bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract TP390: Tetrad Therapy With Antiplatelets, Antihypertensives, High Intensity Statins and a PCSK9 Inhibitor Reduces Vascular Events in Patients With a History of Stroke
Authors: Ramirez Lucas , Saver Jeffrey L
Published: October 2018

Background:
The mainstay of medical secondary prevention of recurrent vascular events in patients with an index stroke of atherosclerotic origin has been the triad of 1) antiplatelet (AP), 2) antihypertensive (aHTN), and 3) high intensity statin agents. The PCSK9 inhibitors (-i) are a new class of cholesterol reducers. Recently, the FOURIER trial demonstrated that Evolocumab, a PCSK9-i, confers additional benefit in reducing recurrent vascular events. Indices of the degree of this additional benefit would be helpful to patients, physicians, and payers.

Methods:
Vascular event rates were extracted for patients with a history of stroke from the FOURIER database. We compared event rates versus those of established medical therapies.

Results:
Vascular events over 3 years in patients with an index stroke were reduced with a PCSK9-i (7.26%) versus control (8.87%) (RR 0.83,95% CI 0.69-1.0), resulting in a NNT of 62. Risk ratios were comparable to the established triad of medical therapies: antiplatelets (RR 0.83,CI 0.79-0.88), antihypertensives (RR 0.91,CI 0.87-0.96) and high intensity statins (RR 0.81,CI 0.71-0.92). Vascular event rates were lower with each sequential addition of medical intervention (AP 22.1%, AP+aHTN 17.1%, AP+aHTN+Statin 9.01%), down to 7.26% with tetrad therapy (triad therapy plus a PCSK9-i). Standard triad therapy results in a 66% reduction in vascular events while tetrad therapy results in a 73% reduction.

Conclusions:
In patients with an index stroke of atherosclerotic origin, tetrad therapy results in a 73% reduction of vascular events to a 3 year event rate of 7.26%. The magnitude of additional benefit with a PCSK9-i is comparable to established medical therapies and may be considered as part the medical armamentarium for the prevention of recurrent cardiovascular events in this high risk population.
Abstract TP399: Identification of Risk Factors for Warning Bleeds in Patients With Spontaneous Subarachnoid Hemorrhage
Authors: Ramakrishnan Anurekha , Nadasdy Zoltan , Shpak Max , Orndorff Kevin , Fanale Christopher V , Cowperthwaite Matthew C
Published: October 2018

Introduction:
Identification of events preceding subarachnoid hemorrhage (SAH) could allow providers an opportunity to prevent SAH and improve outcomes for patients. Studies have suggested that SAH events are preceded by “warning bleeds” that produce symptoms such as migraines, however the results are contradictory and physicians have no indicators for warning bleeds.

Hypothesis:
We hypothesized that symptoms associated with an imminent SAH can be detected in emergency department (ED) visits preceding an SAH event.

Methods:
We studied 11,308 SAH visits that occurred at HCA hospitals between July 2011 and March 2016. A set of 10,000 ED encounters, matched by demographics (age, gender, race/ethnicity, location), was used as a control cohort. For each encounter, we pulled data for all ED or inpatient (IP) encounters within 30 days before the index SAH event. Data for each encounter include demographics, health history, diagnosis codes, and administered medications. Fisher Exact tests were used to study categorical variables; regression modeling was used to build models to assess patient risk.

Results:
2,046 (18%) of all index SAH events were preceded with at least one ED or IP encounter within 30 days of the index event. 200 (9.8%) of the index SAH visits had a diagnosis of headache (including migraine), versus 2.7% in the controls (O.R. = 3.9; p < 0.01). Additionally, eye disorders, hereditary and degenerative nervous system conditions, coagulation and hemorrhagic disorders, and delirium/dementia/amnesia were all over-represented in the visits preceding SAH event (p < 0.01).

Conclusions:
Prior to SAH events, a proportion of patients present with ED or IP encounters associated with headaches, eye disorders, and dementia. It may be possible to use this information to develop a risk score for patients at imminent risk for an SAH and possibly reduce the incidence SAH.
Abstract TP4: Current Practices and Discharge Outcome of Endovascular Coiling and Clipping Amongst Hemorrhagic Stroke Patients
Authors: Patel Urvish K , Jani Vishal , Lunagariya Abhishek , Lekshminarayanan Anusha , Patel Achint , Tadi Prasanna , Lin Eugene , Chamczuk Andrea J , Patil Arun-Angelo , Zaidat Sam O
Published: October 2018

Background:
20% of strokes are hemorrhagic (HS), with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage each accounting for 10%. Most SAHs are caused by ruptured saccular aneurysms. Therapeutic advances like endovascular coiling (EvC) and clipping have added to the armamentarium for treating this malignant process.

Methods:
Data from Nationwide Inpatient Sample (NIS) (years 2003-2013) was analyzed to identify HS (aSAH and ICH) hospitalization using ICD-9-CM codes. EvC and clipping patients were identified from the cohort. A retrospective analysis with multivariate survey logistic regression was done to evaluate the predictors of utilizations of EvC and clipping.

Results:
From years 2003 to 2013, total 1,004,736 patients with HS were hospitalized. Out of them, 47,999 (4.7%) patients had EvC and 55,900 (5.6%) patients had clipping. Predictors of higher EvC utilization were young 35-50 years patients (aOR: 1.20; 95%CI: 1.04-1.38), large hospitals (>100 beds) (aOR: 4.53; 95%CI: 3.54-5.81), and urban teaching hospitals (aOR: 4.66; 95%CI: 3.63-5.97). Clipping utilization was higher among age 65-80 years patients (aOR: 2.02; 95%CI: 1.73-2.37) and age >80 years (aOR: 5.15; 95%CI: 4.25-6.23), male (aOR: 2.02; 95%CI: 1.89-2.15), emergency admissions (aOR: 1.73; 95%CI: 1.52-1.97), and pre-existing co-morbidities like renal failure, solid tumor, hypertension, and diabetes. Utilization of EvC was associated with lower frequencies of in poor discharge disposition: transferred to short-term hospital/skilled nursing facility/intermediate care/long term care facility (45.86% vs. 49.75%; p<0.001) in comparison to clipping.

Discussion:
Historically, coiling was reserved for the treatment of high-grade subarachnoid bleed, has found to be not only safe but also favourable with better discharge disposition. The recent AHA guideline and multiple research trials have shown the same result.
Abstract TP401: Dual Anti-platelet Therapy is Associated With Reduced Risk of Clinical Vasospasm and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage
Authors: Nagahama Yasunori , Nakagawa Daichi , Hasan David
Published: October 2018

Introduction:
Clinical vasospasm and delayed cerebral ischemia (DCI) are devastating complications of aneurysmal subarachnoid hemorrhage (aSAH). Several theories have been postulated as potential etiologies of clinical vasospasm and DCI, involving platelet activation. However, the effects of dual anti-platelet therapy (DAPT: aspirin and clopidogrel) on clinical vasospasm and DCI have not been previously investigated. The objective of this study was to evaluate the effects of DAPT on clinical vasospasm and DCI in aSAH patients.

Methods:
Analysis of patients treated for aSAH during the period from July 2009 to April 2014 was performed in a single-institution retrospective study. Patients were divided into two groups: patients who underwent stent-assisted coiling or placement of flow diverters requiring DAPT (DAPT group) and patients who underwent coiling only without DAPT (control group). The frequency of symptomatic clinical vasospasm and DCI and of hemorrhagic complications was compared between the two groups, utilizing univariate and multivariate logistic regression.

Results:
Of 312 aSAH patients considered for this study, 161 patients met the inclusion and exclusion criteria and were included in the analysis (85 patients in the DAPT group and 76 patients in the control group). The risk of clinical vasospasm (OR: 0.244; CI 95% [0.097 - 0.615]; p = 0.003) and DCI (OR: 0.056; CI 95% [0.01 - 0.318]; p = 0.001) were significantly lower in patients receiving DAPT. Hemorrhagic complications associated with placement of external ventricular drains and ventriculoperitoneal shunts were similar in both groups (4% versus 2%; p = 0.9).

Conclusions:
The use of DAPT was associated with a lower risk of clinical vasospasm and DCI in patients treated for aSAH without an increased risk of hemorrhagic complications.
Abstract TP416: Plasma β-amyloids and Tau Proteins in Patients With Vascular Cognitive Impairment
Authors: Tang Sung-Chun , Yang Kai-Chien , Wu Chau-Chung , Jeng Jiann-Shing
Published: October 2018

Background/Purpose:
Previous studies documented a close relationship between stroke and dementia. Increases in cerebrospinal fluid or plasma β-amyloids (Aβ) and tau proteins have been noted in patients with Alzheimer’s dementia, but whether levels of Aβ and tau proteins showed difference in stroke patients with or without vascular cognitive impairment (VCI) remained uncertain. Our study aimed to investigate the associations of plasma Aβ and tau proteins and the development of VCI in stroke patients.

Methods:
This cross-sectional study recruited patients with chronic stroke and controls free of stroke and dementia at an university medical center stroke clinic. VCI was defined as the scale of Clinical Dementia Ranking (CDR) ≥1. The levels of β-amyloids 42 (Aβ-42) and tau protein in the blood were analyzed using immunomagnetic reduction (IMR). One-way analysis of variance was used to compare the differences of measured proteins between the 3 groups.

Results:
This study included 26 controls (mean age 67.3±7.3 years, 30.8% male), 27 stroke patients without VCI (mean age 70.7±6.9 years, 60.7% male) and 34 stroke patients with VCI (mean age 78.3±5.3 years, 45.5% male). Plasma levels of tau and Aβ-42 were both significantly higher in stroke patients (with or without VCI) than in controls (Figure 1). However, Aβ-42, but not tau levels were significantly higher in stroke patients with VCI than those without VCI (17.6±2.6 versus 15.4±1.8 pg/ml, p< 0.01). Furthermore, after adjustment for age, sex, and vascular risk factors including diabetes mellitus and hypertension, plasma levels of Aβ-42 remained significantly higher in stroke patients with VCI than those without VCI (p= 0.02).

Conclusion:
Not only a potential biomarker for stroke patients with VCI, our finding also suggested the pathophysiological role of Aβ-42 in the development of VCI in stroke patients.
Abstract TP421: Cerebral Microhemorrhages on Susceptibility Weighted Imaging After Aortic Dissection
Authors: Mac Grory Brian , Malhotra Ajay , Youn Teddy , Schrag Matthew
Published: October 2018

Cerebral microhemorrhages (CMHs) are detected on susceptibility weighted (SWI) and gradient recalled echo T2* (GRE-T2*) magnetic resonance imaging (MRI) and are useful biomarkers of microvascular diseases of the brain. Here we describe the characteristics and distribution of cerebral microhemorrhages in a series of subjects with aortic dissection, compared with an age- and sex-matched series of patient with severe, chronic hypertension. CMHs were discovered in 75% of subjects with aortic dissection with a median of 8 per subject and an average diameter of 2.6 mm. CMHs were primarily located within the frontal lobes, parietal lobes and deep white matter tracts in a pattern suggestive of a watershed distribution. The pattern of CMHs after aortic dissection was different from that related to severe hypertension, which may suggest a different mechanism. We propose that injury to distal arterioles from cholesterol microemboli may account for the pattern of CMH observed after aortic dissection. Aortic dissection is an important mimicker of the neuroimaging findings of cerebral amyloid angiopathy and severe hypertension.
Abstract TP425: Cholinergic Pathway Disruptions and Brain Structural Changes in Subcortical Vascular Cognitive Impairment
Authors: Lee Yong-Seok , Kwon Hyung-Min , Lim Jae-Sung
Published: October 2018

Background & Objective:
Interactions between small vessel diseases (SVD) and cognitive functions were reported in the previous studies, and these effects were varied according to SVD burden and distributions. Cholinergic pathway has gained attention for its pivotal role to maintain normal cognitive function. We aimed to investigate the associations between SVD burden and distributions of the cholinergic pathways and structural changes of cholinergic innervated cortical/subcortical regions.

Methods:
We enrolled patients who were diagnosed as subcortical vascular cognitive impairment (scVCI) from Jan 2010 to Feb 2017 in a university hosptial. Subjects were characterized by moderate to severe white matter hyperintensities (WMH), lacunes, and microbleeds. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were assessed to quantify the cholinergic pathway disruptions. Cortical thickness and subcortical volumes of cholinergic-innervated structures were quried from volumetric MRI, and analyzed using Freesurfer. Correlation between CHIPS scores and normalized volumetric parameters of cholinergic-innervated structures were investigated.

Result:
A total of 80 patients were enrolled. Mean age was 78.4 years (SD 6.5), 59 (73.8%) patients were female, and median level of educations were 6 years (IQR 0.5-11.5). Median MMSE score was 17 (IQR 13-20). Median CHIPS score was 11 points (IQR 7-17, min 0, max 37). Total intracranial volume showed significant relationship with age (
r
=-0.23, p=0.04) as well as level of education (
r
=0.36, p=0.001) The CHIPS scores were negatively associated with cortical thickness of inferior temporal cortex (r=-0.26, p=0.02), and showed marginal significance for medial orbitofrontal cortical thickness (r=-0.22, p=0.057) after adjusting for age and level of education. The CHIPS scores were positively associated with subcortical volume of putamen (r=0.37, p=0.001). On the contrary, it was not correlated with other cortical/subcortical structures.

Conclusions:
Our study revealed that the disruption of cholinergic pathways in scVCI may accompany the structural changes of innervated cortical/subcortical regions. These findings may shed light on the understanding the pathophysiology of scVCI.
Abstract TP428: The Beneficial Effects of Chronic Remote Ischemic Conditioning in a VCID Mouse Model are eNOS Dependent
Authors: Khan Mohammad B , Lee Daniel S , Siddiqui Shahneela , Taha Farris A , Hess David C
Published: October 2018

Background and Purpose:
Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This improvement is associated with elevations of plasma nitrite. Our aim was to determine if the beneficial effect of C-RIC was eNOS dependent.

Methods:
Microcoil (01.8 mm) induced BCAS model was used to induce chronic hypoperfusion. Adult eNOS-KO male mice (5-6 months) were randomly assigned to 2-groups (N=5): (1) BCAS and (2) BCAS+RIC. RIC was started 7d post-surgery daily for 3 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. Mice were followed for 4 weeks.

Results:
C-RIC-therapy for 3 weeks did not improve CBF in the BCAS+RIC groups at either a 2
nd
weeks or 4
th
weeks compared to BCAS-Sham RIC groups. There was no significant change between the BCAS and BCAS+RIC groups in the discrimination index as determined by the NOR test or poor motor function as determined by hanging wire and beam walk test.

Conclusions:
The beneficial effect of C-RIC in the BCAS model is abrogated in eNOS KO mice indicating that the effect of C-RIC is eNOS dependent.
Abstract TP51: Does Intracranial Atherosclerotic Disease With Low NIHSS Effect Outcomes in Reperfusion Therapy Eligible Acute Stroke Patients?
Authors: Inoue Manabu , Mlynash Michael , Wada Shinichi , Koga Masatoshi , Nakagawara Joji , Ihara Masafumi , Toyoda Kazunori
Published: October 2018

Background:
Even patients with low National Institutes of Health Stroke Scale (NIHSS) benefit from reperfusion therapy due to its high efficacy and warranted safety by multimodal imaging assessment. On the other hand, having intracranial atherosclerotic disease (ICAD) could be a risk for reperfusion therapy in Asian population. We assessed the safety and efficacy of reperfusion therapy in patients with low NIHSS and ICAD.

Method:
Acute anterior ischemic stroke patients with baseline MRI before reperfusion therapy from National Cerebral and Cardiovascular Center stroke database between 2015-2017 were included. Outcome was assessed by modified Rankin Scale (mRS) at 90 days. DWI volume was measured by RAPID software and ICAD was measured by TOF-MRA as >50% of stenosis in the middle cerebral artery. Baseline DWI volume as a risk factor for having poor outcome (mRS 5-6 at 90 days) was assessed by ROC analysis as a malignant DWI profile and logistic regression analysis was performed to estimate the risk of low NIHSS (≤5) and presence of ICAD. Interaction of Low NIHSS and ICAD was analyzed for having unfavorable outcomes.

Result:
Total of 124 patients (42 women, mean age 72±13 years) were included in this study with mRS <3 before onset. Incident of ICAD was 18.5% (23/124), median (interquartile range: IQR) NIHSS was 9 (5-12) and median onset to MRI time was 109 (IQR 70-217) minutes. Mean (SD) DWI volume was 15.5 (27.3) mL. ROC analysis determined DWI volume larger than 46.0 mL to be associated with poor outcome with 94.8% specificity and 62% sensitivity (AUC 0.86, p<0.001). Interaction between ICAD and low NIHSS showed no difference in association with poor outcome between patients with and without ICAD (p=0.459) in the logistic regression analysis. Low NIHSS was associated with the lower risk of poor outcome in univariate analysis (p=0.05). However, low NIHSS was not an independent predictor of poor outcome (p=0.384) when adjusted for other significant factors (age, DWI volume, systolic blood pressure, chronic heart failure). ICAD was neither associated with outcome independently nor associated with low NIHSS.

Conclusion:
Low NIHSS and ICAD at baseline would not be factors for unfavorable clinical outcome in reperfusion therapy eligible patients in Asian population.
Abstract TP57: Predicting Regional Tissue Fate in Ischemic Stroke Using Color Coded mCTA-based Collaterals Assessment
Authors: Moussaddy Aimen , Sitaram Amith , Al Sultan Abdulaziz S , Maraj Nicholas N , Najm Mohamed , Demchuk Andrew M , Goyal Mayank , Menon Bijoy K
Published: October 2018

Background and Purpose:
Multiphase CT angiography (mCTA) assessment of collaterals has been proven to be predictive of tissue fate on follow-up imaging following an acute stroke. We used the GE FastStroke Software, a novel mCTA image analysis and visualization tool that color codes pial arteries and veins based on delay in vessel enhancement to predict regional tissue fate. Red colored collaterals represented no delay in enhancement, green represented a one phase delay and blue two phase delays.

Methods:
Forty patients with M1-middle cerebral artery occlusions were selected from the prospective database ProVeIT. Baseline CT as well as 24 to 36-hour CT/MRI were analyzed and scored regionally using the Alberta Stroke Program early CT scoring (ASPECTS). Regional vessel filling was assessed using color coded collateral maps, and given a score of 1,2 or 3 based on the predominant color of collaterals (1=blue, 2=green, 3=red). A score of 0 was given if there was less than 50% regional filling compared to the contralateral side. Logistic regression method was used to correlate collateral assessment with tissue fate, adjusting for baseline ASPECTS.

Results:
280 cortical regions were assessed (M1 to M6, Insula). When blue color was predominant, risk of subsequent infarction was 48% (27/56). Green and red colors were associated with 33% (37/111) and 14% (13/88) of subsequent infarction, respectively. A score of 0 had an 80% (20/25) risk of infarction. Using logistic regression methods, collaterals assessment met statistical significance in tissue fate correlation (p<0.001).

Conclusions:
Collateral scoring using color coded collateral maps was highly predictive of subsequent infarction risk. Further work is needed to understand the impact of fast endovascular reperfusion in influencing tissue outcome.
Abstract TP58: A Novel Deep Learning Approach for Automated Diagnosis of Cerebral Infarction on Computed Tomography
Authors: Knight-Greenfield Ashley , Beecy Ashley , Chang Qi , Anchouche Khalil , Baskaran Lohendran , Elmore Kimberly , Kolli Kranthi , Wang Hao , Al’Aref Subhi , Peña Jessica M , Patel Praneil , Sun Peng , Zhang Tong , Kamel Hooman , Min James K , Gupta Ajay
Published: October 2018

Introduction:
Deep learning is a novel machine learning approach that enables automated extraction and classification of imaging features. We aimed to use deep learning to enhance detection of brain infarction.

Methods:
Patients with acute ischemic stroke admitted to our institution between 2011-2015 were prospectively registered in an IRB-approved database. On a subset of these patients, radiologists annotated the images by marking infarct area. Data was split randomly into a training set and test set (80:20). Deep learning models, including a 3D multi-scale fully convolutional neural network, were developed and trained on the training set and independently tested on the test set. The performance of this model was compared to the expert consensus interpretation. Diagnostic test characteristics including the area under the curve (AUC) for the deep learning algorithm were calculated both at a voxel and imaging-study level. Computer-generated heat maps were created to denote the possibility of infarct.

Results:
The study group included 114 patients (training set n = 92, test set n = 22). In the training set of 5,888 images, infarction was present in 602 (10.2%) images. In the testing set of 920 images, infarction was present in 130 (14.1%) images. A total of 1.5 billion voxels were used to train the model. The AUC for the deep learning algorithm for voxel accuracy was 0.973 (95% CI 0.972-0.974). Voxel accuracy, sensitivity, and specificity were 92%, 93%, and 92%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) were 86% and 92%, respectively. The AUC for the deep learning algorithm for automated diagnosis of infarction at the imaging-study level was 0.91 (95% CI 0.90-0.94). Diagnostic accuracy, sensitivity, and specificity were 88%, 65%, and 91%, respectively. PPV and NPV were 49% and 95%, respectively.

Conclusions:
A machine-learned algorithm employing a novel deep learning algorithm enabled accurate diagnosis of brain infarction.
Abstract TP60: Effect of Clinical History in Radiologist Interpretation of Computed Tomography for Acute Stroke
Authors: Hung Peter , Finn Caitlin , Knight-Greenfield Ashley , Baradaran Hediyeh , Patel Praneil , Kamel Hooman , Gupta Ajay
Published: October 2018

Introduction:
Computed tomography (CT) is widely used for suspected acute ischemic stroke. Radiologists often interpret these scans with limited information and may benefit from more complete knowledge of the clinical situation.

Hypothesis:
Providing detailed clinical information improves the interpretation of CTs for acute stroke.

Methods:
In the prospective Cornell AcutE Stroke Academic Registry (CAESAR), we randomly selected 100 patients who underwent noncontrast head CT within 6 hours of transient ischemic attack (TIA) or minor acute ischemic stroke (National Institutes of Health Stroke Scale score ≤3) and underwent magnetic resonance imaging (MRI) within 6 hours of the CT. Three radiologists each twice evaluated CT studies both with and without accompanying information on the patient’s medical history, neurological deficit, and symptom time course. In random sequence, each study was interpreted by each radiologist in one condition (i.e., with or without detailed accompanying information), and then after a 4-week washout period, the same study was interpreted again by each radiologist in the opposite condition. Using MRI diffusion weighted imaging (DWI) as the reference standard for brain infarction, we classified CT interpretations as correct (true positives or true negatives) or incorrect (false positives or false negatives). McNemar’s test was used to compare the proportion of correct interpretations in the condition with detailed clinical information versus the condition without detailed information.

Results:
In patients with DWI-defined infarcts, acute ischemia was correctly called on 20% (95% confidence interval [CI], 14-27%) of CTs with detailed history versus 18% (95% CI, 12-25%) without history. In patients without infarcts, the absence of acute ischemia was correctly called on 77% (95% CI, 70-84%) of CTs with history and 77% (95% CI, 69-83%) without history. The proportion of correct interpretations of CTs accompanied by detailed clinical history (49% [95% CI, 43-54%]) did not differ significantly from those without history (47% [95% CI, 42-53%]) (
P
= 0.67).

Conclusions:
Reported findings on head CT for evaluation of suspected acute ischemic stroke were similar regardless of whether detailed clinical history was provided.
Abstract TP66: IV Thrombolysis May be Safe in Patients With Lower Platelet Counts
Authors: Ander Tracy M , Remmel Kerri , Liu Wei , Wise Elizabeth , Liu Ruolan
Published: October 2018

Background & Purpose:
It has been well established that intravenous alteplase (IVa) administration for treatment of acute ischemic stroke (AIS) improves clinical outcome at 3 months, and earlier treatment is more likely to result in a favorable outcome with reduced symptomatic intracranial hemorrhage (sICH). A platelet count (PC) of <100,000/mm3 remains a contraindication IVa, but the incidence is low. With the limited time to diagnose an AIS and candidacy for IVa, often lab results are received after drug initiation. Research indicates that IVa for AIS may be safe and the risk of developing sICH is low if IVa is given before PC is resulted. According to AHA/ASA guidelines, treatment is not delayed while waiting for hematologic or coagulation testing if there is no reason to suspect an abnormal test. The purpose of this study is to evaluate the incidence of asymptomatic hemorrhage (aICH), functional outcome, and safety of IVa in AIS patients with PC <100,000/mm3 prior to PC results.

Methods:
We retrospectively reviewed charts of patients who received IVa from January, 2009 to July, 2017 at our facility. Patients were identified and treated based on standard FDA approved guidelines. We identified patients with admission PC <100,000/mm3. We compared admission and discharge PC and NIHSS, baseline and discharge mRS, and discharge disposition. We evaluated their medical and social history and antiplatelet use prior to admission. Brain MRI and 24 hour noncontrast CT head were reviewed.

Results:
511 patients received IVa for treatment of AIS at our facility during the study period. Four patients (0.97%) with a PC of <100,000/mm3 (70,000/mm3 – 97,000/mm3) received full dose IVa. None of the 4 subjects had a hemorrhagic complication on 24 hour CT. Upon discharge, all 4 patients had an improvement in the NIHSS (mean 3.7 points) and were functionally independent at discharge (mRS 0-1). All 4 patients were discharged home.

Conclusion:
IVa treatment in AIS with PC <100,000/mm3 did not result in aICH in this group of patients. Our study supports the claim that lower PC is rare in AIS patients and there is no need to wait for PC results before starting IVa. Full dose IVa in lower PCs may be safe, but a larger sample size should be studied to further evaluate safety.
Abstract TP8: Process Modification to Reduce Door to Puncture Time for Patients With Large Vessel Ischemic Stroke
Authors: Orzano Devon , Hollender Kimberly , Lane Judith , Jablonski Amy , Al-Mufti Fawaz , Roychowdhury Sudipta , Rybinnik Igor , Mehta Deviyani
Published: October 2018

Numerous studies have demonstrated the paramount importance of rapid treatment of large vessel occlusion ischemic stroke. We sought to improve our door to reperfusion times (DTRt) so as to ensure we complied with the Joint Commission CSC measure of 90 minutes. We theorized that by reducing the Door To Puncture time (DTPt), we would promote rapid revascularization and improved clinical outcomes. Our goal was to reduce the DTPt to be consistently less than 75 minutes by ensuring rapid identification, streamlining the activation of the neuroendovascular team and providing education to the providers and ancillary staff. We had two scheduled systems evaluations; Pre-intervention (01/15 to 06/16), and post-intervention (01/17 to 07/17). A total of 82 patients were reviewed, 45 pre-intervention, and 37 post-intervention. During the pre-intervention period, the median DTPt was 98 minutes with an intraquartile range of 75 to 127. In the post-intervention phase the median DTPt was 49 minutes with an intraquartile range of 40 to 82. The p value comparing pre-intervention to post-intervention DTPt was 0.000042. In conclusion, we found that the implementation of rapid identification, streamlined activation and education resulted in a statistically significant decrease in Door To Puncture times from a median of 98 minutes to 49 minutes (p=0.000042). This allowed for a decrease in median Door To Reperfusion time from 130 minutes pre-intervention to 66 minutes post-intervention.
Abstract TP88: Delayed Therapeutic Window for Prevention of Progressive Cognitive Impairment After Experimental Stroke
Authors: Ahmed Heba A , Ishrat Tauheed , Pillai Bindu , Fouda Abdelrahman Y , Sayed Mohammed A , Waller Jennifer L , Ergul Adviye , Fagan Susan C
Published: October 2018

Background:
With the aging population, the prevalence and incidence of cerebrovascular disease will continue to rise, as will the number of individuals with post-stroke cognitive impairment (PSCI). Unfortunately, no specific FDA approved treatments for PSCI exist. Although clinical trial evidence supports that renin angiotensin system (RAS) modulation by angiotensin receptor blockers (ARBs) prevent cognitive decline in older adults. The aim of our study was to determine the impact of the ARB candesartan or the AT2R agonist, C21, after stroke, on long-term cognitive function in spontaneously hypertensive rats (SHRs).

Methods:
Thirty three SHRs were subjected to a 60 minute transient middle cerebral artery occlusion (MCAO) and randomly assigned to either Saline/ C21 (0.3 mg/kg, IP) only or Saline/ C21 (7 days) followed by candesartan (0.3 mg/kg) IP for the remainder of the study. Outcome measures included sensorimotor and cognitive function, performed using a sequence of blinded tests, and assessed at baseline and up to 28 days post-stroke. Animals were sacrificed at 30 days and their brains collected for amyloid-β protein determination and histopathologic analyses.

Results:
Chronic administration of C21, or candesartan prevented PSCI, even when treatment was initiated at 7 days after the ischemic insult. The groups treated with C21 and candesartan demonstrated superior performance on the novel NOR test, compared to saline treated animals. C21 (first 7 days) only or C2 and candesartan treatments had markedly lower hippocampal concentrations of Aβ1-42 at 30 days post-stroke than those treated with saline. Sensorimotor deficits (Bederson and beam walk scores) were pronounced at 24 h post-stroke and all treatment groups showed similar recovery at 28 days post stroke. C21 had no effect on BP compared to saline-treated controls.

Conclusion:
Collectively, our findings demonstrate that RAS modulators effectively prevent PSCI, even when treatment is delayed.
Abstract TP93: Ultrasonic Brain Stimulation Regulates Brain Plasticity in Ischemic Mice
Authors: Wang Jixian , Li Guofeng , Mamtilahun Muyassar , Qiu Weibao , Zheng Hairong , Xie Qing , Yang Guo-Yuan
Published: October 2018

Introduction:
Ultrasonic brain stimulation regulates neural activity in different brain regions in normal humans and animals, and promotes neurogenesis in normal mouse brain. However, the role of ultrasonic stimulation in modulating neural plasticity in the ischemic brain is largely unknown.

Hypothesis:
To explore the effect of ultrasonic brain stimulation on neurological rehabilitation and the possible underlying mechanism.

Methods:
Adult CD-1 mice (n=18) underwent transient middle cerebral artery occlusion (60 min). One week after brain ischemia, 0.5M HZ frequency brain stimulation was applied transcranially to the ischemic hemisphere of mice for 7 consecutive days. Brain infarct volume and neurological behavioral tests were assessed at 1, 7 and 14 days after brain ischemia. The expression of proteins critical to neuronal development, in particular BrdU and DCX, and IL-10R were examined to explore the underlying mechanism.

Results:
We found that the brain infarct volume was significantly attenuated in the ultrasonic stimulated mice compared to the non-stimulated mice (
p
<0.05). Similarly, neurological servility scores, elevated body swing test, and corner test performances were significantly improved in the ultrasonic stimulated mice (
p
<0.05). Immunohistochemistry results demonstrated that ultrasonic stimulation increased BrdU
+
/DCX
+
cells in the subventricular zone of ischemic mice, suggesting this stimulation promoted neurogenesis in mice after cerebral ischemia. Furthermore, IL-10R expression was substantially up-regulated in the perifocal region and subventricular zone of ischemic mice after ultrasonic stimulation (
p
<0.05).

Conclusions:
We concluded that ultrasonic stimulation provided a unique technique to promote neurorehabilitation. Ultrasonic stimulation enhanced neural rehabilitation through promoting neural precursor cell proliferation, which may be modulated by IL-10/IL-10R mediated immune-regulation. (Funded by SJTU YG2016MS62)
Abstract WMP103: Role of the Soluble TLR4 Decoy Receptor on ICH Outcomes
Authors: Leclerc Jenna L , Hernandez Damian , Satyavarapu Ishwarya , Chakrabarty Paramita , Golde Todd E , Doré Sylvain
Published: October 2018

Background:
Of all subdivisions of stroke, intracerebral hemorrhagic stroke (ICH) only accounts for around 10-15% but is characterized by the highest mortality and morbidity. Lately, understanding immunological and inflammatory responses post-hemorrhagic stroke allows for the development of alternative therapeutic intervention. Toll-like receptors (TLR) are a large family of recognition receptors which have a regulatory pathway that is a key factor in determining the neurological outcomes of patients with ICH. In this study, we took a closer look at understanding the role that the overexpressing the soluble Toll-like receptor 4 (sTLR4) has on neuroprotection after ICH.

Methods:
Intracerebral injections of autologous blood were used to induce the ICH preclinical model on adeno-associated virus serotype 1 (rAAV1)-mediated FcV5 (control) and FcV5-sTLR4 expression in the brains of mice. Functional outcomes of these mice were assessed using several behavioral testing methods such as rotarod, open field locomotor test, and a neurological deficit score (NDS) at the different time-points of 24h, 48h and 72h. To assess changes to the lesion, hematoma and tissue injury, a histological stain, cresyl violet, was performed.

Results:
The data reveal a 41.9+/-8.2% smaller lesion volume in sTLR4 overexpressed mice. Further analysis with histological and immunochemical stains shows a trend towards a smaller tissue injury and hematoma volume, unchanged heme oxygenase 1 and iron levels, and unchanged microgliosis and astrogliosis levels.

Conclusion:
These findings reveal that the overexpression of sTLR4 does improve preliminary ICH outcomes. We will also discuss mechanisms behind the relationship between sTLR4 signaling and ICH along with possibilities of future methods of therapeutic interventions.
Abstract WMP106: Clinical Benefit of Thrombolytic Removal of Intraventricular Hemorrhage: Number Needed to Treat in the CLEAR 3 Trial
Authors: Kleinman Jonathan T , Saver Jeffrey L , Nguyen Peter T , Khatibi Kasra , Allen Baxter B , Caganap Scott D , Severson Amanda J , Wherry Carl W , Buitrago Blanco Manuel , Hanley Daniel F , Vespa Paul M ,   For the CLEAR III Investigators
Published: October 2018

Introduction:
The CLEAR III trial found that removal of intraventricular hemorrhage was not associated with a dichotomized improvement in 6-month outcome measured by the modified Rankin Scale score (p=0.554). Despite this, shifts towards improved outcome were evident for the alteplase (n=249) versus saline (n=251) group measured by the extended Glasgow Outcome Score (GOS-E). Shared patient/physician decision-making would be aided by characterizing the magnitude of this benefit, using the common clinical metrics of number needed to treat (NNTB), number needed to harm (NNH), and benefit per hundred (BPH) treated.

Methods:
Analyses were performed on CLEAR III findings using a 6-level version of the GOS-E (GOS-E6), in which the 3 poorest outcome levels of the original GOS-E (extremely severe disability, vegetative state, and death) are combined into a single worst outcome category. In this way, shifts between these categories are not counted as improved outcome. For all possible dichotomizations of the GOS-E6 net NNTB values were derived by taking the inverse of absolute risk difference, and net BPHs by multiplying absolute risk difference by 100. For benefits accruing across all disability state transitions on the GOS-E6 (shift analysis), net NNTB, and net BPH, values were derived using automated, algorithmic min-max joint outcome table derivation technique. In addition, NNTB and NNH values for dichotomous and shift outcomes were derived using expert’s joint outcome tables, and are presented as the geometric mean.

Results:
For the 6 level GOS-E, automated algorithmic analysis indicated that the net NNTB for 1 additional patient to have a better outcome by ≥ 1 grade at 6 months, with thrombolytic rather than saline irrigation, was 7.4. Expert joint outcome table analyses indicated that the NNTB for improved final outcome at 6 months was 6.3 (range 5.8-6.7) and NNH 39.0 (32.3-47.6). For every 100 patients treated, 15.9 had a better outcome and 2.6 a worse outcome. The likelihood of help to harm ratio was 6.2.

Conclusions:
Thrombolytic removal of intraventricular hemorrhage confers net benefit on 9% of treated patients. Approximately 1 in 11 patients has a better outcome, while 1 in 39 has a worse outcome.
Abstract WMP107: Efficacy of Intraventricular Administration of Alteplase for Intraventricular Hemorrhage
Authors: Aachi Raghav , Santillan Alejandro , Birnbaum Lee , Goros Martin , Michalek Joel , Woo Daniel
Published: October 2018

Introduction:
The efficacy of extraventricular drain (EVD) alone was compared to EVD with intraventricular alteplase injection for the treatment of intraventricular hemorrhage (IVH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) cohort.

Methods:
ERICH study subjects with IVH and EVD placement were dichotomized by alteplase administration. Propensity score modeling was used to adjust for significant differences in baseline variables and included age, gender, race/ethnicity, initial Glasgow Coma Scale (GCS) score, ICH location, initial ICH volume, primary IVH, and initial IVH volume (Table 1). Outcome measures included 3, 6, and 12-month modified Rankin scale (mRS) as well as IVH volume change on follow-up head CT within 24 hours. Good outcome was defined as a mRS <=3. Mann-Whitney U and Chi-squared tests were utilized for statistical analyses.

Results:
Follow-up mRS scores at 3, 6, and 12 months were not significantly different between the two groups. Compared to the initial head CT on presentation, a significant reduction of IVH volume was seen on the subsequent head CT (Table 2).

Conclusion:
For ERICH subjects with IVH and EVD placement, the administration of intraventricular alteplase resulted in significant IVH volume reduction. The sample size, however, was likely insufficient to detect a difference between mRS outcomes. Our findings in this non-randomized IVH cohort highlight real world clinical practice outcomes and are consistent with the results of CLEAR III.
Abstract WMP111: Assessing Caregiver Commitment and Capacity
Authors: Camicia Michelle , Lutz Barbara , Drake Christiana , Kim Katherine K , Harvath Theresa , Joseph Jill G
Published: October 2018

Care transitions for individuals with disabling conditions, such as stroke, are often ineffective and inefficient, resulting in unmet patient and caregiver (CG) needs, increased safety risks, high rates of preventable readmissions, and increased health care costs. This is particularly problematic for stroke patients transitioning from an inpatient rehabilitation facility (IRF) to home. There is no assessment instrument specifically designed to evaluate a family member’s commitment and capacity to assume the caregiving role following a stroke survivor (SS) discharge from an IRF or sub-acute facility. This is critically needed to facilitate the development of tailored care plans and interventions to mitigate risks associated with the crisis of stroke and the associated health effects on the CG and SS. The purpose of this study is determine the psychometric properties of the Preparedness Assessment for the Transition Home after Stroke (PATH-s) instrument. The PATH-s instrument is a 25-item, 4-point scale based on the foundational work of B. Lutz (Co-Investigator). A prospective cohort study was conducted to establish the psychometric properties of the PATH-s instrument using a convenience sample of 184 SSs and their family caregivers during IRF admission. Data collection from SSs and CGs at IRF admission was conducted to determine the quality of the items, internal consistency, reliability, construct validity, and criterion-related validity. We will describe the characteristics of CG responses on the PATH-s instrument during IRF in addition to correlation with other measures (general health, perceived stress, depression). This novel instrument can support a primary prevention strategy to identify gaps in preparedness for stroke survivor-caregiver dyads following the complex transition from IRF to home, with the long-range goal to mitigate the effects of suboptimal preparation and the associated adverse effects associated with this transition on the health of CGs and SSs. Once gaps are identified, care plans can be tailored to address gaps and better prepare caregivers for the transition home.
Abstract WMP22: Temporal Similarity Perfusion Mapping, An Effective CTP Analysis Method Without Transit Delay Sensitivity
Authors: de Vis Jill B , Song Sunbin , Luby Marie , Glen Daniel R , Reynolds Richard , Kroon Wouter , Dankbaar Jan W , Latour Lawrence L , Bokkers Reinoud P
Published: October 2018

Introduction:
Studies investigating the value of CT perfusion (CTP) imaging in treatment decision or outcome prediction of acute stroke patients have found conflicting results. This may be attributed to variable accuracy and reliability across the different deconvolution algorithms. The aim of this study was to introduce a new, standardized and model-free method, based on similarities in signal time-curves (Pearson’s correlation coefficient) and to increase robustness of CTP analysis and perfusion deficit detection.

Methods:
Acute stroke patients from the Dutch Acute Stroke Study were included. CTP data acquired at admission was analyzed using a deconvolution method (Philips Brain Perfusion software) and with TSP. Acute CTP and follow-up non-contrast images after 3 days were interpreted by experienced and inexperienced raters for presence of perfusion deficits, intra-rater and inter-rater agreement.

Results:
65 patients (68±13 years) were included. Example images are shown in the Figure. A perfusion deficit was detected in 56 patients on the MTT deconvolution maps; TSP detected 54 of these perfusion deficits. The agreement of MTT, TTP and TSP with the presence of ischemia on follow-up was comparable, but noticeably lower for CBV. CBV had the best relationship with final infarct volume (R
2
=0.77, p<0.001), closely followed by TSP (R
2
=0.63, p<0.001). Inter-rater agreement of experienced readers was comparable across maps. Intra-rater agreement of an inexperienced reader was higher for TSP than for CBV/MTT (kappa’s of 0.79-0.84 versus 0.63-0.7).

Conclusion:
TSP offers a very fast, automated, non-proprietary, analysis of CTP data. TSP maps are highly comparable to deconvolution maps, but easier to interpret for inexperienced readers. The relationship of TSP perfusion deficit volume with final infarct volume is comparable to CBV. This suggests that TSP might be a valuable alternative to deconvolution-derived maps, which are known to be prone to tracer delays.
Abstract WMP30: Cardiac Arrest Does Not Increase the Long-Term Risk of Seizures
Authors: Morris Nicholas A , Kamel Hooman
Published: October 2018

Introduction:
Epilepsy is a feared late sequela of acute neurovascular injury. While early seizures after cardiac arrest have received much attention, the long-term risk of seizures in cardiac arrest survivors is not established. We hypothesized that survivors of cardiac arrest face an increased long-term risk for seizures.

Methods:
We performed a retrospective cohort study using 2009-2015 claims data from a nationally representative 5% sample of Medicare beneficiaries ≥66 years old. Our exposure of interest was a hospital diagnosis code of cardiac arrest, defined by previously validated
ICD-9-CM
codes (427.1, 427.4, 427.41, 427.42, 427.5 or 427.69). Since we were interested in long-term risk, we excluded patients who were diagnosed with a seizure or died during the index hospitalization. Our outcome was a diagnosis of seizure, defined using previously validated
ICD-9-CM
codes. Survival statistics were used to calculate seizure incidence and Cox proportional hazards models were used to determine the association between cardiac arrest and long-term seizures after adjustment for demographics and Charlson comorbidities.

Results:
Among 1,764,508 beneficiaries with a mean 4.5 years of follow-up, we identified 57,437 patients with cardiac arrest who survived to discharge without a documented seizure. The annual incidence of seizures in survivors of cardiac arrest was 1.26% (95% confidence interval [CI], 1.20-1.33%) compared to 0.61% (95% CI, 0.61-0.62%) in those without cardiac arrest. In unadjusted analysis, cardiac arrest was associated with an increased risk of post-discharge seizures (hazard ratio [HR], 1.8; 95% CI, 1.7-1.9), but there was no longer an association after adjustment for demographics and Charlson comorbidities (HR 0.9; 95% CI, 0.9-1.0;
P
= 0.12). These findings were similar in a sensitivity analysis using a different set of validated
ICD-9-CM
codes to define cardiac arrest.

Conclusion:
We found that the long-term risk of seizures was not elevated in patients with cardiac arrest who survived to hospital discharge without a seizure.