bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 139: Low Rate of Probable Misdiagnosis of Cerebral Vein Thrombosis in a Multi-State Cohort
Authors: Liberman Ava L , Gialdini Gino , Bakradze Ekaterina , Chatterjee Abhinaba , Kamel Hooman , Merkler Alexander
Published: October 2018

Introduction:
Cerebral vein thrombosis (CVT) is a cerebrovascular disease that affects young adults, is difficult to diagnose, and can result in significant disability and death. Studies aimed to evaluate rates of CVT misdiagnosis are limited.

Hypothesis:
Misdiagnosis of CVT in the emergency department (ED) would be common and associated with adverse outcomes.

Methods:
We performed a retrospective cohort study using ED visits and hospitalizations in California, New York and Florida from 2005 to 2013. We identified patients with CVT using previously validated
International Classification of Diseases, Ninth Revision, Clinical Modification
(
ICD-9-CM)
codes. Primary outcome was a probable misdiagnosis of CVT, defined as an ED visit for benign headache or seizure within 14 days of CVT. In secondary analyses, we assessed whether a probable misdiagnosis of CVT was associated with an increased risk of intracerebral hemorrhage or inpatient mortality. Descriptive statistics was used to calculate crude rates and multivariable logistic regression to compare rates of adverse outcomes. A confirmatory cohort analysis of CVT patients from two tertiary care centers was conducted via detailed chart review.

Results:
We identified 5,966 patients with CVT. Mean age was 44.2 ± 18.4 years and 71.7% were women. A total of 216 patients (3.6%; 95% CI, 3.1-4.1%) had a probable misdiagnosis of CVT. Misdiagnosed patients were younger and less likely to have congestive heart failure, atrial fibrillation, cancer, or trauma, but more likely to have a hypercoagulable state. No pregnant patients with CVT (n=758, 12.5%) had a probable misdiagnosis. In confirmatory cohorts, probable CVT misdiagnosis occurred in 8.1% (6 of 74) and 2.6% (2 of 76) of patients. Misdiagnosis of CVT was not associated with an increased risk of death (OR, 0.1; 95% CI, 0.0-1.1), intracerebral hemorrhage (OR, 1.0; 95% CI, 0.6-1.6), unfavorable discharge disposition (OR, 0.9; 95% CI, 0.6-1.3), but was associated with an increased length of stay (OR 1.7; 95% CI, 1.2-2.3).

Conclusion:
In a large, heterogeneous group of patients, a probable misdiagnosis of CVT occurred in 1 out of 30 patients. No misdiagnosis occurred in a pregnant patient and misdiagnosis was not associated with adverse clinical outcomes.
Abstract 140: Reducing Costs and Length of Stay Using Standardized Dysphagia Evaluation in Acute Stroke Patients
Authors: Werbaneth Katherine , Shum Jennifer , Deane Sandra , Larrenaga Maria , Tse Justin R , Bernier Eric , Vora Nirali
Published: October 2018

Introduction:
Dysphagia is common after acute stroke. Variability in predicting who will require a gastrostomy tube (G-tube) prior to discharge can prolong length of hospital stay (LOS) and increase costs.

Objectives:
We propose a novel protocol to standardize speech therapy evaluation and G-tube recommendations among acute stroke patients with dysphagia to reduce LOS and costs.

Methods:
A cohort of acute stroke patients with dysphagia was identified through an administrative data set using ICD-10 codes for ischemic stroke and CPT codes for speech therapy evaluation, and if applicable, CPT code for G-tube placement. Patients with tracheostomy, comfort care orders, or discharge to hospice were excluded. A multidisciplinary team from speech therapy, neurology, and radiology applied quality improvement principles to design and implement a G-tube indicator score (Figure 1) to address variability in dysphagia evaluation. Median LOS and duration from initial speech therapy evaluation to final diet recommendation were compared between the pre- and post-intervention period. Cost savings were calculated using LOS and average daily institutional bed cost.

Results:
Between January 2016 to January 2017, 174/278 (62%) of acute stroke patients had dysphagia and 61/174 (35%) of these patients received G-tubes. Their median LOS was 21.7 days compared to 5 days for stroke patients without G-tube. In the post-implementation period from Feb-May 2017, 25/45 (55%) of acute stroke patients had dysphagia and 5/25 (20%) received G-tubes. Their median LOS was 16.4 days following the protocol implementation. This resulted in cost savings of $14,654 per G-tube patient.

Conclusions:
This novel G-tube indicator score standardized speech therapy evaluation and reduced LOS by more than 5 days among acute stroke patients requiring G-tube prior to discharge. Future studies will prospectively validate the score. Increased adoption would result in significant cost savings.
Abstract 141: Systolic Blood Pressure and White Matter Hyperintensity Progression in ACCORD-MIND
Authors: de Havenon Adam H , Majersik Jennifer J , Tirschwell David , McNally J Scott , Rost Natalia
Published: October 2018

Introduction:
Small vessel disease can be detected on MRI as white matter hyperintensity (WMH), but its pathophysiology remains elusive. We sought to examine the effect of elevated systolic blood pressure (SBP) and SBP variability on WMH progression in the ACCORD-MIND study of patients with type II diabetes, a prototypical small vessel disease.

Methods:
MRIs were acquired at baseline and 40 months after enrollment. WMH volume (WMHv) was segmented using an automated volumetric algorithm. The primary outcome was ΔWMHv in mm
3
, between the two MRI time points. SBP variability was represented as standard deviation and coefficient of variation. Linear regression models were fitted to ΔWMHv with 10 unit shifts in SBP mean and variability as the primary predictors.

Results:
After excluding one patient for missing data, 502 patients had, on average, 17 (SD±7) SBP readings. In linear regression, SBP variability was not associated with ΔWMHv, while SBP mean was positively associated with ΔWMHv (Table 1). Furthermore, there was an increase in mean ΔWMHv per quartile of mean SBP (Figure 1). The same analysis was performed for diastolic blood pressure and mean arterial pressure, without significant findings.

Conclusions:
In this uniform cohort of patients with type II diabetes, higher SBP mean, but not SBP variability, was associated with WMHv progression. For every 10 mm Hg increase in SBP mean during ACCORD-MIND, there was a 1.4 mm
3
increase in ΔWMHv. These data reinforce the role of hypertension in the pathophysiology of cerebral small vessel disease and provide additional rationale for SBP control to prevent chronic microvascular ischemia in diabetic patients.
Abstract 145: Thrombus Composition is Associated With Endothelial Injury and Stroke Etiology in Patients Undergoing Mechanical Thrombectomy for Emergent Large Vessel Occlusion
Authors: Elijovich Lucas , Arthur Adam , Hoit Daniel , Nickele Chris , Morris David , Vachhani Jay , Belayev Andrei , Kotha JP , Hord Edward , Price Susan , Derrick Vanessa , Cardenas Juan , Jennings Lisa
Published: October 2018

Introduction:
High rates of recanalization of Emergent Large Vessel Occlusion (ELVO) provide an opportunity to examine retrieved thrombi. We studied device and endothelial (ET) interactions to evaluate ET injury and the relationship between thrombi and Acute Ischemic Stroke (AIS) mechanism.

Methods:
Prospective registry examining immunohistochemical characteristics of retrieved thrombi in ELVO patients. Thrombi were categorized histopathologically and ET injury quantified by CD34 staining and immunohistochemistry, ELISA and reverse transcribed quantitative PCR to detect ET components. ET mRNA expression of CD31 was quantified from thrombi RNA. Plasma at the thrombectomy site was tested for ET derived biomarkers: microparticles (MPs), soluble Intercellular Cell Adhesion Molecule-1 (sICAM1) and soluble Thrombomodulin (sTM). Statistical analysis was performed with unpaired student’s t-tests and chi-square tests.

Results:
Twenty-five patients (age 68±3 , NIHSS 16±2, 48% female) were enrolled. The most common sites of occlusion were the MCA (9) and ICA (7). Eighty eight % of patients required three or less attempts at recanalization and 71 % achieved TICI 2b or 3. Histopathology demonstrated fibrin rich (5), erythrocytic (2), layered (7), and serpentine (11) thrombi and four were CD 34 positive. Levels of plasma biomarkers were: sTM 2.2±0.4 (<0.6-10.2ng/ml), MPs 101.4±18.4 (1.33-221nM), and sICAM1 160.0±19.8 (<15-406.1ng/ml). Patients with > 3 revascularization attempts had higher levels of sTM (5.5±0.4 vs 1.7±0.2, p<0.0002), sICAM (261.2±79.2 vs. 146.3±20.3, p<0.03), and CD31CT (27.7±0.8 vs 25.5±0.3, p < 0.03). Patients with PH 1 or 2 ICH had higher levels of microparticles than those without ICH or with HI 1 or 2 (203±19 vs 92±19, p<0.05). Patients with cardioembolic stroke had higher sTM (2.8±0.8 vs. 1.3±0.3, p<0.05) and sICAM1 levels (186±32 vs. 115±29, p<0.05) than those with carotid or intracerebral atherosclerosis.

Conclusions:
ET markers can be detected in the retrieved thrombi and plasma milieu of ELVO patients. ET markers relate to increasing number of attempts at thrombectomy indicating ET disruption. sTM and sICAM are more common in patients with cardioembolic stroke and may serve as thrombus associated markers of AIS mechanism.
Abstract 147: Plaque Inflammation is Associated With Early Cerebral Ischemic Events in Symptomatic Carotid Stenosis
Authors: Sharma Vijay K , Paliwal Prakash R , Ting Eric Y , Chan Bernard P , Teoh Hock L , Sinha Arvind K
Published: October 2018

Background and aims:
Currently, the severity of the symptomatic carotid stenosis determines the treatment approach. However, it explains only the regional hypoperfusion as the mechanism of cerebral ischemia. Artery-to-artery embolisation remains an important pathogenic mechanism in patients with high-risk carotid plaques. Recently, inflammation has been proposed as the initiating event for plaque rupture and cerebral embolism. Using 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) and high resolution magnetic resonance imaging (HR-MRI), we investigated the role of plaque imaging and stroke recurrence in our cohort of patients with recently symptomatic carotid stenosis.

Methods:
This ongoing prospective study included consecutive patients within 30-days of recent stroke and ipsilateral carotid stenosis (≥50%). FDG uptake was quantified as mean standardized uptake values (SUV, g/ml). The ratio of T1 hyperintensity of carotid plaque to the ipsilateral sternocleidomastoid muscle (SCM) was recorded on T1-weighted fat suppressed HR-MRI. Patients were followed prospectively for stroke recurrence within 90-days.

Results:
Of the 70 patients included in the study, 11 (16%) suffered from recurrent cerebral ischemic event in the same vascular territory within 90-days. Compared to patients without subsequent cerebral ischemic events, patients with recurrent cerebral ischemia showed higher mean T1 carotid-SCM ratio (2.24 versus 1.46; p<0.0001) and higher mean SUV value in the carotid plaque (3.26g/ml versus 1.28g/ml; p<0.0001). Higher T1 carotid-SCM ratio on HR-MRI (OR 3.374, 95%CI 1.561-6.253; p<0.0001), higher mean SUV on FDG-PET (OR 3.646, 95%CI 3.172-11.524; p=0.005) were independent predictors of recurrent cerebral ischemia.

Conclusions:
FDG-PET/CT and HR-MRI of carotid stenosis helps in identification of patients at higher risk of subsequent cerebral ischemic events and may aid in better therapeutic decision-making.
Abstract 148: Exome Sequence Study on Extreme MRI Markers of Cerebral Small Vessel Disease
Authors: Mishra Aniket , Violleau Marie-Helene , Chauhan Ganesh , Mazoyer Bernard , Tzourio Christophe , Debette Stephanie
Published: October 2018

We performed an exome sequence association study on extreme MRI-markers of cerebral small vessel disease (extensive-CSVD versus minimal-CSVD) in participants from the 3C-Dijon French population-based cohort study, focusing on genes harbouring causal mutations for Mendelian forms of CSVD (
NOTCH3
,
HTRA1
,
COL4A1
,
COL4A2
,
TREX1
and
CTSA
). The study population comprised 514 participants aged 73.30±4.24 years (59.24% women). The extensive-CSVD group comprised 261 persons in the upper extreme distribution of WMHV residuals adjusted for age, gender, and intracranial volume, prioritizing participants with lacunar brain infarcts within the top quartile of WMHV residuals. The minimal-CSVD group comprised 253 participants without MRI-defined brain infarct who were in the lower extreme distribution of WMHV residuals. These participants were whole-exome sequenced with average depth coverage of 100X. We screened for the presence of known pathogenic genotypes in our cohort, and performed single variant association tests and gene-based burden tests. We identified one individual with extensive-CSVD carrying a heterozygote genotype in
HTRA1
previously described as a CARASIL causing mutation in Asians, and not previously reported in European families with the dominant
HTRA1
phenotype. We also identified significant association of a common intronic variant, rs2293871, in
HTRA1
with extensive-CSVD (p=8.209 х 10
-5
) that remained significant after correction for multiple testing and accounting for regional linkage disequilibrium. Furthermore, the burden of rare and low frequency protein-modifying alleles in
NOTCH3
was significantly associated with increased risk of extensive-CSVD (p=9.990 х 10
-3
). In conclusion, we describe a novel strategy to identify genetic determinants of CSVD using population cohorts of elderly based on an extreme composite phenotype. We report one clinically important case carrying a heterozygote genotype at the CARASIL causing mutation. We show significant association of an intronic common variant in
HTRA1
gene and the burden of rare and low frequency protein damaging variants in
NOTCH3
gene with extensive-CSVD. These associations suggest some shared mechanisms between monogenic and multifactorial CSVD.
Abstract 15: Mortality After Pediatric Arterial Ischemic Stroke: Results From the International Paediatric Stroke Study
Authors: Beslow Lauren A , Dowling Michael M , Hassanein Sahar M , Zafeiriou Dimitrios , Sun Lisa R , Kopyta Ilona A , Chan Anthony K , Biller Jose , Lynch John K , Grabowski Eric F , Titomanlio Luigi , Kolk Anneli , Abdalla Abdalla A , Mackay Mark T , deVeber Gabrielle
Published: October 2018

Introduction:
Stroke is reported among the top 10 causes of death in children in the US. In the Kids’ Inpatient Database, older age and Hispanic ethnicity were risk factors for mortality after pediatric ICH. Limited data is available regarding risk factors for death after pediatric arterial ischemic stroke (AIS).

Objective:
To identify predictors of in-hospital mortality in pediatric patients hospitalized with AIS.

Methods:
Neonates (0-28 days) and children (29 days- <19 years) with AIS were enrolled from 1/2003 to 7/2014 in the IPSS multinational stroke registry. Death prior to hospital discharge and cause of death was ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality.

Results:
Fourteen of 915 neonates (1.5%) and 74/2,285 children (3.2%) died during hospitalization. Of 54 cases with reported causes of death, 32 (59%) were related to AIS (herniation 2, brain death 10, ICH/hemorrhagic transformation 5, care withdrawal due to stroke severity 15), with the remaining deaths attributed to underlying medical disease. Of 356 children with Pediatric NIH Stroke Scale (PedNIHSS) scores, median PedNIHSS was 19 (IQR 14-27) among the 13 children who died and 7 (IQR 3-12) among the 343 children who did not die. In multivariable analysis, congenital heart disease (OR 4.1, 95%CI 1.3-13, p=0.018) and posterior plus anterior circulation stroke (OR 4.3, 95%CI 1.3-14, p=0.017) were associated with in-hospital mortality for neonates, while higher PedNIHSS [OR 1.11 (per 1 point PedNIHSS increase), 95%CI 1.03-1.19, p=0.004], Hispanic ethnicity (OR 7.6, 95%CI 1.8-32.3, p=0.006), and cardiac disease (OR 7.5, 95%CI 1.5-38.6, p=0.015) were associated with in-hospital mortality for children.

Conclusions:
In-hospital mortality occurred in about 2% of pediatric AIS cases with nearly 60% attributable to stroke. Risk factors for in-hospital mortality included cardiac disease and stroke severity, factors also associated with mortality in adults. Hispanic ethnicity, a factor associated with mortality in childhood ICH, was also associated with mortality after childhood AIS; the underlying reasons are unclear. Additional information is needed on stroke-related deaths after hospitalization.
Abstract 150: Cerebral Microbleeds and Cognition in Lacunar Stroke Patients: The Secondary Prevention of Small Subcortical Strokes Trial
Authors: Shoamanesh Ashkan , McClure Leslie A , Pearce Lesly A , Bazan Carlos S , Catanese Luciana , Hart Robert G , Benavente Oscar R
Published: October 2018

Background:
Cerebral microbleeds (CMBs) have been associated with cognitive dysfunction. However, characterization of CMBs and cognitive dysfunction in a large population of stroke patients is lacking. We aimed to characterize the association of CMBs with cognitive function in lacunar stroke patients and the response to assigned treatments in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial.

Methods:
SPS3 was a randomized trial comparing two systolic blood pressure targets and two antiplatelet regimens in 3020 dementia-free patients with symptomatic, MRI-confirmed lacunar stroke. Participants underwent detailed neuropsychological testing covering multiple domains, including short delay recall, long delay recall, discriminability, block design, symbol search, grooved pegboard, controlled oral word association and clock drawing, at baseline and then annually for 5 years. Participants with axial MRI T2*- GRE sequences allowing for CMB detection and Cognitive Abilities Screening Instrument (CASI) Z scores available at baseline were included in the current analysis.

Results:
CMBs were present in 30% of 1225 eligible patients (mean age 63 years, 35% women) with median follow up of 3 years. Patients with CMBs had greater proportion of mild cognitive impairment (MCI; 56% vs. 42%, p<0.0001) and lower cognitive scores at baseline (mean CASI Z score -0.9 vs. -0.5, p<0.0001), including significantly lower scores across most of the individual cognitive domains tested. During follow-up, in 578 participants without MCI, there was no difference in the rate of incident MCI in patients with CMBs (29%, 41/143) and those without CMBs (26%, 111/435; p=0.50). Trends in cognitive decline over time were not statistically significantly different between the two groups. There were no interactions between CMBs and treatment assignments for cognitive outcomes.

Conclusions:
In this largest reported cohort assessing the association between CMBs and post-stroke cognitive impairment, CMBs were associated with lower cognitive scores and greater rates of MCI at baseline. However, changes over time in cognition were similar in lacunar stroke patients with and without CMBs who receive adequate vascular risk management.
Abstract 151: Intracranial Atherosclerotic Disease and Brain Amyloid Deposition: The ARIC Study
Authors: Gottesman Rebecca F , Dearborn Jennifer , Hao Qing , Knopman David S , Mosley Thomas H , Qiao Ye , Wagenknecht Lynne E , Wong Dean F , Zhou Yun , Wasserman Bruce A
Published: October 2018

Background:
Increasing evidence points to intracranial atherosclerosis as a risk factor not only for stroke but also for dementia, but whether it is linked to Alzheimer’s disease-specific pathology itself is less understood. In the community-based Atherosclerosis Risk in Communities (ARIC) study, we evaluated the cross-sectional association between intracranial atherosclerosis and cerebral amyloid deposition, in nondemented participants.

Methods:
In 2011-2014, a subset of participants from the ARIC Neurocognitive Study underwent both a brain MRI, including high-resolution vessel wall imaging, and florbetapir PET, as a marker of amyloid deposition. We analyzed the association between elevated amyloid (defined as a global cortical florbetapir standardized uptake value ratio (SUVR)>1.2) and intracranial arterial plaque presence, frequency, and extent of stenosis, with adjustment for demographic and vascular risk factors. We tested effect modification by APOE ε4 genotype.

Results:
In 300 participants (mean age of 76y, 44% African-American, 56% female, 31% carriers of at least one APOE ε4 allele), intracranial plaque was found in 105 (35%) participants. Mean SUVR was higher in individuals with vs without plaque (1.34 ± 0.29 vs 1.27 ± 0.23, p=0.03). In adjusted models, plaque presence was not associated significantly with elevated SUVR in the total sample, nor was number of plaques. Associations between plaque presence and extent were generally stronger in APOE ε4 carriers than noncarriers (p<0.05 for interaction for some plaque features; see Table).

Conclusions:
Although intracranial arterial plaque or stenosis was not definitively associated with brain amyloid in this sample of nondemented older adults, associations with brain amyloid appeared stronger in carriers of an APOE ε4 allele, consistent with studies demonstrating a similar relationship as that seen with other more traditionally measured vascular risk factors.
Abstract 156: Intravenous Thrombolysis for Acute Ischemic Stroke in the Golden Hour: A Systematic Review and Meta-Analysis
Authors: Tsivgoulis Georgios , Katsanos Aristeidis H , Schellinger Peter D , Köhrmann Martin , Mikulik Robert , Paciaroni Mauricio , Caso Valeria , Alexandrov Anne W , Mitsias Panayiotis D , Alexandrov Andrei V
Published: October 2018

Introduction:
Data are scarce regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset, termed the “golden hour” (GH) window. We present systematic review and meta-analysis of outcomes between AIS patients treated within (+) and outside (-) the GH.

Methods:
We performed a systematic review in MEDLINE and SCOPUS databases for observational studies providing unadjusted rates or adjusted odds ratios (OR) for the following outcomes: symptomatic intracranial hemorrhage (sICH), mortality and favourable functional outcome (FFO), defined as mRS-scores of 0-1.

Results:
We identified 3 eligible studies (range of median NIHSS-scores: 10-11 points), including a total of 72,662 IVT-treated patients (1.5% treated within the GH. GH(+) patients had higher FFO rates (42%, 95%CI:35%-48%) compared to GH(-) patients (31%, 95%CI:30%-31%). In adjusted analyses, IVT within the GH was associated with a two-fold increase in the odds of FFO (OR=2.02, 95%CI: 1.55-2.63, p<0.001) without heterogeneity across studies (I
2
=0, p for Cochran Q=0.93; Figure). No significant differences on the risk of both sICH (OR=0.77, 95%CI: 0.53-1.13, p=0.180; I
2
=0, p for Cochran Q=0.63) and mortality (OR=0.61, 95%CI: 0.29-1.28, p=0.190; I
2
=72, p for Cochran Q=0.03) were documented between the two groups in adjusted analyses.

Conclusions:
AIS treated within the GH have substantially higher odds of FFO compared to IVT administered later during conventional time window independent of potential confounders. Improvement of care systems to achieve the earliest onset to treatment times should remain the goal of the front line stroke treatment.
Abstract 157: Contact Aspiration Versus Stent Retriever for Large Vessel Occlusion in the Anterior Circulation Within Six Hours of Symptom Onset: Effect of Mothership Versus Drip and Ship Paradigms in the ASTER Trial
Authors: Piotin Michel , Blanc Raphael , Gory Benjamin , Labreuche Julien , Duhamel Alain , Marnat Gauthier , Saleme Suzana , Costalat Vincent , Bracard Serge , Desal Hubert , Mazighi Mikael , Consoli Arturo , Lapergue Bertrand
Published: October 2018

Purpose:
The ASTER trial (contact Aspiration versus Stent Retriever for revascularization in patients presenting with acute ischemic stroke and a large vessel occlusion in the anterior circulation within six hours of symptom onset) did not show superiority of contact aspiration over stent retriever regarding successful revascularization (TICI 2B/3) result at the end of the procedure and clinical results at 3 months.

Objective:
To assess whether patient admission modes, directly to a comprehensive stroke center (CSC) versus to a primary stroke center (PSC), impacted the rate of patients with functional independence at 3 months and the rate of favorable angiographic outcome in the ASTER trial.

Methods:
Primary outcomes included degree of functional independence (modified Rankin scale ≤2) at 90 days, the change in National Institute of Health Stroke Scale (NIHSS) at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events. Secondary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis In Cerebral Infarction [mTICI] score of 2b or 3 at the end of procedure.

Results:
Among 381 patients who were randomized in the ASTER trial, 138 were directly admitted to a CSC (Mothership paradigm) and 243 were admitted first in a PSC (Drip-and-Ship paradigm). Aspiration as first strategy was performed in 50.7% of the patients in the Mothership paradigm group, versus 50.2% in the Drip-and-Ship. Onset to groin puncture time was 170 minutes (IQR, 142 to 207) in the Mothership group versus 262 minutes (IQR, 216 to 295) in the Drip-and-Ship group (p<0.001). Primary efficacy outcome was not significantly different in Mothership and Drip-and-Ship groups (50.4% versus 46.2%); the risk ratio (Mothership vs. Drip-and-Ship) was 1.06 (p=0.60, 95% CI: 0.84 to 1.33). Of the angiographic efficacy outcomes (Revascularization after first line strategy and at end of all procedures), adverse events, no significant differences were found between the two paradigms.

Conclusions:
The Mothership treatment paradigm did not result in better functional neurological outcome at 3 months compared to the Drip-and-Ship paradigm, whatever the first line treatment strategy.
Abstract 162: Microhemorrhages in MRI Predict Infectious Intracranial Aneurysm in Infective Endocarditis
Authors: Cho Sung-Min , Rice Cory , Buletko Andrew B , Marquardt Robert J , Zhang Lucy Q , Khoury Jean , Thatikunta Prateek , Uchino Ken , Wisco Dolora
Published: October 2018

Background:
MRI features such as cerebral microbleeds and sulcal susceptibility weighted imaging (SWI) or gradient-echo T2* (GRE-T2*) lesions have been reported to be associated with the presence of infectious intracranial aneurysm (IIA) in infective endocarditis (IE). We aimed to describe the MRI imaging features that predict the presence of IIA.

Methods:
The derivation cohort comprised 116 IE patients with neurological evaluation at a single tertiary referral center from January 2015 to July 2016. The MRI predictors associated with IIA was evaluated, and we developed the MRI imaging predictors and assessed sensitivity and specificity. External validation was performed in a cohort of 129 IE patients who underwent digital subtraction angiogram (DSA) at the same center from 2010-2014. We assessed the validity using a receiver operating characteristic curve (ROC).

Results:
Of 116 IE patients in the derivation cohort, 10 (9%) had IIAs. Of 129 in the validation cohort, 19 (15%) IIAs were identified. The MRI imaging predictors for IIA consist of 1) contrast enhancement with SWI lesions, 2) cerebral microbleeds > 5mm plus sulcal SWI lesions, and 3) any MRI hemorrhages. The sensitivity for the presence of IIA in each group of the derivation cohort was: 90%, 80%, and 100%, respectively. The sensitivity in the validation cohort was: 47%, 68%, and 94% respectively. The specificity in the derivation cohort was: 87%, 85%, and 18%. In the validation cohort, the specificity was similar (87%, 75%, and 27%).

Conclusions:
The suggested MRI imaging predictors can be used as a sensitive and specific tool to support clinical decision-making, especially when invasive DSA is considered for assessment for presence of IIA. The absence of MRI hemorrhages may not necessitate the need for DSA.
Abstract 166: The Brain and Aortic Aneurysm Screening (BAAS) Study - Screening for Occult Intracranial Aneurysms in Those With Abdominal Aortic Aneurysms
Authors: Lescure Tyler N , Rosenbaum Blake L , Rahman Shareena , Green Ilana E , Carrera Joseph F , Berthaud Jimmy V , Thomas Matthew J , Barrett Kevin M , Meschia James F , Southerland Andrew M , Worrall Bradford B
Published: October 2018

Introduction:
Abdominal aortic aneurysm (AAA) rupture has a mortality rate of 64% and intracranial aneurysm (IA) rupture has a mortality rate of 50%. Despite the high mortality rates, early detection and treatment of these vascular lesions prior to rupture can prevent devastating clinical outcomes, underscoring the need to identify high-risk populations for screening. Current evidence demonstrates shared genetic and environmental risk factors for both AAA and IA.

Methods:
The BAAS study sought to establish the co-prevalence of AAA and IA. In one arm of BAAS, we recruited patients presenting with AAA and screened them for IA. All participants underwent a detailed interview to collect demographic, radiographic, and clinical data and also had genetic counseling.

Results:
Of the 126 individuals with an AAA enrolled, 65% (82/126) completed the MRA. Difficulty with logistics of obtaining the research MRA with long distance travel to clinic was the principal reason for failure to obtain MRA. We identified 20.7% (17/82) with one or more IA, including 21 aneurysms found during systematic screening. IA ranged in size from 1.5-14 mm (height) x 1.4-7 mm (width) and varied in location. 9.5% (2/21) had a maximum diameter of 7 mm or more. One participant with a positive MRA underwent early coil embolization with the remainder undergoing continued clinical surveillance. Of the 15 individuals completing the genetic counseling screening, two underwent recommended clinical genetic testing, revealing one negative screen and one variant of unknown significance in the MYH11 gene.

Conclusion:
Consistent with our prior cost effectiveness models, these prospective data support the clinical utility of routine screening for IA in patients presenting with AAA.
Abstract 167: 4D Flow MRI in Patients With Intracranial Aneurysms: a Comparative Analysis Between Evolving vs. Stable Aneurysms
Authors: Nael Kambiz , Shogan Tamer , Fung Maggie , Deleacy Reade , Fifi Johanna , Mocco J
Published: October 2018

Purpose:
Hemodynamic factors may play an important role in the initiation and growth of intracranial aneurysms (IA). In this study we sought to characterize the hemodynamic flow characteristics of evolving aneurysms and compare them against a cohort of patients with stable aneurysms using 4D-flow MRI.

Methods:
From our institution registry of untreated IA, 10 patients who had evolving aneurysm (defined as interval change in size or morphometry i.e. new lobulation, daughter sac, irregular wall) and 10 patients whose aneurysms remained completely stable during their sequential surveillance imaging were identified. These patients prospectively underwent a dedicated MR imaging protocol encompassing MRA, vessel wall imaging and 4D-flow using a 3T MR scanner (GE MR750). 4D-flow data was processed using Arterys software (San Francisco, CA) and hemodynamic parameters including flow velocity, peak wall-shear stress (WSS), flow eccentricity and flow-jet angle in each aneurysm were obtained. The associations of flow parameters and commonly used clinical variables and risk factors, size and morphometric features were assessed using univariate and multivariate analyses in evolving vs. stable IAs.

Results:
There was no significant difference between two groups in regards to age, sex, IA-size, aspect-ratio and size-ratio. The mean, IQR of aneurysm size were 5.4, 3.7-6.7mm in stable and 4.9, 3.5-6 mm in evolving IAs. The mean follow-up time was comparable (43 months in stable and 51 months in evolving IAs, p=0.58). The frequency of IA wall enhancement was higher in evolving IAs (70%) than stable IAs (30%), without statistical significance (p=0.09). The mean ± SD of flow parameters in evolving vs. stable IAs were: peak-WSS: 68.1 ± 18.3 cPa vs. 49.2 ± 17.2 cPa, p=0.04; flow eccentricity: 0.27 ± 0.13 vs. 0.15 ± 0.05, p=0.03; and flow-jet angle: 76.9 ±13.4° vs. 61 ±17.5°, p=0.05. After controlling for clinical and morphometric variables, multivariate logistic regression analysis identified Peak-WSS and flow eccentricity as independent predictors of evolving IAs.

Conclusion:
4D-flow MRI-derived peak WSS and flow eccentricity may help distinguish evolving from stable IAs independent of commonly used size and morphometric features.
Abstract 17: Stroke Alerts in Hospitalized Children
Authors: Barry Megan M , Le Truc M , Gindville Melissa C , Jordan Lori C
Published: October 2018

Introduction:
At our institution, the pediatric stroke alert activations started in April 2011 to allow for rapid evaluation and imaging of children presenting within 48 hours with acute stroke symptoms. In a previously published paper, stroke alerts initiated in the pediatric emergency department confirmed strokes in 25% of children. The purpose of this study was to characterize pediatric stroke alerts in hospitalized children.

Methods:
Demographic and clinical information was obtained from a quality improvement database and medical records for patients (28 days -20 years) at a single institution. Stroke alerts were activated after hospital admission from April 2011 through December 2016. A stroke alert activation means that a neurology resident sees the patient within 15 minutes and MRI is acutely made available. All values were assessed with descriptive statistics.

Results:
There were 56 in-hospital stroke alerts (mean age 7.5 y, SD 6.1y, 52% male) over 5.75 years. Stroke was the final diagnosis for 25 (45%) children, 72% ischemic, 28% hemorrhage (Figure 1). Other diagnoses included other neurological urgencies including seizure (21%), posterior reversible encephalopathy syndrome (9%), transient ischemic attack (5%) and acute demyelinating encephalomyelitis (4%). Of 25 actual strokes, 68% were stroke alerts initiated by the pediatric ICU or pediatric cardiac ICU. Rapid imaging was completed in 91% of stroke alerts; MRI brain was the 1
st
image in 55%. Nine of 25 children with stroke died (36%); 4 secondary to the stroke and the remainder were critically ill prior to stroke diagnosis.

Conclusions:
Pediatric in-hospital stroke alerts were confirmed stroke in 45% of children, while 38% were other neurological conditions requiring urgent neurologic evaluation. The high frequency of stroke and other serious illnesses in already hospitalized children demonstrates the importance of rapid evaluation via a pediatric stroke alert protocol when stroke is suspected.
Abstract 170: Metabolomics Profiling and Risk of Small Vessel Ischemic Stroke
Authors: Fornage Myriam , Sun Daokun , Yu Bing , Gottesman Rebecca F , Mosley Thomas H , Boerwinkle Eric
Published: October 2018

Cerebral small vessel disease (SVD) accounts for 25-30% of strokes and is a leading cause of cognitive decline and disability. Identification of blood-based biomarkers for SVD may aid in the early identification of high-risk patients and in the understanding of stroke etiologies, which will facilitate development of therapeutic options. In 3,904 men and women from the Atherosclerosis Risk In Communities study, we investigated the association of 245 serum metabolites measured at the baseline examination via untargeted metabolomic profiling with incident stroke subtypes. We focused on strokes with a small vessel pathology. First stroke events occurring between the baseline examination and December 31, 2013 were ascertained by annual telephone interview and hospital surveillance, followed case adjudication by a committee of experienced physicians. Cox proportional hazard models were used to estimate the hazard ratio (HR) for small vessel ischemic strokes (SVIS) per standard deviation of the standardized serum level of each metabolites, adjusting for baseline age, sex, race and field center (model 1); and additionally for diabetes, hypertension, current smoking, body mass index, and estimated glomerular filtration rate (model 2). Over a median follow-up of 24 years, 65 incident SVIS were observed. After correcting for multiple testing, we identified 4 serum metabolites associated with incident SVIS. A deamination product of tryptophan, indole-3-propionate (IPA) remained significantly associated in model 2 (HR [95%CI] = 1.13 [1.07-1.18], P<0.0001). Consistently, this metabolite was also significantly associated with incident hemorrhagic stroke (HR [95%CI] = 1.11 [1.03-1.19], P=0.0074) but no other stroke subtype. Additional analyses of MRI markers of SVD with the identified metabolite will also be presented. In summary, we identified a novel circulating metabolite, IPA, associated with incident ISVS independently of known risk factors. This compound is a potent neuroprotective antioxidant endogenously produced by human microbiota. These results are consistent with a role of oxidative stress in cerebral small vessel pathology.
Abstract 171: Endothelial Microparticle Levels and Silent Stroke in the Framingham Heart Study
Authors: Aparicio Hugo J , Himali Jayandra J , Amabile Nicolas , Pase Matthew P , Romero Jose R , Satizabal Claudia L , Cheng Susan , Larson Martin G , DeCarli Charles , Wang Thomas J , Vasan Ramachandran S , Beiser Alexa S , Boulanger Chantal M , Seshadri Sudha
Published: October 2018

Introduction:
Endothelial microparticles (EMP) are membrane vesicles, with a characteristic diameter of 0.1-1.0μ, shed by endothelial cells during cellular activation or apoptosis. EMP are associated with cardiovascular disease and risk factors, but data are lacking on the relations of EMP with subclinical vascular brain injury.

Methods:
We studied 487 individuals (mean age 66.9±8.8 years, 55% women) from the Framingham Offspring Cohort, who were free from clinical stroke. CD31+/CD41- EMP were identified and quantified using flow cytometry. Silent cerebral infarcts (SCI) were quantified as parenchymal lesions on brain MRI >3mm in size with characteristics of previous infarcts. Logistic regression models were used to investigate cross-sectional associations of EMP levels with prevalent SCI. We tested for interaction between EMP levels and statin use in their relationship with SCI.

Results:
SCI was observed in 49 (10%) participants. Figure 1 displays results of the logistic regression analysis. Circulating CD31+/CD41- EMP levels were inversely associated with SCI, adjusting for age, sex, and time interval between blood draw and brain MRI (OR 0.90 [0.82-0.98], p=0.016). Similar results were observed when adjusting for additional vascular risk factors. We observed an interaction between statin use and EMP levels in their association with SCI. There was an inverse association (OR 0.76 [0.64-0.89], p=0.001) among statin users and no association among non-statin users.

Conclusions:
In our analysis of the relationship of CD31+/CD41- EMP with SCI, in a well-defined community cohort, we observed an inverse association of higher EMP levels, primarily in participants on statins. Our data question whether constitutive or induced release of EMP, associated with a pleiotropic effect of statin medication, might mitigate vascular risk factor exposure and reduce risk of SCI. Further studies are needed to determine the associations of EMP with SCI and clinical stroke.
Abstract 172: Duration of Heightened Stroke Risk after Acute Myocardial Infarction
Authors: Merkler Alexander E , Diaz Ivan , Murthy Santosh B , Wu Xian , Gialdini Gino , Navi Babak B , Yaghi Shadi , Weinsaft Jonathan W , Okin Peter M , Safford Monika M , Iadecola Costantino , Kamel Hooman
Published: October 2018

Introduction:
The duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries ≥66 years of age. Our exposure of acute MI and the outcome of ischemic stroke were ascertained using previously validated
ICD-9-
CM diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we only included strokes occurring after discharge from acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge. Confidence intervals (CI) were computed using the nonparametric bootstrap method.

Results:
Among 1,746,476 beneficiaries, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. Compared to patients without acute MI, patients with acute MI were older (mean age 79.0 vs 73.1 years) and had more stroke risk factors. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7; 95% CI, 2.3-3.2), remained substantially elevated during weeks 5-8 (HR, 2.0; 95% CI, 1.6-2.4) and weeks 9-12 (HR, 1.6; 95% CI, 1.3-2.0), and was no longer significantly elevated afterward (Figure).

Conclusions:
Acute MI is associated with a substantially elevated short-term risk of ischemic stroke which appears to extend beyond the 30-day period enshrined in current stroke etiological classification systems.
Abstract 175: Kaiser Stroke Express Program - Population Based Estimate of Potential Accuracy of Field Based Identification of Endovascular Treatment Candidates
Authors: Klingman Jeffrey , Hatfield Meghan , Nguyen-Huynh Mai N
Published: October 2018

Background:
Whether patients with acute stroke and large vessel occlusion (LVO) may benefit from prehospital identification and diversion by EMS to a center offering endovascular therapy (EST) is controversial. The accuracy of prehospital scales as predictors of LVO is only one feature of whether EMS can effectively identify patients suitable for EST. Other factors include accuracy of last known well time (LTKW) and identification of stroke mimics. We performed a population-based estimate of potential accuracy of field based identification of potential EST candidates in a large community setting.

Methods:
In Kaiser Permanente Northern California, all acute stroke patients arriving at its 19 primary stroke centers (PSC) between 7am and 12am were evaluated on arrival by stroke neurologists by video. We reviewed the teleneurology notes to determine the potential accuracy of EST selection based on NIHSS score > 7.

Results:
For 2016, there were 2546 total potential stroke alerts triaged by EMS as having potential acute strokes [Figure]. Of these, 1268 (50%) were not candidates for acute stroke treatment for various reasons including stroke mimics and inaccurate LTKW. Out of 1241 cases deemed candidates for acute stroke treatment, 638 (25.1%) had potential LVO based on NIHSS > 7. Of these, 116 (4.6% of total “potential strokes” and 18.2% of patients who had “severe” strokes) were diagnosed with LVO and treated with EST.

Conclusions:
Even if field based tools were as accurate as clinical scoring by stroke neurologists, less than 1 in 4 patients diverted to endovascular stroke centers and away from closer PSC would benefit by receiving EST. Given that 50% of patients triaged by EMS did not qualify for any acute stroke treatment, a lower percentage of patients would actually benefit from field based diversion. Stroke systems may be better served by focusing on rapid treatment, evaluation, and transfer to endovascular centers than field based diversion strategies.
Abstract 180: Restoration of MiRNA MiR-181c-5p Rescue From the Detrimental Effect of Social Isolation in the Mice Subjected to Ischemic Stroke
Authors: Antony Maria , Byrne Monaza , McCullough Louise , Verma Rajkumar
Published: October 2018

Introduction:
MicroRNAs (miRNAs) are a class of short non-coding RNAs. Dysregulation of a variety of miRNAs have been tied to several neurological disorders including stroke. Recent studies have also found that microRNA profiles can change as a result of social environments. We have previously shown that the social isolation is detrimental to post-stroke recovery. MiR 181c-family of miRNA is one of the evolutionarily conserved and highly expressed miRNA family in the brain. Therefore, in this study we examined the specific role of miR-181c-5p after post-stroke social isolation.

Methods:
2-3-month old C57BL/6 male mice were pair-housed (PH) for at least two weeks. After two weeks, a 60-minute right middle cerebral artery occlusion surgery (MCAO) was performed and mice were randomly assigned to one of two housing conditions, isolation or continued pair-housing (ST-ISO or ST-PH). In the treatment study group, ST-ISO mice were further randomly assigned to receive either miR-181c-5p mimic (7mg/kg i.v/day x drug) or a vehicle control administered through lateral tail vein at 24h and 48h after stroke. The effect of mimic treatment was evaluated at 1, 3, and 7 days after stroke using rotarod, open field test (OFT) and corner test. Mice were sacrificed 7 days after stroke for miRNA analysis.

Results:
Whole miRNone analysis of total RNA revealed miR 181-5p as one of the most affected miRNA in the brain tissue of post stroke socially isolated mice. Temporal profile expression data suggests that, miR-181c-5p was significantly down regulated (p<0.05 vs STPH) 7 days after stroke as compared to ST-PH controls. Treatment with miR-181c-5p mimic successfully increased miR-181c-5p miRNA expression in the treatment group as validated by qPCR analysis. Isolation-induced reduction in miR-181c-5p expression was rescued by mimic treatment. Post treatment with mimic reduced stroke mortality by 25% and partially restored motor deficit in post stroke socially isolated mice.

Summary:
The present data suggest that social isolation reduces miR-181c-5p after stroke. Restoration of this miRNA improved post stroke mortality and behavioral recovery. This microRNA is a valid target to reduce the detrimental effects of social isolation after ischemic stroke.