bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP66: Redefining Stroke Transport Patterns Using the SNOW Scale for Large Vessel Obstruction
Authors: Erpenbeck Sarah , Panichpisal Kessarin , Vilar Paul , Singh Maharaj , Babygirija Reji , Rovin Richard A
Published: January 2019

Background:
The SNOW (Stroke Network of Wisconsin) scale was developed to identify patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). We previously validated the SNOW scale with two retrospective and one prospective datasets of AIS patients evaluated in the Emergency Department of Aurora Health Care System hospitals. In all three studies, the SNOW scale showed a high sensitivity and accuracy and compared favorably to other stroke scales. Based on this, Milwaukee County EMS (MCEMS) implemented a new protocol incorporating the SNOW scale to prehospital triage of AIS patients: a patient with presumed AIS with a positive SNOW score, indicating LVO, paramedics are instructed to bypass the closest stroke hospital in favor of a thrombectomy capable hospital if no more than 15 minutes is added to the transport time. This is the first report of interim analysis of the data.

Methods:
To be SNOW positive, a patient must exhibit at least one of the following findings: gaze deviation, expressive aphasia, or neglect. We prospectively reviewed a cohort of all suspected stroke patients MCEMS transported to the three thrombectomy capable hospitals in Milwaukee, WI, between March 1 2018 and December 31 2018. LVO was confirmed by vascular imaging and included occlusions of the intracranial internal carotid artery, middle cerebral artery (M1 and M2), anterior cerebral artery (A1 and A2), or the basilar arteries.

Results:
In the first four month analysis, 108 suspected stroke transports arrived to Aurora St. Luke’s Medical Center. Of these 108, 21 (19.44%) were confirmed LVO stroke patients. The MCEMS SNOW scoring correctly identified 16 cases of LVO with a sensitivity of 76.19%, specificity of 39.98%, and accuracy (area under the receiving operating characteristics curve) of 0.5764. Aurora St. Luke’s Stroke Responders SNOW scoring correctly identified 20 LVO cases with a sensitivity of 95.24%, specificity of 58.62%, and accuracy of 0.7693. Between the EMS and Hospital SNOW scoring, all confirmed LVO patients were identified.

Conclusion:
Upon analysis of interim data, the SNOW scale shows a high sensitivity and accuracy to predict LVO. Differences in EMS and Hospital scoring may be due to experience with administering the scale and the change in exam over time.
Abstract TMP7: Not All mTICI 2b Are Made Equal: Balancing the Risks and Benefits of the Ideal Reperfusion Target in Endovascular Stroke Therapy
Authors: Haussen Diogo C , Rodrigues Gabriel M , Bouslama Mehdi , Grossberg Jonathan A , Bianchi Nicholas , Belagaje Samir , Anderson Aaron , Frankel Michael , Nogueira Raul G
Published: January 2019

Introduction:
The standard reperfusion target for thrombectomy trials has been modified TICI (mTICI) 2b-3 (≥50% ischemic territory). Recently, full reperfusion (mTICI 2c-3) has been recommended as the ideal target. The potential added benefits of additional procedural maneuvers must be balanced against their risks, particularly when dealing with residual distal occlusions often found in mTICI 2b. It remains unknown whether more precise categorization of the mTICI2b strata leads to more reasonable treatment targets.

Methods:
Retrospective analysis of prospectively collected thrombectomy data spanning Jun 2011-Feb 2018. Inclusion criteria: MCA and intracranial internal carotid artery occlusions. Definitions of reperfusion: mTICI0-1: no or limiteddistal filling; mTICI2a: <50% of territory; mTICI2b-: 50-74% of territory; mTICI2b+: 75-99%; mTICI3: full.

Results:
Of 557 patients, 2.2% had mTICI0-1, 3.6% had mTICI2a, 5.9% had mTICI2b-, 30.2% mTICI2b+, and 58.2% mTICI3. The usage of intravenous tPA was lower in the mTICI2b- vs. mTICI3 (18% vs. 41%;p<0.01) patients but otherwise there were no differences in baseline characteristics (age, gender, hypertension, diabetes, atrial fibrillation, NIHSS, occlusion site). Parenchymal hematomas were comparable between groups. The rates of good outcome (90-day mRS0-2) were comparable between mTICI3 vs mTICI2b+ (52% vs 46%;p=0.2) but were significantly lower in the mTICI2b- (30%;p=0.02), mTICI2a (5%; p<0.001) and mTICI0-1 (9%;p=0.003) groups (mTICI 3 as reference) (
Figure
). Mortality rates were comparable across the mTICI2b-, mTICI 2b+, and mTICI 3 groups but higher with mTICI2a (40%;p=0.01) and mTICI0-1 (50%;p<0.01) vs mTICI3 (16%).

Conclusion:
There is broad variation in outcomes across the different degrees of reperfusion within the mTICI 2b grade. A reperfusion target of 75%-99% (mTICI2b+) may lead comparable rates of independence versus full reperfusion.
Abstract TMP74: Factors Associated With Participation in Self-Management Programs: Findings From the SUCCEED (
S
econdary Stroke Prevention by
U
niting
C
ommunity and
C
hronic Care Model Teams
E
arly to
E
nd
D
isparities) Trial
Authors: Lin Amy , Vickrey Barbara , Barry Frances , Ayala-Rivera Monica , Montoya Ana V , Mojarro-Huang Elizabeth , Gomez Patricia , Castro Marissa , Corrales Marilyn , Sivers-Teixeira Theresa , Tran Jamie L , Johnson Renee , Ediss Chris , Shaby Betty , Willis Phyllis , Sanossian Nerses , Mehta Bijal , Bryg Robert , Song Shlee , Dutta Tara , Razmara Ali , Towfighi Amytis
Published: January 2019

Background:
Self-management programs have been shown to improve quality of life and self-efficacy for stroke survivors, but participation is often low. We are conducting a randomized controlled trial (RCT) of a complex, multidisciplinary, team-based intervention, SUCCEED, to improve risk factor control after stroke in a safety-net setting. Intervention participants are offered Chronic Disease Self-Management Program (CDSMP) workshops. We implemented strategies to increase participation, including monetary incentives, free transportation, workshops at community venues, inviting family and caregivers, and accommodating participants’ schedules.

Objectives:
To determine factors associated with participation and with extent of participation in a series of 6 sessions.

Methods:
From 2014 to 2017, 487 English and Spanish-speaking individuals (age>40 years) with stroke or TIA were enrolled in SUCCEED; 241 were randomized to intervention and offered CDSMP. Multivariable logistic and linear regression analyses were used to identify factors associated with CDSMP participation, including age, race/ethnicity, gender, employment status at 3 months, marital status, competing needs in 6 months prior to index stroke, life chaos, depression (PHQ-9), and disability (modified Rankin score).

Results:
Of 241 in the intervention arm, 29% (n=70) attended at least one CDSMP session (median sessions attended=4; IQR 2, 6). Unemployment at 3 months was associated with participation (adjusted OR=12.6, 95% CI 2.3, 69.7). Individuals were less likely to participate if they were not married or in a domestic partnership (OR=0.4, 95% CI 0.2, 0.9) or had foregone seeing a doctor in the 6 months prior to stroke because of caregiving responsibilities (OR=0.3, 95% CI 0.1, 1.0). Greater disability was associated with attendance at more sessions (p=0.03).

Conclusion:
Less than one third of participants attended CDSMP classes. Although we addressed financial and transportation barriers to participation, employment and caregiving responsibilities adversely impacted engagement. Spousal support was a key facilitator. Those with more severe disability were potentially more motivated to participate in CDSMP.
Abstract TMP79: Use of Intravenous Tissue Plasminogen Activator in Patients With History of Prior Stroke Plus Diabetes Mellitus
Authors: Ehrlich Matthew E , Liang Li , Kosinski Andrzej , Hernandez Adrian F , Schwamm Lee , Smith Eric E , Fonarow Gregg C , Bhatt Deepak L , Peterson Eric D , Xian Ying
Published: January 2019

Background:
Patients with history of diabetes mellitus (DM) plus prior ischemic stroke were excluded from ECASS III trial due to safety concerns. However, there are few data on use of intravenous tissue plasminogen activator (IV tPA) and risk of symptomatic intracranial hemorrhage (sICH) or outcomes in this population.

Methods:
Using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among AIS patients treated with tPA within the 3-4.5 hour window who had a history of prior stroke and DM (n=2129) versus those without either history (n=16,690).

Results:
Compared with patients without either history, those with prior stroke and DM had a higher prevalence of cardiovascular risk factors and more severe stroke (Table). The unadjusted rates of sICH and in-hospital mortality were 4.3% vs 3.8% and 6.2% vs 5.5%, respectively. These differences were not statistically significant after risk adjustment (sICH, adjusted odds ratio [OR] 0.79[95% CI, 0.51-1.21], p=0.28; in-hospital mortality OR 0.77 [95% CI, 0.52-1.14], p=0.19). Unadjusted rate of functional independence (Modified Rankin Scale score [mRS] 0-2) at discharge was lower in those with history of prior stroke and diabetes (30.9% vs 44.8%, p=<0.0001), this difference persists after adjusting for baseline clinical factors (adjusted OR 0.76 [95% CI, 0.59-0.99], p=0.04). During the study period, there were 339 patients otherwise eligible for IV tPA, arriving within 0-3.5 hours, but not treated with IV tPA due to history of prior stroke and DM.

Conclusion:
Among AIS patients treated with intravenous tPA within the 3-4.5 hour window, history of prior stroke plus DM was not associated with statistically significant increased sICH or mortality risk.
Abstract TMP80: Physician Preferences, Beliefs, and Practices on Post-Stroke Dysphagia Management
Authors: Brown Kristin , Bonojo Esther , Ahmed Wamda , Xavier Andreea , Savitz Sean , Sharrief Anjail
Published: January 2019

Introduction:
Dysphagia affects up to 2/3 of stroke patients; however, management practices are widely disparate. Despite lack of evidence for percutaneous endoscopic gastrostomy (PEG) placement, PEGs are placed in up to 23% of stroke patients a mean of 7 days from admission. We surveyed physicians who manage stroke patients in a large network of hospitals to evaluate knowledge and practices around dysphagia management.

Methods:
A 20 question survey was compiled and included questions regarding provider demographics, clinical experience and practice patterns for dysphagia management, knowledge about clinical variables associated with persistent dysphagia and beliefs about patient and system variables that influence decisions about dysphagia management (Table 1).

Results:
171 providers of stroke care in the Memorial Hermann Healthcare System (13 hospitals) were surveyed and 52 (30%) participated (Table 1). Approximately, 67% of providers were extremely or very comfortable with management of post-stroke dysphagia. There was a trend toward an association between provider specialty and comfort, with critical care practitioners likely to feel more comfortable and internal medicine physicians less comfortable (p = 0.07). While 61% of providers recommend PEG placement within 3-7 days of admission, 77% of providers would delay PEG placement if they could. Providers aware of published trials showing poor outcomes after PEG were more likely to want more time (p=0.04). Providers reported that stroke location (86%), dysarthria severity (77%), and age (71%) of patients were most likely to be associated with persistent dysphagia.

Conclusions:
To our knowledge, this survey represents the first to assess provider practices, knowledge, and beliefs regarding PEG placement and dysphagia management. Most providers in our network would like more time to determine recovery of swallow function prior to placing PEG tubes, if length of stay and other factors were not issues.
Abstract TMP83: Long-term Clinical and Health Economic Consequences of Worsened Post-stroke Status in Patients With Pre-morbid Disability
Authors: Ganesh Aravind , Luengo-Fernandez Ramon , Pendlebury Sarah T , Rothwell Peter M ,   Oxford Vascular Study
Published: January 2019

Background:
Patients with pre-morbid disability – generally defined as modified Rankin Scale score (mRS)≥2 – are often excluded from trials of acute stroke therapies. However, increased disability in such patients will adversely affect long-term outcomes if treatments are withheld in routine practice. We assessed the extent to which increased disability post-stroke influences 5-year mortality, institutionalization, and costs in pre-morbidly disabled patients.

Methods:
In a population-based, prospective cohort of ischaemic stroke patients (Oxford Vascular Study, 2002-2014), we tracked mortality, institutionalization, and health/social-care costs during follow-up. We compared 5-year mortality and/or post-stroke institutionalization (Cox regressions), and 5-year health/social-care costs (generalized linear model) in 3-month survivors with pre-morbid mRS 2-4 (excluding extreme disability, mRS=5), based on degree of change in mRS(ΔmRS) from pre-stroke to 3-months post-stroke, adjusting analyses for age/sex/initial NIHSS.

Results:
Among 1,607 patients, 530(33.0%) had pre-morbid mRS=2-4. Only 2 pre-morbidly disabled patients received thrombolysis, but 421(79.4%) were alive at 3-months. ΔmRS was independently associated with 5-year mortality/institutionalization (aHR for ΔmRS=1 vs 0: 1.59,1.20-2.11; ΔmRS=2: 2.39,1.62-3.53; ΔmRS=3: 4.12,1.98-8.60,p<0.001) and costs (margin for ΔmRS≥2 vs 0: $30,011, 95%CI $4,222-55,801,p=0.023). Results were similar on examining patients with pre-morbid mRS 2, 3, 4 separately (e.g. 5-year mortality/institutionalization aHR for pre-morbid mRS=3 with ΔmRS=1 vs 0: 1.60,1.06-2.42,p=0.027; ΔmRS=2: 3.20,1.85-5.54,p<0.001).

Conclusions:
Stroke patients with pre-morbid disability have higher mortality, institutionalization, and costs if they accumulate additional disability due to the stroke. These findings highlight the long-term outcomes expected if acute interventions are routinely withheld in patients with mild-moderate pre-morbid disability, and suggest that trials/registries should include such patients.
Abstract TMP90: Advances in Treatment of Central Retinal Artery Occlusion: Potential Efficacy of Systemic Fibrinolysis
Authors: Schrag Matthew , Lavin Patrick , Youn Teddy , Kirshner Howard , Mac Grory Brian , Greer David
Published: January 2019

Background:
Central retinal artery occlusion (CRAO) results in sudden, painless loss of vision in the affected eye which is usually permanent. Despite 150 years of research, there is no treatment which has been proven to be effective to salvage visual acuity. Acute CRAO may also be amenable to treatment with intravenous tissue plasminogen activator (tPA). In the current work, we evaluated the efficacy of intravenous tPA in an ongoing prospective cohort study.

Methods:
We enrolled 107 patients with acute CRAO within 48 hours of symptoms onset and with a visual acuity of less than 20/200 from January 2009 until now. Those within 6 hours of onset were offered treatment with tPA; this interval was narrowed to 4.5 hours in July 2015 in response to new data. The primary outcomes were safety and functional visual acuity recovery defined as a final visual acuity of 20/100 or better.

Results:
Twenty-two patients (20.5% of the cohort) were treated with tPA. One patient had an asymptomatic intracerebral hemorrhage after tPA treatment and there were no other adverse events. Thirty-six percent of tPA-treated patients had recovery of visual acuity when treated within 4.5 hours while only 12.5% of patients who were not treated with tPA had recovery of visual acuity (p=0.009). None of the patients treated with tPA between 4.5 and 6 hours after onset (0/8) recovered. The median time to arrival in the ER after onset of symptoms for all patients with acute CRAO was 8.0 hrs (IQR 5.5 to 23), but the median time to initial contact with any provider was 3.9 hrs after onset (IQR 2.0 to 12) meaning a significant fraction of patients with acute CRAO may be candidates for fibrinolysis if they are efficiently routed to emergency departments. Finally we incorporated our results and those of several other recent cohort studies into an updated subject-level meta-analysis to estimate the effect-size of tPA treatment on visual acuity across a broader population and demonstrate the reproducibility of our findings.

Conclusions:
This study showed that visual outcomes for acute CRAO are greatly improved with tPA treatment and this treatment can be feasibly applied to a high percentage of affected patients. The results of our study strongly support proceeding to a clinical trial.
Abstract TMP92: Pioglitazone for Secondary Stroke Prevention in Pre-diabetes: Implications for Real-world Practice
Authors: Spence J David , Viscoli Catherine , Dearborn-Tomazos Jennifer , Furie Karen , Ford Gary , Young Lawrence , Inzucchi Silvio , Gorman Mark , Lovejoy Anne , Kernan Walter
Published: January 2019

Pioglitazone reduces insulin resistance and cardiovascular risk among patients with type 2 diabetes. The Insulin Resistance Intervention after Stroke (IRIS) trial randomized 3876 non-diabetic participants with recent stroke/TIA and insulin resistance based on the Homeostasis Model of Insulin Resistance (HOMA-IR) score to pioglitazone (PIO) vs. placebo (PLA). Over 4.8 years, the relative risk reduction (RRR) with PIO was 27% for stroke/myocardial infarction, 25% for stroke, 29% for acute coronary syndrome (ACS), and 52% for new-onset diabetes. PIO could therefore be considered a new therapy for secondary stroke prevention before diabetes onset. However, it is not in widespread use, not only because of increased fracture risk, but perhaps also because HOMA-IR is not commonly assessed in clinical practice. In contrast, the presence of prediabetes is often identified in this population. We therefore analyzed the intention-to-treat (ITT) and the on-treatment effect of PIO (defined as adherence of
>
80%) in IRIS participants with prediabetes by the American Diabetes Association criteria: HbA1C 5.7%-6.4%, or fasting glucose 100-125 mg/dL (n=2885; PIO 1456, PLA 1429). By ITT, for pioglitazone the hazard ratio and 95% confidence interval in Cox regression for stroke/MI was 0.70 (0.56-0.88, p=0.002), for stroke 0.72 (0.56-0.93, p=0.013), for ACS 0.72 (0.52-1.00, p = 0.052), for stroke/MI/hospitalized heart failure (HHF) 0.78 (0.63-0.96, p=0.02), and for new-onset diabetes HR 0.46 (0.34-0.61, p <0.0001). Among participants with good adherence, pioglitazone participants (n=644) were more likely to be men (76.2% vs 70.6%, p=0.02) and more likely to be smokers (15.9% vs. 11.7%, p=0.02) compared to PLA participants (n=810). In this subgroup, the HR for stroke/MI was 0.57 (0.39-0.84, p=0.004), for stroke 0.64 (0.42-0.99, p=0.04), for ACS 0.47 (0.26-0.85, p=0.01), for stroke/MI/HHF 0.61 (0.42-0.88, p=0.008), and for new-onset diabetes HR 0.18 (0.10-0.33, p<0.0001)

Conclusion:
Pioglitazone should be considered efficacious for secondary prevention in stroke/TIA participants with prediabetes, simply assessed by fasting plasma glucose or A1C.
Abstract TP100: Elevation of Admission High-Sensitivity Cardiac Troponin T is Associated With Increased Discharge Disability in Acute Ischemic Stroke Patients Treated With Thrombolysis
Authors: Zhang Yao , Sui Yi , Xu Bing , Zheng Liqiang
Published: January 2019

Introduction:
Elevated levels of cardiac troponin T (cTnT) has been demonstrated to be associated with greater stroke severity, worse clinical outcome and increased mortality. Few studies have discussed the predictive value of high-sensitivity cTnT(hs-cTnT) in thrombolysed patients with acute ischemic stroke (AIS). In the present study, we investigate whether elevated levels of hs-cTnT is associated with greater stroke severity and worse clinical outcomes in Chinese AIS patients treated with intravenous tissue-type plasminogen activator (IV tPA).

Methods:
From January 2017 to February 2018, we prospectively recruited a total of 249 AIS patients treated with IV tPA within 4.5 hours of onset.Hs-cTnT assays were performed on admission and prior to thrombolysis in all these patients.Patients were stratified into either normal or elevated hs-cTnT groups according to a cut-off value of 14 ng/L of the admission hs-cTnT level. Adjusted odds ratios and related 95% confidence intervals were assessed based on multivariable logistic regression model.

Results:
In the univariate comparisons, older age, higher NIHSS on admission, lower eGFR, history of diabetes mellitus, coronary heart disease or atrial fibrillation, involvement of insular cortex and cardioembolism were significantly associated with elevated hs-cTnT levels.In the univariate comparisons,hs-cTnT elevation was significantly associated with disability at discharge(14 days mRS > 2) (
p
<0.001, OR 3.733, 95% CI 2.019-6.905) and 30 days mortality(
p
=0.002, OR 8.190, 95% CI 2.101-31.935).After adjusting for demographic and clinical characteristics in multivariable analysis, hs-cTnT elevation was still significantly associated with disability at discharge (
p
< 0.05, OR 2.82, 95% CI 1.02-7.77). Thirty days mortality showed an increasing trend (
p
= 0.09, OR 4.093, 95% CI 0.81-20.70) in hs-cTnT elevated group.

Conclusions:
Hs-cTnT elevation is associated with increased disability at discharge in AIS patients treated with IV tPA. Further analyses with regard to neurological severity (NIHSS) and disability (mRS)respectively at the time point of discharge, 30 days and 90 days are in process.
Abstract TP108: The Impact of Aggressive Blood Pressure Management in the Post-Thrombolysis Setting
Authors: Harper Bethan , Ranta Anna
Published: January 2019

Introduction:
High blood pressure post-thrombolysis has been associated with an increased rate of bleeding and poorer outcome. Aiming for a maximum systolic blood pressure (SBP) of 180 mmHG often fails to adequately maintain SBP <180 mmHg due to unavoidable treatment delays. We tested whether a more aggressive target of SBP <160mmHg would result in fewer protocol violations, a lower rate of sICH and improved patient outcomes off-setting any potential harm relating to a potentially higher risk of hypotensive events resulting in cerebral hypoperfusion.

Methods:
In late 2014 a new blood pressure (BP) protocol was introduced, aiming for SBP <160mmHg post thrombolysis with a low threshold for using a glycerine trinitrate infusion (GTN). Patients were prospectively captured in a thrombolysis register and registry data was supplemented by retrospective chart review, comparing patients thrombolysed during the 12 months before and 12 months following the introduction of the new protocol, allowing for a 6 month transition period. Results were adjusted for baseline function and stroke severity using regression analysis.

Results:
During the 12 months preceding and the 12 months following the transition to the new protocol 68 and 100 patients were thrombolysed respectively. Baseline characteristics were similar between groups including age, pre-stroke level of independence and stroke severity at presentation. There was a trend for a lower rate of SBPs >180mmHg (adjusted OR 0.49; 95% CI 0.31-1.1; p=0.097) and a significantly higher rate of SBPs <120mmHg (adjusted OR 3.06; 95% CI 1.52-6.17; p=0.002) in the aggressive BP protocol group; although events of extreme SBPs (>200 and <100 mmHg) were similar between groups. Favourable outcomes (mRS = 0-2) at 3 months were not significantly more common in the aggressive BP protocol group (adjusted OR 1.27; 95% CI 0.58-2.8; p=0.56), nor was there a reduced rate of sICH (adjusted OR 1.26; 95% CI 0.28-5.7; p=0.76). However, model fit was improved by adding study group to the model.

Conclusions:
The introduction of a more aggressive post-thrombolysis BP protocol successfully shifted the SBP range into a potentially safer zone, however, this was not conclusively associated with improved patient outcomes.
Abstract TP115: Cellular and Molecular Characterization of Microglia in Secondary Thalamic Injury After Ischemic Stroke
Authors: Cao Zhijuan , Harvey Sean , Chiang Terrance , Foltz Aulden , Cheng Michelle , Steinberg Gary
Published: January 2019

Introduction:
Secondary thalamic injury develops progressively after cortical ischemic stroke. This secondary injury associates with somatosensory dysfunctions and hinders recovery. However, the underlying pathological mechanisms are unclear. Previously our time course histological study characterized neuronal degeneration and inflammatory responses in the secondary thalamic injury after cortical ischemic stroke. In this study, we further investigated the cellular and molecular changes of microglia during the development of secondary thalamic injury.

Methods:
Left middle cerebral artery was permanently occluded to generate cortical ischemic stroke on male C57BL6J mice. Brain sections were collected on post-stroke days (PD) 1, 3, 7, 14 and 28. Immunostaining was used to detect microglia/macrophage activation (Iba-1) in the ipsilesional thalamus (iTH). Flow cytometry was used to discriminate between microglia and peripheral macrophages at PD28. iTH at PD7 and PD28 were processed for NanoString neuropathology transcriptome analysis (780 genes) to investigate the molecular changes. Microglial activation related genes were validated by qPCR.

Results:
In iTH, very few activated microglia/macrophages were detected at PD1. Clusters of microglia/macrophages appeared at PD7, became denser at PD14 and peaked at PD28. Flow cytometry analysis confirmed that at PD28, most of the microglial/macrophage population in iTH was CD11b
+
CD45
low
, indicating they were mainly resident microglia. Furthermore, a subtype of CD11c+ microglia population were identified in iTH. NanoString analysis revealed significant changes in iTH transcriptome, with 50 differentially expressed genes at PD7 and 191 at PD28 when compared to naive mice. Several microglial activation related genes (CX3CR1, CSF1R and TLR2) were significantly increased at PD28 iTH compared to naïve and PD7.

Conclusion:
We have characterized the cellular and molecular changes of microglia in secondary thalamic injury. We demonstrated that the activated microglia/macrophages in iTH were mainly resident microglia exhibiting increased microglial specific genes. Targeting microglial activation may alleviate secondary thalamic injury and promote long-term stroke recovery.
Abstract TP117: Experimental Stroke Induces Chronic Gut Dysbiosis in Male C57BL/6J Mice
Authors: Brichacek Allison L , Gambill Catheryne A , Kenney Sophia , Nwafor Divine C , Hu Heng , Ren Xuefang , Benkovic Stanley A , Brown Candice M
Published: January 2019

Introduction:
Recent literature implicates gut epithelia mucosa and intestinal microbiota as important players in post-stroke morbidity and mortality. As most studies have focused on the acute effects of stroke on gut dysbiosis, our study objective was to measure chronic, longitudinal changes in the gut microbiota and intestinal pathology following ischemic stroke.

Hypothesis:
We hypothesized that mice with experimental ischemic stroke would exhibit chronic gut dysbiosis and intestinal pathology at up to 35 days post-stroke compared to sham controls.

Methods:
Male C57BL/6J mice were subjected to 60 minutes of transient middle cerebral artery occlusion (tMCAO) or sham-surgery followed by reperfusion and euthanasia at day 35. To determine the long-term effects of tMCAO on gut dysbiosis, fecal boli were collected pre- and post-tMCAO on days 0, 3, 14, and 28. Following DNA extraction, amplification of the V3-V4 region of the 16s rRNA gene was performed via PCR, then library preparation and high-throughput sequencing on the HiSeq Ilumina platform. Longitudinal changes between tMCAO and sham-injured mice were analyzed with the DESeq2 pipeline and MicrobiomeAnalyst. Pathological indices of gut dysbiosis were assessed via Periodic acid-Schiff stain and immunolabeling of tight junction and mucin proteins.

Results:
Bioinformatics analysis revealed significant differences in abundance among taxa at the phylum, family, and species levels between baseline samples and post-injury fecal microbiome samples in tMCAO mice compared to sham mice that persisted up to 28 days post-stroke. The most persistent changes in post-stroke microbial abundance were decreases in beneficial bacteria families,
Bifidobacteriaceae
and
Lactobacillaceae
, and significant increases in the harmful bacteria families,
Helicobacteraceae
and
Enterobacteriaceae
. Intestinal histopathology at day 35 showed evidence of chronic intestinal inflammation that included marked increases in immune cell infiltration with mild-moderate epithelial hyperplasia and villous blunting.

Conclusion:
These results demonstrate that acute, post-stroke disruption of the gut-brain-microbiota axis progresses to chronic gut dysbiosis and intestinal inflammation.
Abstract TP118: Post-Stroke Whole Body Vibration Reduces Frailty in Nicotine Exposed Female Rats
Authors: Raval Ami P , Moreno William Javier , Sanchez Juliana , Furones-Alonso Ofelia , Dietrich W. Dalton , Bramlett Helen M
Published: January 2019

Background:
Stroke disproportionately kills more women than men and the risk of stroke remains high even at a young age among women smokers. Smoking prior to stroke is associated with increased post-stroke frailty. Frailty is characterized by an increased vulnerability to acute stressors and the reduced capacity of various bodily systems due to age-associated physiological deterioration. Such age related physiological deterioration of bone in laboratory animals and humans has shown to reverse after therapeutic intervention of whole body vibration (WBV). In the current study we aim to test the efficacy of WBV in reducing post-ischemic frailty and improving physical activity and cognition using a rat model of smoking attributed nicotine.

Methods:
Nicotine or saline exposed adult female rats underwent transient middle cerebral artery occlusion (tMCAO; 90 min) / sham-surgery and randomly assigned (n = 6-8 per group) to either WBV or control groups. Animals placed in the WBV (40 Hz) group underwent 30 days of WBV treatment performed twice daily for 15 min each session for 5 days each week. We monitored the frailty index (FI) prior to and 1 month after tMCAO alone or in combination with WBV. The FI was composed of the following criteria: 1) activity levels, 2) blood pressure (BP), 3) basic metabolic status, and 4) cognitive performance of rats. Animals were sacrificed on the 30th day of WBV treatment, and brain tissue was harvested for histopathological analysis.

Results:
Post-tMCAO WBV did not change activity levels or BP in nicotine or saline treated rats. Post-tMCAO WBV cognitive performance improved in saline group as compared to nicotine exposed rats. Sensorimotor function was also improved in tMCAO WBV saline group compared to nicotine-exposed rats. We observed 56% reduction in infarct volume of WBV treated rats as compared to control (p < 0.05). This difference was not seen in nicotine treated groups.

Conclusions:
The post-ischemic WBV intervention had no detrimental effects on the frailty parameters, decreased brain damage, and reduced frailty in control female rats, but not in the nicotine-exposed group. This suggests that WBV may be a potential therapy for non-smokers to reduce post-ischemic frailty and improve functional and cognitive outcomes after stroke.
Abstract TP122: Overexpression of miR-133b in Reactive Astrocytes Enhances Their Released Exosomes Which Contribute to Neurite Remodeling and Functional Recovery After Stroke
Authors: Liu Zhongwu , Chopp Michael , Li Yanfeng , Gan Xinling , Wang Fengjie , Shang Xia , Zhang Zheng , Xin Hongqi
Published: January 2019

Introduction:
Astrocyte exosomes participate in the maintenance of axons and plasticity of neuronal networks. Overexpression of miR-133b in reactive astrocytes increases the release of exosomes which contribute to neurite outgrowth in vitro. Here, we investigate whether in vivo overexpression of miR-133b in reactive astrocytes enhances exosome release and subsequently promote the neurite remodeling and functional recovery after stroke.

Methods:
Mice (n=8) subjected to permanent middle cerebral artery occlusion were intranasally infused with the lentivirus generated from pLVX-GFAP-CherryPicker1 (Control) and pLVX-GFAP-CherryPicker1~miR-133b (miR-133b overexpression) at 24h post stroke. Functional tests including pellet reaching were performed and mice were sacrificed at 28 days post stroke. Neurite remodeling was determined with immunohistochemistry and reactive astrocyte released exosomes were isolated based on the CherryPicker tag and quantified. In vitro studies were performed to verify the effects of miR-133b modified astrocyte exosomes on neurite outgrowth. Level of a miR-133b targeted protein, PIKFYVE, a phosphoinositide kinase which facilitates lysosomal maturation and degradation was measured by Western blot.

Results:
Compared with control lentivirus treatment, miR-133b overexpressing lentivirus treatment significantly improved functional recovery after stroke (p<0.05). Numbers of reactive astrocyte exosomes from miR-133b lentivirus treated mice were significantly increased and their miR-133b cargo was upregulated. Neurite outgrowth (branches and length) of in vitro cultured mouse cortical neurons was significantly enhanced in miR-133b overexpression astrocyte exosome treated group compared to control astrocyte exosome treated group (p<0.05, respectively). Western blot data showed that stroke increased PIKFYVE expression was downregulated by the miR-133b overexpression.

Conclusions:
Overexpression of miR-133b in reactive astrocytes increases their exosome release and increases the miR-133b content within these exosomes possibly via downregulation of PIKFYVE, and the enhanced reactive astrocyte exosomes subsequently promote neurite remodeling and functional recovery after stroke.
Abstract TP14: Predictors of Neurological Worsening Among Patients Presenting With Large Vessel Occlusions and Mild Symptoms
Authors: Saleem Yasir , Kim Song J , Sharashidze Vera , Nogueira Raul G , Frankel Michael , Al-Bayati Alhamza , Bianchi Nicolas , Rodrigues Gabriel M , Haussen Diogo C
Published: January 2019

Introduction:
We aim to evaluate the predictors of poor neurological outcome among patients presenting with large vessel occlusion (LVO) and mild symptoms who did not undergo upfront thrombectomy.

Methods:
Single-center retrospective study of consecutive patients with NIHSS≤5 and LVO on CT/MR angiography within 24h from symptom onset and baseline modified rankin score (mRS)0-2 from Jan 2014-Dec 2017. Acute neurologic deterioration definition: change in NIHSS≥4 within 24h. Primary outcome: NIHSS shift ≥4 (discharge NIHSS minus admission NIHSS score).

Results:
Among 1156 patients with acute minor strokes, 134 (11%) met criteria. 78% underwent CTA/22% MRA, performed <4h of arrival in 83%. Median age was 64[53-71]years, 58% were male, and last-normal-to-hospital-arrival was 5[2- 8]h. Median baseline NIHSS 3[1- 4] and initial systolic blood pressure 161[137-177]mmHg. Median glucose was 114[100- 143]mg/dL, ejection fraction 55[52- 60]%, and NCCT ASPECTS 10[9-10]. Occlusion site was intracranial carotid in 10%, middle cerebral M1 30%, M2 26%, M3 9%, anterior cerebral 3%, extracranial carotid 11%, basilar 7%, and posterior cerebral 2%. RAPID CT perfusion was performed in 42%, with median core 0[0-5]cc, Tmax>4s 152[62-232]cc, Tmax>6s 57[25-108]cc, Tmax>10s 10[0-33]cc. Orthostatic challenge was performed in 28 (21%) with NIHSS worsening ≥1 in 46%. Twenty-four (18%) patients had acute neurological deterioration of NIHSS≥4 at a median of 2[1-16] hours from arrival. Median discharge NIHSS was 2[0- 4] and the NIHSS shift -1[-3- 0]. Etiology was cryptogenic in 24%, cardioembolic in 25%, and large vessel atherosclerosis in 26%. Parenchymal hematomas occurred in 7%. Overall, 22% had an unfavorable NIHSS shift ≥1, 15% NIHSS≥2, and 11% had NIHSS shift≥4. At discharge, only 62% were independent (22% mRS0, 27% mRS1, 12% mRS2). Multivariable regression indicated acute neurological deterioration (OR 7.9; 96%CI 1.4-41.9;p=0.01) and discharge mRS (OR 3.6; 96%CI 1.6-8.4;p=0.01) independently associated with NIHSS shift ≥4.

Conclusion:
Acute neurological worsening occurs early and predicts an NIHSS shift≥4 at discharge, which in turn is associated with worse discharge mRS. The optimal therapeutic window in LVO with mild NIHSS may be relatively narrow.
Abstract TP143: Potential of Cerebellum-derived Stem Cells in Human Brain to Regenerate Functional Neurons Following Ischemic Stroke
Authors: Beppu Mikiya , Nakagomi Takayuki , Takagi Toshinori , Nakano-Doi Akiko , Sakuma Rika , Kuramoto Yoji , Tatebayashi Kotaro , Matsuyama Tomohiro , Yoshimura Shinichi
Published: January 2019

Introduction:
Despite the availability of effective reperfusion therapies, only a few prove beneficial to the patients after stroke, owing to their limited time window. We had earlier demonstrated that adult brain pericytes develop stemness following ischemia, and these ischemia-induced multipotent stem cells (iSCs) can self-propagate and differentiate into mature neural cells, including neurons (Nakagomi et al. Eur J Neurosci. 2009, Stem Cells. 2009, 2015). More recently, we have shown putative iSCs to be present within post-stroke human cerebral tissues (Tatebayashi K et al. Stem Cells Dev 2017). The current study aimed to establish iSCs from cerebellar infarction of two patients and examine their characteristics.

Methods:
We isolated iSCs from post-stroke human cerebellum, examined their characteristics by Polymerase chain reaction and immunocytochemistry, and compared their traits with those of others by microarray and flow cytometry analyses. Furthermore, we investigated the cerebellar-iSCs (cl-iSCs) for multi-potency and differentiation into functional neurons. Electrophysiological properties were analyzed using multi-electrode arrays.

Results:
The isolated cl-iSCs exhibited multi-potency and differentiated into electrophysiologically active neurons (Fig. A). Neurogenic potential was confirmed in single-cell suspensions (Fig. B.C). Highly similar gene expression patterns were observed between pericytes and iSCs (Fig. D), and a strong lineage resemblance between cl-iSCs and cerebral ischemia-induced multi-potent stem cells (cr-iSCs) was revealed, although cl-iSCs differentially expressed certain cerebellum-specific genes.

Conclusions:
Putative iSCs are present in post-stroke cerebellum and possess region-specific traits, suggesting their potential to regenerate functional neurons following an ischemic stroke.
Abstract TP146: Intracranial Microvascular Calcification: A Cadaveric Study
Authors: Moussouros Daniel J , Plummer Maria M , Savinova Olga V
Published: January 2019

Introduction:
Stroke and brain ischemia are associated with macrovascular calcification. Microvascular calcification may also contribute to cerebrovascular disease, yet its prevalence and pathophysiological significance remain unclear.

Hypothesis:
Calcification associated with intracranial microvasculature is prevalent in elderly populations and correlates with calcification of proximal macrovascular supply.

Methods:
Tissues were dissected from 20 cadavers (16 female, 4 male; median age = 81 y; range = 56-94 y) unilaterally on the left side. Three vascular territories were examined representing anterior, middle, and posterior brain regions supplied by distal M4 branches of the middle cerebral artery (MCA). Proximally, two putaminal regions supplied by lenticulostriate arteries (from M1 of the MCA) were examined. Extra- and intracranial internal carotid arteries (ICA) and M1 segments of the MCA from the same subjects were previously scored for calcium; those data were used for correlation analysis. A sensitive and specific calcium detection protocol (alizarin red) was used in all studies alongside H&E. Light microscopy was performed to grade small- (< 20 micron) and large-caliber (20-200 micron) vessels for calcification.

Results:
Calcification was detected in all subjects, with 95% in small-caliber and 50% in large-caliber microvessels. Non-parametric Spearman correlation analysis revealed significant correlation between calcification of large-caliber microvessels in M4 (but not M1 putaminal vessels) and medial calcification of the MCA (M1 segment; r = 0.6533, p < 0.05). Contrary to our hypothesis, no correlations were found between microvascular calcification and calcification of the ICA. Additionally, no correlations were found between microvascular calcification and atheromatous calcification of either the MCA (M1 segment) or ICA (extra- and intracranial parts).

Conclusions:
Our study implies that intracranial microvascular calcification is highly prevalent in elderly populations. Additionally, we discovered significant correlation between microvascular calcification and that of the media in mascrovasculature, suggesting a causal link between medial sclerosis and dysfunction of the neurovascular unit.
Abstract TP153: Cognitive Profile in Patients With Hemodynamic Failure Due to Severe Carotid Stenosis
Authors: Palmer Mathias E , Marshall Randolph S , Chen Qixuan , Slane Kevin J , Lazar Ronald M , Pavol Marykay
Published: January 2019

Background:
Severe carotid stenosis can reduce cognition due to hypoperfusion. Published cognitive profiles for vascular disease are variable, however, precluding identification of hemodynamic failure as a specific cause. We investigated the relationship among carotid stenosis, hemodynamic failure, and cognition by characterizing cognition in patients with severe carotid stenosis, with and without hemodynamic failure.

Methods:
Sixty-one patients (18 with TIA, none with stroke) with ≥80% carotid stenosis were drawn from two study cohorts, RECON and BFC
1
. Hemodynamic status was assessed using oxygen extraction fraction by positron emission tomography (RECON) or mean flow velocity by transcranial Doppler (BFC) and dichotomized into normal (n=30) vs impaired (n=31). Cognition was assessed with 16 tests. Sixteen linear regressions, one for each cognitive test, were performed to assess the influence of hemodynamic failure on test scores, adjusting for side of occlusion, depression, age, gender, education, and study cohort. Multiple comparisons were adjusted using false discovery rate (FDR) correction.

Results:
Hemodynamic failure was a significant independent predictor for Rey Complex Figure Test-Copy (RCFT-C, p=0.007), RCFT-Delayed Recall (RCFT-D, p=0.003), and Trail Making Test-B (TMT-B, p=0.006) and remained so after FDR correction. The other tests were not predicted by hemodynamic status.

Conclusions:
Tests of mental flexibility, visuospatial skill, and organization were sensitive to hemodynamic failure in patients with severe carotid stenosis. A larger sample is required to validate this cognitive profile in such patients. Cognitive assessment with RCFT-C, RCFT-D, and TMT-B may detect the effects of hemodynamic failure specific to large vessel disease, having research and treatment utility.
1
NINDS NS048212 (Randomized Evaluation of Carotid Occlusion and Neurocognition -RECON), R01NS076277 (Blood Flow and Cognition - BFC)
Abstract TP157: Ethnic Difference in Stroke Recurrence for Patients With Intracranial Atherosclerotic Stenosis
Authors: Hao Qing , Qiao Ye , Williams Nicole , Johnson Brenda , Wasserman Bruce A , Gottesman Rebecca
Published: January 2019

Background:
Intracranial atherosclerotic stenosis (ICAS), one of most common stroke subtypes worldwide, carries high risk of stroke recurrence despite maximal medical treatment. ICAS more commonly affects non-white populations including Asian, African-American and Hispanic individuals. It is plausible that non-white stroke patients with ICAS might also have more active disease, and thus higher risks of stroke recurrence. We aim to compare the rate of stroke recurrence in stroke patients with ICAS in white and non-white population. Method: We retrospectively reviewed a consecutive series of patients with ischemic stroke due to ICAS in major vessels (MCA, ACA, PCA, intracranial segment of ICA and VA, BA) with >50% stenosis identified on MRA or CTA. The clinical characteristics, risk factors and rate of stroke recurrence were compared in white and non-white patients, using Chi-square (for categorical variables) test and t-test (for continuous variables).

Results:
A total of 183 patients [66.3% non-white, mean (SD) age, 63 (±14) years] who were hospitalized between January 2005 and December 2010 and satisfied the inclusion criteria were included in the analysis. Compared with white patients, non-white patients had a higher rate of HTN, DM and drug abuse (Table 1), as well a nonsignificantly higher stroke recurrence rate (3 months: OR 1.29, 95% CI 0.59-2.82; long term: OR 1.63, 95% CI 0.84 - 3.18). History of CKD was the only factor associated with 3-month stroke recurrence (OR 3.73, 965 CI 1.13-12.31).

Conclusion:
White and non-white ischemic stroke patients with ICAS have distinct risk factor profiles and possibly distinct stroke recurrence rates. Analysis with a larger sample size is ongoing to verify this finding.
Abstract TP16: Collateral Flow in Posterior Circulation Ischemic Stroke Predict Outcome in Basilar Artery Occlusion: Undergoing Mechanical Thrombectomy
Authors: Ahmed Muhammad K , Sarraj Amrou , Kamal Haris
Published: January 2019

Basilar artery thrombosis is typically associated with devastating outcomes. EVT has proven to be highly effective in the anterior circulation yet outcomes and ways of selecting patients for EVT for basilar artery occlusion remain unclear. Mainly limited by relatively small number of patients as well as different center-specific practices, we evaluated clinical and radiographic variables associated with EVT outcomes.

Methods:
A single-center retrospective cohort of acute ischemic stroke patients with any LVO between January 2014 and January 2018 were reviewed which underwent EVT. Patients with basilar artery occlusion were identified based on presenting CTA/MRA (n=35). We stratified patients into good outcomes (37.1 % vs 62.9 % p=0.133) and good collaterals vs poor collaterals while adjusting for clot length, posterior circulation collateral score, reperfusion status.

Results:
A total of (n=334) patients were identified to have an LVO. Out of these (n=35) had basilar artery occlusions. (n=30) had emergent EVT while (n=5) were initially treated with medical management and taken for EVT as a rescue therapy. After stratifying for good vs poor outcomes, multivariate analysis showed that poor collateral score is associated with poor outcome (mRS=3-6) (OR 0.98 p=0.60 CI 0.67-0.97). Clot length greater than 10 mm is associated with poor outcome at 90 days (HR 0.325 p=0.045 CI 0.56-0.833).

Conclusion:
Basilar artery occlusions carry a worse prognosis in cases with poor collateral scores, clot length >10mm and longer time to reperfusion from symptoms onset.