bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract WP197: Autonomic Nervous System Parameters to Predict the Occurrence of Ischemic Events After Transient Ischemic Attack or Minor Stroke
Authors: Guan Ling , Collet Jean-paul , Mazowita Garey , Claydon Victoria , Brant Rollin
Published: October 2018

Background:
Stress response is tightly regulated by the autonomic nervous system (ANS) which can be measured by heart rate variability (HRV). Traditional risk factors and acute triggers for ischemic stroke and transient ischemic attack (TIA) are considered as chronic and acute stressors, respectively. These risk factors all contribute to the recurrent ischemic events and are related to ANS dysfunction. The moderate predictive value of ABCD2 score may be due to assessing a limited number of stressors.

Aims, Objectives and Hypotheses:
We proposed to 1) assess whether HRV parameters, as markers of ANS function and stress, can predict secondary ischemic events after TIA or minor stroke, and 2) compare the HRV-based predictive tools with ABCD2 score. We expected that using HRV indicators can enhance the prediction of ischemic events.

Methods:
This is a prospective observational study. Patients developed TIA or minor stroke within 48 hours were eligible. The main study variables included: ABCD2 score, HRV assessment from 24-hour Holter recording, and psychological stress. HRV measurement included calculations of both absolute values and changes of HRV frequency-domain parameters: high frequency (HF), normalized HF, HF +low frequency, and total power. Patients were followed for 90 days to assess the development of outcome events. Logistic regression was employed for data analyses. Area under the curve (AUC) and diagnostic tests were used to assess models’ predictive power.

Results:
Final analyses include data collected from 201 patients. The most useful HRV predictors were Daytime HF changes (AUC=0.70) and Morning HF value (AUC=0.61). AUCs for the Best Stress Model and the Most Practical Model were 0.82 and 0.76, respectively, which were significantly higher than AUC of ABCD2 score (AUC=0.63), p <0.05. The optimal cut-off points for Daytime HF changes and Morning HF might be increase of 12.5% and 50 ms
2
, respectively. The exploratory models that involved both values and changes of HF had AUCs ≥0.82.

Conclusions:
Assessing the effects of stress on ANS may be an innovative way to stratify the risk of TIA or minor stroke. Models using HRV parameters, especially HF, provide superior predictive values to ABCD2 score. Future research is needed to validate these results.
Abstract WP202: A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring After Embolic Stroke of Unknown Source
Authors: Ricci Brittany A , Chang Andrew D , Hemendinger Morgan , Dakay Katarina , Cutting Shawna M , Burton Tina , MacGrory Brian , Narwal Priya , Panda Nikhil , Chu Antony , McTaggart Ryan , Jayaraman Mahesh , Furie Karen , Yaghi Shadi
Published: October 2018

Background:
Occult paroxysmal atrial fibrillation (AF) is detected in up to 30% of patients with Embolic Stroke of Unknown Source (ESUS). We aim to identify predictors of AF on outpatient cardiac monitoring in patients with ESUS.

Methods:
We included ischemic stroke patients with ESUS subtype between January 1
st
, 2013 and December 31 1st, 2016 who underwent an inpatient diagnostic evaluation, including 24 hour telemetry, followed by outpatient cardiac monitoring with 30-day cardiac monitors and/or implantable cardiac monitor (ICM). Patients were divided into two groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, NIHSS, and cardiac biomarkers (left atrial enlargement on echocardiography, PR interval on ECG) between the two groups. Multivariable models were used to identify independent predictors of AF and to develop an AF prediction-risk scoring system.

Results:
We identified 296 consecutive patients during the study period; 38 (12.8%) demonstrated previously undetected AF on outpatient cardiac monitoring. Compared to non-AF patients, AF patients were older (72.0 ± 11.0 vs. 62.7 ± 14.9; p <0.001), less likely to be current smokers (10.5% vs. 27.2%, p = 0.027), had lower NIHSS (3, IQR 1-7 vs. 3, IQR 1-5; p=0.002), and larger left atrial diameter in mm (39.3 ± 6.0 vs. 35.2 ± 6.4; p=0.001). In multivariable regression analysis, advanced age (ages 65-74: odds ratio 2.36, 95% confidence interval 0.85-6.52; ages ≥75: odds ratio 4.08, 95% confidence interval 1.58-10.52) and moderate-to-severe LAE (odds ratio 4.66, 95% confidence interval 1.79-12.12) were predictive of AF detection on outpatient monitoring. NIHSS, current smoking status, and mild LAE did not contribute significantly to AF prediction. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, ≥ 75 years: 2 points) and left atrial enlargement (moderate/severe: 2 points) with good prediction of AF (AUC 0.725). The percentage of patients in each score category were: 0: 4.2%, 1: 14.8%, 2: 20.8%, 3: 22.2%, 4: 55.6%.

Conclusion:
In this large sample of patients with ESUS, the Brown ESUS-AF score predicts AF detection on prolonged outpatient monitoring. More studies are needed to externally validate our findings.
Abstract WP204: The Advantage of the Routine: Using Conventional Transthoracic Echocardiography in Establishment of Stroke Mechanism
Authors: Johansen Michelle C , Williams Nicole L , Gottesman Rebecca
Published: October 2018

Introduction:
Cardioembolic (CE) stroke is the most devastating type of ischemic stroke. Prior research has focused on choice of monitoring for occult tachyarrhythmia, but earlier identification of cardiac anatomical dysfunction, utilizing routine transthoracic echocardiogram (TTE), may expedite appropriate management.

Methods:
All inpatients admitted to Johns Hopkins Hospital from 7/1/13-7/1/15 with imaging-confirmed ischemic stroke with a TTE within 7 days of admission were included. TTE reports were reviewed for structural features as well as systolic/diastolic function. Stroke subtype (CE vs. other) was defined using TOAST criteria, blinded to echo data. CE stroke was the outcome of interest using multivariable logistic regression to test the association with TTE structural measurements after adjusting for potential confounders.

Results:
443 patients met inclusion criteria. CE strokes (N=123) did not significantly differ from other stroke subtypes by age/gender but did by race (black 46% v 57%) and stroke severity (NIHSS≈8 v 5). In adjusted models, odds of CE significantly increased with increasing left atrial systolic diameter, Mitral E point velocity, decreasing ejection fraction, absence of mitral annular calcification and presence of mitral valve dysfunction or wall motion abnormality (
Table 1
).

Conclusions:
Further understanding the relationship between TTE markers of cardiac structure and function and stroke subtype could potentially impact clinical practice, as TTE data are currently underused in the consideration of stroke mechanism and management. Confirmation of the reported associations, using more advanced imaging techniques, would enable more meaningful interpretation of these parameters, thereby leading to early initiation of medical management (anticoagulation) or further workup (event monitors).
Abstract WP208: Elevated Troponin Levels in Ischemic Stroke is Independently Associated With Cardioembolism
Authors: Yaghi Shadi , Chang Andrew D , Ricci Brittany A , Jayaraman Mahesh V , McTaggart Ryan A , Hemendinger Morgan , Narwal Priya , Dakay Katarina , Mac Grory Brian , Cutting Shawna M , Burton Tina , Song Christopher , Mehanna Emile , Siket Matthew S , Madsen Tracy , Reznik Michael , Merkler Alexander , Lerario Michael P , Kamel Hooman , Elkind Mitchell S , Furie Karen L
Published: October 2018

Background:
Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk in the general population. In the acute stroke setting, we hypothesize that elevated troponin levels are more prevalent in patients with embolic stroke subtypes [cardioembolic (CE) and embolic stroke of unknown source (ESUS)] as opposed to known non cardioembolic subtypes (NE) (large vessel disease, small vessel disease, and other).

Methods:
We abstracted data from our prospective stroke database and included all patients with ischemic stroke over a 22 month period. We defined positive troponin as ≥ 0.1 ng/mL. Patients diagnosed with acute myocardial infarction were excluded (n = 3).We compared clinical, laboratory and echocardiographic findings, and stroke subtypes using ESUS criteria between the two groups: Troponin+ and Troponin-.

Results:
We identified 1231 patients; 1129 had troponin levels available and 10.0% (113/1129) were trop+. On univariate analyses, Troponin+ patients were more likely to be older (77.4 ± 12.6 vs. 70.8 ± 15.0, p<0.001), have hypertension (85.8% vs. 74.2%, p=0.003), coronary heart disease (31.3% vs. 20.1%, p=0.003), congestive heart failure (20.9% vs. 9.5%,p<0.001), smoking (42.5% vs. 26.4%, p<0.001), and atrial fibrillation (42.5% vs. 26.4%, p<0.001), higher admission NIHSS (14 vs. 6, p<0.001), eGFR < 60 (53.7% vs. 33.4%), larger left atrial diameter (40.9 ± 8.8 vs.37.1 ± 7.6, P<0.001), lower ejection fraction (60 vs. 65, p<0.001), and wall motion abnormalities (26.1% vs. 11.5%, p<0.001) compared troponin- patients. When compared to NE subtype, troponin+ patients were more likely to have CE (79.0% vs. 52.4%, p<0.001) and ESUS (75.0% vs. 58.9%, p=0.001) subtypes. In multivariable models, factors associated with troponin+ are NIHSS (adjusted OR per 1 unit increase1.05, 95% 1.02-1.08; p<0.001), eGFR < 60 (adjusted OR 2.41 95% CI 1.40-4.13; p=0.001), CE subtype (adjusted OR 3.37 95% CI 1.35-8.43,p=0.009), and ESUS subtype (adjusted OR 2.77 95% CI 1.15-6.66,p=0.023).

Conclusion:
Elevated troponin levels in ischemic stroke is independently associated with a cardiac embolic source. Studies are needed to test anticoagulation vs. antiplatelet in patients with ESUS and elevated troponin.
Abstract WP210: Patterns and Predictors of Stroke Subtypes in Patients With LVAD: Single Center Analysis
Authors: Vaddiparti Aparna , Staff Ilene , Gluck Jason , Nouh Amre
Published: October 2018

Background:
Left ventricular assist devices (LVAD) have emerged as the mainstay in advanced heart failure patients either as a bridge to transplant (BTT) or destination therapy (DT). Strokes, ischemic from pump thrombosis and hemorrhagic from combination of anti-platelets and anti-coagulants, remain a major cause of morbidity and mortality.

Objective:
To identify the prevalence, timing and risk factors of ischemic and hemorrhagic in LVAD patients

Methods:
A retrospective analysis of all the LVAD implantations at HH from July 2012 to December 2016 comprising a total of 78 patients with 63 HMII (axial flow) and 15 Heartware (centrifugal flow) implantations to serve as DT in 51 and BTT in 37 patients. Demographics and clinical variables were collected and analyzed. Categorical variables were analyzed using Chi-square test of proportions with statistical significance set at 0.05.

Results:
For all patients the median age was 65 years, 82% Caucasian and 16% female. The overall stroke incidence was 27% (n=21, 16 ischemic in 12 patients and 9 hemorrhagic in 9). Age > 65 years had a higher incidence of stroke (36% vs 14%; p <0.05). Mean time from implantation to ischemic and hemorrhagic strokes were 205 and 98 days respectively, with high peri-operative (35 days post implant) risk at 33% for both cohorts. At least two arterial territories were involved in 45% (n=5) and multi-compartmental hemorrhage noted in 66% (n=6). LVADs as DT had a higher incidence of ischemic stroke (24% vs 6% as BTT; P=0.05). Non-Caucasians had a higher incidence of hemorrhagic stroke (55% vs 20% with p = <0.05). The median INR was 1.7 and 2.8 while the median mean arterial pressures was 75 and 84 in the ischemic and hemorrhagic strokes respectively (p <0.05). Age, gender, history of A.fib, HTN, PAD, or aspirin dosage did not predict risk of stroke. Mortality from stroke was 33% (n =4) with ischemic and 66% (n = 6) with hemorrhagic strokes, with a total risk of 47% compared to 17.5% in the non-stroke LVAD population(p = 0.005).

Conclusion:
In our study, 1/3 of strokes occurred in the perioperative period with high risk after age 65 years. Non-Caucasians, high mean arterial pressure and high INR were associated with hemorrhagic stroke. Further studies are needed to evaluate modifiable risk factors among LVAD patients.
Abstract WP214: Serum Claudin-5, a Potential Biomarker Reflecting Blood-Brain Barrier Dysfunction in Acute/Subacute Cerebral Venous Thrombosis With Venous Infarct
Authors: Duan Jian Gang , Han Ziping , Cai Yanning , Song Haiqing , Ovbiagele Bruce , Feng Wuwei , Ji Xunming
Published: October 2018

Objective:
To evaluate whether claudin-5, occludin and MMP-9 proteins in serum and cerebrospinal fluid(CSF) reflect blood-brain barrier(BBB) dysfunction in cerebral venous thrombosis(CVT) with venous infarct.

Methods:
It is a prospective observational study. Blood and CSF samples were obtained from CVT patients in acute, subacute and chronic stages respectively. 7 healthy subjects without central nervous system disease were included as control group. Serum and CSF Claudin-5, occludin and MMP-9 were measured using ELISA kits. Values of continuous variables are presented as mean ± SD and compared with ANOVA.

Results:
Between Jul 2015 to Dec 2016, 52 CVT patients(age: 35.9±14.1 years; female:53.9%) were enrolled. 43 patients were at acute/ subacute stage(30 had venous infarct, while 13 did not have). 9 patients were at chronic stage. CSF occludin and MMP-9 were not detectable in most of the subjects. Serum occludin and MMP-9 were similarly expressed in all four groups. The value of CSF Claudin-5 was 257.1±44.1pg/ml for the control group, 458±223.6pg/ml for chronic CVT patients, 593.1±262.7pg/ml for acute/subacute CVT patients with venous infarct, and 529.1±334.6pg/ml for acute/subacute CVT patients without venous infarct. Compared with the control subjects, CSF Claudin-5 significantly increased in acute/subacute CVT patients with and without venous infarct(p=0.003, p=0.031, respectively). The values of CSF claudin-5 between acute/subacute CVT patients with and without venous infarct were similar (p=0.464). The value of serum Claudin-5 was 1760.6±374.2pg /ml for control subjects, 3150.7±1197.6pg/ml for acute/subacute CVT patients with venous infarct, and 2411.6±565.2pg/ml for acute/subacute CVT patients without venous infarct. Compared with control subjects, serum Claudin-5 significantly increased only in acute/subacute CVT patients with venous infarct(p=0.001), which had also significantly higher value than without venous infarct(p=0.025).

Conclusions:
Serum claudin-5 might reflect disruption of BBB in acute/subacute CVT patients with venous infarct. In future, larger cohorts are warranted to precisely evaluate cutoff value of serum claudin-5 in reflecting BBB dysfunction in acute/subacte CVT patients with venous infarct.
Abstract WP215: Geospatial Visualization of Mobile Stroke Unit Dispatches: A Method to Optimize Service Performance
Authors: Rhudy James P , Alexandrov Anne W , Rike Joseph , Bryndziar Tomas , Hossein Zadeh Maleki Ana , Swatzell Victoria , Dusenbury Wendy , Metter E. Jeffrey , Alexandrov Andrei V
Published: October 2018

Background:
Understanding geospatial regional stroke burden and emergency medical services (EMS) response locations may benefit attainment and distribution of prehospital resources, enabling rapid diagnosis and treatment. We sought to understand the spatial distribution of all Mobile Stroke Unit (MSU) dispatches and diagnosed strokes during the first year of operation.

Methods:
All MSU dispatched cases from July 2016 to July 2017 were assembled and aggregated into groups based on stroke diagnosis status. The raw count of incidents was aggregated by zip code, normalized to population, and geocoded. The resulting incidence rate was symbolized by standard deviation and mapped by zip code for inspection. Five- and ten-minute drive time service areas were defined around our MSU base.

Results:
A total of 420 dispatches for suspected stroke occurred, of which 394 were able to be geocoded. On the initial analysis of all 394 cases, a five-minute service area was sufficient to rapidly reach areas with high rates of suspected stroke burden (> 1.5 SD) (figure 1). However, repeating the analysis on 123 cases diagnosed as
true strokes
redefined the areas that were strongly positive for high stroke burden requiring a ten-minute service area from our MSU base (figure 2).

Conclusions:
Use of geospatial findings helps plan EMS and MSU dispatch to high burden regional pockets of stroke, and may assist in improving dispatch scripting for 911 calls.
Abstract WP219: Decision Analysis Tool for Prehospital Stroke Triage in the Era of Endovascular Therapy
Authors: Vora Nirali , Jung Jongbin , Govindarajan Prasanthi
Published: October 2018

Introduction:
With the undisputed benefit of acute endovascular therapy and anticipated extended treatment window among select stroke patients, there is an urgent and unmet need for a regional prehospital decision-making tool to triage patients to centers with endovascular therapy). Existing tools with severity-based triage do not capture important regional variation.

Objectives:
To create a model to guide prehospital triage of suspected acute stroke patients.

Methods:
We designed a model to estimate the probability of a favorable functional outcome at 90 days when a patient receives acute stroke therapy with either IV thrombolysis (modified Rankin Scale 0-1) or endovascular therapy (modified Rankin Scale 0-2) at stratified time thresholds. We used published pooled patient-level outcomes data with region-specific variables including distribution of door to needle, door to groin, and estimated travel times, as well as time last normal. We created an online tool based on the model for easy use by emergency medical services and other stakeholders in acute stroke care to choose the triage destination with the highest estimated probability of the desired outcome.

Results:
Figure 1 illustrates the basic structure of the decision tool from which optimal transportation decisions can be found by applying region specific time data (top) and presents an example plot using hypothetical variables where the model estimates a 36% likelihood of a favorable outcome in a patient who is 75% likely to be eligible for endovascular therapy if triaged to either a primary or comprehensive stroke center (bottom).

Conclusions:
This novel decision analysis tool demonstrates that region-specific triage algorithms can be designed for acute stroke care. Future objectives are to validate this decision model in multiple stroke systems. The tool may help guide regional policy decisions on when to bypass a hospital capable of IV thrombolysis for one capable of endovascular therapy.
Abstract WP224: Hispanics are Transported With Slower and Less Capable Ambulances During Inter-Hospital Transfer: A Threat to Fairness in the Era of Thrombectomy
Authors: Vaughan Sarrazin MAry S , Samaniego Edgar , Guerrero Waldo , Alkasab Sami , Sheharyar Ali , Limaye Kaustubh , Ortega Santiago , Rossen James , Hasan David , Leira Enrique
Published: October 2018

Background & Purpose:
In the mechanical thrombectomy (MT) era, it is imperative to ensure that patients with stroke have a fair access to advanced ground ambulances (AGA) or the more rapid Helicopter Emergency Medical Services (HEMS) to avoid disparities in functional outcomes. In this study we investigated racial/ethnic disparities in the use of AGA or HEMS for inter-hospital transfer of stroke patients in the US.

Methods:
We used Medicare claims for years 2010-2013 for Medicare beneficiaries with a new diagnosis of atrial fibrillation. Cases were patients with a primary diagnosis of ischemic or hemorrhagic stroke that underwent an inter-hospital transfer between acute facilities within the day of the stroke. Transportation was categorized as basic ground, AGA or HEMS. A multinomial logit model was used to adjust for confounders such as patient’s characteristics, distance and geographical location.

Results:
A total of 11,172 acute hospital to hospital transfers were analyzed. In unadjusted analysis, 17.7% of black, 20.9% of Hispanic and 21.7% of white patients were transferred by HEMS, and 73.7% of black, 67.3% of Hispanic and 69.9% of white patients were transferred by AGA (p=0.003). These differences, however, disappeared after controlling for confounders. The exception were Hispanic patients, who remain less likely to be transported by HEMS (OR=0.64; 0.45-0.90; p=0.01) or AGA than white patients (OR=0.74; 0.55-1.00; p=0.048)

Conclusion:
Hispanic patients with stroke undergoing an acute inter-facility transfer are less likely to be transported by HEMS or advance ground ambulances after adjusting for all possible confounders, including distance and insurance. This unacceptable disparity is a barrier to timely access to a thrombectomy-capable hospital and best care en-route for these patients, which may result in worse outcomes after MT.
Abstract WP225: Similar Outcomes for Patients Treated With Off-Label vs On-Label Tissue Plasminogen Activator via Telestroke
Authors: Bozorgui Shima , Wu Tzu-Ching , Bambhroliya Arvind B , Malazarte Rene M , Ankrom Christy M , Cossey Tiffany D , Trevino Alyssa D , Savitz Sean I , Jagolino-Cole Amanda L
Published: October 2018

Introduction:
As acute ischemic stroke (AIS) management via Telestroke (TS) increases and the inclusion criteria for tPA expands, it is crucial to evaluate the long term outcomes of patients treated with off-label tPA. Off-label tPA, was defined as treating patients with at least one exclusion criteria, which is either being outside the time window (more than 4.5 hours after last known well time) or having relative contraindications per the AHA 2013 scientific statement for the early management of patients with AIS.

Objective:
To compare outcomes of AIS patients who were treated with off-label tPA to those who were treated with on-label tPA via TS.

Methods:
From 9/2015-12/2016, we identified 424 suspected AIS patients who were treated with tPA in our TS registry of patients who were evaluated by video consultation at one of 17 spoke hospitals. We compared the baseline characteristics and the outcomes of patients who received off-label vs on-label tPA.

Results:
Of 424 suspected AIS patients who were treated with tPA, 86 (20.3%) received off-label tPA. Of 86 patients who received off-label tPA, 60 (69.8%) had relative contraindications and 35 (40.7%) were outside the time window. There was no significant difference between age, gender and race/ethnicity in receiving off-label tPA. Patients with more severe strokes were more likely to receive off-label tPA (p=0.023). The outcome measures including tPA complications, discharge disposition, length of stay and 90-day mRS were not significantly different between off-label and on-label groups after controlling for baseline characteristics.

Conclusion:
Our study suggests that patients evaluated via telestroke with more severe stroke were more likely to receive off-label tPA. There was no significant difference between outcome measures of the off-label and on-label group suggesting that the off-label group does not have more tPA complications or worse outcome.
Abstract WP226: Bypassing Interhospital Transfers for Large Vessel Occlusions in the Era of Mobile Stroke Units
Authors: Patel Payal , Sheikhi Lila , Mullaguri Naresh , Reimer Andrew , George Pravin , Toth Gabor , Hussain Muhammad S , Uchino Ken , Russman Andrew N
Published: October 2018

Introduction:
Mobile stroke units (MSU) provide prehospital intravenous thrombolysis (IVT) for patients with acute ischemic strokes and transport to thrombectomy-capable stroke centers. Door-in-door-out (DIDO) time is recognized as a measure of efficient workflow for interhospital transfer of patients for thrombectomy. We applied this measure to the MSU and compared with our Primary Stroke Center (PSC) transfer process in patients presenting with large vessel occlusions.

Methods:
We identified 50 patients who underwent thrombectomy for large vessel occlusion in a retrospective review. Mode of transport included MSU (n=18), conventional ambulance from PSC to Comprehensive Stroke Center (CSC) (n=19), or directly presenting to a CSC (n=13) in 2016-2017. Measured outcomes included times for PSC DIDO, MSU DIDO (MSU door to scene departure), door-to-CT, door-to-needle (DTN), and door-to-groin.

Results:
Among thrombectomy patients, IVT was more likely to be administered in a MSU (55.6%, n=10), than either a PSC (36.8%, n=7) or CSC (38.5%, n=5). Door-to-CT completed times were significantly lower in the MSU versus PSC (27 vs. 44 minutes, p<0.01). DTN times in MSU were significantly shorter than PSC DTN times (27 vs. 56 minutes, p<0.01), as were the median DTN times between CSC vs. PSC (27 vs. 56 minutes, p=0.09). Median DTN times comparing CSC vs. MSU were the same (27 minutes, p=0.33). DIDO time was reduced for MSU patients compared to PSC patients (27 vs. 87 minutes, p<0.01). Door-to-groin times for MSU patients compared to PSC patients was significantly reduced (97 minutes vs. 171 minutes, p<0.01). Door-to-groin times for CSC patients were comparable to MSU patients (100 minutes vs. 97 minutes, p=0.97).

Conclusion:
Advanced stroke systems of care which include a MSU are highly efficient in both IVT and transport for potential thrombectomy among patients presenting with large vessel occlusion. We introduce a concept of a MSU functioning as a mobile PSC, thus bypassing interhospital transfers.
Abstract WP228: Imaging Findings Associated With Ultra-Early Neurological Deterioration in EMS-Transported Intracerebral Hemorrhage Patients
Authors: Shkirkova Kristina , Vilaisaktipakorn Pitchamol , Villablanca Pablo , Wong Gregory , Weng Julius , Starkman Sidney , Hamilton Scott , Liebeskind David S , Eckstein Marc , Stratton Samuel , Pratt Franklin , Conwit Robin , Sanossian Nerses , Saver Jeffrey L
Published: October 2018

Background:
With the rise of prehospital intervention, intracerebral hemorrhage (ICH) management is increasingly migrating to the field setting. Ultra-early neurologic deterioration (U-END), during prehospital transport and the first minutes after ED arrival, is a novel target for therapy, imaging determinants could provide useful pathophysiologic insights for treatment.

Methods:
We analyzed all ICH patients enrolled in the NIH Phase 3 Field Administration of Stroke Therapy - Magnesium (FAST-MAG) prehospital trial who had both ED-arrival and 6-48h follow-up brain CT or GRE-MRI. Deterioration was defined as worsening by ≥2 on the Glasgow Coma Scale (GCS), performed serially by paramedics in the field, upon ED arrival, and early in the ED course.

Results:
Among 213 ICH patients, age was 65.4 (±13.4) and 33.3% were female. Timing from last know well (LKW) to early serial GCS assessments were: field GCS by paramedic, 23 mins (IQR 14-39); ED arrival GCS, 57 mins (IQR 45-75); and early ED course GCS, 89 mins (IQR 65-107). Initial brain imaging was performed 80 min (IQR 66-98) after LKW, using noncontrast CT in 96%. Overall, 38.5% of ICH patients experienced ultra-early neurological deterioration, including 12.7% in prehospital phase only, 12.2% in early ED course only, and 10.3% in both. Initial imaging findings associated with U-END were: larger hematoma volume 28.3 vs 17.6 cc, p<0.001; larger edema volume 15.4 vs 9.8 cc, p=0.001; moderate-severe midline shift 45.5% vs 6.8%, p<0.001; hematoma irregularity, 53.2% vs 33.0%, p=0.002; hematoma heterogeneity, 63.6% vs 40.8%, p=0.001; and basal ganglia location, 64.9% vs 46.3%, p=0.006. In multivariate analysis, U-END in the prehospital phase was associated with hematoma margin irregularity, OR 1.5 (95%CI 1.1-2.2); while U-END during the early ED course was associated with midline shift, OR 7.2 (95%CI 1.9-26.4) and hematoma margin irregularity, OR 2.3 (95%CI 1.1 - 5.1).

Conclusions:
ICH patients with ultra-early neurological deterioration have larger hematoma and edema volumes on initial brain imaging. Greater hematoma shape irregularity suggests ongoing, multiphasic and multifocal, bleeding is an important, and potentially avertable, contributor to prehospital and early ED course deterioration.
Abstract WP23: Off-Hour Presentation and Outcomes in Patients With Large Vessel Occlusion After Endovascular Therapy: a Matched Case-Control Study
Authors: Bouslama Mehdi , Perez Hilarie , Haussen Diogo C , Grossberg Jonathan A , Barreira Clara M , Belagaje Samir R , Bianchi Nicolas A , Doppelheuer Shannon , Schindler Kiva M , Frankel Michael R , Nogueira Raul G
Published: October 2018

Background:
Patients who are admitted during off-hours (nights and weekends) are thought to have worse outcomes. This might be explained by delayed times to treatment. We sought to determine the effect of off-hour presentation on processes of care and outcomes at a comprehensive stroke center.

Methods:
We reviewed our prospectively collected endovascular database at a tertiary care academic institution between Sep 2010-Dec 2016. All patients that underwent endovascular therapy for large vessel occlusion acute ischemic stroke were included and categorized into two groups: those arriving during regular hours (weekday 7AM-7PM) or off-hours. The 2 groups were then matched for age, baseline NIHSS and glucose levels using a weighted Euclidian distance method. Baseline, procedural, and radiological characteristics, as well as outcome parameters were compared.

Results:
926 (463 pairs) patients were included. Patients presenting off-hours had higher rates of hypertension (78.2% vs 66.7%, p<0.01) and longer median time from last-known normal to picture (273 minutes [167-421] vs 253[145-472], p=0.04). Other baseline characteristics including comorbidities, NIHSS, ASPECT scores, occlusion site were well balanced. There was no difference between groups in picture to puncture median time (57 minutes [38-95] vs 52[36-78], p=0.11) and utilization of CT angiography (p=0.56) or CT perfusion (p=0.82) imaging or IV t-PA use (p= 0.37). Moreover there were no differences between groups in terms of rates of successful reperfusion (mTici 2b-3) (p=0.26), parenchymal hematomas (p=0.12), 90-day good outcomes (mRS 0-2) (p=0.99) or mortality (p=0.52). In multivariate analysis, off-hour presentation was not associated with 90-day good outcome.

Conclusions:
Our study shows that patients presenting off-hours have similar picture to puncture times and clinical outcomes as those presenting during regular hours.
Abstract WP234: Improved Response, Neurologic Evaluation, and Treatment Timing With a Mobile Stroke Unit in a Large Urban Population
Authors: Kowalski Robert G , Vela Duarte Daniel , Schimpf Brandi , Poisson Sharon N , Simpson Jennifer R , Jones William J
Published: October 2018

Background:
The University of Colorado Mobile Stroke Unit (UC MSU) began clinical operation in January 2016, providing ambulance-mounted CT scanning and tele-stroke neurologic assessment in the Denver, CO, metropolitan area. As one of the first U.S. tertiary stroke centers to utilize a mobile stroke protocol we sought to evaluate characteristics of response, neurologic evaluation, and treatment of the MSU.

Methods:
The study assessed patient, stroke, ambulance response, neurologic evaluation, and treatment characteristics of the UC MSU for its initial year in service. Variables included time from stroke alert (MSU dispatch) to brain CT in the field, treatment decision, tPA administration, and transport to a hospital stroke center. Time intervals from last seen normal were calculated for all patients. Study variables were compared for patients treated with thrombolysis on the MSU, and those who were not; and with reported times for other MSUs, and hospitals.

Results:
Between Jan. 15, 2016 and Jan. 9, 2017, 47 individuals received prehospital management with the UC MSU. Median age was 67 years (IQR 58-77), and 51% were female. Median initial NIH Stroke Scale score was 5 (IQR 2-11), and 36% were moderate to severe (NIHSS ≥8). Thirteen (28%) of patients were treated with IV tPA on the MSU. Median times from stroke alert to MSU arrival on the scene and first CT were 7 minutes (IQR 5-8), and 20 minutes (IQR 18-24), respectively. Median time to tPA administration was 39 minutes (IQR 35-45) from stroke alert, and 52 minutes (IQR 48-77) from the last time the patient was seen normal. Times from stroke alert and last seen normal to arrival at a stroke hospital were a median of 51 minutes (IQR 45-54) and 71 minutes (IQR 56-118), respectively.

Conclusions:
In this study of the initial year of an urban MSU’s operation, time intervals from stroke alert to initial brain CT imaging, neurologic evaluation and administration of thrombolysis were found to be substantially reduced compared to conventional, hospital-based stroke protocols, and some earlier MSUs. Intervals from last seen normal to these procedure time points were similarly reduced. These results suggest prehospital management with an MSU has potential to aid the goal of earlier thrombolysis after ischemic stroke symptom onset.
Abstract WP238: Using the Adaptive Learning Model to Reduce Door to-Needle Time in Acute Ischemic Stroke
Authors: Adcock Amelia , Dabir Aman , Pawar Gauri , Alvi Muhammad
Published: October 2018

Introduction:
A significant burden of acute ischemic stroke (AIS) can be decreased by timely administration of tissue plasminogen activator (tPA). Door-to-needle (DTN) time is a nationally reported quality measure for patients with AIS. In a majority of primary and comprehensive stroke centers, acute stroke care is provided by teams comprising of trainees (residents/fellows). Adaptive learning is a well-studied paradigm to improve the quality of medical education. Conceptually, this model consists of four parts starting with planning, and subsequently involving learning, assessing and adjusting. It is a learner driven process.

Hypothesis:
Utilizing the adaptive learning model will reduce DTN time in AIS patients who present to the emergency department of a rural, tertiary care medical center staffed by neurology residents.

Methods:
Successive patients who received IV tPA for AIS in the emergency department of our academic medical center between January 1, 2014 and December 31, 2016 were included in the study. During months 1-18 (pre-intervention) DTN times were not shared with residents. During months 19-36 of study (post-intervention), we utilized our monthly stroke meeting to share DTN times anonymously. Discussions were held and emphasis was placed on the processes which led to shorter DTN times. Residents assessed responses, planned changes, and made adjustments in real time. Descriptive statistics were used to analyze the data.

Results:
A total of 313 patients received IV tPA during the study period (150 pre-intervention, 171 post intervention period). After the implementation of the quality improvement initiative, mean and median DTN time significantly reduced from 54.7 minutes to 43.0 minutes (p<0.0001) and 52 minutes to 39 minutes (p<0.0001) respectively.

Conclusions:
Our study exemplifies the success of the adaptive learning model in the care of patients with acute ischemic stroke. Our quality intervention led to significantly reduced DTN times. Furthermore, this educational initiative provided residents with objective feedback about their performance - one of the requirements of the accredited council of graduate medical education (ACGME).
Abstract WP239: Potential Impact of C-STAT for Prehospital Stroke Triage up to 24 Hours on a Regional Comprehensive Stroke Center
Authors: Adeoye Opeolu , Sucharew Heidi , Broderick Joseph , Katz Brian , Schmit Pamela , McMullan Jason
Published: October 2018

Introduction:
Thrombectomy may be beneficial up to 24 hours since last normal. We previously reported the feasibility of the Cincinnati Stroke Triage Assessment Tool (C-STAT) for prehospital triage. We estimated the potential impact of the expanded thrombectomy time window on overtriage to our comprehensive stroke center (CSC).

Methods:
From June-November, 2015, Cincinnati Fire Department (CFD) providers performed C-STAT after a positive prehospital “FAST: face, arm, speech, time” stroke screen in suspected stroke/TIA patients. Preferential triage was not employed at that time. Final diagnoses and presence/absence of large vessel occlusion (LVO) was ascertained via chart review. Impact on triage volumes by positive C-STAT up to 24 hours from last seen normal was estimated.

Results:
Of 158 patients with prehospital suspicion for stroke/TIA, 105 were FAST positive, within 24 hours of onset, and had complete C-STAT and clinical data available. The Table shows the characteristics of enrolled subjects. Forty six percent (17/37) of C-STAT+ patients were non-strokes. C-STAT sensitivity and specificity for LVO were: 71% (36, 92) and 69% (55, 80). Within six hours of symptom onset, 57% (12/21) of C-STAT+ prehospital suspected stroke patients were not triaged to the CSC. From 6-24 hours, 62% (10/16) C-STAT+ patients were not triaged to the CSC. Overall, preferential triage using C-STAT would increase transport of prehospital suspected stroke cases to the CSC by 11% (12/105) within six hours and 21% (22/105) within 24 hours.

Conclusions:
Within CFD, preferential triage using C-STAT would increase transport of prehospital suspected stroke cases to the CSC by 11% within six hours and an additional 10% within 24 hours. Almost half of prehospital C-STAT+ cases were non-strokes. More stringent criteria for CSC triage (e.g., exclusion of seizure/hypoglycemia) may improve performance. Acceptable overtriage rates for prehospital suspected stroke should be established.
Abstract WP245: Improving EMS Identification of Patients With Large Vessel Occlusion
Authors: Grewal Parneet , Lahoti Sourabh , Aroor Sushanth , Snyder Kaitlin M , Pettigrew L C , Goldstein Larry B
Published: October 2018

Introduction:
The 9- point Rapid Arterial oCclusion Evaluation (RACE) score was developed to aid emergency responders identify patients with stroke related to large vessel occlusion (LVO) for transport to a center for endovascular management. We determined whether the addition of historical features available at the time of EMS evaluation will improve the detection of LVO.

Methods:
We conducted a retrospective medical record review of patients admitted in 2014 to a Comprehensive Stroke Center with a presumed cardioembolic ischemic stroke based on ASCO criteria. Occlusion of a relevant proximal vessel was determined by initial CT or MR angiography. Candidate variables were selected based on univariable comparisons between those with and without an occlusion (p<0.1) and their independent association with LVO identified with multiple logistic regression with backwards selection.

Results:
The sample included 100 patients with LVO and 128 without an occlusion. RACE score (mean 4.64±0.31 vs 2.20±0.21, p=0.007), known atrial fibrillation (AF, 40% vs 23%, p=0.005), no anticoagulation (92% vs 83%, p=0.048), higher blood glucose (mean 150±7 vs 132±5 mg/dL, p=0.001) a history of hypertension (89% vs 81%, p=0.085) or diabetes (47% vs 34%, p=0.053) were associated with LVO in univariable analyses. The risk was particularly high in those with AF who were not anticoagulated (44% vs 16%, p<0.001). In the multiple logistic regression analysis, RACE score (OR 1.30, 95% CI 1.17-1.45), AF (OR 3.25, 95% CI 1.62-6.54), diabetes (OR 2.03, 95% CI 1.08-3.82), and anticoagulant therapy (OR 0.17, 95% CI 0.06-0.48) were independently associated with LVO.

Conclusions:
The inclusion of selected historical features (AF, diabetes, anticoagulation status) will improve the accuracy of the RACE score in the pre-hospital identification of stroke due to LVO who might benefit from acute thrombectomy.
Abstract WP246: Automated Detection of Facial Weakness Using Machine Learning
Authors: Uribe Omar A , McDonald Mark M , Zhuang Yan , Lin Iris L , Arteaga Daniel F , Dalrymple William A , Worrall Bradford B , Rohde Gustavo K , Southerland Andrew M
Published: October 2018

Background:
Early recognition and treatment of stroke improves outcomes. Pre-hospital screening tools offer promise for early detection of acute stroke but have inconsistent performance. An automated screening tool could minimize inter-operator variability and operator error. We hypothesize that machine learning algorithms can assist in the detection of pathologic facial weakness using computational visual analysis.

Methods:
Two senior neurology residents scored images (n = 333) showing normal smile and facial weakness on a 5-point scale. Only images rated concordantly by both raters as likely normal or likely abnormal were included for analysis. Facial landmarks were extracted using an open-source face-detection and landmark localization algorithm. A penalized linear discriminant analysis method was used to process the data with a k-nearest neighbor algorithm as the classifier. We used a 5-fold cross-validation scheme and calculated accuracy, sensitivity, and specificity to evaluate performance.

Results:
Of the 199 images analyzed, 18 images were excluded due to limitations in facial landmark extraction. Of the remaining 181 images, 87 were rated as likely normal and 94 were rated as likely having facial weakness. The algorithm performed with 93.8% accuracy (95% CI [93.4-94.2]), 95.8% sensitivity [95.4-96.2] and 93.8% specificity [93.4-94.2].

Discussion:
In this pilot study, we demonstrate that machine learning algorithms can accurately identify facial weakness in static images. These results support further evaluation of machine learning algorithms in the early detection of acute stroke symptoms. Future research will examine video analysis algorithms in detecting facial weakness and other signs in acute stroke patients.
Abstract WP252: Mechanism of Secondary Thalamic Injury Induced by Focal Cortical Stroke
Authors: Kim Gab Seok , Hong Sung-Ha , Marrelli Sean P.
Published: October 2018

Remote secondary injury in the thalamus has been observed following rodent and human stroke and is associated with poorer recovery. However the mechanisms and resultant molecular changes whereby cortical infarction leads to remote injury in distant regions of brain are not well defined. The present studies utilize a mouse model of permanent distal MCAO (pdMCAO) with delayed secondary thalamic injury. We have measured time dependent molecular and cellular events, focusing on glial activation and neuronal death in the thalamus. These studies provide an important foundation for future studies aimed at reducing secondary brain injury.

Methods:
Cortical infarction by pdMCAO was induced by microcauterization of the distal MCA in male C57BL/6J mice (11-13 wks). Cresyl violet (CV), fluoro-jade C (FJC) and immunochemical staining were performed at 24 hours, 3 days, 1 week, and 2 weeks after stroke (n=5, each time point) and in shams (n=3).

Results:
First, we confirmed with TTC staining that the primary infarction induced by pdMCAO was restricted to the cortex of the MCA territory at 72 hours, and that no infarct was seen in the thalamus. Microglia and astrocyte activation (IBA-1 and GFAP, respectively) was first detectable in the ipsilateral ventral posteromedial nucleus (VPN) of the thalamus at 3 days after stroke, and progressively increased at 1 and 2 weeks. However, thalamic neuronal injury (by FJC staining) was not evident until 1 week after stroke. At 2 weeks following stroke, the number of FJC positive neurons further increased and significant morphological changes were evident by CV staining, including shrunken cytoplasm and condensed pyknotic nuclei.

Conclusions:
We present a mouse stroke model for studying the mechanisms of secondary thalamic injury. In this model, primary cortical injury results in delayed cellular events in the ipsilateral thalamus, including an initial activation of microglia and astrocytes with subsequent neuronal injury and death. These studies provide necessary foundation for designing future interventional strategies aimed at reducing secondary injury following stroke.
Abstract WP253: CaMKII Inhibition Protects Against Purkinje Cell Damage Following Global Cerebral Ischemia
Authors: Patsos Olivia , Chalmers Nicholas , Steklac Katie , Traystman Richard J , Herson Paco S , Quillinan Nidia
Published: October 2018

Introduction:
Ischemic damage triggers glutamate excitotoxicity, resulting in neuronal cell death. Previous research has demonstrated that NMDA receptor activity triggers downstream calcium-dependent signaling pathways, specifically Ca2+/calmodulin-dependent protein kinase II (CaMKII). We hypothesize that Death Associated Protein Kinase I (DAPKI) and receptor interacting protein (RIP) are downstream of CaMKII, contributing to necroptosis. Focal and global ischemia studies have shown that inhibiting CaMKII is protective against hippocampal damage, but there is little known about cerebellar cell death mechanisms. The aim of this study is to examine the neuroprotective potential of inhibiting CaMKII in Purkinje cells using a global ischemia model.

Methods:
C57BL/6 male adult mice were subjected to 8 minutes of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Mice were randomized to tat-CN19o or control peptide (tat-SCR), administered 30 minutes after CA/CPR, and cerebellar injury analyzed 7 days after CA/CPR. Western blot analysis of cerebellar homogenates performed 6 hrs after CA/CPR. Phosphorylated and total CAMKII, DAPKI, and total RIP was quantified. Statistical analyses were performed using 1-WAY ANOVA, with P<0.05 considered significant.

Results:
Analysis of Purkinje cell death revealed injury at 7 days after CA/CPR that was prevented with tat-CN19o at doses of 0.1 and 1 mg/kg. We observed an increase in T286-P of CAMKII at 6 hours after CA/CPR, concurrent with increased DAPK1 activity (reduced phosphorylation) and increased RIP expression. Administration of tat-CN19o prevented CA/CPR-induced changes in DAPK1 and RIP, while having no effect on CAMKII.

Conclusions:
Autonomous activity of CAMKII is increased by ischemia in the cerebellum, which contributes to cell death. Neuroprotection with tat-CN19o occurred at doses 10-fold higher than that needed for protection in the hippocampus (Deng, Cell Reports, 2017). Importantly, we have identified signaling pathways downstream of CAMKII that may contribute to Purkinje cell death, DAPK1 and RIP. In summary, our findings indicate that inhibition of autonomous CaMKII activity is a promising therapeutic approach.