bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WMP51: Towards a Simplified Method for Ischemic Stroke Subtyping Suitable for Electronic Medical Record Systems
Authors: Ryan Kathleen A , Ay Hakan , Worrall Bradford B , McArdle Patrick F , Cole John W , Meschia James F , Brown Robert D , Abedi Vida , Zand Ramin , Wassertheil-Smoller Sylvia , Sudlow Cathie L , Rundek Tatjana , Sacco Ralph L , Rexrode Kathryn , Lindgren Arne , McDonough Caitrin W , Grewal Raji P , Ribases Marta , Mitchell Braxton D , Kittner Steven J
Published: October 2018

Background:
Current ischemic stroke (IS) subtyping systems are very labor-intensive and costly to implement in large samples. There is a need to develop phenotyping approaches for genetic and other studies that can be implemented using generally available items captured in electronic medical records.

Objective:
In this report, we seek to validate a simplified approach using results from a genetic association study. Specifically, the strength of association for known genetic signals in the NINDS Stroke Genetics Network study (SiGN) is compared between the established IS subtyping systems (TOAST and Causative Classification System (CCS) subtypes) and phenotyping based on a single item within the CCS.

Methods:
Non-mutually exclusive “Simple” IS subtypes were defined from single CCS items as follows: 1) Small vessel stroke- lacunar infarct on imaging (with no other imaging or other requirements); 2) large artery stroke - vascular imaging showing > 50% stenosis or <50% stenosis with plaque rupture or thrombosis judged to be due to atherosclerosis in clinically relevant artery; and 3) cardioembolic stroke - persistent or paroxysmal atrial fibrillation. We compared the GWAS signals using these definitions to the published SiGN GWAS results for TOAST and CCS, among those of European ancestry only.

Results:
The Table shows that, for loci significant in SiGN GWAS study, the “Simple” IS subtypes had similar strengths of association and p-values compared to results from TOAST and the causative and phenotypic CCS subtypes.

Conclusions:
“Simple” IS subtypes perform as well in GWAS analyses as more complex phenotyping systems and could potentially be derived through automated or semi-automated methods applied to electronic medical record systems. Since the ‘Simple” phenotypes were based on high quality CCS data, the current findings reflect optimal performance. Additional validation studies will be required for implementation in other settings.
Abstract WMP60: Serial Body Temperature Evaluation and Long-Term Clinical Outcomes in Stroke
Authors: Margolin Emily , Saver Jeffrey L , Starkman Sidney , Liebeskind David S , Hamilton Scott , Sanossian Nerses ,   FAST-MAG Investigators and Coordinators
Published: October 2018

Background:
Elevated body temperature is a known marker of poor outcome in stroke. Some studies have shown that elevated body temperature early in the course of stroke is associated with better outcomes. We sought to characterize the relationship of body temperature and long-term clinical outcomes by evaluating serial measurements over 24 hours.

Methods:
All subjects were enrolled <2 hours after stroke symptom onset into the Phase 3 NIH Field Administration of Stroke Therapy Magnesium (FAST-MAG) clinical trial testing magnesium for prehospital neuroprotection. Presenting temperature in the emergency room and follow-up temperatures at 8, 16 and 24 hours after arrival were recorded. Clinical outcome was measured using the modified Rankin Scale at 90 days with last observation carried forward. Mean temperature was compared for each outcome on the modified Rankin Scale (mRS) utilizing ANOVA.

Results:
Among the 1700 enrolled patients 1586 (93%) had temperature recorded on ED arrival, 1594 at 8 hours, 1611 at 16 hours, 1594 at 24 hours. Mean age was 69 years, 43% were women, final diagnosis cerebral ischemia in 73.3%, intracranial hemorrhage in 22.8%, and mimic in 3.9%. At presentation mean body temperature was higher among those experiencing better long-term outcomes (Figure 1A). As of 8 hours and continuing through all subsequent measures worse outcome across the modified Rankin Scale spectrum was associated with higher body temperature (Figure 1B-D).

Conclusions:
Although higher body temperature at presentation was noted in subjects achieving better long-term outcomes, subsequent measures as of 8 hours demonstrated higher body temperatures in those experiencing worse long-term outcomes.
Abstract WMP62: Remote Home Monitoring of Risk Factors After Stroke or TIA to Improve Secondary Prevention - A Pilot Study
Authors: Ijas Petra , Mäkitie Laura , Kivelä Satu , Wahlman-Muranen Taina , Kiukkonen Niko , Selonen Petri , Stirbu Vlad , Taivalsaari Antero , Myyryläinen Lea , Koskimies Oskari , Honkanen Mauri , Forss Nina
Published: October 2018

Background:
Up to 90% of strokes could be prevented by effective treatment of the risk factors. However, there are major problems with the implementation of prevention. For example, only 40% of patients taking medication have blood pressure (BP) at treatment goals and 60% of patients with atrial fibrillation (AF) use anti-coagulant medication.

Hypothesis:
Remote home monitoring of risk factors after minor stroke or TIA may lead to better control of risk factors by increasing measurements and patient awareness and uncovering undetected risk factors. This pilot study investigates the feasibility of home monitoring of risk factors after minor stroke or TIA.

Methods and Patients:
Patients (n=30, mean age 57 yrs, range 34-79, 37% females) with recent minor stroke or TIA were supplied with a remote home monitoring system at discharge. The system comprised of a cloud backend for data storage and processing, patient user interface (UI), and wireless BP meter and light-weight EKG device with secured connection to clinician UI, through which BP and EKG could be followed real-time and individualized alarm limits could be set. EKG was automatically analyzed in the cloud backend to detect AF. The patients were contacted by phone at two weeks by stroke nurse and they returned the remote home monitoring system at final visit at three months. Additionally they were contacted if AF was detected or their BP required medication adjustment.

Results:
Twenty-nine (97%) patients completed the study. One patient discontinued due to unrelated serious illness. One patient did not follow the monitoring program. Of the remaining 28 patients (93%) with complete monitoring data, BP medication needed adjustment in 11 patients (39%) and new AF was detected in 3 patients (11%). Patients appraised that the home monitoring system was easy to use (score 8.6/10) and most would recommend it to peers (score 8.9/10).

Conclusions:
Remote home monitoring of risk factors after minor stroke or TIA is feasible and may be an efficient way to improve secondary prevention.
Abstract WMP65: Left Atrial Enlargement Without Atrial Fibrillation: A Risk Factor for Ischemic Stroke?
Authors: Saeed Omar , Saleem Muhammad A , Wallery Shawn S , Qureshi Adnan I
Published: October 2018

Background:
Left atrial enlargement without atrial fibrillation can be seen during evaluation of patients with cerebral ischemic events. However, it remains unclear whether such patients should be considered high risk for further cerebral ischemic events and may benefit from long term anticoagulation may be considered.

Methods:
We analyzed data from the Cardiovascular Health Study participants aged ≥65 years who underwent echocardiogram (included M-mode, 2-D, spectral, and color Doppler studies) and electrocardiogram (EKG) at baseline evaluation. All recordings were interpreted by central reader and left atrial diameter dimensions were recorded. We classified atrial dilation into four grades: 2.7-3.8 cm (ref), 3.9-4.2 cm (mild), 4.3-4.6 cm (moderate), and ≥4.7 cm (severe). We excluded patients with atrial fibrillation on EKG. Incident stroke was identified during annual follow-up examinations and at 6-month telephone contact and adjudicated by a central committee. Hazards ratio for all strokes, ischemic stroke, and hemorrhagic stroke during follow up were estimated using Cox proportional Hazards analysis.

Results:
Severe atrial dilation was observed in 298 (6.8%) of 4,384 study participants without atrial fibrillation (35.6% women, 2.3% African American; mean baseline age, 72.9 ± 5.2 years). The rate of ischemic stroke and any stroke was similar among patients with and without severe atrial dilation over a mean follow up period (mean ±SD) of 7.2 ±1 years. The risk of ischemic stroke (HR 1.3, 95% confidence interval [CI] 0.8-2.0) and all strokes (HR 1.2, 95% CI 0.8-1.8) was not different among patients with severe atrial dilation(compared with those without) after adjusting for age, race, gender, body mass index, heart disease, systolic blood pressure and cigarette smoking. The risk of hemorrhagic stroke (HR 1.1, 95% CI 0.3-3.6) was not significantly different among patients with and without severe atrial dilation.

Conclusions:
There was no increase in risk of any stroke or ischemic stroke in patients with severe atrial dilation without atrial fibrillation.
Abstract WMP67: Arterial Velocity on Carotid Ultrasonography Can Predict the Stenosis Progression in Patients With Vertebro-basillar Dissection
Authors: Wada Shinichi , Koga Masatoshi , Nakamura Yuki , Makita Naoki , Ide Toshihiro , Yamaguchi Yoshitaka , Ihara Masafumi , Toyoda Kazunori
Published: October 2018

Purpose:
Morphological changes of affected arteries in intracranial artery dissection often occur in the acute phase. The usefulness of carotid ultrasonography (CU) to evaluate the changes is not well investigated. The purpose of this study was to assess the value of CU indexes to detect artery stenosis progression on magnetic resonance angiography (MRA).

Methods:
This is a retrospective, single-center, observational study. We enrolled patients with intracranial vertebro-basilar artery dissection diagnosed based on criteria by the expert group (Debette S, et al: Lancet Neurol 2015) who were admitted within 30 days after onset from 2011 January to 2017 June. Carotid ultrasonography was performed on admission (median 0 days after onset) and follow-up (median, 40 days after onset; interquartile range, 11-106) to examined the flow velocity of both vertebral arteries. MRA was done on admission and follow-up just before or after the follow-up CU. Two stroke neurologists who were blinded to patients’ information assessed the change of vessel forms on MRA; stenosis progression was defined as an follow-up arterial diameter of <50% as compared to that at baseline on MRA. Patients were divided into two groups: those with stenosis progression (P group ) and the others (non-P group). Peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV) and pulsatility index (PI) were measured by CU and each baseline to follow-up ratio (follow-up/baseline) was compared between the two groups.

Result:
Of 26 patients (11 women, 53±8 years old) who were enrolled, 10 (28%) showed stenosis progression (P group). The P group had lower EDV ratio (0.34±0.63 vs 1.05±0.39, P<0.01) and higher PI ratio (1.95±0.76 vs 0.85±0.30, P<0.01) than the non-P group. Using Receiver Operating Characteristic (ROC) curve analysis, the area under the curve (AUC) of EDV ratio to predict stenosis progression was 0.87 (P<0.01) with the cut-off value of 0.54, sensitivity of 87.5% and specificity of 93.3% and that of PI ratio was 0.93 (P<0.01) with 1.17, 88.9% and 82.3%, respectively.

Conclusion:
Carotid ultrasonography is useful to predict the chrocnic stenosis progression of vertebra-basilar artery dissection.
Abstract WMP72: The "Three Territory Sign": An Under-Recognized Radiographic Marker of Malignancy-Related Ischemic Stroke
Authors: Nouh Amre M , Staff Ilene , Finelli Pasquale
Published: October 2018

Background:
Multiple cerebral territory infarcts of undetermined origin are typically attributed to cardioembolism; and most frequently atrial fibrillation. However the significance of three territory involvement in association with malignancy is under-recognized.

Objective:
To highlight the “Three Territory Sign” (bilateral anterior and the posterior circulation DWI lesions), as a radiographic marker of stroke due to malignancy.

Methods:
We conducted a retrospective analysis of patients at our institution from Jan 2014-Jan 2016 who suffered an acute ischemic stroke with MRI-DWI. We identified all ischemic strokes of undetermined etiology in patients with known malignancy (60 patients) and patients with stroke, atrial fibrillation and no malignancy (167 patients). Patients with both atrial fibrillation and malignancy were excluded. All DWI images were reviewed for 3, 2, and 1 territory lesions. Fisher Exact tests were used to identify statistical significance between the two groups. Statistical significance was set at 0.05.

Results:
There was a significant association between both cohorts (malignancy vs. atrial fibrillation) and the number of territory infarcts found. While the number of 1 {71.6% (n=43) vs. 79% (n=132)} and 2 territory infarcts {10.0% (n=6) vs. 17. 4% (n=29)} were similar between the two groups, 3 territory infarcts were > 5 times more frequent in malignancy as compared to atrial fibrillation {18.3% (n=11) vs. 3.5% (n=6)} (
p < 0.002
). Post-hoc pairwise comparisons using the Bonferroni correction for multiple tests support that the 3 territory pattern differs from both 1 territory (
p=0.0033
) and 2 territory (
p =0.0037
) patterns.

Conclusion:
Cerebral territory infarctions involving the bilateral anterior and posterior circulation are 5 times more frequent in malignancy-related ischemic stroke than atrial fibrillation. The “Three territory sign” is a robust marker of malignancy-related stroke and should prompt evaluation for malignancy after exclusion of other known causes.
Abstract WMP73:
Adck5, Mtnr1b
And
Kndc1
: Atherosclerosis-related Epigenetic Biomarkers Identified From Peripheral Leukocytes of Atherosclerotic Patients
Authors: Kim Jeeyeon , Jelinek Jaroslav , Hwang Junha , Shin Jong Wook , Jeong Hye Seon , Lee Young Ho , Issa Jean-Pierre , Kim Jei
Published: October 2018

Background and objectives:
The present study initially profiled and identified gene-specific promoter methylation changes in peripheral leukocytes (WBC) of patients having severe atherosclerosis. Then, the gene-specific promoter methylation changes of WBC were validated in atherosclerotic plaques by comparison with normal intima.

Methods:
We first profiled and identified specific genes showing promoter methylation differences between WBC of 8 patients having severe atherosclerosis and of other 8 patients having no-atherosclerosis in extra- and intra-cranial vessels using Digital Restriction Enzyme Analysis of Methylation (DREAM) sequencing. To select candidate CpG sites from DREAM sequencing data, we used criteria; located in -1,000 bp from transcription start sites, < or >5% of methylation differences between two groups, and <0.05 false positive rate. Significance of the gene-specific promoter methylation changes identified from WBC were validated from normal intima and atherosclerotic plaques obtained from common carotid artery of 20 human cadaveric donors (male, 13, age, 62.2±14.2 years).

Results:
On DREAM sequencing, CpG sites located in promoter regions of
ADCK5
(no-atherosclerosis, 67.57% vs. atherosclerosis patients, 55.18%),
KNDC1
(67.08% vs. 56.81%),
MTNR1B
(11.5% vs. 3.8%) had over 5% of the methylation differences with <0.05 false positive rate. On validation experiments using human vascular tissues, all
ADCK5
(normal intima, 4.02±1.02; plaque, 4.79±1.14,
p<
0.05),
KNDC1
(9.76±2.25 vs. 12.11±2.91,
p<
0.05),
MTNR1B
(14.08±2.93 vs. 17.53±5.07,
p<
0.05) showed significant higher promoter methylation in atherosclerotic plaques than normal intima.

Conclusion:
The present study identified promoter methylation changes in
ADCK5
,
KNDC1
, and
MTNR1B
from WBC of atherosclerotic patients, and validated their significance in human atherosclerotic tissues. The three genes showed possibilities as epigenetic biomarkers for atherosclerosis, even though future validations are needed for their significance in atherosclerosis development.
Abstract WMP79: Favorable Outcome of Stroke in Immunodeficient Mice is Preceded by Faster Normalization of T2 Relaxation
Authors: Janowski Miroslaw , Lyczek Agatha , Xu Jiadi , Bulte Jeff W , Walczak Piotr
Published: October 2018

Introduction:
Despite the success of rtPA and thrombectomy stroke continues to be a major disease burden to our society. Preventing secondary brain injury after stroke, given the broad therapeutic window, has gained increasing interest. It has been hypothesized that immunological processes substantially contribute to secondary brain damage. Indeed, the outcome of stroke in immunodeficient animals is more favorable compared to that in their immunocompetent counterparts. Here, we followed the evolution of stroke in the presence vs. absence of lymphocytes using serial MRI and T2 measurements.

Methods:
Adult immunodeficient

rag2
-/-

mice (n=6) and immunocompetent
BALB/c
mice (n=6) were subjected to stroke by intracerebral injection of 0.5 μl of 5 mM ouabain. Brain T2 relaxation times were measured using an 11.7T scanner at 1, 5, and 16 days following stroke induction. Post-mortem analysis of tissue sections included H&E and immunohistochemical staining for myelin basic protein, neurofilament, CD8, and CD68.

Results:
While the increase in T2 values was identical for immunocompetent and immunodeficient animals one day post-stroke (70.88±4.58 vs. 69.88±1.78 ms, respectively, p=0.72), the normalization of the T2 relaxation time (“fogging effect”) proceeded faster in immunodeficient animals over the next few days. Over five days, T2 relaxation times decreased in both groups, but it was significantly shorter in immunodeficient animals compared to immunocompetent animals (41.88±3.68 vs. 59.91±14.95 ms, respectively; p<0.001). On day 16, the T2 relaxation time decreased further in both groups and the difference between infarcted area in immunodeficient and immunocompetent animals as well as healthy tissue was no longer observed. Post-mortem analysis revealed a better preservation of infarcted tissue in immunodeficient animals.

Conclusions:
In immunodeficient
rag2
-/-
mice, the restoration of T2 relaxation times in the brain is faster and translates into less profound destruction of brain tissue within stroke lesions. We hypothesize that T2 relaxation time can be used for assessment of immunotherapies aimed at the reduction of secondary brain injury in stroke victims.
Abstract WMP87: Comparison of Patient-centered Quality of Life Utilities Using 3 Different Methods Across Modified Rankin Scale Scores - Experience From the ARTSS-2 Trial (Randomized, Multi-center Trial of Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)
Authors: Barreto Andrew D , Ford Gary , Shen Loren , Pedroza Claudia , Tyson Jon , Cai Chunyan , Rahbar Mohammad H , Grotta James C ,   on behalf of the ARTSS-2 investigators
Published: October 2018

Background and Purpose:
Although the modified Rankin Score (
mRS
) is broadly used as a measure of stroke outcome, quality of life (
QOL
), expressed in 0-1 numerical
utility
values (0=death, 1=perfect health), more accurately reflects patients’ value for particular health states. 3 methods for eliciting utility include: visual analog scale (
VAS
), standard gamble (
SG
) and time trade-off (
TTO
). SG, considered the classic method for obtaining utilities, involves making decisions under uncertainty or risk. We hypothesized that utilities from standard gamble (
SG
) would be systematically different than TTO & VAS and utility values would
not
be linearly associated with mRS scores.

Methods:
Utilities were elicited from ischemic stroke patients or proxy family members in the ARTSS-2 randomized trial; clinicaltrials.gov/NCT01464788. A societal perspective was performed using TTO (EuroQol-5D) and 2 patient-centered utility methods: VAS, a “feeling thermometer” and the SG. Certified raters blinded to utilities assessed 90-day mRS. Mean utilities were mapped across the mRS. As SG can be cognitively complex, requiring simultaneous assessments of both benefit and harm, patients’ capacity was determined using the validated Assessment of Capacity Evaluation. Only patients demonstrated capacity were able to perform the QOL evaluations.

Results:
86 of 90 (96%) patients had utilities at 90-days. Excluding missing and deaths, 70 patients had utilities generated by either the patient (N=48; 70%) or the proxy (N=22; 30%). TTO and VAS utilities declined in a non-linear fashion with increasing mRS. In general, SG utilities were larger and varied the least across mRS (Figure).

Conclusions:
Patient elicited standard gamble utilities of stroke health states do not appear to correlate with the mRS. Further research is necessary to understand divergence between SG and other methods of QOL elicitation in stroke patients.
Abstract WMP88: Comparing Behavioral Principles in Mailed Messages to Activate Patients at High Risk for Stroke
Authors: Williams Linda S , Clark Daniel O , Myers Laura , Daggy Joanne , Baye Fitsum , Martin Holly , Blackwell Layne , Snow Kathy , Teal Evgenia , Damush Teresa
Published: October 2018

Objectives:
To compare the effect of behaviorally-tailored mailed messages on patient activation to reduce stroke risk.

Methods:
We used EHR data to construct Framingham Stroke Risk Scores (FSRS) in primary care patients in one VA and one non-VA urban healthcare system. Patients in the highest risk quintile were eligible. We recruited 15 subjects to develop four stroke risk messages: standard, incentive ($5 gift card), salience, and incentive plus salience. Patients were randomly assigned to receive one of the messages. All letters asked the patient to call a stroke prevention coordinator. Response to the messages (calling the prevention coordinator) was modeled separately in the two healthcare system cohorts using logistic regression.

Results:
From 6,695 eligibles, 1,759 Veterans (mean age 75.6, 99% male, 61% White, mean FSRS 18.6) and 2,084 non-Veterans (mean age 65.6, 36% male, 68% Black, mean FSRS 13.1) received a letter. Overall call response rate was 23% among Veterans and 13% among non-Veterans. Both cohorts were significantly more likely to respond to the incentive and to the incentive plus salience message compared to the standard message (Table). Older age (for Veterans) and Black race (for non-Veterans) were also significantly associated with response, but FSRS and medical comorbidity were not. Among 631 subjects calling the stroke prevention coordinator, 26% (100/390) of Veterans and 30% (73/241) of non-Veterans were unaware of their risk factors.

Conclusions:
A mailed letter including a small monetary incentive may be more effective than standard or salience-related messages in engaging high-risk patients with their health care system. Many patients are unaware of their stroke risk. Future analyses will examine the relationship between messages and primary care follow-up.
Abstract WMP93: Trends in Stroke Hospitalizations in California: 2005-2014
Authors: Wang Limin , Holliday-Hanson Merry , Hoegh Holly , Krawczyk Christopher
Published: October 2018

Objectives:
Little information is known about the recent trends of sex-, age-, race/ethnicity-, and stroke type-specific stroke hospitalizations in California. Understanding the information is important for the evaluation of regional health policies, healthcare planning and resource allocation, and stroke prevention strategies. The study reports statewide trends in hospitalization rates and mortality of stroke in California from 2005 to 2014.

Methods:
Adult patients admitted to California-licensed acute care hospitals for acute stroke from 2005 to 2014 were included in the study. Data were from the California patient discharge data. Sex-, age-, race/ethnicity- and stroke type-specific stroke hospitalization rates were calculated based on the California population.

Results:
Of 2,085,120 adult hospitalizations with stroke from 2005 to 2014, 831,236 patients were admitted for acute stroke. From 2005 to 2014, the overall stroke hospitalization rate decreased 9.7% (309.4 to 279.5 per 100,000). The decrease in hospitalization rates for women (14.0%) was significantly greater than that for men (4.8%). However, there was a significant increase of hospitalization rates in younger groups for both men and women, which was mainly driven by ischemic stroke: Men aged 18 to 34 years had the highest increase in ischemic stroke hospitalization rates (37.2%), followed by men aged 35 to 44 years (32.0%), aged 45 to 54 years (23.0%), and aged 55 to 64 years (12.1%), while men aged ≥ 65 years had a significant decrease (13.7%). Women had the similar, but less steep trend compared to men. Blacks had the highest hospitalization rates, followed by Whites and Asians. The rates decreased for Whites (12.4%), but increased for Native Americans (34.7%) over a decade. The overall in-hospital mortality rate decreased from 7.2% in 2005 to 6.1% in 2014; the decrease was not significantly different by sex, age (< 55 years) or stroke type.

Conclusions:
Overall California stroke hospitalization rates decreased from 2005 to 2014, but hospitalization rates for ischemic stroke increased, with a significant increase in younger groups. The trends of stroke hospitalization rates over the decade varied by sex, age, race/ethnicity and stroke type.
Abstract WMP94: Effectiveness and Safety of Rivaroxaban versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Peripheral Artery Disease
Authors: Martinez Brandon K , Sood Nitesh A , Bunz Thomas J , Coleman Craig I
Published: October 2018

Introduction:
Comorbid peripheral artery disease (PAD) is a risk factor for ischemic stroke in patients with nonvalular atrial fibrillation (NVAF) and has been incorporated into the CHA
2
DS
2
-VASc risk score.

Objective:
To assess the effectiveness and safety of rivaroxaban vs. warfarin in NVAF patients with PAD treated in routine practice.

Methods:
Using US MarketScan claims data from 11/2011-3/2016, we identified oral anticoagulation (OAC) naïve NVAF patients with PAD and ≥12 months of continuous insurance coverage prior to the qualifying OAC dispensing. Propensity scores were derived based on demographics, comorbidities, stroke and bleeding risk factors and concomitant medications and used to 1:1 match rivaroxaban to warfarin users. Balance between cohorts was evaluated by inspecting standardized differences for baseline covariates (differences >0.1 indicating imbalance). Patients were followed until an event, OAC discontinuation or switch (30 day permissible gap), insurance disenrollment or end of follow up. Rates of stroke/systemic embolism (SSE), ischemic stroke and intracranial hemorrhage (ICH) per 100 person years (PYs) were compared using Cox regression.

Results:
We included 1030 rivaroxaban (35% received a reduced dose) and 1030 warfarin users with NVAF and PAD with a median (25%, 75% range) available follow up of 1.5 (0.7, 2.5) years. All baseline covariates had a standardized differences <0.1. Median age was 76 (69, 83) years and median CHA
2
DS
2
-VASc and HAS-BLED scores were 4 (3,4) and 2 (2,3). Rivaroxaban was associated with a 70% relative hazard reduction in SSE (absolute rate reduction [ARR]=1.48 events/100 PY; number needed to treat [NNT]=68) and a 75% reduction in ischemic stroke (ARR=1.42 events/100 PY; NNT=71) vs. warfarin
(Figure).
Only 1 ICH (in the rivaroxaban cohort) was observed.

Conclusions:
In this real-world study, rivaroxaban was associated with reductions in SSE and ischemic stroke alone in NVAF patients with comorbid PAD.
Abstract WMP98: Genetic Deletion of Haptoglobin Ameliorates Intracerebral Hemorrhage-induced Brain Damage
Authors: Jean Stacy , Leclerc Jenna , Li Chris , Sylvain Dore
Published: October 2018

Background:
The presence of extracorpuscular hemoglobin (Hb) exacerbates brain damage following intracerebral hemorrhage (ICH). Systemically, haptoglobin (Hp) is an acute phase glycoprotein that reduces brain injury by binding to extracellular Hb, which stabilizes the protein and prevents further toxic reactions. However, the properties of Hp within the brain during ICH are not well understood. This study aims to investigate the acute and chronic effects of haptoglobin deletion following ICH and the possibility that age influences the recovery outcomes.

Methods:
The ICH was induced in young and older aged (WT) controls and Hp
-/-
C57BL/6 mice using the autologous whole blood and collagenase injection models. Behavioral assessments of neurological deficit scoring, open field locomotor activity, and rotarod were conducted to investigate functional outcomes at 1d, 2d, 3d, 4d, 7d, and 10d. Various anatomical outcomes were measured through the staining for specific biomarkers following animal sacrifice at 3d and 10d.

Results:
At 3d, Hp
-/-
mice display 36.7±6.9% smaller lesions, 35.8 ± 9.5% less residual blood volume and 36.9±6.5% less tissue injury. At 10d, young Hp
-/-
mice show significant reduction in lesion volume. Behavioral assessments exhibit a reduction in neurological deficits in Hp mice. Similarly, young and old Hp
-/-
mice show significant differences in neurological deficit scores and open field locomotor activity at 3d and 10d. Additionally, Hp
-/-
mice display significantly less heme oxygenase 1 expression, less iron, and, less blood-brain barrier breakdown at 3d conversely, no significant differences are observed at 10d. Furthermore, Hp
-/-
mice show a reduction in hematomal vascular endothelial growth factor expression and ipsilateral motor cortex expression at 3d. Additionally, ipsilateral thalamic astrogliosis was less in young Hp
-/-
mice but no significance observed at 10d.

Conclusion:
The results of this study display the acute and chronic ameliorating effects of haptoglobin deletion in mice following ICH. Initially, Hp
-/-
mice have significant reductions in brain injury and later, perform similarly and occasionally better than WT controls.
Abstract WP1: Intravenous Cangrelor as a Rescue Platelet Inhibitor for Emergent Stenting in Ischemic and Hemorrhagic Stroke
Authors: Grigoryan Mikayel , Badr Yaser , Jocson Michelle , Ayala Angela , Lee Lance
Published: October 2018

Background:
Platelet inhibitor loading is commonly used in emergent settings for neurondovascular interventions in which permanent device implantation (eg, a stent or a flow-diverter) is planned. Oral/enteral load of antiplatelets may delay time-sensitive intervention in emergency settings, and intravenous glycoprotein inhibitors have a long half-life making them difficult to reverse should the treatment strategy change or complications (eg, bleeding) occur.

Objective:
To investigate the safety and utility of Cangrelor, an intravenous P2Y12 receptor inhibitor with immediate onset (within 2 min) and rapid offset (elimination half-life of 3-6 min) of antiplatelet activity for acute stenting in patients with ischemic and hemorrhagic stroke.

Methods/Patients:
A total of seven patients (at the time of this submission) received intravenous Cangrelor intraprocedurally. Of those, three patients had tandem cervical/intracranial occlusions, necessitating carotid stenting; two underwent intracranial stenting for thrombectomy-resistant intracranial large vessel occlusions, and two had flow-diverting stents for aneurysmal subarachnoid hemorrhage where use of traditional endovascular/microsurgical techniques was deemed suboptimal. In each case, the infusion was started five minutes before the device implantation, after selective access had been obtained and stent placement was imminent.

Results:
Endovascular device implantation was successful in all patients. P2Y12 inhibition testing was conducted intraprocedurally (5-10 minutes after the bolus dose) and showed adequate platelet inhibiton in all seven cases (PRU 60-151). Upon completion of interventions, all patients underwent head CT which showed no intracranial hemorrhage (or no worsening hemorrhage). The Cangrelor infusion was then terminated and all patients immediately received oral/enteral antiplatelet load. No immediate/early postoperative complications were noted and follow-up (24-96 hours) angiographic or noninvasive imaging confirmed patency of all the implanted devices.

Conclusion:
Intravenous Cangrelor could serve as a safe and convenient alternative to traditional antiplatelets or glycoprotein inhibitors in emergent neuroendovascular stenting
Abstract WP100: Investigation of Secondary Thalamic Injury After Ischemic Stroke: A Time Course Study
Authors: Cao Zhijuan , Cheng Michelle , Foltz Aulden G , Steinberg Gary K
Published: October 2018

Introduction:
After a cortical stroke, secondary degeneration can occur in remotely connected regions such as thalamus. This progressive secondary thalamic injury leads to somatosensory dysfunctions and hinders recovery. The pathophysiology of primary ischemic injury has been well characterized; however, the mechanism underlying secondary thalamic injury is poorly understood. We conducted a time course study to identify the critical time window of thalamic injury development after stroke and to investigate the involved mediators.

Methods:
Cortical ischemic stroke was generated by permanent occlusion of left middle cerebral artery in male C57BL6J mice (12-15 weeks). Brain sections were collected on post-stroke days (PD) 1, 3, 7, 14 and 28. Fluoro Jade C and TUNEL staining were used to detect degenerative injury and apoptosis, respectively. Immunostaining were used to detect neuronal loss (NeuN & MAP2) and inflammatory responses (CD68 & GFAP).

Results:
In the somatosensory cortex, degenerative injury and apoptosis were detected as early as PD1. Reduced NeuN and MAP2 expression confirmed the cortical neuronal injury starting at PD1. Activated microglia (CD68) were initially detected around the infarct at PD1 and gradually showed in the infarct core at PD14. Activated astrocytes (GFAP) appeared sparsely around the infarct on PD3 and became densely packed and elongated at PD7. In the ipsilesional thalamus, degenerative injury and apoptosis were detected at PD7 and became aggravated on day 28, indicating a development of thalamic injury. Reduced NeuN and MAP2 expression in the thalamus began at PD14. Activated microglia were detected at PD1 and activated astrocytes were detected at PD3 in the ipsilesional thalamus. Clustered microglia/astrocytes started at PD7 and became more densely at PD14 and 28.

Conclusion:
Our data shows that thalamic degenerative injury begins on PD7 and continues to develop until at least PD28. Our data also shows robust inflammatory responses during thalamic injury development. Future study will identify the subtypes of activated microglia/astrocyte and the related molecular mediators. Our findings will enrich the understanding of thalamic injury and define specific cellular and molecular targets for stroke treatments.
Abstract WP101: Progesterone Counteracts Stress-Induced Microglial Priming by Reducing NLRP3 Inflammasome Activation After Ischemic Injury
Authors: Espinosa-Garcia Claudia , Sayeed Iqbal , Atif Fahim , Yousuf Seema , Neigh Gretchen N , Stein Donald G
Published: October 2018

Introduction:
Cerebral ischemia, a consequence of cardiac arrest and stroke, is a leading cause of death and disability in the U.S. To improve translational studies, STAIR recommends augmenting animal models with comorbidities that “better reproduce the pathophysiological state” of stroke patients. Therefore, we incorporated social stress into our ischemia model (Espinosa-Garcia et al., 2017). Prior exposure to social stress upregulates the inflammatory status of microglia. They become primed—sensitized to activation by subsequent ischemia—worsening outcome. Such potentiated activation may result from the release of danger signals in the brain, such as HMGB-1, which binds to TLR4 receptors and activates inflammasomes. The NLRP3 inflammasome consists of a sensor molecule, NLRP3, the ASC adaptor, and caspase-1, whose activation leads to pro-inflammatory IL-1β production. We hypothesized that progesterone (P4) administration will reduce NLRP3 inflammasome activation, one of the molecular mechanisms underlying P4’s neuroprotective effects against ischemia combined with stress.

Methods:
Adult male rats were exposed to social defeat stress for 8 days and then subjected to global ischemia. P4 was administered 2 and 6h after occlusion and then daily for 7 days. Animals were killed at 7 or 14 days post-ischemia and their hippocampi dissected for western blots. The hippocampus is highly sensitive to stress and selectively vulnerable to global ischemia.

Results:
Consistent with previous reports, stress primed microglia and increased (
p
<0.05) HMGB1 and NLRP3 levels, with no changes in IL-1β production in non-ischemic controls. Stressed ischemic animals showed potentiated (
p
<0.05) NLRP3 inflammasome activation and increased IL-1β production. P4 treatment robustly reduced (
p
<0.05) HMGB1, TLR4, phospho-IκB, NLRP3, ASC, cleaved caspase-1, and IL-1β levels in both stressed and non-stressed ischemic animals.

Conclusion:
Our data show that P4 can modulate stress-induced microglial priming to subsequent ischemic injury by counteracting NLRP3 inflammasome activation in the hippocampus. P4 may thus prove a promising neuroprotective agent to reduce inflammation associated with poor outcome in stroke patients with comorbid stress.
Abstract WP106: Acetazolamide Stabilizes Stroke Induced Respiratory Dysfunction and Improves Longterm Cognitive Outcome
Authors: Patrizz Anthony , Atadja Louise , Mulkey Daniel , McCullough Louise , Li Jun
Published: October 2018

Background:
Respiratory dysfunction is a common complication of stroke, with an incidence more than 60% in first time stroke patients, leading to poorer recovery and increased mortality. We developed a mouse model of stroke induced respiratory dysfunction (SIRD) characterized by hypoventilation and apnea. Mice that had the highest incidence of post-stroke apneas developed
progressive
cognitive decline. Acetazolamide (Act), a carbonic anhydrase inhibitor, promotes metabolic acidosis increasing respiratory activity.

Hypothesis:
Acetazolamide will stimulate basal respiratory activity, eliminating apneas and hypoxic events, and will enhance post stroke cognitive outcomes.

Methods:
Whole body plethysmography was performed on WT C57/B6 young (2-3 month) male mice to establish baseline breathing frequency, tidal volume, minute ventilation and number of apneas. Mice were subjected to 60 MCAO or sham surgery. Plethysmography was performed on day 3, 7 and weekly thereafter. Act (40mg/kg) continuous administration via SQ implanted Alzet pump or vehicle (n=11/group) was initiated on day 14. Cognitive tests were conducted over six weeks.

Results:
Act treatment improved respiratory frequency (152.6±6.49 vs. 318.4±61.9, p<0.05) and decreased the number of apneas (5.4±0.7 vs. 1±0.5, p<0.001) in stroke mice (Fig. 1). Spatial learning/memory assessed on day 42 with Barnes Maze found Act-treated mice had a shorter escape time than vehicle (median escape time 160.48 vs. 14.16s, survival curve for time to escape p=0.0001, Mantel-Cox test).

Summary:
Apnea and hypoxia are seen in a murine model of SIRD, the severity of which correlated with post-stroke cognitive decline. These deficits were reversed with chronic Acetazolamide treatment. Research supported by the NCATS Award Number TL1TR000369.
Abstract WP11: Use of Endovascular Thrombolysis or Thrombectomy for the Treatment of Cerebral Venous Thrombosis: An Observational Study From the US Nationwide Inpatient Sample
Authors: Siddiqui Fazeel M , Weber Matthew , Dandapat Sudeepta , Ortega-Gutierrez Santiago , Aksan Nazan , Scaife Steve , Coutinho Jonathan
Published: October 2018

Background:
Anticoagulation is considered the first-line treatment for cerebral venous thrombosis (CVT). However, a subset of patients does not respond. Data from case studies suggest endovascular treatment (ET) may be beneficial in such cases. The Nationwide Inpatient Sample (NIS), representing a 20% stratified sample of 7 million annual hospital admissions was used to evaluate the safety and efficacy of ET compared to conservative management in CVT.

Methods:
We extracted cases from NIS database for years 2004-2013 using ICD 9-CM codes: 437.6, 325, and 671.5. Data related to mechanical thrombectomy (MT) and/or thrombolysis was searched using ICD 9 CPT codes 39.74 and 99.10. Weights were applied to each admission per NIS recommendations to obtain national representation. Groups were matched with respect to age, gender and Charlson index. Data was further adjusted for injury severity score (presence of ICH, stroke, paralysis, midline shift, coma, status epilepticus or need for intubation).

Results:
Out of 42,889 weighted estimates of CVT cases, 1058 (2%) received ET (616 cases of thrombolysis alone and 442 cases of MT +/- thrombolysis). Patients who received ET were slightly older with higher comorbidity score, and CVT associated complications including ischemic stroke, ICH, coma, status epilepticus, cerebral edema with midline shift and need for endotracheal intubation. Patients who received ET had higher likelihood of having hematological disorders and severe dehydration and lesser likelihood of infection and trauma as underlying etiology of the condition. ET (thrombolysis alone and mechanical thrombectomy +/- thrombolysis) appeared to be significantly associated mortality and bad discharge outcomes in stepwise logistic regression analyses as well as matched paired analyses (Table 1).

Conclusion:
ET appears to be associated with increased mortality and poor discharge outcomes when compared to conservative treatment in the real-world setting.
Abstract WP111: Post-stroke Remote Limb Conditioning Shifts Monocyte to a Pro-inflammatory Subset and Improves Functional Recovery in Chronic Stroke
Authors: Yang Jiwon , Beltran Cesar , Cho Sunghee
Published: October 2018

Objective:
Post-stroke remote limb conditioning (PSLC) has been shown protective effect in preclinical and clinical studies. However, underlying protective mechanisms are multiple but not clearly defined. Although inflammation exacerbates stroke injury, studies showed inflammation also plays a key role in conditioning-mediated protection. This study investigated if PSLC induces changes of monocyte/macrophage (MM) subsets and the changes contribute to PSLC-induced functional benefits.

Method:
C57BL/6 male mice (12-week-old) were subjected to transient middle cerebral artery occlusion (MCAO) for 30 min. PSLC was induced 2h after MCAO by applying 5 cycles of 5 min inflation (200 mmHg) and 5 min deflation with a cuff on left hind limb. Mononuclear cells were isolated from the spleen, blood and brain at 3D and analyzed by flow cytometer. Acute injury size was measured at 3D. Motor and gait functions were assessed up to 4-month using Rotarod and Catwalk. Additionally, naïve spleen cells were treated sera obtained from sham-conditioned or PSLC animals, and MM subset shifts were determined.

Results:
PSLC significantly decreased anti-inflammatory (Ly-6C
low
) monocytes without changing pro-inflammatory (Ly-6C
high
) subset in blood, while there were no changes in the spleen (Fig A). Similarly, PSLC decreased Ly-6C
low
and increased Ly-6C
high
subset in the stroked brain (Fig B). The shift to a pro-inflammatory MM subset did not attenuate brain injury size but was associated with improved motor and gait function (Fig D). PSLC serum reduced Ly6-C
low
and increased Ly-6C
high
subset in splenocytes (Fig C). There was bigger MM shift and greater behavioral benefits of PSLC in animals with bigger injury (Fig E&F).

Conclusion:
The study demonstrates a contributing role of pro-inflammatory monocytes to PSLC-induced functional benefits in chronic stroke. This study provides a potential application of PSLC as a neuroimmune-based strategy for ischemic stroke patients.
Abstract WP114: Basilar Artery Dolichoectasia is Associated With Lacunar Stroke and With Neuroimaging Markers of Small Vessel Disease
Authors: Del Brutto Victor J , Satyanarayan Sammita , Brorson James R
Published: October 2018

Introduction:
Among patients with ischemic stroke, 3-17% are found to have at least one intracranial dolichoectatic artery. Atherosclerosis was previously thought to most commonly underlie abnormally dilated arteries, but recently the correlation of dolichoectasia with imaging markers of small vessel disease has suggested a shared underlying vascular process. Further clarification of this association is needed.

Hypothesis:
Basilar artery dolichoectasia is more frequent in patients with lacunar infarctions in comparison to other stroke subtypes. Imaging markers of small vessel disease are associated with basilar artery dolichoectasia.

Methods:
Among consecutive ischemic stroke admissions to a single medical center over three years, the 100 cases initially classified as lacunar stroke, and a randomly sample of 100 non-lacunar strokes cases were selected. For the present study, only patients with vascular imaging (MRA or CTA) were included resulting in a final cohort of 86 patients in the lacunar stroke group and 92 in the non-lacunar stroke group. Basilar artery ectasia and dolichosis were defined following Smoker’s criteria. MRIs were reviewed for the presence of old lacunar infarcts, deep cerebral microbleeds, enlarged perivascular spaces and moderate-to-severe white matter hyperintensities. These markers were added for estimating the total small vessel disease score ranging from 0 to 4 points.

Results:
The mean age was 65.5±1.9 years (53.9% men). Basilar artery dolichoectasia was present in 29.1% of patients with lacunar infarctions and in 15.2% of non-lacunar strokes (
p:
0.04). The mean basilar artery diameter was significantly higher in patients with lacunar mechanism of stroke (3.87±1.04 mm versus 3.30 ±0.9 mm,
p:
0.0001). Patients with basilar artery dolichoectasia were more likely to have a small vessel disease score of 2 or higher than those without (
p:
<0.05).

Conclusions:
Our results support a stronger link between dilative arteriopathy and small vessel disease than with other stroke subtypes. Basilar artery dolichoectasia and small vessel disease might have common triggers that activate a cascade of events resulting in the pathological changes characteristics of these conditions.