bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 190: North Dakota Mission: Lifeline Stroke Survey of Symptom Awareness Indicates Need for Public Education
Authors: Cook Mindy , Hyder Shiraz , Sather Jeffrey , Meyer Chrissy , Pietrzak Janna
Published: January 2019

Introduction:
The American Heart Association (AHA) Mission: Lifeline Stroke program is a 3-year statewide initiative in North Dakota which aims to improve consistency of guideline-based care of stroke patients thereby improving outcomes. In year one a public awareness assessment of stroke awareness was completed.

Purpose:
The intent of this survey was to establish a baseline of symptom awareness related to the F.A.S.T acronym, actions and behaviors when stroke is suspected, and media preferences in ND.

Methods:
The AHA commissioned Marketing & Advertising Business Unlimited, Inc., to conduct a telephone survey. Four hundred phone interviews were completed with ND residents by random selection from a list of 24,000 residential landlines and 8,000 mobile phones. Numbers were stratified into five distinct regions to ensure a proper urban/rural balance. Data was also weighted by gender, age, and region to conform to the latest statewide census projects. The telephone survey had a 4.9% margin of error and a 95% confidence interval.

Results:
Forty seven percent of respondents stated that they had learned the signs of stroke, however only 17% classified themselves as very familiar. The most common signs identified were “Speech/Slurred Words” and “Face/Drooping Face” at 39% and 30%, respectively. In terms of F.A.S.T. awareness, 46% of survey respondents correctly identified “Face” while only 15% identified “Time.” “Arm” and “Speech” were identified 32% and 23%, respectively. Respondents indicated they would call 9-1-1 64% of the time. When asked why it may be better to be transported by personal vehicle, 74% responded you may be able to get to the hospital faster. Men and those over 65 were far less likely to correctly identify the components of F.A.S.T. Media preferences expressed were: 1) F.A.S.T. acronym over other longer options, 2) visual examples with real humans versus icons, 3) the tagline “Care Starts When You Call”, and 4) television and Facebook were the preferred mediums.

Conclusions:
Overall, the survey data is encouraging and may provide guidance for future rural programs. A significant portion of the respondents were deficient in stroke symptom awareness, however most survey respondents expressed interested in learning these symptoms.
Abstract 193: Sex-Specific Patterns of the Influence of Age on Functional Outcome After Acute Ischemic Stroke
Authors: Liu Zuolu , Sanossian Nerses , Starkman Sidney , Liebeskind David S. , Avila-Rinek Gilda , Ng Kwan L. , Eckstein Marc K. , Sharma Latisha K. , Conwit Robin , Hamilton Scott , Saver Jeffrey L.
Published: January 2019

Background:
Age is a major determinant of stroke outcome, but few studies have investigated whether the effect of age differs between men and women.

Methods:
Analysis of all patients enrolled in a multicenter acute stroke trial (FAST-MAG) presenting with acute cerebral ischemia and treated without intravenous thrombolysis. Effects of age and sex were evaluated for: 1) disability or death (modified Rankin Scale, mRS, 2-6); 2) reduced stroke-related quality of life (Stroke Impact Scale, SIS < 80); and 3) mortality, unadjusted and adjusted for baseline NIHSS, ASPECTS, and 7 additional prognostic variables.

Results:
Among the 772 patients meeting entry criteria, age was 71.2, 44.0% were women, and presenting NIHSS 6.8. Overall, men were slightly younger than women (69.9 vs 73.0), without difference in initial NIHSS (6.4 vs 7.2), nor in 3m outcomes: mRS 2-6, 44.7% vs 50.2%, p=0.13; SIS<80, 44.6% vs 44.1%, p=0.90; mortality 9.5% vs 9.7%, p=0.92. However, the sexes differed in age-functional outcome patterns. Among women, there were U-shaped relationships between age and rates of both mRS 2-6 (Figure) and SIS <80. In contrast, among men, a much more attenuated U-shaped relationship was visualized, did not reach statistical significance. For both sexes, mortality showed a generally linear increase with age. Compared to those aged 40-64, mortality rates in the oldest old (age ≥85) were: women - HR 4.81 (95CI 0.98-23.39); men - HR 4.06 (95CI 1.17-14.14).

Conclusions:
The relationship between age and functional outcome in supportively treated acute cerebral ischemia patients differs between the sexes, with women but not men showing better outcomes in early senescence than either midlife or very late-life. This contrasting outcome profile may reflect sex-specific biological differences in ischemic stroke mechanism and neuroplasticity, cultural differences in social roles and support, or additional factors that merit further study.
Abstract 2: Outcomes After Endovascular Stroke Therapy in High Versus Low Volume Centers
Authors: Saber Hamidreza , Navi Babak , Kamel Hooman , Liang Conrad W , Chen Peng R , Blackburn Spiros , Yoo Albert J , Vahidy Farhaan S , Savitz Sean I , Sheth Sunil A
Published: January 2019

Background:
Given the time-sensitivity of endovascular stroke therapy (EST), an increased availability of these treatments to lower-volume centers may improve patient outcomes. However, clinical trials demonstrating efficacy of EST were performed at larger volume centers, and our understanding of outcomes at lower volume centers is lacking.

Methods:
Using validated diagnosis codes from administrative data on all discharges from hospitals in Florida (2005-2016), and New York (2006-2014) we identified patients with acute stroke treated with EST. Primary endpoint was good outcome defined as discharge home without intracerebral hemorrhage. Descriptive statistics were used to calculate the number of EST performed. Multivariate logistic regressions adjusted for age, sex, and comorbidities were used to evaluate the association between year of treatment and hospital volume with outcome.

Results:
Among 5,699 patients (at 439 hospitals) treated with EST, median age was 72[60-81], 52% were female, and 54% received IV tPA. Annual EST procedures increased from 158 in 2007 to 423 in 2010 to 925 in 2014, as did the number of hospitals performing EST, from 30 in 2007 to 50 in 2010 to 68 in 2014. During the study period, an increasing proportion of total EST procedures were performed at lower volume centers (
Figure 1a
). Adjusting for age and comorbidities, the likelihood of good outcome increased yearly (OR 1.1 [1.05 -1.14]). Adjusting for age, comorbidities and year of treatment, increasing annual hospital EST volume was associated with increasing likelihood of good outcome (
Figure 1b
).

Conclusions:
In two large and diverse states, clinical outcomes with EST improved over time. Higher volume centers performed better than lower volume centers, a finding that persisted despite the overall trend towards improvement. These findings support the need for further study on the efficacy of EST outside of specialized centers.
Abstract 21: Effect of Oral Factor Xa Inhibitors on the Risk of Subdural Hematoma: COMPASS trial Results and Systematic Review
Authors: Catanese Luciana , Eikelboom John W , Bosch Jackie , Shestakovska Olga , Perera Kanjana S , Ng Kelvin , Nayar Sumiti , Sharma Mukul , Hart robert G
Published: January 2019

Background:
Subdural Hematomas (SDHs) are an uncommon but important complication of anticoagulation therapy. Data on SDHs has been underreported from major randomized trials testing novel oral anticoagulants, and the risk of SDHs relative to aspirin has not been defined.

Methods:
We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international COMPASS randomized trial comparing aspirin 100mg daily, Rivaroxaban 5mg twice daily, and Rivaroxaban 2.5mg twice daily plus aspirin. A systematic literature review of randomized trials comparing factor Xa inhibitors versus aspirin on SDH risk was undertaken.

Results:
A total of 28 SDHs among 27,395 COMPASS participants were identified. The incidence was 0.04 -0.06 per 100 patient-years during the mean 23-month follow-up. The frequency of SDH according to assigned antithrombotic therapy was 11 for Aspirin, 7 for Rivaroxaban and 10 for combined antithrombotic therapy. The rates of SDHs did not differ per treatment groups. Three RCTs comparing Factor Xa inhibitors versus Aspirin and reporting data on SDHs were identified. They involved 16,177 participants (mean age 65) with a total of 11 SDHs. The incidence of SDHs ranged from 0.06 to 0.1 per 100-patient-years (HR 1.51 in one study).

Conclusions:
The frequency of SDH was similar in all three treatment arms of the COMPASS trial. Based on available evidence from four randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared to aspirin. The COMPASS trial results triple the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin.
Abstract 27: Mir-494 Elicits Th1 Shift and Neurotoxic Responses to Promote Acute Ischemic Brain Injurythrough Targeting Hdac2
Authors: Zhao Haiping , Li Guangwen , Wang Rongliang , Tao Zhen , Ma Qingfeng , Zhang Sijia , Han Ziping , Yan Feng , Li Fangfang , Liu Ping , Ma Shubei , Ji Xunming , Luo Yumin
Published: January 2019

Background:
T helpler type 1 (Th1)-shifted inflammation after acute ischemic stroke (AIS) affects neurological function. However, the molecular switch is poorly defined. The objective of this study is to identify functionally important and therapeutically relevant pathways downstream of microRNA (miR)-494 in modulation of neurotoxic Th1 shift after AIS.

Methods:
Blood samples from 76 AIS patients and 52 heathy controls were collected, and miR-494 levels were detected by quantitative real-time PCR. Overexpression or knockdown of microRNA-494
in vivo
and
in vitro
was achieved by lentivirus vector. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion and cortical neurons were subjected to oxygen-glucose deprivation (OGD). Chromatin immunoprecipitation sequencing using anti-HDAC2 antibody was performed to assess the mechanism behind the regulation of transcription.

Results:
MiRNA-494 levels were increased in lymphocytes of AIS patients, and is inversely correlated with NIHSS score. Conversely,
in vivo
inhibition of miR-494 by intravenous administration markly improved the neuronal survival and neurological outcome of ischemic mice. Moreover, lymphocytic miR-494 level of AIS patients is specially positively associated with a key Th1 cytokine interferon (IFN)-γ. Enforced expression of miR-494 actually leads to Th1 shift
in vitro
, and this conditioned medium advanced neuronal death and axonal damage upon OGD. Mechanistically, histone deacetylase 2 (HDAC2) is a direct miR-494 target whose repression blunted miR-494 antagomir-reduced Th1-shift and brain injury after ischemic stroke.

Conclusions:
This work illustrates a novel miR-494/HDAC2 axis in promoting Th1-shifted inflammation after AIS, represents a potential therapeutic target.
Abstract 41: Cerebral Microbleeds and the Effect of Anticoagulation on Outcomes in 3699 Patients With Embolic Strokes of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial
Authors: Shoamanesh Ashkan , Hart Robert G , Kasner Scott E , Smith Eric E , Marti-Fabregas Joan , Liu Yan Yun , Uchiyama Shinichiro , Mikulik Robert , Veltkamp Roland , Ntaios George , Muir Keith , Field Thalia S , Santo Gustavo C , Olavarria Veronica , Olavarria Veronica , Mundl Hardi , Lutsep Helmi , Berkowitz Scott D , Sharma Mukul ,   on behalf of the NAVIGATE ESUS Investigators
Published: January 2019

Background:
Cerebral microbleeds (CMBs) are reported to predict recurrent stroke and antithrombotic-related intracerebral hemorrhage (ICH). We characterize CMBs in a well-defined population of embolic strokes of undetermined source (ESUS). Notably, we report for the first time interactions between CMBs and effects of random assignment to anticoagulant therapy.

Methods:
Subgroup analyses of the NAVIGATE ESUS randomized trial comparing rivaroxaban 15 mg vs. aspirin 100 mg daily were performed. CMBs were rated on T2*-GRE sequences obtained at baseline MRI in 3699 participants (mean age 67y). Multivariable regression analyses were used to identify variables independently associated with CMBs. Cox proportional hazards models were used to estimate the contribution of CMBs to risk of recurrent stroke, ischemic stroke, ICH and all-cause mortality. Analyses followed the intent-to-treat paradigm.

Results:
CMBs were present in 11% of participants. CMBs were strictly deep in 55%, lobar in 26%, and mixed in 19% of cases. Most (68%) had 1-2 CMBs, 27% had 3-10, and 5% >10. Advancing age (OR per yr 1.0, 95% CI 1.01-1.04), East Asian ethnicity (1.6, 1.0-2.4), hypertension (2.2, 1.5-3.2), multi-territorial ESUS (2.0, 1.4-2.7), chronic infarcts (1.8, 1.4-2.2), and occult ICH (5.2, 2.8-9.9) were independently associated with CMBs. During a median follow-up of 11 months, 5.1% of participants had recurrent stroke (4.8% ischemic stroke; 0.3% ICH) and 1.3% died. The presence of CMBs was associated with a 50% increased risk of recurrent stroke (HR 1.5, 95% CI 1.0-2.3), four-fold risk of ICH (4.2, 1.3-13.9), and two-fold risk of all-cause mortality (2.1, 1.1-4.3), and strictly lobar CMBs with a ~2.5-fold risk of ischemic stroke (2.3, 1.3-4.3). There were no interactions between CMBs and treatment assignments for recurrent stroke (p-value for interaction=0.2), ischemic stroke (p=0.3), or all-cause mortality (p=0.6). The hazard ratio (HR) of ICH on rivaroxaban was similar between persons with CMBs (HR 3.1, 95% CI 0.3 - 30.0) and persons without CMBs (HR 3.0, 95% CI 0.6 - 14.7; interaction p=1.0).

Conclusions:
CMBs mark an increased risk of recurrent ischemic stroke, ICH and mortality in ESUS, but do not appear to influence effects of rivaroxaban, particularly on the outcome of ICH.
Abstract 47: Incidence of Cervical Artery Dissection Across Age Groups
Authors: Atalay Yahya B , Chatterjee Abhinaba , Piran Pirouz , Murthy Santosh B , Navi Babak B , Kamel Hooman , Merkler Alexander E
Published: January 2019

Introduction:
Dissection of a cervical artery has been well described as a cause of ischemic stroke in the young. The role of dissection as a cause of stroke among older adults is less clear, but there are no obvious reasons why older patients would have less of a predisposition to dissection than younger patients.

Hypothesis:
We hypothesized that the incidence of dissection-related ischemic stroke would remain constant across age.

Methods:
We used inpatient discharge data included in the 2012-2015 releases of the National Inpatient Survey (NIS). We used previously validated
ICD-9-CM
codes to identify adults who were hospitalized with ischemic stroke and a concomitant diagnosis of either carotid- or vertebral-artery dissection. We compared the prevalence of concomitant dissection among stroke hospitalizations across patient subgroups defined by age. Survey weights provided by the NIS were used to calculate nationally representative estimates. Population estimates from the U.S. census were used to calculate the incidence of hospitalization with stroke and concomitant dissection per million person-years.

Results:
From 2012-2015, there were 17,325 hospitalizations with ischemic stroke and a concomitant dissection in the US. The prevalence of cervical-artery dissection among stroke hospitalizations was highest among those under 40 years of age and gradually decreased across increasing 10-year age intervals (Figure 1A). On the other hand, the overall incidence of hospitalization for stroke and concomitant dissection increased with increasing age (Figure 1B).

Conclusions:
In a nationally representative sample, we found that cervical-artery dissection accounts for a greater proportion of ischemic strokes among younger patients, but the absolute incidence of dissection-related stroke increases with age.
Abstract 49: White Matter Hyperintensity Spatial Pattern Variations reflect distinct Cerebral Small Vessel Disease Pathologies
Authors: Phuah Chia-Ling , Chen Yasheng , Liu Ziyang , Yechoor Nirupama , Hwang Helen , Laurido-Soto Osvaldo , Marcus Daniel S , Lee Jin-Moo
Published: January 2019

Introduction:
Cerebral small vessel disease (SVD) comprise of heterogeneous pathologies affecting small cerebral vessels. A novel phenotyping approach using etiology-based SVD imaging markers may improve discovery of SVD-related mechanisms. Topographical patterns seen in common SVD subtypes (hypertension-related (HTN) and cerebral amyloid angiopathy (CAA)) suggest that spatial location may reflect regionally different SVD pathology. We propose a machine-learning method leveraging spatial location information to partition WMH (a representative SVD imaging marker) into patterns that can discriminate underlying SVD pathology.

Method:
We selected subjects with WMH on FLAIR MRI from the Alzheimer’s Disease Neuroimaging Initiative database and created WMH segmentation maps using a custom deep learning algorithm. We performed voxel-based spectral clustering analysis on aligned WMH maps to group image voxels into clusters, maximizing within-group and minimizing between-group similarities. HTN-SVD risk was scored using serial blood pressure measurements and medication history. We quantified CAA risk using the Boston criteria. We used multivariable regression to evaluate extent to which different WMH clusters influenced CAA and HTN-SVD risks. Demographics and total WMH volume were included as covariates.

Results:
We analyzed 878 subjects; 39% were hypertensive, 4.4% had probable CAA. We observed partitioning of WMH into five distinct clusters, which demonstrate recognizable spatial distributions that suggest biological relevance (deep, periventricular, subcortical, anterior horns of lateral ventricles, posterior predominant). Multivariable regression models revealed independent associations of WMH clusters with CAA (posterior predominant WM; p=0.02; ß=0.63), and HTN-SVD (deep WM; p=0.01; ß=0.20).

Conclusion:
WMH occur in unique spatial patterns that reflect different underlying SVD pathology. WMH spatial pattern variations may serve as etiology-based SVD imaging markers, providing a critical new tool in efforts to resolve homogeneous disease mechanisms among heterogeneous disease presentations. Such strategy enhances genomic studies, allowing more comprehensive modelling of genetic effects on SVD pathogenesis.
Abstract 50: Interrelationship Between Lacunes and Cortical Microinfarcts in Cerebral Amyloid Angiopathy
Authors: Gokcal Elif , van Veluw Susanne J , Fotiadis Panagiotis , Pasi Marco , Viswanathan Anand , Greenberg Steven M. , Gurol M. Edip
Published: January 2019

Background:
Cerebral amyloid angiopathy (CAA) is known for its hemorrhagic manifestations, but ischemic features of the disease are also recognized such as white matter hyperintensities (WMH). We aimed to investigate the interrelationship between two emerging ischemic markers related to CAA: lacunes and cortical microinfarcts (CMI).

Methods:
CMI were scored on MRIs using high resolution FLAIR, double inversion recovery and MEMPRAGE sequences, in prospectively enrolled patients with CAA. The presence, number, and topography of lacunes (deep vs. subcortical), cerebral microbleeds (CMB), cortical superficial siderosis (cSS), and enlarged perivascular spaces (EPVS) were identified.
FreeSurfe
r was used for volumetric analyses. The relationship of CMI and lacunes as well as the association of these lesions with other CAA-related markers were analyzed.

Results:
The cohort consisted of 122 nondemented probable CAA patients (mean age, 69.4±7.6 years, 73% men). Lacunes were present in 31 (25.4%) of the patients and all but 1 were located in subcortical as opposed to deep brain regions. Lacunes were not associated with age, sex, or vascular risk factors. CMI were found in 35 patients (28.7%). CMI were more common in patients with lacunes compared to patients without lacunes (51.6% vs. 20.9%, p=0.002) and this association remained significant in a multivariable model adjusting for age, sex and hypertension (odds ratio: 4.2, 95% CI: 1.75-10, p=0.001). WMH volume, EPVS, WM volume, cortical thickness, and hemorrhagic markers did not differ between patients with or without lacunes (p>0.2 for all comparisons). CMI did not correlate with these markers except showing a positive association with presence/extent of cSS.

Conclusion:
Lacunes and CMI were common in CAA, and lacunes were more commonly found in subcortical WM as opposed to deep gray structures. Our study shows that CMI are more likely to occur in probable CAA patients with lacunes than without lacunes, suggesting that these two lesion types may be part of a common spectrum of small CAA-related ischemic infarcts. These pathologies did not correlate with markers of more widespread damage, however, suggesting that the mechanism for CAA-related infarcts is distinct from other more widespread effects of CAA.
Abstract 57: Exosomes Derived From Ischemic Cerebral Endothelial Cells Promote Axonal Growth
Authors: Zhang Yi , Chopp Michael , Li Chao , Liu Xian Shuang , Wang Xinli , Zhang Li , Zhang Zheng Gang
Published: January 2019

Axonal remodeling is a critical aspect of spontaneous brain repair after stroke. Stroke activates cerebral endothelial cells (CECs) in ischemic blood vessels. Communications between activated CECs and axonal remodeling in ischemic brain have not been fully investigated. Exosomes play vital roles in intercellular communication. We investigated the effect of exosomes derived from CECs harvested from vessels of ischemic rat brains (isCEC-exos) on axonal growth of cortical neurons. Application of isCEC-exos into axons of the neurons cultured in a microfluidic device which separates axons from their somata resulted in significant (p<0.05, n=45 axons) increases of axonal growth (982±24 μm) compared to CEC-exos derived from non-ischemic vessels (nCEC-exos, 793±19 μm). nCEC-exos significantly enhanced axonal growth compared to non-treatment (567±14 μm). Axonal internalization of CEC-exos was confirmed by tracking GFP-exosomes. qRT-PCR and miRNA PCR array analysis revealed that compared to nCEC-exos, >50 mature miRNAs were enriched within isCEC-exos, including miR-19a. Axonal application of isCEC-exos elevated these miRNAs and their pre-miRNAs in axons and somata (from 21 to 85 folds, n=3, p<0.01) compared to non-treated group. Because CEC-exos do not contain the precursor form of miRNAs, these data suggest that CEC-exos transfer their mature miRNAs into distal axons, which triggered increases in precursor and mature miRNAs in distal axons and somata. Moreover, compared to the non-treated group, Western blot analysis (n=3/group) showed that axonal application of isCEC-exos locally reduced axonal growth inhibitory proteins, PTEN (~90%), Sema6A (~75%), and RhoA (~99%), which was inversely associated with increased miRNAs that target these proteins. Furthermore, transient blockage of ribosome translocation with emetine, a protein synthesis inhibitor, in axons abolished the effect of isCEC-exos on distal axonal growth and on alteration of miRNAs and their target proteins. Collectively, our data demonstrate that isCEC-exos internalized by distal axons facilitate axonal growth by altering miRNAs and their target protein profiles in recipient neurons, and these exosomes may potentially provide a therapeutic means to enhance axonal growth.
Abstract 60: Ischemic Conditioning Improves Brachial Artery Flow Mediated Dilation in Chronic Stroke Survivors
Authors: Durand Matthew J , Nguyen Jennifer , Wright Michael T , Gutterman David D , Schmit Brian D , Hyngstrom Allison S
Published: January 2019

Introduction:
Brachial artery flow mediated dilation (FMD) is a well-established measure of vascular endothelial health and is pathologically low in chronic stroke survivors. Ischemic conditioning (IC) is a cardioprotective stimulus and has been shown to improve FMD and enhance motor function in healthy humans. We recently showed that IC can improve paretic muscle strength and increase self-selected walking speed in stroke survivors. These improvements could be, in part, mediated by improved peripheral vascular function and increased blood flow to the exercising muscle. The effects of IC on vascular endothelial function post-stroke have not been investigated.

Hypothesis:
Two weeks of IC on the paretic leg of chronic stroke survivors will improve FMD in the non-paretic brachial artery.

Methods:
This was a prospective, randomized, blinded and controlled pilot study. Twenty chronic stroke survivors (>1-year post-stroke) received either IC (cuff inflation on the paretic leg for five minutes to 225 mmHg) or Sham IC (cuff inflation to 10 mmHg) every other day for two weeks (five on-off cycles per session). Brachial artery FMD was assessed using ultrasonography within 48 hours of the beginning and end of the intervention period.

Results:
Eight men and twelve women participated in this study. The mean age was 59 ± 16 years and the mean time post-stroke was 9 ± 9 years. Brachial artery FMD increased in the IC group from 6.2 ± 4.9% to 8.9 ± 3.9% (n=10; p=0.023, 2-way Repeated Measures ANOVA) while no change was observed in the Sham IC group (pre- vs. post = 3.8 ± 3.9% vs. 2.7 ± 3.1%, respectively; p=0.32, n=10). Expressed as the mean change in FMD, IC increased FMD by 2.8 ± 3.7% while no change was observed in the Sham IC group (delta FMD = -1.1 ± 3.4%; p=0.024 IC vs. IC Sham, unpaired t-test).

Conclusions:
Two weeks of IC increases brachial artery FMD in chronic stroke survivors. Taken together with our previous work that shows IC increases paretic muscle strength and walking speed in chronic stroke survivors, IC has the potential to improve both motor and cardiovascular function post-stroke. Future larger studies are needed to evaluate the efficacy of IC to improve stroke recovery and to identify the pathways involved which confer benefit to both the nervous and cardiovascular systems.
Abstract 61: Non-enzymatic Fragmentation of the Amino Terminus of NOTCH3 in Inherited Cerebral Small Vessel Disease
Authors: Young Kelly , Cartee Naw M , Lee Soo J , Zhang Xiaojie , Wang Michael M
Published: January 2019

Introduction:
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the most common genetic cause of cSVD, stroke, and vascular dementia. CADASIL is characterized by NOTCH3 mutations, NOTCH3 protein accumulation in arteries, and granular osmiophilic material. The mechanisms underlying CADASIL protein accumulation are currently unknown. We test the hypothesis that post-translational modification of NOTCH3 populations occurs within CADASIL cerebral vasculature.

Methods:
We generated monoclonal antibodies against the N-terminal region of NOTCH3. Antibodies were used for immunohistochemistry on 19 CADASIL and 6 age-matched control brains. Epitope mapping was performed on defined NOTCH3 fragments. Proteins treated with reducing agents were scored for antibody reactivity by western blotting. NOTCH3 complex formation was tested by co-immunoprecipitation.

Results:
NOTCH3 ectodomain undergoes cleavage into an N-terminal fragment (NTF) in diseased human cerebral vessels. The site of fragmentation was mapped to the peptide bond following D80. Mutagenesis of P81 abolished fragmentation. Both acidic and reducing conditions promote NOTCH3 cleavage
in vitro
. Finally, NTF is capable of forming dimers and detergent-resistant complexes with full length NOTCH3.

Conclusion:
Our studies demonstrate non-enzymatic fragmentation of NOTCH3 in CADASIL that could drive protein aggregation events that hallmark CADASIL. As in Alzheimer’s disease, protein fragmentation may contribute to neuropathology. Future studies will include testing the pathogenicity of fragmented NOTCH3, a potential novel target for cSVD therapy.
Abstract 67: Contributions of the Unaffected Hemisphere to Outcome Predictions of Acute Aphasia
Authors: Schlaug Gottfried , Norton Andrea , Chenausky Karen , Marchina Sarah , Kernbach Julius
Published: January 2019

Making accurate predictions about a stroke patient’s language/speech-motor outcome and recovery potential is a challenge. We previously showed that a combined variable of lesion site and size, the Arcuate Fasciculus lesion load (AF-LL), correlated highly with measures of speech fluency in chronic aphasic patients. However, in bi-hemispherically organized systems (such as the speech-motor system), there might also be contributions from the unaffected hemisphere to outcome that have to be determined.

Methods:
Over a period of several years, ischemic stroke patients presenting with acute aphasia were evaluated using a bedside version of the Western Aphasia Battery complemented by picture naming tests, automatic speech measures, and a custom-made word/phrase spoken and sung test. A total of 110 acute patients were assessed acutely of which 60 followed up at 3 months for outcome assessments. Lesion maps drawn on diffusion-weighted images were used to calculate lesion loads of a probabilistic Arcuate Fasciculus (AF) tract. The homotop version of the AF of the right hemisphere was used to extract regional fractional anisotropy (FA) values. FA values serve as a measure of white matter fiber alignment and integrity. Several prediction models were constructed testing whether or not adding either lesion load measures, or right hemisphere structural measures (tract FA values) and right hemisphere functional measures (singing-speaking dissociation) to acute bedside aphasia assessments would improve outcome predictions.

Results:
The overall bedside WAB score in the acute stroke period was the best single predictor of overall WAB score outcome at 3 months explaining about 50% of the in-sample and 45% of the out-of-sample variance. This prediction was improved when a AF-lesion-load measures were added to the model (R2=0.62 for out-of-sample predictions). When right hemisphere structural (tract FA values) and functional information (singing-speaking difference) was added, out-of-sample prediction in language outcome at 3 months improved to 83%.

Conclusion:
A combination of a bedside aphasia test, lesion load of the left hemisphere, as well as structural and functional measures of the unaffected hemisphere predict language outcome.
Abstract 69: The Influence of Motor Cortex Inhibition on Upper Limb Recovery: A Multimodal Study
Authors: Cirillo John , Mooney Ronan , Ackerley Suzanne J , Borges Victor , Smith Marie-Claire , Mangold Christine , Barber P A , Clarkson Andrew , Stinear Cathy M , Byblow Winston D
Published: January 2019

Background:
After stroke, there may be abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. The present study examined primary motor cortex (M1) inhibition in patients over the first 12 weeks after stroke, and in a cohort of age-similar healthy controls.

Methods:
Excitatory/inhibitory (E/I) balance was assessed from glutamate/glutamine (Glx) and gamma aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 2 and 6 weeks after stroke. Threshold tracking paired-pulse transcranial magnetic stimulation (TMS) was used to assess motor cortex inhibition at 2, 6, and 12 weeks after stroke. Upper limb impairment and function were assessed with Fugl-Meyer Upper Extremity Scale and Action Research Arm Test at 2, 6, 12 and 26 weeks after stroke.

Results:
By 12 weeks, patients with a functionally intact corticospinal pathway as evident by the presence of MEPs in paretic upper-limb exhibited a proportional recovery such that upper limb impairment resolved by ~70% of the maximum possible (proportional recovery), whereas patients without MEPs had relatively poorer and more variable outcomes. Spectroscopy results indicated that there was an E/I in Glx:GABA ratio in both hemispheres compared to age-similar controls. Long-latency intracortical inhibition measures from TMS indicated an elevated GABA
B
-receptor mediated inhibition in both hemispheres during the spontaneous recovery period after stroke compared to controls. Patients with higher tonic inhibition in ipsilesional M1 tend to have a longer recovery period.

Conclusion:
The ability to modulate tonic inhibition levels early after stroke may have implications for upper limb recovery during the spontaneous recovery period.
Abstract 74: The Role of Race in Comfort Care Determination After Acute Ischemic Stroke
Authors: Ali Syed F , Hemmen Thomas , Singhal Aneesh , Nalleballe Krishna , Onteddu Sanjeeva , Schwamm Lee H
Published: January 2019

Intro:
Death after acute stroke often occurs in the context of transitioning from life-sustaining interventions to comfort measures only (CMO). We sought to evaluate if black race was associated with the decision to transition to CMO care in the setting of substantial post stroke disability.

Methods:
Using GWTG stroke registry data from three large comprehensive stroke centers in the Northeast, South and West, we analyzed 9,913 stroke admissions from 01/2009 - 12/2017. Overall rates and temporal trend in the rates of CMO were computed. Factors associated with CMO were evaluated with univariate and multivariable (MV) regression.

Results:
Of the 9,913 patients, 996 (10%) transitioned to CMO during the hospitalization: 10.8% (807/7,475) white, 5.7% (92/1,609) black and 11.7% (97/829) other. The figure shows the overall temporal trend in the rates of CMO, stratified by Black versus White race. CMO patients were significantly older, more often female and White, while less often Black, and had higher rates of CAD/MI, atrial fibrillation and heart failure. CMO patients had higher NIHSS and more often presented with weakness, altered level of consciousness and language problems. CMO patient had higher rates of reperfusion therapies and higher rates of in-hospital complications. On MV analysis, Black race was associated with lower odds of CMO use (OR 0.51 (95% CI 0.35, 0.73, p<0.001).

Conclusion:
Black patients were less likely to transition to CMO care after stroke. While this difference declined over time, it suggests an influence of race in end of life decision-making. Further research is needed to understand the factors that contribute to differences in utilization of CMO care.
Abstract 84: Idarucizumab in Patients Treated With Dabigatran Suffering Cerebral Ischemia or Intracranial Hemorrhage: A Retrospective Case Series From Germany
Authors: Kermer Pawel , Eschenfelder Christoph C , Diener Hans-Christoph , Grond Martin
Published: January 2019

Reversal of anticoagulation in patients treated with NOACs is a rare but sometimes urgently needed therapeutic demand. Idarucizumab is a monoclonal antibody fragment with high affinity for dabigatran reversing its anticoagulant effects within minutes. It is approved for patients on dabigatran with life-threatening or uncontrolled bleeding and those requiring emergency intervention. Case reports and smaller case series suggest a benefit for dabigatran-treated patients suffering ischemic stroke to regain eligibility for rt-PA thrombolysis. To provide insights into the clinical use of idarucizumab in patients under effective dabigatran anticoagulation presenting with signs of ischemic stroke or intracranial hemorrhage in clinical routine, we asked all German Departments of Neurology and Neurosurgery to contribute their retrospective data on the use of idarucizumab collected following product launch in January 2016 to June 2018. In 64 responding stroke centers 112 patients presenting with signs of stroke received idarucizumab. 74 patients treated with dabigatran presented with ischemic stroke. In patients receiving rt-PA thrombolysis following idarucizumab, 87% had a benefit from i.v. thrombolysis with a median NIHSS improvement of 6 points. No symptomatic bleeding complications were observed. Nine patients did not improve functionally. Of those, 4 patients deceased during hospital stay (5.4%). Bolus administration of idarucizumab did not delay thrombolysis indicating its value in this emergency situation. A total of 38 patients had intracranial bleeding (SAH n=1, SDH n=12, ICH n=25). Out of 25 patients presenting with intracerebral hemorrhage and treated with idarucizumab, hematoma growth with clinical worsening was documented in three. Outcome was favorable with a median NIHSS improvement of 4 points in 35 patients. Overall mortality was 13%. In conclusion, idarucizumab is a beneficial therapeutic option for patients under dabigatran treatment presenting with ischemic stroke or intracranial hemorrhage in daily German stroke center routine. A prospective registry with controls is ongoing in Germany.
Abstract 87: Factors Affecting Readmission Rates for Patients With Ischemic Stroke Hospitalized in an Integrated Health System of Stroke Care
Authors: Le Scott M , Fussner Julie , Sila Cathy
Published: January 2019

Objective:
We looked for factors associated with hospital readmission rates in patients diagnosed with ischemic stroke.

Methods:
The Stroke Program Quality Initiative developed a MIDAS™ report of all inpatient encounters to all hospitals within an integrated health system within 30 days of a stroke discharge. A focus study guided a detailed case review including demographics, index admission stroke subtype, discharge treatment and disposition, readmission diagnosis, and location. The dependent variable was readmission to the hospital within 30 days. Characteristics were compared between patients that were not readmitted versus patients that were readmitted using odds ratios (OR).

Results:
The analysis included 1843 stroke discharges from June 2016 to May 2018. The overall 30-day all-cause readmission rate for ischemic stroke patients was 13%; 14% at the comprehensive stroke center and 10 to 16% at the primary stroke centers. The principal diagnoses for readmission were sepsis or infection (14%), recurrent stroke (13%), and cardiovascular events (7.3). During this period, compliance with evidence-based guidelines for inpatient stroke care exceeded benchmarks. Mean time between admissions was 10 days. Of the patients that were readmitted, 30% of the patients were admitted to a different facility than their initial admission. Patients that received either tissue plasminogen activator (tPA) or mechanical thrombectomy seemed to be associated with decreased readmission rates (OR 0.5). Higher readmission rates were associated with length of stay (Overall OR 2.3; individual facilities (IF) ORs 2.1, 1.6, 2.2, 2.3, 3.5), females (Overall OR 1.3; IF ORs 1.3, 1.3, 1.3, 0.68, 0.69), age > 75 (Overall OR 1.5; IF ORs 1.8, 1.6, 1.7, 1.88, 1.7), and patients discharged to a skilled nursing facility (Overall OR 1.3; IF ORs 1.5, 0.94, 1.3, 0.98, 0.57). Widows and divorced patients had an overall OR of 1.5.

Conclusion:
A combination of demographic and disposition factors can consistently predict higher readmission rates amongst ischemic stroke patients within a large hospital system that shares a cohesive stroke care policy amongst the individual facilities, whereas acute treatments with either tPA or mechanical thrombectomy were protective.
Abstract 97: Pre-Existing Anticoagulation Does Not Affect Stroke Rates in Patients With Left Sided Infective Endocarditis
Authors: Petty Stephen A , Huang Glen , Davis Kyle A , Peacock James E , Tan Walter A
Published: January 2019

Introduction:
Stroke is a devastating and relatively frequent complication of infective endocarditis (IE), especially infection involving left-sided valves. Management of anticoagulation (AC) in left sided IE (LSIE) is controversial as it is unclear whether or not AC impacts stroke risk in this population. Current guidelines are equivocal on their recommendations regarding AC management. The objective of this study was to evaluate the effect of AC on neurologic outcomes in patients with LSIE.

Methods:
All patients admitted to a tertiary academic hospital in North Carolina, with a diagnosis of left sided IE between December 2011 and April 2018 were identified. Patients were stratified based on the receipt of therapeutic AC. The primary outcome measure was the rate of radiographically confirmed stroke at 10 weeks. Relevant data were analyzed with univariate and multivariate analysis.

Results:
Two-hundred and fifty-eight consecutive patients with LSIE were identified. Individuals receiving AC (n=50) were older (median age of 63 vs 52, p = 0.02) more likely to have a history of atrial fibrillation (34% vs 5%, p < 0.01), had more prosthetic valve IE (38% vs 10.1%, p <0.01) and had lower incidence of mitral valve IE (40% vs 62%, p < 0.01). There was no significant difference in the rate of stroke, cerebrovascular hemorrhage, or mortality at ten weeks between the two cohorts. Mitral valve involvement (OR 2.20, 95CI 1.25-3.988) and intravenous drug use within 3 months of presentation (OR 2.10, 95CI 1.11-3.95) were identified as independent risk factors for stroke.

Conclusions:
AC therapy did not appear to have an effect on stroke in patients with LSIE. Furthermore, use of AC did not result in a greater occurrence of cerebrovascular hemorrhage or increased mortality. Continuation of AC in patients with a pre-existing indication should be considered in patients with LSIE in the absence of other contraindications. More robust studies are warranted to substantiate this recommendation.
Abstract NS6: Neuroscience Healthcare professionals want Training for End of Life Management in Catastrophic Stroke Patients
Authors: Lightford Mallory , Olowu Adeola , Achilike Saviour , Ahmed Wamda , Zha Alicia , Gonzales Nicole
Published: January 2019

Background:
There is a paucity of literature on EOL management in patients with catastrophic stroke (CS). CS is unique due to the acuity of the injury and the unresponsive state of the patient. In CS, the families are the decision makers and it is imperative to have the communication skills necessary to begin a difficult conversation with families regarding prognosis and treatment planning. We performed a needs assessment to determine how our Neuroscience staff viewed our current EOL management process and areas for potential improvement.

Methods:
A multidisciplinary team created a survey with 3 main categories: Process of EOL management, Comfort Level with EOL communication, and roles and responsibility for EOL treatment and decision making. We administered the survey to neuroscience faculty, fellows and advance practice providers (APP), residents, nurses, case managers and social workers. Qualtrics Program pooled the responses of the EOL questionnaire for counts and proportions.

Results:
The survey was distributed to 419 people with 102 respondents (39.6% MDs, 52.5% RNs, 8.0% others). We found that only 48% of our employees felt comfortable beginning a conversation regarding EOL topics; 67% do not feel trained to address EOL topics and the overwhelming majority felt EOL communication should be part of educational training (Figure).

Conclusion:
We found that our Neuroscience staff does not have formal training in EOL communication, does not feel comfortable initiating EOL conversations and desires more training in EOL management. Future work should prioritize a patient/family centered approach to EOL care and training for healthcare professions so we are better prepared to handle the needs of our families and patients with CS.
Abstract NS7: Identifying and Understanding Factors Associated with Post-Stroke Anxiety
Authors: Sanner Jennifer , Casameni Montiel Tahani , Cron Stanley G , Ancer Leal Andrea , Baltazar Nicole , Hinojosa Evelyn , Okpala Munachi , Savitz Sean , Sharrief Anjail Z
Published: January 2019

Background and Purpose:
Prior data indicate that the profile of stroke survivors differs from those with anxiety in the absence of other clinical comorbidities. The purpose of this study was to determine the prevalence of PSA and to understand factors associated with PSA in a cohort of stroke survivors.

Methods:
A retrospective study (August 2017-May 2018) of electronic health records from 194 ischemic stroke survivors were examined. Stroke survivors were screened for PSA using the Generalized Anxiety Disorder 7-Item (GAD-7; range 0-21) scale two to eight weeks post-hospitalization for stroke during a stroke clinic visit. GAD-7 scores ≥ 10 indicated moderate to severe anxiety. Examples of factors examined included medical, social, stroke severity, excessive daytime sleepiness (Epworth Sleepiness Scale; ESS), and depression (Patient Health Questionnaire-9; PHQ-9). Univariable analysis were used to determine significance (p < 0.05). T-tests were used for continuous variables and the chi-square test for categorical variables.

Results:
Twenty-five percent of stroke survivors had a GAD-7 score ≥ 10 and significantly higher mean ESS (11 ± 5) and PHQ-9 (13 ± 6) scores (p<.0001) indicating co-morbid symptoms. Although not significantly different in this sample size, 32% of women had a GAD-7 score ≥ 10 compared to 21% men (p = .05). Stroke survivors with moderate to severe anxiety were more likely to be single, divorced, or widowed (p = 0.0006).

Conclusions:
PSA is common after ischemic stroke and may occur more frequently in women and those who are single, divorced, or widowed. Post-stroke trials of psychological interventions should consider PSA and its relationship to excessive daytime sleepiness and depression as well as treatment approaches for concurrent co-morbid conditions.
Abstract TMP100: Hypoechogenicity, Ulceration and Presence of Debris in Carotid Plaques Are Associated With Higher Prevalence of Silent Brain Ischemic Lesions (SBIL) in Patients With Carotid Atheromatosis
Authors: Colla Machado Pedro E , Balian Natalia R , Cea Clarisa , Luzzi Ariel A , Zurru Maria C
Published: January 2019

Introduction:
Hypoechogenicity, ulceration and presence of debris in carotid plaques are associated with higher risk of embolization. When compared to echodense plaques, echolucid plaques are associated with a higher risk of ischemic stroke (IS) (3% vs 0.8%). However, the definition of symptomatic carotid plaque only takes clinical manifestations in account, disregarding the presence and accumulation of SBIL.

Objective:
To assess the prevalence of non-lacunar SBIL ipsilateral to a carotid stenosis superior to 50%, and establish a correlation with carotid doppler ultrasonography.

Methods:
Patients that had a carotid stenosis ≥50%, a brain MRI and a carotid doppler ultrasonography, and were evaluated at the Hospital Italiano of Buenos Aires between 01/01/2010 and 01/01/2018 were included. Every patient was under medical treatment.

Results:
Six hundred and forty six patients were included, 25% of which had bilateral carotid plaques, so 807 carotid plaques were analyzed. SBIL were found in 119 patients, being the most frequent: multiple patchy lesions (4%), single cortical lesions (3%), watershed territory lesions (3%), single subcortical lesions (2%) and cortico-subcortical lesions (1%). When comparing patients with SBIL against those without them (table 1), echolucid plaques were more frequent (73% vs. 14%, p=0.001), plaque-associated debris was more prevalent (43% vs 2%, p=0.001) and so were ulcerated plaques (36% vs 3%, p=0.001).

Conclusions:
These findings suggest patients with carotid atheromatosis with any of such aforementioned features present an elevated risk for developing SBIL. Although none of these patients suffered an IS, development of such SBIL might facilitate the future onset of cognitive and functional decline.