bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 93: Increased Blood Pressure Variability After Acute Ischemic Stroke Increases the Risk of Death
Authors: de Havenon Adam , Saini Monica , Bath Philip , Majersik Jennifer ,   on behalf of the VISTA Collaboration
Published: January 2019

Introduction:
Increased visit-to-visit blood pressure variability (BPV) is linked to a higher risk of incident ischemic stroke in large epidemiologic studies.

Hypothesis:
Increased BPV in the acute phase after ischemic stroke will be correlated with death and poor outcome.

Methods:
This is a secondary analysis of patients in the placebo arms of the Virtual Stroke International Stroke Trial Archive (VISTA) with 4 or 5 blood pressure readings in the 24 hours after enrollment. Our primary outcome is death and the secondary is poor outcome, defined as a modified Rankin Scale of 3 to 6, both at 90 days from enrollment. We calculated BPV using 6 statistical methodologies (Table 1) and compared the highest to lowest tercile for each measure of BPV.

Results:
We included 1,947 patients, of whom 907 (46.6%) were female and the mean±SD age was 69.7±12.3 years. The mean±SD time from stroke onset to study enrollment was 4.8±2.4 hours and 534 (27.4%) received intravenous tPA. Of the 1,947 patients, 332 (19%) died within 90 days and 1,125 had a poor outcome (58%). We found that higher systolic BPV had a robust association with all-cause death, but not poor outcome (Tables 1 & 2). Diastolic BPV had a less consistent association with either outcome.

Conclusion:
Increased BPV in the first day after acute ischemic stroke is associated with a higher risk of death within 90 days, in the VISTA database. Prospective studies can establish if this is causal or an epiphenomenon.
Abstract 99: Early Anticoagulation or Antiplatelet Therapy is Critical in Cranio-Cervical Artery Dissection: Results From the COMPASS Registry
Authors: Rosati Lauren M , Redd Kolby T , Dodds Jodi A , Sen Souvik
Published: January 2019

Introduction:
Craniocervical artery dissection (CeAD) is a leading cause of stroke in the young. Recent studies reported a low rate of major adverse cardiac events (MACE) in patients with CeAD, with no significant difference between patients randomized to antiplatelet or anticoagulation.

Methods:
All patients from 2015-2017 consecutively identified by an electronic medical record-based application were enrolled in this prospective longitudinal registry. CeAD was confirmed by imaging and graded using the Denver scale for blunt cerebrovascular injury. Patients were followed for 12 months for MACE (stroke/transient ischemic attack [TIA]/death).

Results:
The cohort included 111 CeAD patients, (age 53 ±15.9 years, 56% white, 50% female) detected by magnetic resonance (5%), computed tomography (88%) and catheter (7%) angiography. CeAD was noted in the carotid (66%), vertebral (42%) and basilar (2%) arteries, with 83% of them being extracranial. CeAD was classified as grade 1, 2, 3 and 4 in 16%, 33%, 19%, and 32%, respectively. A total of 40% of dissections were due to known trauma. A predisposing factor was noted in the majority (78%), including 21% violent sneezing, 19% carrying heavy load, 11% sports/recreation activity, 9% chiropractic manipulation, 9% abrupt/prolonged rotation of head, and 9% prolonged phone use. At presentation, 41% had stroke, 39% had headache, 5% had TIA, and 15% were asymptomatic. Favorable outcome defined as modified Rankin score of 0-2 was noted in 68% at 3 months and 71% at 12 months. Rate of MACE was 14%, with more events observed in patients not on antiplatelet/anticoagulant therapy due to contraindications (p=0.008, Fig 1).

Conclusions:
We report diagnostic characteristics and short- and long-term outcomes of CeAD. A high MACE rate was observed within the first week of CeAD diagnosis, especially in patients not initiated on antiplatelet/anticoagulant therapy.
Abstract NS8: Effectiveness of a Caregiver-Centered Empowerment Program for Chinese Stroke Family Caregivers
Authors: Xichenhui Qiu , Sit Janet W , Chan Aileen W
Published: January 2019

Background:
Family caregivers play a crucial role in providing long-term home care to stroke survivors. Identifying an effective intervention is needed to meet the demands of stroke family caregivers. We developed a 13-week Caregiver-centered Empowerment Program (CEP), which is guided by empowerment process theory, to enhance the self-care and ability of family caregivers to cope with stroke caregiving.
Objective
To examine the effects of CEP (two 60 min in-patient face-to-face sessions and six biweekly 30 min phone follow-ups) compared with usual care (UC) in terms of self-efficacy (SE), caregiving competence (CCS), health promoting behavior, adaptive coping, social support, caregiver burden and quality of life (QOL) of caregivers, and the use of health and social services among stroke survivors.

Methods:
In this randomized controlled trial, Mainland Chinese stroke family caregivers (mean age=53 years; 61% women) received 13 weeks of CEP+UC (n=72) or UC only (n=72). Generalized estimating equations were used to assess the changes in SE, CCS, health promoting behavior, coping, social support, caregiver burden and QOL of caregivers, and the use of health and social services between groups of stroke survivors over time (baseline=T0, immediate=T1, and 1-month post-intervention=T2) using the intention-to-treat concept.

Results:
Compared with the participants in the UC group, members of the CEP+UC group exhibited significantly better SE, CCS, health-promoting behavior, adaptive coping, and perceived social support and a lower level of caregiving burden (see Table 1). Changes in the QOL of caregivers and hospital readmission of stroke survivors and nursing home placement rates showed no significant difference over time between groups. Attrition was low at 17%.

Conclusions:
CEP is easily implemented and can be incorporated in existing stroke rehabilitation services to foster support for family caregivers in providing long-term community care to stroke survivors.
Abstract TMP107: Microbiome Signature of Cerebral Cavernous Malformation Patients
Authors: Polster Sean P , Shen Le , Sharma Anukriti , Stadnik Agnieszka , Carrion-Penagos Julian , Girard Romuald , Koskimäki Janne , Romanos Sharbel , Lyne Seán , Shenkar Robert , Cao Ying , Yan Kimberly , Lee Connie , Akers Amy , Morrison Leslie , Robinson Myranda , Zafar Atif , Tang Alan , Mericko-Ishizuka Patricia , Gilbert Jack A , Kim Helen , Kahn Mark , Awad Issam A
Published: January 2019

Background:
Cerebral cavernous malformation (CCM) patients have lesions comprised of dilated capillaries in the brain. Despite the knowledge that mutations of three CCM genes can cause this disease, other genetic and environmental factors that contribute to lesion formation are likely given the highly variable disease expression. Genome-wide association studies in CCM cohorts and mouse models of CCM, both point to a role of lipopolysaccharide. Mouse studies have shown that the microbiome, particularly Gram-negative bacteria, drive CCM lesion development. These data point to a possibility that CCM disease is affected by the gut microbiome. In this study, we investigated if human CCM disease could be linked to the gut microbiome.

Methods:
Fecal samples from 88 CCM patients, from four sites, were assayed using 16S rRNA gene sequencing. Following taxonomic classification by exact sequence variant analysis (ESV) using DeBlur, microbiome composition was compared with those of a reference non-CCM population (n=348), or between subgroups of CCM patients based on clinical data elements.

Results:
Analyses of microbiome composition statistics identified bacterial ESVs belonging to Clostridiales
,
Lachnospiraceae, Ruminococcaceae
,
and the genus
Bacteroides
that were significantly enriched in CCM patients compared to healthy controls. Within our CCM cohort, patients with germline
CCM
mutations had stool-associated enrichment of ESVs annotated to Clostridiales, and the genera
Bacteroides
and
Prevotella
, when compared to sporadic CCM patients, while patients with
CCM1
and
CCM2
mutations had different proportions of Clostridiales, Lachnospiraceae, and the genus
Ruminococcus
. Furthermore, Lachnospiraceae and
Bacteroides
proportions differentiated disease aggressiveness (All p<0.05, false discovery rate corrected).

Conclusions:
These data are the first to show that CCM patients have a distinct microbiome signature. Germline mutation and disease aggressiveness can correlate with further unique microbiome composition. This study supports further investigation into the mechanistic link between CCM disease and the microbiome. This will enhance our understanding of the brain-gut axis in CCM disease and the use of microbiome as a therapeutic target.
Abstract TMP112: Evidence of Diffuse Cortical Vascular Dysfunction in Patients With White Matter Hyperintensities
Authors: Poublanc Julien , Crawley Adrian , Mcketton Larissa , Sam Kevin , Mikulis David J
Published: January 2019

Introduction:
White matter hyper intensities (WMHs) on T2 FLAIR images, are associated with cognitive decline in older populations. WMHs exhibit diminished vascular reactivity compared to normal appearing white matter (Sam et al. AJNR 2016). We hypothesize that patients with WMHs have diminished cortical vascular reactivity compared to controls.

Methods:
23 patients with WMHs and 21 controls were studied. Patient inclusion criteria were: no cortical infarcts, Fazekas Grade >= 2, no vascular stenoses >= 70%, and no history of cardio/pulmonary disease.

MRI protocol and vasodilatory stimulus

The 3T MRI protocol included a 1 mm isotopic T1 3D sequence and a 3.5 mm isotropic T2* BOLD sequence (30 msec echo time). Cerebrovascular reactivity (
CVR
) was measured using 2 step changes in end-tidal pCO2 (from 40 to 50mmHg) using a controlled gas delivery system (RespirAct
TM
) during BOLD imaging. Recent work has shown an age invariant cortical response to this stimulus delivery method (McKetton et al Neuroimage 2018).

Image Analysis

CVR
magnitude maps, expressed in %BOLD/mmHg, were generated by calculating the linear regression of the BOLD response with the pCO2. The BOLD response was fitted with an exponential function in order to measure its time characteristic
TAU
providing a measure of speed of vascular response. Maps were corrected for partial volume errors. (Figure 1A). Average CVR and TAU within frontal, occipital, parietal and temporal grey matter were calculated for all subjects. t-tests corrected for multiple comparisons were calculated between patients and controls.

Results:
CVR magnitude was lower and TAU longer in patients with WMHs compared to normal controls in all four lobes (p < 0.05) (Figure 1B).

Conclusions:
Patients with moderate to severe WMHs show diffuse impairment of vascular reactivity affecting the cerebral cortex even in the absence of significant large vessel steno-occlusive disease and in the absence of visible cortical disease on MRI.
Abstract TMP113: Vascular Dementia Amongst Patients Included in the National Inpatient Sample Database 2006-2014 is not on the Decline
Authors: Simpkins Alexis N , Sarayani Amir , Nagaraja Nandakumar , Christina Wilson A , Youn Teddy S , Yuzefovich Khanna Anna , Joshua Brown D , Kelly Adam G
Published: January 2019

Introduction:
Vascular dementia is a significant cause of cognitive decline, gait instability, and is associated with stroke risk factors, ischemic and hemorrhagic stroke. The incidence of ischemic stroke has been declining over the past several decades with improved secondary stroke prevention and care systems. Of several stroke risk factors, diabetes and atrial fibrillation have been identified as co-variates associated with rates of vascular dementia in hospitalized patients. We hypothesize that the frequency of secondary diagnosis for vascular dementia will decline over time between 2006 to 2014 and that the rates of vascular dementia diagnosis may vary by region (Northeast, Midwest, South, West).

Methods:
The Healthcare Cost and Utilization Project Nationwide Inpatient Sample Database from 2006-2014 was used to query patients with vascular dementia using ICD-9 codes 290.40, 290.41, 290.43. Two-way ANOVA was used to assess for differences in vascular dementia diagnosis frequency over time. Multivariable logistic regression was performed to test the trend of vascular dementia diagnosis code usage in the database over study years and its interaction with region while, controlling for age, gender, race, and diagnosis of diabetes and atrial fibrillation.

Results:
On average, there were 31,123,558 ± 800,912 total admissions per year between 2006-2014. The mean age was 79, 55% female, 31% non-Caucasian. There were no significant differences in patient demographics between the regions. The mean frequency of vascular dementia diagnosis per year nationwide was 0.33% (SD, 0.03), ranging from 0.28% in 2006 to 0.34% in 2014. The frequency of vascular dementia diagnosis did not decrease during the study period. After controlling for race, age, gender, diagnosis of atrial fibrillation, and diabetes, there was no association between frequency of vascular dementia diagnoses and region.

Conclusion:
Despite advances in cardiovascular disease risk reduction, the frequency of hospitalizations associated with vascular dementia diagnoses in this database remained unchanged over a nine-year time span. This demonstrates that more research is needed to develop more effective preventative therapies to decrease vascular dementia.
Abstract TMP116: Higher Lipoprotein(a) is a Risk Factor for Cognitive Impairment in Black but Not White Americans: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Cushman Mary , Callas Peter W , Manly Jennifer J , Zakai Neil A , Unverzagt Fred , Wadley Virginia , McClure Leslie A
Published: January 2019

Background:
Increased lipoprotein (a) [Lp(a)] is a risk factor for heart disease, and levels vary greatly by race, with blacks having 2-4-fold higher levels than whites. Despite the large body of evidence relating Lp(a) to cardiovascular risk, there is less known on its relation to cognitive function.

Hypotheses:
Lp(a) is a risk factor for cognitive impairment, and the association will be greater for blacks than whites.

Methods:
REGARDS recruited 30,239 black and white U.S. men and women between 2003-7 and a cognitive battery was administered every 2 years. With 3.4 years mean follow up, baseline Lp(a) was measured in 495 cases of incident cognitive impairment and 587 controls. All were free of prebaseline cognitive impairment and stroke. The association of Lp(a) and cognitive impairment was analyzed with logistic regression.

Results:
With multivariable adjustment, among black individuals the OR of cognitive impairment per SD higher increment of Lp(a) was 1.39 (95% CI 1.05, 1.84). There was no association in whites (OR 1.03; 95% CI 0.87, 1.21); p interaction race*Lp(a) =0.03. With further stratification by sex, among blacks the association was greater in women (OR 1.52; 95% CI 1.02-2.26) than men (OR 0.95; 95% CI 0.51, 1.76); p interaction by sex*Lp(a) =0.33. Compared to those in the lowest quartile of Lp(a), the risk of cognitive impairment in black women with Lp(a) above the median was more than doubled (Table).

Conclusions:
Lp(a) might explain part of the racial disparity in cognitive dysfunction with aging, especially in women (though confirmation required). To understand this, study is needed of racial differences in apo(a) size, interaction with environmental factors, and/or production or catabolization rates.
Abstract TMP20: Association Between Intravenous Thrombolysis and Anaphylaxis Among Medicare Beneficiaries With Acute Ischemic Stroke
Authors: Lerario Michael P , Grotta James C , Merkler Alexander E , Omran Setareh S , Chen Monica L , Parikh Neal S , Yaghi Shadi , Murthy Santosh , Navi Babak B , Kamel Hooman
Published: January 2019

Introduction:
Anaphylaxis has been reported as a potential adverse event after intravenous thrombolysis in patients with acute ischemic stroke, but the magnitude of risk remains unclear.

Methods:
We performed a retrospective cohort study using inpatient and outpatient claims between 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with ischemic stroke, defined by validated
ICD-9-CM
diagnosis codes. Our exposure was treatment with an intravenous thrombolytic agent during the index hospitalization (
ICD-9-CM
code 99.10). Our primary outcome was anaphylaxis, defined using an accepted
ICD-9-CM
code algorithm (989.5, 995.0-4, 995.6x, E905, E905.3, E905.5, or E905.8-9). Our secondary outcome was anaphylactic shock (995.0 or 995.6x). Multiple logistic regression was used to evaluate the association between intravenous thrombolysis and anaphylaxis after adjustment for demographics, vascular risk factors, the Charlson comorbidity index, exposure to intravenous contrast dye, treatment with mechanical thrombectomy, and history of allergic reactions.

Results:
Among 66,989 patients with acute ischemic stroke, the 3,176 (4.7%) who underwent intravenous thrombolysis more often had atrial fibrillation (47.7% vs 37.4%) and more often received intravenous contrast dye (44.3% vs 21.9%), but were otherwise similar in terms of demographics and comorbidities. Anaphylaxis developed in 17 (0.54%; 95% CI, 0.31-0.86%) patients who received intravenous thrombolysis versus 45 (0.07%; 95% CI, 0.05-0.09%) who did not. After adjustment for demographics, comorbidities, contrast dye, mechanical thrombectomy, and history of allergies, there was a significant association between receipt of intravenous thrombolysis and anaphylaxis (OR, 7.3; 95% CI, 4.1-13.0). We found a similar association for anaphylactic shock.

Conclusions:
Although a rare occurrence, the risk of anaphylaxis among patients with acute ischemic stroke was significantly higher among those who received intravenous thrombolysis.
Abstract TMP22: Do Other Factors Influence the SPAN-100 Index Prognosticator for ICH after IV-tPA?
Authors: Viswanathan Vyas , Stone David K , Ballur Narayna Reddy Varalakshmi , Almeida Leonardo , Khanna Anna
Published: January 2019

Introduction:
Age and stroke severity influence patient outcomes following acute stroke. Individuals with a combined age and NIHSS of greater than 100 (SPAN-100 positive) are associated with increased rates of intracranial hemorrhage (ICH) after r-tPA administration. We evaluated whether thrombocytopenia (platelet count < 100K), antiplatelet use, or time to r-tPA administration affected ICH or symptomatic ICH (sICH) in SPAN-100 positive patients at our institution. These factors have been questioned previously as having potential to increase risk for hemorrhagic transformation. We also describe the type of hemorrhages present.

Methods:
This is a single center retrospective review of all patients who received r-tPA, had an initial NIHSS recorded, and follow up post-tPA imaging between 2012 and 2016. ECASS III criteria were used to define sICH. Univariate analysis was performed using Fischer exact or Chi square for categorical variables and Wilcoxon Mann-Whitney for non-parametric continuous variables. A logistic model was used to obtain odds ratios when controlling for covariates.

Results:
A total of 415 patient charts (68 SPAN-100 positive, 347 SPAN-100 negative) were analyzed. There was a female predominance in the SPAN-100 positive (71%) group compared to the negative (59%) group (p < 0.001). There were similar rates of thrombocytopenia (p=0.26), antiplatelet use (p=0.86), and minutes to r-tPA (SPAN-100 positive 155 ± 57; SPAN-100 negative 157 ± 52, p=0.74). The rate of ICH was significantly higher in the SPAN-100 positive (n=21, 31%) compared to negative (n=38, 11%) groups (p < 0.001). The rate of sICH was doubled in the SPAN-100 positive (n=5, 7.3%) compared to negative (n=13, 3.7%) group, but there was no statistically significant difference (p=0.19). When controlled for thrombocytopenia, time to r-tPA, and antiplatelet use, SPAN-100 positive patients had a 3.59 increased odds of intracerebral hemorrhage (95% CI 1.89, 6.83). There was no increase in parenchymal hematoma type 2 in SPAN-100 positive patients.

Conclusions:
SPAN-100 positive patients have a significantly increased risk of ICH even when controlled for thrombocytopenia, antiplatelet use, and time to r-tPA.
Abstract TMP24: No Rebound Effect After Clopidogrel Discontinuation in Patients With Acute Transient Ischemic Attack or Minor Stroke: Subanalysis of the CHANCE Trial
Authors: Meng Xia , Zhang Xinmiao , Zhao Xingquan , Liu Liping , Jing Jing , Wang Anxin , Pan Yuesong , Wang Yilong , Wang Yongjun
Published: January 2019

Objectives:
The combination of clopidogrel and aspirin was superior to aspirin alone in reducing recurrent stroke in patients with acute minor stroke or TIA. Previous studies demonstrated that discontinuation of clopidogrel in patients after ACS was associated with a rebound increase in risk of recurrent events. However, limited data investigated the rebound effect of clopidogrel after discontinuation of clopidogrel therapy in patients with TIA or stroke.

Methods:
All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Patients who discontinued clopidogrel and switched to aspirin monotherapy during 90 days and 1 year in the clopidogrel plus aspirin arm, and patients who who continued aspirin monotherapy during 90 days and 1 year in the placebo plus aspirin arm were included to our final analysis. The outcomes included risk of recurrent ischemic stroke, recurrent TIA, and composite events during 90 days and 1 year. The prevalence of each outcome was compared between 2 groups for every 30 days.

Results:
Among 3346 patients included, a total of 34 patients in group who discontinued clopidogrel and switched to aspirin monotherapy presented stroke recurrence, and a total of 42 patients in group continued aspirin monotherapy presented stroke recurrence during the 90 days-1 year period. The inter-group comparisons were not significant, except during day 211 to day 240 (P=0.03). Similar results were found for recurrent ischemic stroke, recurrent TIA, and composite events in these two groups.

Conclusions:
we found no rebound increase in risk of stroke, ischemic stroke, TIA, and composite events during the 270 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke.
Abstract TMP26: Age Exacerbates the Pathogenicity of Neutrophils in Ischemic Stroke
Authors: Royoreilly Meaghan , Ahnstedt Hilda , Spychala Monica , Munshi Yashasvee , McCullough Louise
Published: January 2019

Introduction:
Ischemic stroke is a major cause of disability and mortality worldwide. Neutrophils may exacerbate stroke-related injury via the release of reactive oxygen species (ROS) and granule proteins. As age is the strongest risk factor for poor outcomes after ischemic stroke, we hypothesized that age exacerbates the deleterious functions of neutrophils after brain ischemia.

Methods and Results:
Young (3 month) and aged (20-22 month) mice were subjected to middle cerebral artery (MCAO) stroke. Aged mice had higher mortality than young mice at 7 days (0% young, 60% aged, p<0.05, n=5/group). Aged mice also had greater neurodeficits than young mice (p<0.05). Flow cytometry showed that aged animals display an increase in neutrophil proportions in the blood, spleen, lung and bone marrow (p<0.001) after ischemic stroke compared to young. Furthermore, flow cytometry demonstrated that neutrophils from the blood of aged animals produced ROS at higher levels than neutrophils from young animals (p<0.05). Aged stroke animals had higher serum IL-6 (p<0.0001) and CXCL1 (p<0.01), two powerful neutrophil activating cytokines, at 24 hours after stroke. Follow-up serum measurements in human ischemic stroke patients (n=143) demonstrated that increased age was associated with higher levels of IL-6 (p=0.014) and IL-8 (p<0.0001) at 24 hours. We then used anti-Ly6G, a neutrophil specific monoclonal antibody, to deplete circulating neutrophils as a potential treatment for ischemic stroke. Mice were randomized to receive 500ug anti-Ly6G IP or control at 4, 24 and 48 hours after stroke (n=6-7/group). Treatment conferred no benefit to young mice, but resulted in a significant improvement in behavioral recovery in aged mice as measured by adhesive test at 7 days (p<0.01), corner test at 14 days (p<0.001) and hangwire test at 14 days (p<0.05).

Conclusions:
Neutrophils from aged animals exhibit altered organ trafficking and a higher reactive oxygen species generation. Elevated levels of neutrophil-activating cytokines were seen in both aged animals and aged ischemic stroke patients at 24 hours. Finally, anti-neutrophil depletion therapy had no effect in young animals, but resulted in significantly enhanced behavioral recovery in aged animals.
Abstract TMP27: Laser Stimulation of Brain Drainage and Recovery After Hemorrhagic Stroke
Authors: Semyachkina-Glushkovskaya Oxana , Navolokin Nikita , Bragin Denis , Khorovodov Alexander , Klimova Maria , Terskov Andrey , Mamedova Aysel , Kurths Juergen
Published: January 2019

In our previous data we observed the presence of products of degraded blood (the iron/hemosiderin) in the meningeal lymphatics (ML) and in the deep cervical lymph node (dcLN) in patients who died after hemorrhagic events (brain trauma and stroke). Here we demonstrate novel data related to the brain clearance from the blood after hemorrhagic stroke (HeStr) via the ML in rats. For the first time, we show non-invasive laser method for stimulation of ML drainage for the brain recovery after HeStr using laser irradiation though the intact skull and skin.

Experiments were carried out in adult mongrel rats (250-280 g) using model of HeStr. All procedures were performed in accordance with the “Position of the American Heart Association on Research Animal Use“ (Circulation 1985; 71:849A). The new generation laser 1268 nm (30 nm, 7 min) was used for stimulation of the ML drainage through the intact skull and skin that was analyzed in vivo (two-photon, fluorescent, optical coherent tomography imaging) and ex vivo (immunohistochemical, confocal data) using markers of lymphatic endothelium (LYVE-1/LYVE-1 conjugated with Alexa 488 and Prox-1).

The results clearly demonstrated that 1h after HeStr the iron/hemosiderin (detected by atomic absorption spectroscopy and histological method) accumulated in the dcLN and observed in the ML. The laser application caused stimulation of the ML drainage (analyzed by dextran movement in vivo) and was accompanied by decrease in the iron/hemosiderin level in the brain tissues with an appropriate increase of their level in the dcLN. The application of laser (one time a day) during one week contributed a better recovery after HeStr vs. the control group (without laser) that was confirmed by analysis of inflammatory factors (C-reactive protein, IL-6 and lipoprotein-associated phospholipase A2, immunoassay analysis), macrophages infiltration (confocal imaging), edema, necrotic and ischemic events (histological data).

In sum, our results suggest that laser 1268 nm by stimulation of endogenous processes of brain lymphatic drainage might be a novel auxiliary non-invasive method for brain recovery after HeStr.

The research was supported by grant of Russian Science Foundation No 17-15-01263.
Abstract TMP35: Perivascular Astrocytes Alter the Basement Membrane Through TGF-Beta in an Aged Brain Post-Stroke
Authors: Maniskas Michael E , Howe Matthew D , Furr Josephy W , Munshi Yashasvee , McCullough Louise D , Urayama Akihiko
Published: January 2019

Individuals over 65 make up the majority of stroke patients in the United States. Post-stroke recovery within the elderly population maybe impeded through enhanced glial scarring and reduced glymphatic flow. Following stroke, reactive astrocytes remodel the basement membrane through transforming growth factor-beta (B) signaling (TGF-B), altering glymphatic flow. Impaired glymphatic flow leads to a buildup of waste products, such as amyloid-beta, further inhibiting post-stroke recovery.

We
hypothesize that post-stroke astrogliosis and basement membrane fibrosis are induced through TGF-B signaling, resulting in chronic glymphatic impairment in aged mice.
To test this hypothesis, we used an
in vivo
model of ischemia to measure TGF-B signaling and reactive astrogliosis.
In vivo
studies used young (3 month, n=5-8) and aged (20-month, n=5-8) male C57/Bl6 mice that underwent distal middle cerebral artery occlusion (DMCAO). Outcome measurements included TGF-B signaling, reactive astrogliosis within the glymphatic system, and impaired glymphatic flow. As a potential therapy, an implantable subcutaneous osmotic pump was inserted post-stroke with a TGF-B antagonist (GW788388 Hydrate-10mg/kg/day) to determine the impact on astrogliosis, glymphatic flow, and functional outcome. Results for
in vivo
studies using immunohistochemistry demonstrated a significant increase (p<0.05) in TGF-B expression in aged sham/DMCAO compared to young sham/DMCAO. There was a significant (p<0.01) increase in astrogliosis in aged sham/DMCAO compared to young sham/DMCAO. Glymphatic flow was assessed using an injected dextran dye, results demonstrated a significant (p<0.05) reduction in glymphatic flow for aged DMCAO compared to naïve mice. Functional measurements demonstrated that aged DMCAO had a significant reduction (p<0.05) in Paw Area/Time (Digigait) compared to naïve. Following TGF-B antagonist treatment, there was no difference between aged DMCAO and naïve mice in astrogliosis, glymphatic flow, or Paw Area/Time. This demonstrates that TGF-B impairs post-stroke recovery through astrogliosis, and impaired glymphatic flow. While this study demonstrated positive effects post-stroke, future studies should target downstream pathways of TGF-B.
Abstract TMP36: miR-17-92 Cluster Enriched MSC Exosomes Promote Myelination and Axonal Extension Which Contribute to Increased Emg Conduction and Functional Recovery After Stroke in Rats
Authors: Xin Hongqi , Liu Zhongwu , Buller Benjamin , Li Yanfeng , Golembieski William , Gan Xinling , Wang Fengjie , Shang Xia , Zhang Zheng , Chopp Michael
Published: January 2019

Introduction:
MiR-17-92 cluster enriched exosomes derived from multipotent mesenchymal stromal cells (MSCs) increase neural plasticity and functional recovery after stroke. Here, we investigate the mechanisms underlying this functional recovery.

Methods:
Rats (n=10) subjected to 2h of transient middle cerebral artery occlusion (MCAO) were intravenously administered control liposomes and exosomes (100 μg total exosome protein/rat) derived from MSCs infected with miR-17-92 expression lentivirus (Exo-miR-17-92
+
) and control lentivirus (Exo-Con) at 24h post stroke. Threshold currents of intracortical microstimulation on the contralateral cortex for evoking impaired forelimb movements were measured 4 weeks after stroke, followed with biotinylated dextran amine (BDA) injection to anterogradely label the corticospinal tract. The cervical cord (C4-7) was processed for vibratome longitudinal sections for BDA-labeled axon measurement at 6 weeks post MCAO. The myelination in the central nervous system (CNS) was indicated by Luxol fast blue stain. In vitro cultured rat organotypic brain slices were employed to further investigate whether the PTEN/PI3K/Akt/mTOR pathway mediates the effect of miR-17-92 enriched exosomes on increasing myelination.

Results:
Compared to the liposome treatment, Exo-Con treatment significantly reduced the threshold current (47.8±8.67 mA vs 54.9±6.49 mA, p<0.05), increased BDA-labeled contralesional axons sprouting into the denervated spinal cord and re-myelination in the CNS (p<0.05, respectively). Exo-miR-17-92
+
treatment enhanced the restorative therapeutic effects compared with that from EXO-Con treatment (40.9±5.71 mA, p<0.05, respectively). In vitro data showed that Exo-miR-17-92
+
significantly increased myelination of neurons, and the induced myelination significantly reduced by applicating of inhibitors for the PI3K/Akt/mTOR pathway (p<0.05, respectively).

Conclusions:
Our studies suggest that the enhanced neurological functional recovery after treatment of stroke with the miR-17-92 cluster enriched MSC exosomes may be attributed to the increase of the axonal extension and re-myelination of neuronal axons, and possibly via PTEN mediated activation of the PI3K/Akt/mTOR pathway.
Abstract TMP48: Understanding Optimal Dosage Frequency and Patient Engagement on Improving Outcomes Using Digital Therapy
Authors: Kiran Swathi , Gerst Kyle , Dubas Emily
Published: January 2019

Research suggests more intense therapy may facilitate improvements in stroke patients. Technological advances provide opportunities for stroke patients to practice more intensely and consistently than the typical weekly/biweekly clinic visits. Constant Therapy (CT) is a personalized treatment tool for people with cognitive-communication disorders designed for home practice. The current study investigates the relationship between intensity of CT practice and change on in-app domain scores. Data was anonymously aggregated and analyzed from 1195 CT users with stroke (median age=67; 720 survivors <6 months post onset). Users consented that their data be analyzed for research purposes. CT’s tasks are grouped into one of 12 domains and arranged by difficulty. Progress through a domain is represented by a domain score. As a user demonstrates recovery by succeeding in exercises they previously struggled with, more difficult exercises are presented, and their domain score increases. Users engaged in CT at any frequency they desired and were divided into 5 dosage groups based on the median days per week they used CT for 10 weeks. Improvement rate was calculated as the change in domain score relative to baseline. A linear mixed effects model was applied to examine the relationship between dosage group and change in domain score (controlling for baseline domain score, time, age, and months since stroke). Across all domains, results revealed significant improvement over time (p<.001) as well as significant effects of dosage group (all p<.001). Specifically, 2 (p<.001), 3 (p<.001) , 4 (p<.001) , and 5-7x/week (p<.001) groups showed greater improvement rates compared to 1x/week. Furthermore, 3, 4, and 5-7x/week were all significantly significantly different from 2x/week. Per current practice, 86.5% of stroke patients receive <2 sessions per week (ASHA NOMS, 2017). After 10 weeks of activity, our results show that users that engaged in CT more than 2x/week had significantly faster progress compared to 1-2x/week, which provides support to the idea that increased treatment dosage results in improved outcomes. Computerized rehabilitation programs can increase the opportunity for increased therapy dosage and thus a greater rate of improvement and recovery.
Abstract TMP49: Increasing Prevalence of Cerebrovascular Risk Factors in Native Americans With Ischemic Stroke
Authors: Jillella Dinesh V , Uchino Ken , Hatcher Lauren , Vigil Caity , Lin Andrew , Ikram Asad , Farooqui Mudassir , Quadri Syed , Zafar Atif
Published: January 2019

Introduction:
Prior epidemiological studies have reported ethnic differences in cerebrovascular risk factors. There is a paucity in the literature detailing the burden of these risk factors in the Native American population. We aim to elucidate the risk factor prevalence in the Native Americans with IS.

Methods:
Data were extracted from the Cerner electronic health record database which is a nationwide database of about 700 hospitals across the United States. We retrospectively identified IS patients encompassing all ages who were of Native American ethnicity during the years 2000-2016. Demographic parameters and cerebrovascular risk factors were collected.

Results:
Of the 5540 patients belonging to Native American ethnicity diagnosed with stroke from 2000 to 2016, 4729 had IS. Of these patients, 2175 (46%) were male, 3145 (66.6%) had a diagnosis of hypertension (HTN), 1834 (38.8%) had diabetes mellitus (DM), 1102 (23.4%) had coronary artery disease (CAD), 1020 (21.6%) were smokers, 583 (12.3%) had heart failure (HF), 495 (10.5%) had atrial fibrillation, and 65 (1.4%) had a diagnosis of atrial flutter. Trends in risk factors over time were analyzed using logistic regression model adjusted for age and gender, with year range of subgroup as the independent variable. Except for DM all other cerebrovascular risk factors including HF (p=0.02), HTN (p<0.001), CAD (p<0.015), atrial fibrillation (p<0.006), atrial flutter (p=0.01), and smoking (p<0.001) showed a statistically significant increasing prevalence during the years 2000 to 2016.

Conclusion:
We recognized increasing prevalence of cerebrovascular risk factors in Native American patients with ischemic stroke. These results highlight the importance of stroke prevention aimed at the Native American population by targeting individual cerebrovascular risk factors.
Abstract TMP5: Social Media Campaign with Traditional Community Consultation for Successful Exception from Informed Consent Approval - the SEGA Trial Experience
Authors: Chen Peng R , Sanzgiri Aditya R , Sheth Sunil A , Savitz Sean I , Sridhar Sujatha , Artime Carlos A , Inam Mehmet Enes , Pedroza Claudia , Barreto Andrew D
Published: January 2019

Introduction/Background:
Patients with severe stroke deficits due to large vessel occlusion are unable to provide consent and thus routinely excluded from emergency research participation – breaching the ethical principle of justice. The Food and Drug Administration has issued regulations for Exception from Informed Consent (EFIC) to facilitate research on potentially life-saving interventions in emergencies. We describe our novel approach to EFIC approval for an ongoing randomized trial that compares two anesthetic modalities for endovascular therapy (EVT) – sedation versus general anesthesia – the SEGA trial (Clinicaltrials.gov NCT-03263117).

Methods:
Partnering with our Institutional Review Board (IRB), we used a multifaceted approach to inform the Houston, Texas metropolitan area about EFIC in SEGA. In addition to in-person community consultations and surveys with focus groups (stroke survivors, advisory councils, etc.), we created a novel social media campaign on Facebook to users ≥ 25 years old within a 50-mile radius from the Texas Medical Center. Advertisements linked to a university-created SEGA trial website that included details on EFIC regulations, trial aims, survey questions, and opt-out procedures. A press release was issued with information about the trial and links to the webpage.

Results:
Between 6/17-9/17, we held 7 community consultations, placed Facebook ads, and issued a press release with trial information and website. Total of 193 individuals (65% female; average age 46.7 ± 16.6) participated in focus group community consultations. Of the 144 (75%) that completed surveys, 98% agreed to have themselves or a family member enrolled in SEGA under EFIC. Facebook ads had 134,481 views (52% female; 60% ≥ 45 years old) followed by 1,630 clicks to learn more and 1,130 website views (56% regional and 44% national). Users spent an average of 3 minutes and 51 seconds on the webpage. The IRB received zero emails requesting additional information or to opt-out.

Conclusion:
Our novel community consultation method reached far more potential stroke patients than traditional in-person EFIC focus groups. We propose this method as a standard practice for trials seeking such approval.
Abstract TMP54: Carotid Artery Inflammation Following Air Pollution Exposure
Authors: Shkirkova Kristina , Lamorie-Foote Krista , Connor Michelle , Patel Arati , Liu Qinghai , Morgan Todd E , Sioutas Constantinos , Finch Caleb , Mack William
Published: January 2019

Background:
The hallmark of inflammation is activation of the immune system, recruitment of leukocytes and induction of proinflammatory cytokines. Air pollution induced nano-size particulate matter (nPM) from vehicular exhaust is a potent environmental source of inflammation. The carotid arteries, a principle source of blood flow to the brain, are susceptible to inflammatory changes. Objective: To examine the effects of nano-size particulate matter (nPM) exposure on vascular tissue inflammation in the common carotid artery in mice.

Methods:
Particulate Matter was collected from an urban area in central Los Angeles, transferred to aqueous suspension by vortexing and sonication and reaerosolized for animal exposure. Mice were exposed to filtered air (n=7) or nPM (n=7) for a duration of 10 weeks, 3 days a week for 5 hours. Following the exposure period, animals were sacrificed and common carotid arteries were extracted, frozen, cut axially at 20um, and mounted on slides. Immunohistochemical analysis was performed. Staining was analyzed for presence of Intercellular Adhesion Molecule 1 (ICAM-1), endothelial surface adhesion molecule activated by leukocytes, and leukocyte antigen 6G precursor (Ly6g), a maker for monocytes and neutrophils.

Results:
An average of 5 axial sections were taken from carotid arteries of 14 mice (Filter n=7, nPM =7). Mean ICAM-1 values were computed for each carotid artery. Group averages were compared between cohorts of mice exposed to filtered air and nPM. Semiquantitative immunohistochemical analysis of the intimal and medial layers of the common carotid arteries demonstrated increased ICAM-1 in mice exposed to nPM (filter 15.6 SD +/-1.7 vs nPM 19.7 SD +/-3.4, p=0.01), but did not demonstrate differences in Ly6g values (filter mean 19.4, SD +/-3.9 vs nPM mean 16.1, SD +/-2.7, p=0.1)

Conclusion:
Higher ICAM-1 concentrations on carotid arteries exposed to nano-size particulate matter indicates inflammatory upregulation of adhesion molecules. However, there is no clear increase in circulating leucocytes within the vessel wall.
Abstract TMP55: Abdominal Obesity Predicts Stroke Risk in the Framingham Study
Authors: Aparicio Hugo J , Demissie Serkalem , Himali Jayandra J , Pase Matthew P , Satizabal Claudia L , Dukes Kimberly A , Lioutas Vasileios-Arsenios , Romero Jose R , Vasan Ramachandran S , Beiser Alexa S , Seshadri Sudha
Published: January 2019

Background:
Previous studies have suggested that measurements of abdominal fat, such as waist circumference or waist-to-hip ratio, more accurately predict risk of stroke than body mass index (BMI). We assessed the risk of ischemic stroke associated with BMI, waist circumference, and waist-to-hip ratio in a community sample.

Methods:
We pooled Framingham Heart Study (FHS) participant data from FHS clinic examinations for the Original cohort (Exam 21, date range 1988-1992) and Offspring cohort (Exam 4, 1987-1991, and Exam 7, 1998-2001). Offspring participants who did not have stroke at the end of the first 10-year observation period could contribute data to the subsequent observation period. We included stroke-free participants 45 years of age or older who obtained measurements of BMI (kg/m
2
) and both waist and hip circumference. Multivariable Cox proportional hazards regression models were used to separately relate BMI, waist circumference, and waist-to-hip ratio to risk of incident ischemic stroke over 10 years.

Results:
We analyzed data from 6,533 observation periods (mean age of participants 62±10 years, 54% female) with mean follow up time of 9.2 ±2 years. There were 240 (3.7%) incident ischemic stroke events. Each of the three body weight measurements was associated with increased stroke risk in models that adjusted for age and sex (Table). In full models, additionally adjusting for vascular risk factors that are more frequent in obese persons, only waist-to-hip ratio predicted risk of ischemic stroke. The hazard ratio (HR) per standard deviation increase in waist-to-hip ratio was 1.18, 95% CI 1.02-1.37, p=0.030.

Conclusions:
Higher waist-to-hip ratio predicted 10-year risk of ischemic stroke. Waist-to-hip ratio is a simple measure of abdominal obesity that should be used in future studies investigating weight loss interventions for stroke prevention.
Abstract TMP58: Preliminary Population-Based Temporal Trends in Stroke Incidence: Racial Disparity and Stroke Incidence From 1993-2015
Authors: Kleindorfer Dawn O , Alwell Kathleen , Khoury Jane , Moomaw Charles , Woo Daniel , Adeoye Opeolu , Flaherty Matthew L , Khatri Pooja , Ferioli Simona , Demel Stacie , Star Michael , De Los Rios La Rosa Felipe , Walsh Kyle , Martini Sharyl , Mackey Jason , Jasne Adam S , Slavin Sabreena , Broderick Joseph P , Kissela Brett M
Published: January 2019

Introduction:
We previously reported that the incidence of stroke was decreasing for whites but stable for blacks from 1993/94 to 2005. We sought to describe recent temporal trends and racial disparities in stroke incidence within our large, bi-racial population, by including 2010 and preliminary data from 2015.

Methods:
The Greater Cincinnati/Northern Kentucky region includes two southern Ohio and three Northern Kentucky counties on the Ohio River, a population of 1.3 million representative of the US population in terms of sociodemographics and percent black race. Our study ascertained all hospitalized strokes that occurred in the population between 7/1/93 and 6/30/94 and in calendar years 1999, 2005, 2010 and 2015. For 2015, nursing review of medical records is complete but physician review is not; thus 2015 rates are preliminary. The denominator for the calculation of incidence rates (in those aged ≥20 years) was estimated from the U.S. Census Bureau website (www.census.gov). The 95% confidence intervals (CI) for the incidence rates were calculated assuming a Poisson distribution. Rates are age, sex, and race adjusted, as appropriate, and standardized to the 2010 U.S. population.

Results:
First-ever stroke incidence rates stratified by subtype, race, and study period are presented in the Table. We project that stroke incidence did not significantly change in 2015 vs. 2010 for either blacks or whites, regardless of stroke subtype. Blacks have a substantially higher incidence of stroke compared with whites in all study periods, without significant change in disparity over time.

Discussion:
In contrast to the significant decline in stroke incidence among whites from 1993-94 to 2005, we did not observe a statistically significant decrease in 2010 and 2015. This may be due to true stabilization of rates over time, or less statistical power to detect smaller declines. The substantial black/white racial disparity in stroke incidence has not changed over time.