bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TMP43: Rehabilitation Provider Type Influences Functional Outcome and Survival of Acute Ischemic Stroke Patients With Severe Neurological Deficits: Findings From the China National Stroke Registry II
Authors: Liu Chelsea , Duan Wanying , Liu Liping , Wang Yilong , Pan Yuesong , Meng Xia , Wang Chunjuan , Xian Ying , Yang Qing , Li Zixiao , Wang Yongjun , Bettger Janet P
Published: October 2018

Background:
Task-shifting rehabilitative care from rehabilitation therapists to physicians, nurses, and relatives may supplement the shortage of specialized rehabilitation personnel in China. However, it is unknown how this practice affects patient outcomes. This study examined the association of rehabilitation provider type with functional dependence and mortality among patients with acute ischemic stroke (AIS) in China.

Methods:
Patients with AIS hospitalized at participating China National Stroke Registry II hospitals were eligible if they had no pre-stroke disability (modified Rankin Scale [mRS]=0-2), had moderate to severe neurological deficits at admission (NIHSS>4), and returned home after hospital discharge. Using multivariable logistic and Cox regression models, we compared rehabilitation care provided by therapists versus physicians, nurses, or relatives on functional dependence (mRS=3-6) and mortality at 3, 6, and 12 months after discharge, adjusting for patient characteristics.

Results:
A total of 3741 patients received in-hospital rehabilitation, 56.21% from rehabilitation therapists and 43.79% from others. Among patients with NIHSS=5-9 and NIHSS=10-14, there were no differences between groups for any of the outcomes (Table 1). However, for severe stroke patients (NIHSS>14), non-therapist care was associated with higher odds of mortality at 3-months follow-up (HR=2.13, 95%CI 1.11-4.07, P=0.02) and 12-months follow-up (HR=1.88, 95%CI 1.17-3.01, P=0.01). Hospital-level analysis showed that it was more common for nonteaching hospitals to be without rehabilitation therapists.

Conclusions:
This study suggests a lower mortality risk for patients with severe stroke when treated by a rehabilitation therapist versus others. Future studies should explore the dose, frequency and focus of acute stroke rehabilitation by different providers to better delineate the mechanisms for improving patient outcomes.
Abstract TMP45: An Intensive Multidisciplinary Protocol for Improving Adherence to CPAP Therapy During Inpatient Rehabilitation May Improve Recovery in Stroke Patients
Authors: Khot Sandeep P , Barnett Heather , Siv Jenny , Davis Arielle , Kunze Allison , Crane Deborah , Bunnell Aaron , Li Lue Denise , Ciol Marcia , Rappisi Korren , Thomazin Brett , McCann Barbara , Bombardier Charles , Longstreth W.t. , Watson Nathaniel , Billings Martha
Published: October 2018

Introduction:
Obstructive sleep apnea (OSA) is associated with worse outcome after stroke. Treatment with continuous positive airway pressure (CPAP) may improve recovery after stroke but has been limited by poor adherence.

Methods:
In a single-arm ongoing study, adults with stroke underwent an intensive CPAP adherence protocol during inpatient rehabilitation, including motivational interviewing and help with CPAP by nurses and respiratory therapists. A 3-night run-in period of auto-titrating CPAP was used to test for tolerance and to diagnose OSA, based upon the apnea-hypopnea index and flow resistance. Qualifying patients were asked to continue CPAP for 3 months. The outcomes included CPAP adherence, defined as ≥ 4 hours of use on ≥ 70% of nights, and stroke recovery, measured by change in NIH Stroke scale (NIHSS) and Functional Independence Measure (FIM) over 3 months.

Results:
During the run-in, 39 of 60 (65%) patients had presumed OSA, 5 (8%) had no evidence of OSA, 4 (7%) had evidence of central sleep apnea, and 12 (20%) were intolerant of CPAP. Among the 34 of 39 patients who chose to continue CPAP after the run-in, the median use per night was 5.3 hours (IQR 4.1, 6.0) with 56% (n=19) adherent during rehabilitation. The median CPAP use per night for the 22 who completed the study was 5.1 hours (IQR 2.5, 6.4) with 54% (n=12) adherent over the 3-month period. Unadjusted for baseline factors, there was a significant change in the NIHSS in adherent patients (n=10) vs. non-adherent patients (n=10) [5 (SD 3) vs. 2 (SD 2),
p
=0.02]. Comparing adherent (n=7) to non-adherent patients (n=5), the change for total FIM trended towards significant [42 (SD 18) vs. 30 (SD 11),
p
=0.20] and the change for cognitive component of the FIM was significant [10 (SD 7) vs. 2 (SD 3),
p
=0.05].

Conclusion:
After an intensive adherence intervention, over half of stroke patients with presumed OSA and CPAP tolerance were adherent over 3 months. CPAP adherent patients had greater improvement in NIHSS and the cognitive component of the FIM, although the associations may be confounded by patients’ characteristics influencing both adherence and outcomes. Future studies are needed to evaluate in a randomized trial if the intensive intervention will lead to long-term CPAP adherence and improved stroke recovery.
Abstract TMP47: Pre-Existing White Matter Disease Burden Impacts Cognitive Outcome After Inpatient Rehabilitation for Ischemic Stroke
Authors: Khan Muhib , Heiser Heather , Packard Laurel , Bernicchi Nathan
Published: October 2018

Background:
White matter hyperintensities (WMH) have been shown to impact functional outcomes after ischemic stroke. However, their role in cognitive recovery after ischemic stroke is unclear. Therefore, it is important to evaluate if WMH can predict the degree of cognitive recovery after inpatient rehabilitation.

Methods:
We retrospectively studied 162 patients admitted to inpatient rehabilitation after an acute ischemic stroke. We reviewed patient demographics, presence of co-morbidities, infarct volume, pre-admission Modified Rankin Scale, TOAST criteria, acute interventions for their stroke, rehabilitation length of stay, and Functional Independence Measure (FIM) scores (motor and cognitive) at admission and discharge from rehab. WMH were graded according to the Fazekas scale on the basis of visual assessment in both periventricular and subcortical areas.

Results:
162 patient charts reviewed, 53 were excluded due to primary intracerebral hemorrhage and insufficient imaging. 109 patients were included in the final analysis. Multiple linear regression analysis revealed that, when adjusted for infarct volume, NIHSS stroke scale and age; severity of WMH as graded on Fazekas scale independently predicted Functional Independence Measure (FIM) cognitive scores at discharge (p < 0.0084). WMH severity did not predict Functional Independence (FIM) motor scores.

Conclusions:
In this retrospective analysis, we found that severity of WMH hyperintensities as graded by Fazekas scale is an independent predictor of cognitive FIM scores after inpatient rehabilitation for acute ischemic stroke.
Abstract TMP50: Smoking Increases Risk of Ischemic Stroke in Young Men
Authors: Markidan Janina , Cole John W , Merino-Juarez Jose , Cronin Carolyn A , Phipps Michael , Wozniak Marcella , Kittner Steven J
Published: October 2018

Introduction:
There is a strong dose-response relationship between smoking and risk of ischemic stroke (IS) in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an IS in men under age 50.

Methods:
The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for IS in 1145 men ages 15-49. Controls were identified by random-digit dialing and were balanced to cases for geographic region of residence, age, and ethnicity. Logistic regression models were used to calculate the odds ratio for IS occurrence comparing smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus and body mass index. Interaction terms were used to examine potential effect modification by other risk factors. Statistical tests were 2-tailed and P-values less than 0.05 were considered statistically significant.

Results:
The table shows that IS risk increased with amount of current smoking and that 2 packs per day current smokers had over a 5-fold increased risk of IS. There were no significant interactions with other risk factors.

Conclusions:
We found a strong dose-response relationship between the number of cigarettes smoked daily and IS among young men. While complete smoking cessation is the goal, even reducing the number of cigarettes smoked may reduce the risk of IS in young men.
Abstract TMP51: Nationwide Estimates of Opioid Abuse in Young Stroke Patients
Authors: Indupuru Hari Kishan R , Fraher Christopher , Bambhroliya Arvind B , Meyer Elizabeth , Meeks Jennifer R , Vahidy Farhaan
Published: October 2018

Introduction:
Substance abuse (SA) is a risk factor for stroke. Opioid abuse (OA) can be a precursor for SA, and national prevalence of OA particularly in young stroke patients (YSP) has not been described. We report prevalence and factors associated with OA in YSP. We also explore in-hospital outcomes in YSP with OA.

Methods:
We identified ischemic stroke, intracerebral hemorrhage, and sub-arachnoid hemorrhage patients and patients abusing Opioids, Cocaine, Alcohol, Cannabis, Amphetamines and Hallucinogens using ICD-9 codes, from the National Inpatient Sample for the years 2006 - 2011. Patients aged 18-45 were categorized as YSP. Logistic regression methods are used. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported.

Results:
A total of 163 469 YSP were identified. YSP had a significantly higher proportion of SA as compared to non-YSP for all substances (Table 1). Among YSP, 2 320 had been coded for OA. Among OA YSP, 53% patients also abused at least one additional substance. Males were more likely to be opioid abusers (OA) (OR: 1.23, CI: 1.30-1.47) and more OA were in the lower household income group (Table 2). OA was also associated with higher disease severity and mortality risk, likelihood of being on ventilator support, and longer length of stay. Higher proportion of OA was treated at urban and teaching hospitals, and in the Northeast as compared to other national regions. OA had a greater likelihood of in-hospital death (OR: 1.70, CI: 1.24-2.33) and had poorer discharge disposition (Table 1).

Conclusions:
OA in YSP is associated with greater disease severity, poor in-hospital outcomes including death, and higher utilization of resources. Although OA has not been independently identified as a risk factor for stroke, OA is frequently accompanied by or is a precursor to SA. Routine screening and counselling are required in YSP to prevent recurrence and poor outcomes associated with OA and SA.
Abstract TMP56: Comparison of Incident Stroke in Veterans and Non-Veterans in a National Cohort
Authors: Lyerly Michael J , Albright Karen C , McCaskill Gina M , Williams Linda S , Howard George , Howard Virginia J
Published: October 2018

Introduction:
Veterans represent a unique population who may be at higher risk of stroke. However, the association between veteran status and stroke remains poorly defined.

Methods:
Veteran status was determined among 12,932 participants in the REasons for Geographic and Racial Differences in Stroke Study, a national population-based cohort. Demographics, socioeconomic (SE) factors, and vascular risk factors including Framingham Stroke Risk Score (FSRS) were compared between veterans and non-veterans. Veterans were further characterized as enlisted or commissioned officers. Hazard ratios for incident stroke were calculated for male and female veterans.

Results:
In this cohort, 3,405 veterans were identified. After adjusting for age, race, geographic region, income, and education, there were no substantial differences in vascular risk factors and FSRS between veterans and non-veterans other than a higher proportion of current smokers in male veterans (particularly enlisted) than non-veterans. Among those free of stroke at baseline, male veterans were at similar risk for incident stroke compared to non-veterans (Figure 1a), even with adjustment for age, race, SE factors, and vascular risk factors (HR 1.10, 95% CI 0.82-1.47). Female veterans were at an increased risk for incident stroke (Figure 1b, HR 2.30, 95% CI 1.21-4.34), although this difference was not significant when adjusted for SE and vascular risk factors. Risk for incident stroke was similar between enlisted and commissioned officers (Figure 1c,d).

Conclusions:
This is the one of the first studies to examine incident stroke among veterans and is not limited to those seeking care within the Veterans Health Administration. From this national cohort, military exposure did not increase the risk of incident stroke among males. Female veterans seem to be at a higher risk for incident stroke; however, this association was primarily driven by differences in vascular risk factors compared to non-veterans.
Abstract TMP59: Predictors of Readmissions After Aneurysmal Subarachnoid Hemorrhage
Authors: Liang John W , Ostojic Lili Velickovic , Cifrese Laura , Shah Syed O , Dhamoon Mandip S
Published: October 2018

Objective:
To identify factors associated with readmission after aneurysmal subarachnoid hemorrhage (SAH) using nationally representative data

Background:
Readmission rate is a common metric linked to hospital compensation and as a proxy to quality of care. Prior studies in SAH have reported higher risk of readmission among those with longer length of stay (LOS) and discharge to skilled nursing facility. These studies were limited by small sample sizes and single-center design.

Methods:
The Nationwide Readmissions Database is a de-identified national database of readmissions with data on 49% of U.S. admissions in 2013. We used International Classification of Disease, Ninth Revision, Clinical Modification codes to identify index SAH admissions, comorbidities, and outcomes. Unadjusted and adjusted Poisson models were used to identify factors associated with increase readmission rate up to 1 year after discharge.

Results:
Out of 14464 index admissions for SAH, 8587 (59.4%) were female, average age was 61.2±16.1 years, with an even distribution of socioeconomic status. Among 11035 who survived to discharge, there were 2765 readmissions (25.1%) up to 1 year. In univariate analysis, variables associated with increased readmission rate included age, atrial fibrillation, CHF, diabetes, renal impairment, COPD, tracheostomy, percutaneous endoscopic gastrostomy, discharge not to home, and greater LOS. In multivariable analysis, significant predictors of higher readmission rate included LOS (0.001 greater rate per day increase, 95% CI 0.0001-0.002), CHF (rate ratio [RR] 1.08, 1.02-1.14), diabetes (RR 1.09, 1.05-1.14), renal impairment (RR 1.15, 1.09-1.2), COPD (RR 1.08, 1.02-1.14). Factors associated with lower readmission rate were age (0.0013 lower rate per year increase, -0.003, 0.0001) and discharge home (RR 0.92, 0.88-0.95).

Conclusions:
In this nationwide database several medical comorbidities were associated with higher readmission rates after SAH, in addition to previously reported variables of discharge disposition and LOS. Given that 1 out of 4 SAH patients are readmitted within the year, prospective studies are warranted on the feasibility and efficacy of interventions tailored to high-risk subgroups.
Abstract TMP6: Temporal Trends in Endovascular Therapy and Clinical Outcomes for Acute Ischemic Stroke at a Single Comprehensive Stroke Center in Japan
Authors: Ohara Nobuyuki , Imamura Hirotoshi , Todo Kenichi , Murakami Yasutaka , Kono Tomoyuki , Funatsu Takayuki , Tokunaga So , Adachi Hidemitsu , Kohara Nobuo , Sakai Nobuyuki
Published: October 2018

Background and Purpose:
Endovascular therapy (EVT) for acute ischemic stroke (AIS) is now proven by pivotal randomized controlled trials (RCTs) to produce clinically large benefits. In early 2015, following publication of these RCTs, we implemented a new institutional acute stroke care protocol to improve outcomes of patients with AIS, especially by reducing onset-to-reperfusion (OTR) time. We sought to analyze the temporal trends in EVT for AIS at our hospital and evaluate the effect of this intervention.

Methods:
We analyzed the temporal trends in EVT for AIS and compared patients who underwent EVT for AIS in the pre intervention (April 2010 - March 2015) and post intervention (April 2015 - March 2017) period. Using univariate methods and multivariable logistic regression, we assessed the associated factors with favorable outcomes.

Results:
Among 2657 patients with AIS, 322 (12.1%) underwent EVT. The mean age was 74.4 and the median baseline NIHSS was 19. The percentage of patients with EVT significantly increased from 9.7% pre intervention to 18.0% post intervention. Patients over 90 years old, with M2 occlusion, and received IV-tPA were significantly increased in post intervention period (P<0.01). The median (interquartile range) door-to-puncture (DTP) times was reduced from 120 (93-144) minutes to 52 (39-73) minutes (p<0.001), and OTR times was reduced from 368 (263-554) minutes to 256 (163-440) minutes (P=0.006). The percentage of patients with favorable outcomes (modified Rankin scales 0-2 at 90days) improved from 28.8% to 39.9%. Multivariable model showed an association of favorable outcomes with younger age (OR 0.93, 95%CI 0.90-0.96, P<0.001), lower baseline NIHSS (OR 0.89, 95% CI 0.85-0.93, P<0.001), administration of tPA (OR 2.17, 95%CI 1.05-4.49, P=0.038), and shorter OTR times (per10min, OR 0.99, 95%CI 0.97-1.00, P=0.047).

Conclusions:
EVT for AIS accelerated markedly in the two years following RCTs publication and our new institutional acute stroke care protocol reduced DTP and OTR times. Reducing OTR times was associated with improving patient outcomes.
Abstract TMP60: Validation of an Education Gauge for Measuring Stroke Outreach Efforts
Authors: Morgan Tiffany , Brown Aliza T , Onteddu Sanjeeva , Joiner Renee , Benton Tina , Culp William , Lowery Curtis
Published: October 2018

Background:
To improve rural population access to telestroke sites for referral and treatment, hospitals are required to fulfill monthly educational outreach. Telehealth sites that provide stroke outreach through awareness educational campaigns remain unaware of the efficacy of their outreach efforts. This study sought to apply a measurable scale to their outreach efforts and determine if the values correlated to the sites referral and treatment rates.

Hypothesis:
Measurable differences of outreach efforts in rural populations positively correlate to referral and treatment rates at telestroke hospital sites.

Methods:
A large telestroke network (n=48 spoke sites) had 12 consecutive months during 2016 of community outreach efforts evaluated on an educational gauge scale. Events were categorized as active or passive depending on the type of event. All events were assigned a value based on the type of event, audience size and the crowd’s level of attention/participation. Total monthly values for all spoke sites were calculated and compared by month and category. Regression analysis was used to determine significance of correlative analysis of education vs. number of referrals and vs. number of tissue plasminogen activase (tPA) treatments.

Results:
Outreach efforts promoting stroke awareness from all 48 sites totaled 2,625 educational points. There was a temporal trend of active events occurring in the spring (April through June) and in the fall (October). In regression analysis there was a positive correlation in the number of referrals vs. educational gauge (R=0.23; P=0.0013) and in the number of tPA treatments (R=0.20; P=0.0055). One spoke site was evaluated for their community events due to their high referral rate in the first quarter of the year. Outreach efforts during these months included stroke awareness events at local high schools, a sporting race event and to apartment residents.

Conclusion:
Targeted outreach efforts can now be measured for efficacy of reaching diverse populations with direct effects on referral and treatment rates.
Abstract TMP65: The Minnesota Stroke System, 2012-2017: Development and Impact of a Statewide System of Stroke Care
Authors: Tsai Albert W , Lindgren Paula G , Hicks Megan M , Peacock James M
Published: October 2018

Background:
The Minnesota Stroke System is comprised of hospitals able to deliver state-of-the-art stroke treatment. The system is designed to increase access to acute stroke treatment and improve outcomes for stroke patients. Between 2011 and 2013, the Minnesota Department of Health convened health care providers and stroke patient advocates to plan and create the components of a statewide stroke system for Minnesota. To launch the system, the Minnesota legislature gave MDH statutory authorization to designate Acute Stroke Ready Hospitals (ASRHs) and recognize Primary and Comprehensive Stroke Centers certified by national accreditation bodies. The ASRHs meet ten criteria corresponding to the 2013 Brain Attack Coalition recommendations.

Analysis:
Stroke patient data are reported to the Minnesota Stroke Registry by hospital-based abstractors. Data are combined for 2012-2013, 2014-2015, and 2016-2017. Performance metric statistics were calculated using SAS (Cary, NC). The resident population living within 30 minutes of designated hospitals was calculated from 2010 US Census Bureau data using ArcGIS 10.3 Network Analyst.

Results:
From 2012 to 2017, the number of designated ASRHs increased from zero to 89, out of 111 eligible hospitals. The percentage of residents living within 30 minutes of any designated facility increased from 60% to 90%. The percentage of all stroke patients whose computed tomography image was initiated within 25 minutes of arrival increased from 34.2% to 42.9%. Intravenous thrombolytic therapy increased from 8.8% to 11% of all ischemic stroke patients. Median door-to-imaging time decreased from 40 to 33 minutes. Median door-to-needle time decreased from 56 to 53 minutes. 28.7% of patients in 2012-2013 who received IV tPA were treated within 4.5 hours of time last known well, increasing to 35.6% in 2016-2017.

Conclusions:
The Minnesota Stroke System has successfully catalyzed and supported significant improvements in acute stroke treatment in Minnesota.
Abstract TMP7: Endovascular Recanalization of Intracranial Arterial Stenosis in Patients With Recurrent or Progressive Symptoms Despite Medical Management
Authors: Aghaebrahim Amin , Aguilar-Salinas Pedro , Santos Roberta , Siddiqui Adnan H , Levy Elad I , Shallwani Hussain , Lopes Demetrius , Saied Ahmed , Kim Song J , Haussen Diogo C , Nogueira Raul G , Jovin Tudor G , Jadhav Ashutosh , Kaustubh Limaye , Turk Aquilla S , Spiotta Alejandro M , Turner Raymond D , Brasiliense Leonardo B , Dumont Travis , Cherian Jacob , Kan Peter , Sauvageau Eric , Hanel Ricardo A
Published: October 2018

Background and Objective:
The optimal management of intracranial arterial stenosis is unclear, particularly in patients who have failed medical management. We report a multicenter real-world experience of endovascular recanalization of intracranial atherosclerotic stenosis refractory to aggressive medical therapy.

Methods:
Retrospective multicenter case series of consecutive endovascularly treated patients presenting with symptomatic (TIA or stroke) who had failed medical therapy were identified. All of the patients were considered to be at high risk with unstable symptomatic intracranial stenosis and progression or recurrence of symptoms despite the best medical management and underwent endovascular intervention either with stenting and/or balloon angioplasty.

Results:
98 patients presented with recurrent TIAs (n= 40) or recurrent or progressive strokes (n= 58) and were treated in 8 stroke centers from 2009 to 2017. All patients were treated either with dual antiplatelet therapy (84%) or anticoagulation and all had statin therapy prior to recurrence or progression of their symptoms. There was one periprocedural perforation resulting in patient death. There were 3 patients who had periprocedural strokes and 2 patients had symptomatic intraparenchymal hemorrhage with a total of four (4%) periprocedural mortality. The all-cause mortality rate at discharge was 6%. At 90-day follow-up, 7 (10%) patients had TIAs and 2 (3%) patients had ipsilateral strokes, and 78% of patients had mRS of 2 or less.

Conclusion:
Endovascular recanalization of unstable intracranial atherosclerotic stenosis who have failed medical therapy is feasible and safe.
Abstract TMP79: Delays in Recognition of Perioperative Strokes Following Cardiac Surgery
Authors: Hormes Joseph , Katema Anna , Edwards J. Kirk , Esper Gregory , Binongo Jose N , Lasanajak Yi , Keeling Brent , Halkos Michael , Nahab Fadi
Published: October 2018

Introduction:
Previous studies have suggested that perioperative stroke (PS) following cardiac surgery has a bimodal distribution of timing with more than half of cases identified beyond postoperative day one (POD1). The objective of our multicenter study was to determine preoperative and intraoperative factors that are associated with PS following cardiac surgery and to identify factors that may contribute to PS that is identified after POD1.

Methods:
Patients undergoing coronary artery bypass surgery (CABG) or isolated valve surgery from January 2, 2015 to April 28, 2017 at three Southeastern US centers were identified from the Society of Thoracic Surgeons (STS) Registry. Multivariable logistic regression analysis was employed to identify preoperative (patient-related) and intraoperative (procedure-related) variables from the registry to identify factors associated with PS, defined by STS as any confirmed neurological deficit of abrupt onset caused by a disturbance in blood supply to the brain that did not resolve within 24 hours and occurring within 30 days of surgery. Neurologists performed retrospective chart review on PS patients to determine last seen well time and mechanism of stroke.

Results:
During the study period, 2795 patients underwent cardiac surgery (mean age 64 ± 11 years, 71% male, 71% Caucasian, 9% history of stroke) of which 43 (1.5%) had a PS; 31 (72%) patients had an embolic mechanism of stroke based on neuroimaging. In multivariable analysis, PS was independently associated with increasing age (OR 1.04, 95% 1.01-1.07), history of stroke (OR 2.73, 95% CI 1.47-5.06), and history of thoracic aorta disease (OR 3.36, 95% CI 1.16-9.71). Strokes were identified after POD1 in 32 (74%) patients, 26 (81%) of which had a preoperative last seen well time.

Conclusion:
Given the high frequency of
pre
operative last seen well times in PS patients who are identified after POD1, delayed stroke recognition may contribute to the bimodal distribution in timing of PS; frequent neurological monitoring within 24 hours of surgery should be considered for patients who are elderly, have a history of stroke or thoracic aorta disease to improve early stroke recognition.
Abstract TMP82: When Does Having a Mobile Stroke Unit Make Sense in a Metropolitan Area From a Patient Outcome Perspective?
Authors: Holodinsky Jessalyn K , Kamal Noreen , Zerna Charlotte , Zhu Luke , Hill Michael D , Goyal Mayank
Published: October 2018

Introduction:
The Mobile Stroke Unit (MSU) has brought stroke imaging and alteplase administration to the field, possibly shortening onset to needle time in some situations. However, for patients needing endovascular therapy (EVT) onset to groin puncture times may be lengthened due to additional travel time. For patients with suspected large vessel occlusion (LVO) using the Los Angeles Motor Scale (LAMS) we compare the probability of good outcome for patients taken direct to Comprehensive Stroke Centre (CSC) (mothership) and patients utilizing the MSU.

Methods:
Using conditional probability models for patients with suspected LVO (LAMS ≥4) the probability of good outcome for the mothership and MSU scenarios were generated. Good outcome was defined using a sliding dichotomy, where for LVO patients it was defined as mRS 0-2 as 90 days, and for non-LVO patients it was defined as mRS 0-1. Data from the HERMES collaboration was used for EVT patients, data from the Emberson meta-analysis (extrapolated to the HERMES population for LVO) was used for alteplase treated patients. Probability of good outcome for intracranial hemorrhage and stroke mimics was considered time invariant.

Results:
The results are visualized in a small metropolitan area with one CSC and one MSU which is housed at the CSC. In the area immediately surrounding the CSC both the MSU and mothership methods predict equivalent outcomes, however moving further away from the CSC mothership predicts better outcomes due to the additional travel time for the MSU. If the MSU does not lead to time savings when the patient arrives at the CSC this mothership area is expanded.

Conclusions:
From a patient outcomes perspective in a system where a single MSU is housed at a single CSC there are no area where the MSU shows benefit over the mothership approach. In the area where both models predict equivalent outcomes the individual environment and cost-effectiveness must be taken into context when deciding the best transport strategy.
Abstract TMP83: Drip and Ship vs. Mothership: The Effect of Large Vessel Occlusion Screening Tools on Conditional Probability Modelling
Authors: Holodinsky Jessalyn K , Williamson Tyler S , Demchuk Andrew M , Zhao Henry , Zhu Luke , Malik Fizzah , Goyal Mayank , Hill Michael D , Kamal Noreen
Published: October 2018

Introduction:
Ischemic stroke with large vessel occlusion (LVO) cannot be definitively diagnosed without imaging. Clinical screening tools to help identify LVO in the field have variable positive predictive value (PPV). The accuracy and PPV of a clinical screen tool for LVO impacts transport decisions.

Methods:
Using conditional probability modelling, we estimated the effect of screening tool diagnostic properties for LVO. The PPV of various screening tools (generated from a prospective study of suspected stroke patients), including two hypothetical scales with PPVs of 60% and 75% respectively, were combined with the efficacy decay of alteplase and EVT over time to predict the probability of good outcome (mRS 0 - 1 at 90 days) for the drip and ship [alteplase at a Primary Stroke Centre (PSC) and then transfer to a Comprehensive Stroke Centre (CSC) for endovascular therapy (EVT)] and mothership (bypassing the PSC in pursuit of EVT at a CSC) transport strategies.

Results:
The results are shown in the Figure. As the PPV of the tool increases, the areas where mothership predicts the best outcome increases. At longer treatment times at the PSC the drip and ship area also decreases as PPV increases. The absolute probability of good outcome also decreases as PPV increases because more LVO strokes, with inherently poorer outcomes than most false positives, are identified.

Conclusions:
The PPV of the screening tool greatly impacts transport decision making. Due to the efficacy of efficacy of EVT for LVO stroke as PPV increases so does the area where mothership predicts the greatest probability of good outcome.
Abstract TMP84: Substantial Rise in tPA Utilization for Acute Ischemic Stroke in the United States Corresponds with Significant Improvement in Outcomes
Authors: Lunagariya Abhishek , Patel Achint , Dalal Shaman , Jani Vishal , Nagaraja Nandakumar , Huisa Branko , Hemmen Thomas , Ovbiagele Bruce , Patel Urvish
Published: October 2018

Background:
Tissue plasminogen activator (tPA) is known to improve outcomes in Acute Ischemic stroke (AIS). Earlier studies showed low tPA utilization rates (1-4%) in AIS, ~6% hemorrhagic conversion (HC) with tPA and ~50% mortality in those who had HC. Results from interval studies and enhanced stroke systems of care have likely led to higher tPA utilization in recent times.

Objective:
To assess real-world trends in tPA utilization in AIS, and corresponding clinical outcomes in the United States.

Methods:
Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample database was reviewed from 2002 to 2014. Hospitalizations with AIS were identified using ICD-9-CM codes 433.xx-436, tPA use by procedure code 99.10 and post tPA and HC with ICD-9 431 as secondary diagnosis. Cochran Armitage trend test and survey logistic regression procedure were used to analyze trends and outcomes.

Results:
Of 5,577,707 hospitalizations with diagnosis of AIS, 264,643 (4.74%) received tPA. There is an ~950% increase in tPA utilization in AIS from 2002 to 2014 (Table). In-patient mortality in tPA group has been reduced by ~50%, with 35% increase in discharge to home. There was an ~80% increase in hemorrhagic conversion in tPA group (5.15% to 9.47%; p<0.001). Although HC increased, there was a ~60% decrease in in-patient mortality and ~60% increase in discharge to home among HC.

Conclusions:
Over the last decade, there was a substantial increase in tPA utilization for AIS in the United States. HC remains a major concern, however outcomes in those with HC were remarkably better than perceived earlier. Though enhanced stroke systems of care may be a confounding factor, decreased mortality and improved functional outcomes should drive the treating physicians to be aggressive with tPA utilization in AIS.
Abstract TMP95: A Role for Gut Dysbiosis in the Progression of Cerebral Small Vessel Disease
Authors: Bryan Robert M , Nelson James W , Durgan David J
Published: October 2018

We tested the hypothesis that a pathological imbalance of the gut microbiota, or dysbiosis, contributes to the inflammation that drives the progression of cerebral small vessel disease (CSVD). To test our hypothesis, we used SHRSP rats, a model for hypertension-related CSVD, and their parent strain, WKY. We sought to alter the gut microbiota to affect the onset of CSVD. Given that the gut microbiome is strongly influenced by the nursing mother, we cross-fostered SHRSP and WKY pups with mothers of the same or different strain. All measures, except where noted, were made at 20 weeks. Relative abundance of bacterial genera in fecal samples (representing gut) was analyzed by sequencing the 16S rRNA bacterial gene. When SHRSPs were fostered on WKY mothers, the relative abundance of Akkermansia, a bacterial genus that maintains gut health and reduces GI inflammation, was increased by 107% (P=0.002, N=8/gp). Alternatively, when WKYs were fostered on SHRSP mothers, Akkermansia was decreased by 40% (P<0.05). Thus, the relative abundance of Akkermansia was increased, regardless of strain, when fostered on WKY mothers. Consistent with the relative abundance of Akkermansia, rats fostered on SHRSP mothers showed increased expression of IL-1α and NF-κB1 in the proximal colon regardless of the strain of the pup (P=0.003, N=5/gp). Blood-brain barrier disruption, as measured by IgG extravasation, was increased 2-fold (P<0.001, N=4/gp) in SHRSPs fostered on SHRSP mothers compared to WKYs fostered on WKY mothers. When SHRSPs were fostered on WKY mothers IgG extravasation decreased 31% (P<0.05). Gene expression for NF-κB1, TLR-2, and TLR-4 in brain increased 2.5 to 3 fold in SHRSPs fostered on SHRSP mothers compared to WKYs fostered on WKY mothers (P=0.003, N=5/gp) and was completely normalized when SHRSPs were fostered on WKY mothers. Blood pressure at 16 weeks was increased by ~ 25 mm Hg (P<0.001, N=11/g), regardless of strain, when fostered on SHRSP mothers compared to the same strain fostered on WKY mothers. Although SHRSPs are a genetic model for hypertensive CSVD, our studies demonstrate that gut dysbiosis has a significant contribution to the onset of CSVD. A decrease in the abundance of healthy gut bacteria likely contributes to CSVD onset and progression.
Abstract TMP97: Rho Kinase Inhibition Blunts Lesion Development in Murine Models of Aggressive
Pdcd10/Ccm3
Disease Through Rock2
Authors: Shenkar Robert , Moore Thomas , Lightle Rhonda , Girard Romuald , Hobson Nicholas , Cao Ying , Zeineddine Hussein A , Peiper Amy , Gallione Carol , Marchuk Douglas A , Awad Issam A
Published: October 2018

Introduction:
Previously, murine models

Ccm1
+/-
Msh2
-/-

and

Ccm2
+/-
Trp53
-/-

showed a reduction or no effect on cerebral cavernous malformation (CCM) burden and favorable effects on lesional hemorrhage by RhoA kinase (Rock) inhibitor fasudil and by simvastatin (with weak pleiotropic Rock inhibition effect). Herein we investigated treatment of the more aggressive
Ccm3/Pdcd10
model with these drugs, and higher dose and intensity atorvastatin, and determined which Rock isoform is involved in CCM development and hemorrhage.

Hypothesis:
Rock inhibition blocks CCM burden in
Ccm3
models, through Rock1 or Rock2 isoforms.

Methods:
The murine model

Ccm3
+/-
Trp53
-/-

was concurrently treated from weaning to 5 months of age with fasudil (100 mg/kg/day in drinking water, n=7), simvastatin (40 mg/kg/day in chow, n=8), atorvastatin (80 mg/kg/day in chow, n=7) or with placebo (n=10). We assessed CCM volume in mouse brains by micro-computed tomography. We then concurrently bred

Rock1
+/+

(n=15) and

Rock1
+/-

(n=17),

Rock2
+/+

(n=17) and

Rock2
+/-

(n=15) mice with

Ccm3
+/-

mice and assessed respective lesion burden. We further analyzed chronic hemorrhage in CCM lesions by intensity of Perl staining in brain sections.

Results:
In the

Ccm3
+/-
Trp53
-/-

model, mean CCM lesion volume/brain volume (X 10
3
) per mouse decreased from 12.2 in placebos to 2.5 (p=0.002) by fasudil, and to 3.0 (p=0.002) by atorvastatin treatment, but was not changed significantly by simvastatin. CCM lesion volume/brain volume (x 10
6
) per mouse decreased from 19.6 in

Ccm3
+/-
Rock2
+/+

to 2.3 (p=0.011) in

Ccm3
+/-
Rock2
+/-

animals, and not significantly in

Ccm3
+/-
Rock1
+/

mice. Hemorrhage intensity per brain was commensurately decreased by
Rock
2 but not
Rock1
transheterozygocity.

Conclusion:
CCM lesion development was inhibited by fasudil and atorvastatin but not lower dose and intensity simvastatin therapy. The benefit of Rock inhibition on lesion development and blunting of hemorrhage resulted from effects through Rock2, predominantly expressed in heart and brain, but not Rock1 isoform.
Abstract TP10: Endovascular Treatment for Acute Ischemic Stroke With Intracranial Atherosclerotic Occlusive Disease
Authors: Ueda Toshihiro , Takada Tatsuro , Takaishi Satoshi , Fukano Takayuki , Tokuyama Yoshiaki , Tatsuno Kentaro , Hamada Yuki
Published: October 2018

Background:
Treatment strategy for acute ischemic stroke with intracranial atherosclerotic disease remains unknown. The aims are to evaluate whether revascularization rates, procedural complications, functional outcomes in patients with emergent endovascular treatment for intracranial atherosclerotic occlusive disease.

Methods:
A retrospective review of emergent endovascular treatment from 2003 to 2016 was carried out for acute ischemic stroke patients who had intracranial atherosclerotic occlusion or severe stenosis. Patients were underwent endovascular treatment which included intra-arterial thrombolysis, balloon angioplasty and stenting. Intracranial atherosclerotic disease was defined as significant focal stenosis at the occlusion site, which was evident on final angiographic assessment or observed during endovascular treatment.

Results:
A total of 58 consecutive patients were identified. Forty-five were male (78%) and the mean age was 68 years. Atherosclerotic arteries were 24 in middle cerebral artery, 8 in internal carotid artery, 22 in basilar artery, and 4 in vertebral artery. Successful recanalization (TICI 2b and 3) was observed in 45 patients (78%). Intra-arterial thrombolysis, balloon angioplasty without stenting, and balloon angioplasty with stenting by coronary stents were performed in 31 patients (53%), in 45 patients (78%), and in 19 patients (33%), respectively. Acute in-stent thrombosis was observed in 4 patients. Stent retriever and Penumbra system were used in 5 patients and 9 patients, respectively. The postprocedural hemorrhagic complication was observed in 5 patients (8.6%). The incidence of good outcome (90-day modified Rankin scale ≤2) were 68% in anterior circulation and 38% in posterior circulation.

Conclusion:
Our data suggest that emergent endovascular treatment for patients with intracranial atherosclerotic occlusive disease is safe and feasible. Particularly, balloon angioplasty with or without stenting have a high rate of recanalization and favorable outcome.
Abstract TP102: Delayed Interleukin-1 alpha Treatment is Profoundly Neuroreparative in Experimental Ischemic Stroke
Authors: Salmeron Kathleen E , Edwards Danielle N , Wong Raymond , Roberts Jill M , Pinteaux Emmanuel , Bix Gregory J
Published: October 2018

Despite recent advancements in blood vessel recanalization, ischemic stroke remains a leading cause of significant morbidity. Therefore, new stroke therapies are urgently needed, but have thus far failed in clinical trials despite promising animal data. Studies in our lab have suggested that proteolytic fragments of the extracellular matrix heparan sulfate proteoglycan perlecan are neuroprotective and neuroreparative in experimental ischemic stroke. Further studies have suggested that one such fragment, perlecan LG3, is generated by multiple cells of the neurovascular unit in response to the pro-inflammatory cytokine, interleukin-1alpha (IL-1α). Long thought to be deleterious to the brain after stroke, we now provide data that suggests that IL-1α is neuroreparative upon delayed intravenous administration in experimental ischemic stroke. Coupled with other work in our lab that suggests that acute post-stroke IL-1α administration is neuroprotective, we here aim to show that IL-1α is also an attractive therapeutic target in later phases of stroke. 3-month-old C57Bl6 mice underwent transient middle cerebral artery occlusion for one hour and received either vehicle or IL-1α treatment (1ng/mouse) intravenously 3 days following experimental stroke. For up to 14 days after stroke, all groups were evaluated on an 11 point neuroscore. Mice were sacrificed 7 or 14 days post stroke and their brains analyzed for cellular dysmorphia, endothelial cell activation, overall cerebral vascularization, and evidence of neurogenesis at the subventricular zone (SVZ). IL-1α treated mice have less brain dysmorphia (p > 0.0001), greater overall vascularization (p > 0.05), a trending increase in neurogenesis at the SVZ, and significantly improved behavioral outcomes. Collectively, our results suggest that IL-1α could represent an unexpected and novel therapeutic approach for ischemic stroke with a broad therapeutic window.
Abstract TP105: Knocking Down Cofilin Expression Prevents Hemorrhagic Stroke Induced Microglial Activation and Inflammation
Authors: Shah Zahoor , Alhadidi Qasim
Published: October 2018

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high mortality and morbidity. It is more severe than ischemic stroke and half of the patients die during the first month following the attack. The pathogenesis of ICH injury is complex and it involves primary insult triggered by hematoma mass effect and secondary insult triggered by brain tissue response to hematoma constituents. Cofilin, a ubiquitous actin associated protein, was found to be involved in many neurodegenerative diseases. Disruption of cofilin dynamics leads to cofilin-actin rod formation in different cellular compartments initiating neuronal cell death and apoptosis. In the present study, nanoparticle delivery of small interfering RNA (siRNA) to silence cofilin and investigate its effects using
in vitro
and
in vivo
models of inflammation. In primary cortical neurons subjected to oxygen and glucose deprivation, an ischemia model, cofilin was found to be highly activated and resulted in neuronal apoptosis, which was significantly inhibited by cofilin knockdown using siRNA. In microglia, cofilin knockdown significantly inhibited LPS-induced microglial cell activation through antagonizing NF-κB and JAK-STAT pathways. The release of proinflammatory mediators, microglial proliferation and microglial migration rates were significantly reduced by cofilin knockdown. In collagenase-induced ICH in mice, cofilin expression and phosphorylation was found to be significantly upregulated in the perihematomal area. Importantly, cofilin knockdown by using cofilin siRNA significantly reduced the volume of injury and improved the neurobehavioral deficits via combating oxidative/nitrosative stress and modulating neuroinflammation. In conclusion, targeting cofilin activity in diseases involving inflammation could become a novel therapeutic drug intervention.
Abstract TP106: Sex Differences After Mesenchymal Stem Cell Treatment on Post-Stroke Neurological Outcome
Authors: Nalamolu Koteswara Rao , Chelluboina Bharath , Klopfenstein Jeffrey D. , Pinson David M. , Wang David Z. , Veeravalli Krishna Kumar
Published: October 2018

Introduction:
A major problem exists in stroke management because of the sex differences in frequency and severity of disease and in treatment outcomes. Our recent studies demonstrated the potential of human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) in attenuating the post-stroke brain damage.

Methods:
Sprague-Dawley rats of both sexes were obtained and randomly assigned to various groups. Rats were subjected to a two-hour middle cerebral artery occlusion (MCAO) procedure by inserting a silicone rubber-coated monofilament suture followed by fourteen days of reperfusion. The body weight of rats on the day of the MCAO procedure and the size of the monofilament for male and female rats were standardized to obtain the same depth of post-stroke infarction. Previously standardized effective dose (0.25 million cells/animal) of HUCB-MSCs were intravenously injected via tail vein 24 hours post-MCAO to the designated groups of rats. Rats were subjected to neurological evaluation at various reperfusion time points by modified neurological severity scores (
mNSS), modified adhesive removal (
sticky-tape) beam walking and accelerating Rotarod performance tests.

Results:
The fourteen-day post-stroke survival period in males and females is approximately 20% and 70%, respectively. Females are more resistant to stroke-induced mortality. Although the difference in post-stroke percent survival is prominent in both sexes, there was no change in the body weight gain of both sexes. It was evident from the mNSS and sticky-tape tests that the magnitude of natural neurological recovery is the same in both sexes. However, the improvement in coordination and integration of motor function in females is better than males as evidenced by other tests. Stem cell treatment prevented mortality in males without any change in the treatment-induced body weight gain. Further, stem cell treatment improved neurological recovery in males, and the coordination and integration of motor function in females.

Conclusions:
Sex differences exist in post-stroke mortality and neurological function. Stem cell treatment improved neurological recovery and there was no sex difference in the magnitude of stem cell treatment improved neurological function