections. Most of the ICAS ranged 40 - 60%. Patients with a heterogenous plaque, having a HI higher than the median, had a more than 4-fold increased risk (p < 0.05) of suffering an ipsilateral neurologic event. The Kaplan-Meier analysis also demonstrated that patients with a heterogenous plaque suffer more neurologic events (Log-rank p = 0.02). We did not find a significant association of the combined neurologic events and the GSM measured with 2D-US but there was a trend towards a lowered mean GSM in the symptomatic patients measured with 3D-US.

Conclusion:
The HI of ICAS was predictive for cerebrovascular events. The HI is probably a better predictor for cerebral events than GSM alone.
Abstract W MP64: Evaluation of Deep Venous Thrombosis in Cryptogenic Stroke and Patent Foramen Ovale
Authors: Liberman Ava L , Daruwalla Vistasp , Bergman Deborah , Bernstein Richard A , Curran Yvonne , Carr James C , Collins Jeremy D , Prabhakaran Shyam
Published: July 2021

Background and Purpose:
In cryptogenic stroke (CS), paradoxical embolus has been suggested as a stroke mechanism. A prior study found a significant rate of pelvic deep venous thrombosis (DVT) using magnetic resonance venography (MRV). We sought to evaluate the yield of diagnostic tests for lower extremity (LE) and pelvic DVT in stroke patients with patent foramen ovale (PFO) and in the subset with CS.

Methods:
A single center retrospective study was performed to identify consecutive ischemic stroke or TIA patients with PFO who underwent contrast-enhanced 3D pelvic MRV imaging (Ablavar, Lantheus Medical Imaging, N. Billerica, MA) between 2009 and 2013 as part of an inpatient diagnostic evaluation. Results of pelvic MRV, LE Doppler ultrasound (US) as well as clinical data were abstracted. Ischemic subtype was retrospectively assigned using the Causative Classification System (CCS). Patients with possible cardio-aortic embolism and undetermined cause by CCS were classified as CS. We estimated point estimates and 95% confidence intervals (CI) for DVT prevalence among stroke subtypes using the Wald method and compared these using Chi-square tests.

Results:
Of 130 patients who met study criteria, mean age was 56 +/- 17 years and median time from admission to MRV was 2 days (IQR 1-3). Overall DVT prevalence was 7.7% (95% CI, 4.1 to 13.7); the prevalence of pelvic DVT was 1.6% (95% CI, 0.07 to 5.8) and that of LE DVT was 7.2% (95% CI, 3.7 to 13.3). Of the patients with pelvic DVT (n=2), one patient also had a LE DVT by US. When MRV or US was obtained within 72 hours following admission, the prevalence of pelvic DVT was 2.1% (95% CI, 0.12 to 7.7) and that of LE DVT was 7.8% (95% CI, 3.8 to 14.8). Comparing patients with CS (n=97) to other subtypes (n=33), there was no difference in the prevalence of pelvic DVT (2.1% vs. 0%, P=1), LE DVT (6.3% vs. 10.3%, P=0.43) or any DVT (7.2% vs. 9.1%, P=0.71).

Conclusion:
Patients with CS and PFO have similar prevalence of DVTs compared to other stroke subtypes. The majority of detected DVTs were in LE veins rather than pelvic veins. Only a single patient with a pelvic DVT did not have a coexistent LE DVT. Our results suggest that the utility of pelvic MRV may be much lower than previously reported.
Abstract W MP65: Accuracy of Two-Dimensional Echocardiography using Second Harmonic Imaging for the Diagnosis of Intracardiac Right-to-Left Shunt: A Meta-Analysis of Prospective Studies
Authors: Mojadidi M. Khalid , Winoker Jared , Roberts Scott C , Msaouel Pavlos , Zaman Muhammad O , Gevorgyan Rubine , Tobis Jonathan M
Published: July 2021

Background:
Right-to-left shunting (RLS), often through a patent foramen ovale (PFO), has been associated with cryptogenic stroke, migraine with aura, and hypoxemia. With emerging observational studies and clinical trials on the subject of PFO and its association with stroke and migraine, there is a need for accurate diagnosis of PFO in patients being considered for transcatheter closure. While transesophageal echo (TEE) bubble study is the current standard reference for diagnosing PFO, transthoracic echo bubble study with second harmonic imaging (TTE-HI) may be a preferable screening test for RLS as it is a non-invasive and low cost technique. The aim of this meta-analysis was to determine the accuracy of TTE-HI compared to TEE used as the reference test.

Methods:
A systematic review of Medline, Cochrane and Embase was done to look for all the prospective studies assessing for intracardiac RLS using TTE-HI compared to TEE as the reference; both TTE-HI and TEE were performed with a contrast agent and a maneuver to provoke RLS in all studies.

Results:
A total of fifteen studies with 1995 patients (mean age 53.6 ± 6.1; 43% male) fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TTE-HI were 90.5% (95% CI: 88.1 to 92.6%) and 92.6% (95% CI: 91.0 to 94.0%) respectively. The overall positive likelihood ratio (LR+) was 13.52 (95% CI: 6.99 to 26.12) and the overall negative likelihood ratio (LR-) was 0.13 (95% CI: 0.07 to 0.24).

Conclusion:
TTE-HI is a reliable, non-invasive alternative diagnostic modality to TEE which is highly sensitive and specific for detecting RLS. TEE is limited by patient tolerance. If delineation of the precise anatomy is required, then TEE can be obtained before scheduling a patient for transcatheter PFO closure.
Abstract W MP66: Are Carotid Artery Stenosis-Isolated and Carotid Artery-Plus Two Distinct Entities?
Authors: Jani Vishal B , Malik Adil , Hussain Sayed , Qureshi Adnan I
Published: July 2021

Objective:
To test the hypothesis that isolated carotid artery stenosis (CAS-isolated) and CAS as part of concurrent coronary artery disease (CAD) and/or peripheral arterial disease (PAD) are two distinct entities.

Methods:
We used the data from Multi-Ethnic Study of Atherosclerosis (MESA) which is a population-based sample of 6,814 men and women aged 44-84 years recruited from six US field centers. Baseline measurements include measurement of coronary calcium using computed tomography; carotid intimal-medial wall thickness and stenosis severity using ultrasonography; and measurement of peripheral vascular disease using ankle and brachial blood pressures. Participants were followed for identification and characterization of cardiovascular events. We defined CAS-isolated based on presence of CAS without any CAD (calcium score of 0 with no history of angina/myocardial infarction) or PAD (arm-brachial index 1.0-1.4).

Results:
Of the 858 persons with CAS ranging in severity from 25 to 100%, 155 (18%) and 703 (82%) were classified as CAS-isolated and CAS-plus, respectively. Persons with CAS-isolated were younger (mean age ±SD; 61±8 versus 70±8, p=0.001) and more likely to be women (63.2% versus 41.8%, p=<.0001). The proportion of persons with hypertension (51.6% versus 66.3%, p=0.0006) and family history of heart attack (37.2% versus 51.1%, p=0.003) were lower among those with CAS-isolated. The proportion of persons with current cigarette smoking (19.6% versus 14.5%, p=0.01) and current alcohol abuse (73.4% versus 62.8%, p=0.03) were higher among CAS-isolated. Persons with CAS-isolated were more likely to have smooth carotid lesions (80.6% versus 69.3%, p=0.004). The relative risk for ischemic stroke was similar among patients with CAS-plus compared with CAS-isolated (RR, 1.1 95% CI 0.3-4.1) after adjustment for age and gender.

Conclusions:
CAS-isolated and CAS-plus appear to be two distinct entities with unique demographic and clinical attributes.
Abstract W MP75: Docosahexaenoic Acid Upregulates Iduna Expression in the Ischemic Penumbra and Protects Rat Brains Against Focal Ischemia
Authors: Bazan Nicolas G , Mukherjee Pranab K , Balaszczuk Veronica , Khoutorova Larissa , Anzola Daniela V , Hong Sung-Ha , Belayev Ludmila
Published: July 2021

Introduction:
Ring finger protein 146, also called Iduna, has been identified, as a neuroprotective protein. Iduna facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or cerebral ischemia. Recently, we have shown that docosahexaenoic acid (DHA; 22:6n-3) therapy improves functional and histological outcomes following experimental stroke. This study evaluated the time course expression of Iduna in the ischemic penumbra and the role of DHA in cerebral ischemia and its potential mechanism.

METHODS:
Thirty-six male SD rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. DHA (5 mg/kg) or vehicle (saline) was administered IV at 3 h after the onset of MCAo and animals were sacrificed on days 1, 3 and 7 (n=6 rats per group). The neurological function was evaluated during occlusion (60 min), and on days 1, 3 and 7 after MCAo; a grading scale of 0-12 was employed (0=normal and 12=maximal deficit). Western blot and double immunostaining (Iduna/NeuN and Iduna/GFAP) were used to analyze Iduna expression in the ischemic penumbra on days 1, 3 and 7.

RESULTS:
All animals showed similar values for rectal and cranial temperatures, arterial blood gases, and plasma glucose during and after MCAo. Behavioral deficit was significantly improved by treatment with DHA compared to vehicle on days 1 (by 30%), 3 (by 31%) and 7 (by 32%). Western-blot analysis showed that DHA treatment increased Iduna expression in the ischemic penumbra compared to vehicle on day 1 (2.2±0.3 vs. 0.6±0.1) and day 3 (0.44±0.05 vs. 0.3±0.01, respectively). There were no differences in Iduna expression on day 7 between DHA and vehicle-treated groups (0.33±0.02 and 0.35±0.02). Immunostaining revealed that Iduna expression was increased in the penumbra of DHA-treated rats.

Conclusions:
DHA protected the brain from severe damage caused by MCAo. This effect may be through upregulation of Iduna expression in the ischemic penumbra. Thus, it is reasonable to hypothesize that DHA has potential for the effective treatment of ischemic stroke in patients.
Abstract W MP77: The Role of Ischemia/Reperfusion Generated Nitrative Stress on VEGF Angiogenic Signaling in Diabetic rats.
Authors: Abdelsaid Mohammed A , Prakash Roshini , Li Weiguo , Coucha Maha , Fagan Susan , Ergul Adviye
Published: July 2021

Diabetes worsens the outcome and impairs recovery after stroke. We have previously shown that diabetes caused a nitration-dependent dysfunctional cerebral neovascularization via increased vascular endothelial growth factor (VEGF) signalling. Our recent study showed that ischemia/reperfusion (I/R) impaired vascular repair in the post-stroke period in diabetes. Yet, the molecular mechanism is unclear. Our present hypothesis is that I/R-mediated excess peroxynitrite formation impairs VEGF survival and angiogenic signal in a nitration-dependent manner.

Methods:
Acute ischemic stroke was induced via 90 min middle cerebral artery occlusion in Wistar (Wis) and diabetic Goto-Kakizaki rats (GK). 14 days later brain sections were examined for peroxynitrite generation (nitrotyrosine), survival markers (Akt and P38 activation), and apoptosis markers (caspase-3 and cleaved PARP). Brain micro-vascular endothelial cells (BMVEC) were isolated from Wis and GK rats and subjected to 6 hr hypoxia (0.2% oxygen) followed by 18 h normoxia. Nitrotyrosine, P85 nitration, Akt and P38 activity and caspase-3 cleavage were determined. VEGF signal was assessed via cell proliferation, tube formation and cell migration assay.

Results:
There was increased basal tyrosine nitration in diabetes. I/R increased nitrotyrosine in control (*2-fold) and diabetic (*3-fold) rats (*p<0.05). This increase was associated with decreased survival signal (20%, *60%) and increased apoptic signal (1.5-fold and *6-fold in Wis and GK, respectively, *p<0.05). In parallel, BMVEC isolated from GK rats showed increased nitrative stress compared to controls (*p<0.05). A second hit by hypoxia/reoxygenation dramatically increased the nitration of P85 subunit of PI3kinase* and activation of p38 MAPK* while decreased Akt activation* (*p<0.05). These effects were associated with impairment of VEGF-induced migration* and restored by treatments with peroxynitrite scavenger FeTPPS* (5 uM) or nitration inhibitor Epicatechin* (200uM) (*p<0.05).

Conclusion:
Our results demonstrate that I/R diverts prosurvial/angiogenic effects of VEGF to a proapoptotic pathway and suggest peroxynitrite as a novel therapeutic target for improvement of reparative angiogenesis after stroke in diabetes.
Abstract W MP81: Excess Salt Increases Infarct Size Produced by Photothrombotic Middle Cerebral Artery Occlusion Without Increasing Blood Pressure in Spontaneously Hypertensive Rats
Authors: Yao Hiroshi , Nabika Toru
Published: July 2021

Background and Purpose:
Cerebral circulation is known to be vulnerable to excess salt (e.g., impaired vasodilation, increased oxidative stress, accelerated spontaneous stroke, and enhanced blood-brain barrier [BBB] disruption). To our knowledge, however, no study has investigated the effects of excess salt on focal ischemic injury.

Methods:
After 14 days of salt loading or water, spontaneously hypertensive rats (SHR, Izumo strain, n=43) or normotensive Wistar-Kyoto rats (WKY, n=11) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO. Brain albumin and hemoglobin contents, as indices of BBB disruption, were determined with SELDI-TOF-MS in ischemic brain tissue. Effects of excess salt on the lower limits of cerebral blood flow (CBF) autoregulation were also determined.

Results:
Two-way analysis of variance confirmed a significant effect of saline on the volumes of drinking in SHR (p=0.000). Resting mean arterial blood pressure (BP) in SHR was 137±15 (S.D.) mmHg and 141±7 mmHg in the salt loading and control groups, respectively. After MCAO, regional CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p=0.002), while albumin and hemoglobin levels in discrete brain regions were not different between the groups. In WKY, salt loading did not significantly increase infarct size. CBF response to hemorrhagic hypotension (i.e., autoregulation) was not affected by excess salt.

Conclusions:
We demonstrated that excess salt increased infarct size produced by photothrombotic MCAO without increasing BP in SHR but not in WKY. Excess salt did not deteriorate both vasogenic edema and hemorrhagic transformation of ischemic brain tissue after MCAO. The detrimental effects of excess salt were considered to be the result of compromised CBF in the ischemic brain tissue supplied by collateral circulation. A future study will investigate the mechanisms underlying the salt sensitivity to focal brain ischemia independent of BP changes.
Abstract W MP88: Reduced Platelet Activity is Associated With Intraventricular Hematoma Clearance
Authors: Maas Matthew B , Romanova Anna L , Berman Michael D , Guth James C , Liotta Eric M , Naidech Andrew M
Published: July 2021

Background:
Reduction of intraventricular hematoma (IVH) burden is a novel therapeutic target for patients with intraventricular extension of intracerebral hemorrhage, yet little is known about clinical factors that may mediate IVH clearance. We tested the hypothesis that coagulation and platelet function abnormalities were associated with IVH clearance.

Methods:
Patients with primary intracerebral hemorrhage were enrolled into a prospective registry between December 2006 and June 2013. We studied patients with IVH who underwent ventricular drainage and survived to discharge. Diagnostic and surveillance neuroimaging studies were analyzed for the presence of IVH and quantified by Graeb score. We used univariate analysis to select candidate variables (p<0.25) into a logistic regression model to identify clinical and radiographic factors independently associated with IVH clearance, defined as a decrease between highest to final Graeb score over up to 7 days. We assessed coagulation function by international normalized ratio (INR) and platelet function by aspirin reaction units (ARU), with decreasing ARU indicating aspirin-associated platelet dysfunction.

Results:
There were 289 subjects in the cohort, of which 53 met inclusion criteria for this analysis. Univariate analysis identified age, hematoma volume, hydrocephalus, development of ventriculitis, INR, ARU, and observation interval between peak Graeb score and follow up imaging as potentially associated with IVH clearance. Multivariate modeling confirmed that platelet function by ARU (OR 0.990 IQR 0.992-0.998, p=0.019) and the observation interval (OR 1.024 per hour IQR 1.004-1.025, p=0.021) were independently associated with observing IVH clearance.

Conclusion:
After correction for observation interval, aspirin-related platelet dysfunction is the clinical variable most strongly associated with IVH clearance in patients with intraventricular extension of intracerebral hemorrhage. These findings suggest an important interaction between platelet function and hematoma stability.
Abstract W MP91: Does Recurrent Intracerebral Hemorrhage Have the Same Etiologic Subtypes According to SMASH-U Classification Method?
Authors: Yeh Shin-Joe , Tang Sung-Chun , Tsai Li-Kai , Jeng Jiann-Shing
Published: July 2021

Background and Purpose:
Etiologic classification of intracerebral hemorrhage (ICH), such as SMASH-U, is important to predict functional outcome and mortality in ICH patients. This study aimed to investigate whether recurrent ICH has the same etiologic subtypes or not.

Methods:
We analyzed 4,332 consecutive ICH patients treated at National Taiwan University Hospital from January 1995 to December 2012. The ICH etiology was classified in each patient according to the SMASH-U method as structural vascular lesions, medication-related, cerebral amyloid angiopathy (CAA), systemic disease, hypertensive angiopathy (HA), or undetermined.

Results:
Among all of the ICH patients, 3,659 patients was first-ever ICH patients (male, 62.9%; mean age, 59.8±16.8 years). The most common etiology was HA (54%), followed by systemic disease (14%), CAA (12%), undetermined (10%), structural vascular lesions (8%), and medication (3%). The interrater agreement for ICH classification was high (
κ
, 0.89; 95% CI, 0.84-0.94,
P
<0.001). During a mean follow-up of 4.8 years, 175 (4.8%) patients had recurrent ICH. Of these patients, 32 (18%) had different etiologies between the two ICH events, mostly were CAA to HA, or vice versa. In the first ICH event, 41 patients were classified as CAA, and 88 patients as HA. Of the 41 CAA patients, 28 (68%) remained as CAA in the second ICH event, but 10 (24%) changed to HA. Of the 88 HA patients, 74 (84%) remained as HA in the second ICH event, but 8 (9%) changed to CAA.

Conclusions:
One-fifth of recurrent ICH patients had different etiologic subtypes in the two ICH events according to SMASH-U classification, particularly for CAA. Therefore, over-diagnosis of CAA is likely if we follow the proposed classification method of SMASH-U.
Abstract W MP97: Trends in Volume and Mortality in CEA after Introduction of CAS in Medicare population
Authors: Kumamaru Hiraku , Jalbert Jessica J , Nguyen Louis L , Liu Jun , Gerhard-Herman Marie D , Chen Chih-Ying , Williams Lauren A , Seeger John D , Setoguchi Soko
Published: July 2021

Background:
Inverse relationship between outcome and physician volume for carotid endarterectomy (CEA) has been previously established. Following the 2005 National Coverage Determination which reimburses carotid artery stenting (CAS) for Medicare beneficiaries, the number of CAS procedures increased and the number of CEA declined. We hypothesized that the reduced number of CEA procedures resulted in lower case volumes for surgeons, adversely affecting patients' peri-procedural outcomes.

Methods:
We identified inpatient CEA procedures and performing surgeons in the Medicare claims files 2001-2008. We calculated surgeon volume as the number of CEAs performed in the past 365 days and categorized volume as very low (<5), low (5-9), medium (10-29) and high (≥30). Yearly trend of: 1) rate of CEA procedures, 2) proportion of CEAs performed by categories of surgeon volume , 3) patient characteristics , and 4) 30-day mortality overall and by categories of surgeon volume, were analyzed.

Results:
We identified 450,727 Medicare beneficiaries undergoing CEAs. The rate of CEA procedures per 10,000 beneficiaries declined consistently after 2002, resulting in decrease in the proportion of procedures performed by high volume surgeons (from 46% in 2002 to 33% in 2008). Patients selected for CEA became older and increased in the proportion of patients with atrial fibrillation, COPD, and chronic kidney disease, but decreased in the proportions with prior myocardial infarction and concurrent CABG. Thirty day mortality improved consistently over the years from 1.41% (95% confidence interval: 1.35-1.48) in 2001-2002 to 1.18% (1.12-1.25) in 2007-2008. This trend persisted after adjustment for patient characteristics, and in all volume categories.

Conclusion:
The rate of CEA procedures decreased substantially between 2001-2008 as have performing surgeon case volumes . Dissemination of CAS has not adversely impacted the peri-procedural mortality of CEA Medicare patients.
Abstract W P101: Surgical Revascularization Reverses Decreased Cerebral Oxygen Metabolism in Young Patients with Moyamoya Disease
Authors: Kuroda Satoshi , Kashiwazaki Daina , Houkin Kiyohiro
Published: July 2021

Purpose:
This prospective study was aimed to evaluate the effects of surgical revascularization on cerebral oxygen metabolism in moyamoya disease.

Methods:
This study included totally 41 patients who underwent STA-MCA anastomosis and indirect bypass for moyamoya disease between 2000 and 2011. There were 12 children and 29 adults. Totally 67 hemispheres underwent surgery. MR imaging and 15O-gas positron emission tomography (PET) were performed before and 3 to 4 months after surgery. Hemodynamic and metabolic parameters were precisely quantified.

Results:
Preoperative PET scans revealed that cerebral metabolic rate for oxygen (CMRO2) was kept normal in 15 hemispheres (22%), but decreased in other 52 (78%). The incidence did not differ between pediatric and adult patients. Pronounced cerebral ischemia was observed in all hemispheres with decreased CMRO2. After surgery, CMRO2 value significantly improved to the normal level in 20 (38%) of 52 hemispheres, but did not change in other 32 (62%). Multivariate analysis showed that the predictors for postoperative CMRO2 normalization were patient’s age (younger than 40 years) and no parenchymal damage on MRI.

Conclusion:
These findings strongly suggest that cerebral oxygen metabolism is often depressed in response to dense and chronic cerebral ischemia in moyamoya disease. The phenomenon may be advantageous to protect the involved hemispheres against ischemia. Surgical revascularization may readily normalize oxygen metabolism in young patients without any parenchymal damage.
Abstract W P105: Comparison of Intracranial Stent Placement and Best Medical Treatment Alone for Treatment of Symptomatic Intracranial Stenosis
Authors: Jadhav Vikram , Qureshi Mushtaq , Mian Nidaullah , Qureshi Adnan I
Published: July 2021

Objective:
To compare the short and long term rates of transient ischemic attack (TIA)/ ischemic stroke and mortality between intracranial stent placement and medical therapy alone for treatment of symptomatic intracranial arterial stenosis.

Methods:
We identified all prospective and retrospective studies comparing intracranial stent placement and medical management using a search on PubMed and Cochrane libraries, stroke trials database, proceedings of neurology and neurosurgery related conferences, and supplemented by a review of bibliographies of selected publications. The incidences of adverse effects, namely TIA/stroke and/or death at 30 days post treatment and TIA/stroke, myocardial infarction and/or death at 1 year post treatment were ascertained from all studies. For the meta-analysis, Forest plots and calculation of odds ratios [OR] with 95% confidence intervals [CI] using both fixed and random models were performed. The presence of publication bias was interrogated by funnel plot of Standard Error by log odds ratio.

Results:
Three prospective studies including two randomized clinical trials and one retrospective study were identified and included in the meta-analysis. There were a total of 46/347 (13.2%) stroke-and/or-deaths reported in the stent treatment group compared with 16/351 (4.5%) TIA/stroke-and/or-deaths in the medical therapy alone group at 30 days (OR, 2.97; P<0.001; CI 1.64-5.39). The pooled incidence of 1-year TIA/stroke-and/or-deaths in patients with stenting was 51/347 (14.7%), compared with 45/351 (12.8%) in the patients managed with medical therapy alone (OR 1.093; P = 0.815; CI 0.51-2.30). There was no publication bias.

Conclusions:
Despite the higher risk of 1 month TIA/stroke-and/or-deaths, patients undergoing intracranial stent placement have similar rates of TIA/stroke-and/or-deaths at 1 year compared with medical treatment alone.
Abstract W P112: Natural History and Outcomes of Ischemic Stroke Patients with Mild Presenting Symptoms and Large Vessel Occlusion
Authors: Russell Cerejo , Cheng-Ching Esteban , Hussain M Shazam , Uchino Ken , Hui Ferdinand , Toth Gabor
Published: July 2021

Introduction:
Large vessel occlusion (LVO) is thought to be an independent predictor of clinical outcome in acute ischemic stroke (AIS). Despite various available treatment modalities, optimal therapy for LVO patients presenting with mild symptoms is not known. These patients remain a significant challenge in clinical practice.

Methods:
Retrospective chart review of AIS patients admitted between January 2010 and August 2012 at a large tertiary care center. Inclusion criteria: symptom onset within 8 hours, LVO as cause of symptoms, initial NIH stroke scale (NIHSS) < 8. Patients with bilateral lesions, distal small vessel involvement or single vertebral artery disease were excluded. Tandem lesions were included. Patient demographics, administered therapies and short term clinical outcomes were analyzed.

Results:
A total of 51 patients (56.9% male; mean age 66.4±14.5) fulfilled our strict criteria for inclusion. MCA involvement was seen in 31 (60.8%), ICA 13 (25.5%), basilar 3 (5.9%) and tandem ICA-MCA in 4 (7.8%). A total of 15 (29.4%) received acute therapy with IV t-PA and/or endovascular intervention (TX); both were used only in 6 (11.8%). Follow-up at 30 days was available in 64.7% of patients: 58.3% with TX and 80% without. Mean NIHSS remained relatively stable showing 4.3±2.1 on admission, and 2.6±3.4 on discharge (NS), with 75.8% of patients having same or better NIHSS on follow-up. There was a significant difference in functional outcome: mRS≤2 was present in 98% of patients on admission, but only in 63.6% at follow-up. If extended the mRS range, 90.9% of patients had mRS≤3 on follow-up. Only 33.3% at follow-up had same or better mRS than on admission. Results were consistent, irrespective of receiving acute therapy.

Conclusion:
Acute LVO with mild presenting symptoms remains a difficult therapeutic challenge. Our data shows that despite stable gross clinical examination (by NIHSS) on follow-up, a large proportion of patients experience mild to moderately worse functional outcome, irrespective of receiving acute therapy. Our study limitations include retrospective analysis and suboptimal patient follow-up, especially in untreated patient population. We believe that a prospective, larger cohort is warranted to find optimal treatment approach.