bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 88: Sphingolipid Profiling Identifies Large Vessel Occlusions at Early Time Points: Results of the ASPIRE-Stroke Study
Authors: Sheth Sunil A , Lee Songmi , Iavarone Anthony T , Wong Gregory J , Liou Raymond , Malhotra Konark , Starkman Sidney , Liebeskind David , Saver Jeffrey L , Savitz Sean I , Gonzalez Nestor R
Published: October 2018

Background:
Rapid identification and transport of patients with large vessel occlusions (LVO) to endovascular-capable hospitals has become increasingly important. We previously demonstrated that brain-specific sphingolipids (SLs) serve as useful plasma markers of brain injury. Here, we test and validate SL biomarkers to differentiate LVO from non-LVO acute ischemic stroke (AIS) and stroke mimics.

Methods:
We enrolled consecutive patients with symptoms concerning for AIS and performed SL profiling using HPLC-MS/MS on blood samples obtained at hospital arrival. MS data were aligned and automated peak picking was performed using XCMS, and SLs were identified by exact mass. A classification method using SL plasma concentrations was created using step-wise logistic regression in a derivation arm, and then tested in an independent validation arm.

Results:
Among 184 patients with AIS or AIS-mimics, 84 (46%) were female and age was 73 years (IQR 63-84). 81 (44%) were diagnosed with AIS, 32 (17%) with TIA, and 71 (39%) as stroke mimics. Median time from last known well to blood collection was 124 minutes (IQR 65-275) and Los Angeles Motor Scale was 1 (IQR 0-2). Among patients with AIS, median NIHSS was 3 (IQR 2-8) and 33 (41%) had LVO on CTA or MRA. Among 24 SLs definitively identified, 3 (12.5%) were ceramides, 3 (12.5%) were sphingosines, and 18 (75%) were sphingomyelins. Using step-wise regression, a panel of 8 SLs differentiated LVO from non-LVO AIS or stroke mimic with very good accuracy (AUC 0.76 in derivation; 0.72 in validation), comparable to LAMS alone (AUC 0.73). Combining the SL panel with LAMS resulted in superior discrimination (AUC 0.84 in derivation; 0.79 in validation and Figure).

Conclusions:
Plasma levels of SLs accurately differentiate LVO from non-LVO AIS and stroke mimics at early time points. A point-of-care SL assay in the field may help triage LVO patients to appropriate centers.
Abstract 92: Endovascular Thrombectomy Access in the United States: the Current Status and an Optimization Model
Authors: Sarraj Amrou , Farrell Christine M , Reishus Katelin , Sharrief Anjail Z , McCullough Louise , Savitz Sean I
Published: October 2018

Background:
Endovascular therapy (EVT) is established for acute ischemic strokes (AIS) with large vessel occlusion (LVO). Timely direct access to EVT-capable centers is integral for EVT utilization and success. We describe and map current EVT access then utilize modeling to optimize it.

Methods:
US designated stroke centers were identified and mapped utilizing geo-mapping. Centers were stratified into EVT or non-EVT if they reported ≥1 thrombectomy code for AIS in 2016 to Centers for Medicare and Medicaid Service. Ground and air transportation times (30, 60 and 90 min) to EVT centers were calculated from validated trauma models previously adapted for stroke. An optimization model utilizing a greedy algorithm was employed to maximize population ground access within 60 min, as the standard “golden hour” for patients. Ground transport was utilized over air given current transport practices for stroke. A second optimization was done for 30 minutes to give LVOs the best chance to be taken directly to EVT centers, increasing probability of good outcomes.

Results:
1645 stroke centers were identified (577 were EVT capable). Approximately 137 million/44%, 195 million/63%, 234 million/76% Americans had 30, 60 and 90 min EVT ground access ; leaving 37% of the population beyond 60 min driving distance to EVT centers. 172 million/56%, 268 million/87%, 296 million/96% of the Americans have air access within 30, 60 and 90 mins. 50 hospitals were identified for “flipping” from non-EVT to EVT, which improved 60 min ground access from 63% to 71% giving access to almost 20 million more Americans. 50 hospitals were flipped to improve the 30 min ground access from 44% to 49%, increasing the coverage by 15 million. Figure 1 shows the current and optimized EVT access map.

Conclusion:
Only 2/3 of the US population has direct access to EVT within an hour. State and national Efforts should focus on improving access and shorten times to EVT to give patients the best chance for excellent outcome after large strokes.
Abstract 94: Ultra-Fast Performance and Yield of a High-Resolution CT With Head and Neck CT Angiography on a Mobile Stroke Unit
Authors: Alexandrov Anne W , Bryndziar Tomas , Rike Joseph , Swatzell Victoria , Dusenbury Wendy , Koury Dave , Rogers Keri , McCormick Sarah , Carlow Jordan , Rhudy James , Hossein Zadeh Maleki Ana , Chulpayev Boris , Krishnaiah Balaji , Nearing Katherine , Malkoff Marc , Arthur Adam S , Alexandrov Andrei V ,   REACH-MOST Investigators
Published: October 2018

Background:
MSU’s are capable of ultra-early treatment of acute stroke patients in the field. We tested field use of a high-resolution CT and CT-angiography on our MSU.

Methods:
We designed and implemented the first of its kind MSU equipped with a 16 slice CT scanner (24-row adaptive detector array, fixed 70 cm gantry, auto-injection system, Somatom Scope, Siemens), led by stroke fellowship trained MDs or ANVP-board certified nurse practitioners without telemedicine support. Head/neck CTA was performed on all suspected stroke patients immediately following noncontrast CT. The MSU is embedded within local Fire/EMS and is activated by 911, or by on-scene medics 14 days/month. Transport and drug re-stock agreements were developed with Comprehensive, Primary, and CSC-Capable (CSC-cap) competing stroke centers.

Results:
Of 420 activations in the first year, our MSU transported a total 206 patients: 127 (62%) strokes and 79 (38%) stroke mimics. In all 127 acute stroke patients (68±16 years, 58% women, 65% African American, 34% White, 1% Hispanic), median CT/CTA completion time, from start of scan, to images ready for diagnostic viewing, was 3.5 minutes (IQR 3-4). Diagnosis was 15 (12%) hemorrhages, 12 (9%) suspected TIA, 100 (79%) acute ischemic stroke (AIS). AIS median NIHSS was 9, IQR 7-17. IV-tPA treatment rate was 38% with median scene arrival to bolus time of 13 min, IQR 11-16. Large vessel occlusion (LVO) was found in 30% of ischemic strokes. No patients required repeat imaging on arrival due to image quality, and 100% were accurately triaged to CSC, PSC, or CSC-cap hospitals without the need for subsequent transfer.

Conclusions:
MSUs can effectively operate a high-resolution automated CT similar to in-hospital radiology settings. The addition of head/neck CTA in the field yields a high rate of LVO detection supporting definitive prehospital triage to Comprehensive Stroke Centers.
Abstract 95: EMS Triage to CSC Reduces Time to Treatment and Improves Outcomes in Patients With Large Vessel Occlusion
Authors: Jayaraman Mahesh V , Hemendinger Morgan , Baird Grayson , Yaghi Shadi , Cutting Shawna , Saad Ali , Siket Matthew , Madsen Tracy E , Williams Kenneth , Furie Karen L , McTaggart Ryan A
Published: October 2018

Introduction:
Treatment for large vessel occlusion is profoundly time dependent. Two potential mechanisms to reduce time to treatment are optimizing transfers from Primary Stroke Centers (PSC) and transporting selected patients directly to a Comprehensive Stroke Center (CSC). In our region, we sequentially implemented both interventions. We sought to evaluate the impact of 1) Optimization of PSC transfer protocols and 2) implementation of a severity based EMS triage protocol on times to treatment and outcomes.

Methods:
All thrombectomy patients in our state treated over 24 months were retrospectively reviewed. We included patients with anterior circulation LVO, presenting within 6 hours, with an NIHSS of 6 or higher. An EMS protocol was introduced such that patients with a field LAMS score of 4 or higher, within 30 minutes of the CSC, would be directly transported to the CSC. Patients from adjacent states (where the EMS protocol would not apply) as well as inpatient strokes were excluded. We examined the proportion of patients who were directly transported to the CSC, as well as trends in time to treatment with IV tPA and thrombectomy from the time of first hospital arrival (PSC or CSC). Time periods were as follows: 7/1/2015 to 12/31/2015 (Pre-optimization and pre-triage); 1/1/2016 to 12/31/2016 (PSC optimization; pre-triage) and 1/1/2017 to 6/30/2017 (PSC optimization and triage). Primary outcome measures were times to treatment, discharge to home, and in-hospital mortality.

Results:
The results are summarized in the table below. Marked decreases in median time from first hospital arrival to recanalization were seen, from 156 to 109 minutes over time. In addition, there were increases in discharge home, and decreases in in-hospital mortality across each of the time periods.

Conclusions:
Through a combination of field triage and optimization of PSC workflow, it is possible to reduce times to thrombectomy and improve outcomes across an entire region.
Abstract 99: Diagnosis of Uncertain Origin Benign Transient Events (DOUBT)
Authors: Coutts Shelagh B , Hill Michael D , Moreau Francois , Goyal Mayank , Camden Marie-Christine , Asdaghi Negar , Field Thalia , Penn Andrew , Swartz Richard , Boulanger Jean-Martin , Campbell Bruce , Krause Martin , Mikulik Robert , Mandzia Jennifer
Published: October 2018

Background and Aims:
TIA and minor stroke offer a massive opportunity for stroke prevention. Patients with motor or speech symptoms have a higher risk of early recurrent stroke. Many patients with transient or mild neurological deficits do not have high-risk features (eg sensory symptoms). The aim of the DOUBT study was to assess what proportion of these lower risk patients have true brain ischemia and secondarily to establish whether clinically we can predict what clinical factors predict a higher risk of brain ischemia.

Method:
DOUBT was a multicentre, international, prospective, observational, cohort study assessing the diagnosis and prognosis of patients with lower risk focal neurological symptoms. Patients aged ≥ 40, with no previous stroke, with either very brief (<5 minutes) motor or speech symptoms, or non-motor or speech focal neurological symptoms were included. Patients had a detailed neurological assessment and an MRI brain within 7 days of onset. Proportion of patients with an acute DWI lesion on MRI was the primary outcome.

Results:
1047 patients in Canada, Europe and Australia were prospectively enrolled in the study. All patients had a detailed neurological assessment prior to undergoing MRI brain. Preliminary analysis shows 13% true brain schema rate (DWI positive). Patients were less likely to have a DWI lesion if their symptoms were fully resolved at assessment (RR 0.57, 95%CI: 0.38-0.79, p <0.001), if they reported any psychological stress (RR 0.57: 0.33-0.99, p=0.04) or if male (RR 0.58, 0.42-0.81, p=0.001). Patients were more likely to have a DWI lesion if they had any motor or speech symptoms (RR 1.7 (0.17-2.55, p=0.009). Secondary analysis looking at detailed clinical predictors of DWI lesions status will be presented.

Conclusion:
We found a low but real risk of true brain ischemia in these lower risk patients. Further analysis is needed to explain why woman are more likely to have DWI lesions with low risk symptoms. Detailed neurological assessment may help us stratify these patients further.
Abstract TMP10: Is There a Correlation With Number of Passes With a Stentriever and Hemorrhagic Transformation?
Authors: Hassan Ameer E , Shariff Umar , Sanchez Christina , Malik Ahmed , Qureshi Adnan
Published: October 2018

Background and Purpose:
Intracranial hemorrhage (ICH) presents as a major complication for patients undergoing endovascular treatment (EVT) for acute ischemic stroke (AIS). Our study aims to assess the risk and correlation with the number of passes with a stentriver involved in EVT and hemorrhagic transformation.

Methods:
We utilized our endovascular database and analyzed all the patients admitted from 2012-2017, who underwent EVT with stentrievers. We collected baseline demographics, clinical characteristics, admission NIHSS, and modified Rankin Scale (mRS) at discharge, as well as groin puncture and recanalization times. The number of stentriver passes during each procedure as well as presence of ICH post procedure were recorded. A logistic regression analysis was done to determine the association between hemorrhagic transformation and number of passes.

Results:
277 patients (mean age 71.6 ± 12.6 years; 52% female) with AIS underwent EVT with stentrievers. There was no difference in baseline demographics. (Table 1) Of the 277 patients, 47 (17.0%) were diagnosed with ICH after EVT. Ninety-day mortality was higher in patients with ICH than in patients without ICH (15.7% vs 42.6%; P=.001). On multivariate analysis, the number of passes with a stentriever were not significantly associated with ICH after EVT (OR, 1.3; 95% CI, 0.89-1.9). There was no significant difference in rates of intracranial hemorrhage occurrence with ≥5 passes (OR, 5.0; 95% CI, 0.31-82.4).

Conclusions:
Our study shows that endovascular treatment with multiple passes of a stentreiver does not increase the incidence of symptomatic hemorrhage in AIS, even up to 5 passes. Large prospective studies are warranted to study the factors that lead to hemorrhagic transformation in AIS.
Abstract TMP100: Safety & Accuracy of Superselective Wada Testing Prior to Brain Arteriovenous Malformation Embolization: A Single Center Experience
Authors: Male Shailesh , Tore Huseyin , Mehta Tapan , Quinn Coridon , Grande Andrew , Tummala Ramachandra , Jagadeesan Bharathi
Published: October 2018

Introduction:
Brain arteriovenous malformations (bAVMs) are sometimes embolized in preparation for surgical resection or radiosurgery. In some cases, super-selective Wada testing (SSWT) can help determine the safety of trans-arterial embolization prior to injection of the embolic agent from a specific intracranial vessel. We evaluated the safety and accuracy of SSWT in a series of patients who underwent bAVM embolization.

Methods:
We retrospectively evaluated the performance of SSWT in a series of consecutive patients with bAVMs who underwent trans-arterial embolization between 2009 and 2017. Prior to bAVM embolization, SSWT was performed during the same session using either methohexital or sodium amytal with or without lidocaine as per institutional availability and operator preference. The test was considered positive if the patient developed a neurological deficit and negative if there was no change from the baseline neurological exam. The accuracy of SSWT was assessed based on the neurological outcomes following each endovascular embolization session in the form of negative predictive value (NPV).

Results:
Over 8 years, 21 SSWTs were performed in total of 10 patients (8 males) with bAVMs (Median Spetzler-Martin grade was 3, range 2-5). The median age at the time of treatment was 42. The test involved the dominant hemisphere in 33.3%, and the anterior circulation in 81.8%. The test was positive in 3/21 (16.7%), negative in 17/21 (80.9%) and indeterminate in 1/21 (4.8%) session. Positive testing resulted in an altered management plan each time. In one patient, SSWT was presumed indeterminate as patient exhibited similar symptomatology regardless of the artery from which SSWT was performed. Following each negative and/or indeterminate test, the patient underwent embolization as planned with either nBCA glue 1/18 (5.6%) or Onyx-18 17/18 (94.4%). None of the patients who had SSWT developed neurological or other systemic complication post-procedure with or without embolization. This translated to NPV of the SSWT test prior to bAVM embolization to be 100%.

Conclusion:
SSWT appears to be safe in patients undergoing bAVM embolization, and has a high NPV. This can alter the management in a subset of patients where the bAVM is at or near eloquent cortical areas.
Abstract TMP101: Magnetic Resonance Quantitative Arterial Tortuosity Reveals Evidence of Otherwise Occult Arteriopathy in Pediatric Patients With Cryptogenic Arterial Ischemic Stroke
Authors: Taylor J Michael , DeVela Gabe , Leach James L , Vadivelu Sudhakar , Zhang Bin , Linscott Luke , Chen Alan , Furthmiller Andrew , Abruzzo Todd
Published: October 2018

Background and Purpose:
Quantitative arterial tortuosity (QAT) has been reported as an imaging biomarker of arteriopathy in pediatric arterial ischemic stroke (AIS) due to dissection and transient cerebral arteriopathy. We sought to determine if QAT abnormalities are present in cryptogenic pediatric AIS patients.

Methods:
Children with non-cardiogenic non-traumatic AIS and normal case controls who underwent MRA of the head and/or neck were identified by retrospective electronic medical record review. Patients with pre-existing clinical risk factors for AIS were excluded. The remaining cases were classified according to stroke subtype. The study population consisted of cryptogenic stroke cases. Patients with AIS due to spontaneous dissection were compared as positive case controls. Patients considered to have Bow Hunter’s Physiology (BHP), and normal case controls were also compared. QAT indices of 5 cervicocerebral arterial segments were measured in all patients using automated image processing software, and differences between groups were analyzed.

Results:
In normal children, QAT of the cervicocerebral arteries showed significant age-related variability, but no sex-related differences. In pediatric patients with cryptogenic stroke, QAT indices of the cervicocerebral arteries were significantly different relative to normal case controls (p<0.05), and similar to those measured in positive case controls with spontaneous dissection. The cervicocerebral QAT indices of pediatric AIS patients with BHP were not significantly different than those measured in normal controls.

Conclusions:
QAT is a specific and independent biomarker of arteriopathy in otherwise cryptogenic pediatric AIS, even when conventional clinical or imaging biomarkers of arteriopathy are absent. QAT shows promise as an independent diagnostic criterion for arteriopathy in children with AIS.
Abstract TMP104: Stroke in Paediatric Bacterial Meningitis
Authors: Dunbar Mary J , Shah Hely , Shinde Siddharth , Vayalumkal Joseph , Vanderkooi Otto G , Kirton Adam
Published: October 2018

Introduction:
Bacterial meningitis is a severe intracranial infection with a high complication rate. Neurological morbidity relates to parenchymal involvement where vascular mechanisms and stroke may predominate. Here, we systematically identified all neonates and children with bacterial meningitis and compared those with and without MRI-confirmed stroke. We hypothesized that patterns of stroke would correlate with causative organism and neurological outcome.

Methods:
Population-based (2.2 million), ten-year retrospective (2002-2012) cross-sectional study in Southern Alberta, Canada. Inclusion criteria were: (1) age from newborn (including prematurity) to 18 years, (2) brain MRI including DWI during admission, and (3) laboratory confirmed acute bacterial meningitis. Demographics, clinical presentations, risk factors, and laboratory findings were extracted. Original imaging was blindly reviewed and classified for stroke and injury pattern. Outcomes were extrapolated to the Pediatric Stroke Outcome Measure (PSOM).

Results:
Twenty-four patients had confirmed bacterial meningitis and acute MRI (6 neonates, 83% male, and 18 children, mean age 3.14+/-3.9 years, 67% male). Arterial ischemic stroke was confirmed in 9/24 (38%). Strokes were often multifocal (89%), particularly in neonates (100%). Subjects with stroke were more likely to have longer duration of illness prior to presentation, meningismus, prolonged fever, seizures, and new focal neurological signs. The most common organisms were S. pneumonia in older children (44%) and group B streptococcus in neonates (33%). Three patients received steroids, 3 ASA and 1 heparin and ASA. Mortality was 22% in children with stroke and zero in those without (p=0.16). Survivors with stroke were more likely to have motor deficit (71% vs. 25%, p = 0.07), cognitive deficit (75% vs. 38%, p = 0.5), and speech deficit (60% vs. 10%, p = 0.08).

Conclusions:
More than a third of children with bacterial meningitis warranting MRI have stroke. Associations include longer duration of illness, meningismus, focal neurological signs and common causative organisms. Stroke was associated with higher mortality and morbidity, warranting consideration of increased MRI screening and new approaches to treatment.
Abstract TMP106: Humanized Sickle Mice Are Sensitive to Hypoxia-Ischemia-Induced Stroke, but Respond to Tissue Plasminogen Activator Treatment
Authors: Sun Yu-Yo , Lee Jolly , Huang Henry , Wagner Mary B , Joiner Clinton H , Archer David R , Kuan Chia-Yi
Published: October 2018

Introduction:
Stroke, a devastating complication in children with Sickle Cell Anemia (SCA), consists of silent cerebral infarct (SCI) and large overt stroke. The current management relies on blood transfusion without the use of thrombolytic agents. However, a recent study showed that co-existent SCA does not impact the safety of tissue plasminogen activator (tPA) treatment. This finding calls for systemic analysis of the effects of thrombolysis in experimental stroke.

Hypothesis:
We hypothesize that sickle mice are highly vulnerable to hypoxia/ischemia-induced stroke, but respond to tPA-thrombolytic therapy.

Methods:
Townes sickle mice (knock-in/out mice that express the human α, γ, and sickle-β hemoglobin genes) were subjected to Doppler measurement of the carotid artery and evaluated for their responses to repetitive-mild hypoxia-ischemia (rmHI) and transient hypoxia-ischemia (tHI)-induced stroke at 3 and 6 months of age, respectively. The effects of tPA treatment after tHI in sickle mice were also examined.

Results:
First, 3-month-old sickle mice of SS genotype with a higher resistive index (RI) in common carotid artery were also prone to rmHI-induced cerebral infarct and mortality. Second, 6-month-old SS mice developed elevated flow velocity and greater RI without stenosis of the carotid artery akin to those previously implicated in large overt stroke in SCA. Finally, 6-month-old SS mice endured 20-min, but manifested enhanced leukocyte and platelet adherence to cerebral blood vessel, as well as, extensive vascular perfusion deficits and fibrin deposition at 4 h post-injury, followed by greatly increased mortality than AA and AS mice at 24 h recovery (p<0.0001, n>8 for each group). Importantly, intravenous tPA treatment at 0.5 h post-tHI markedly improved vascular reperfusion, mitigated fibrin deposition, and cut the mortality of SS mice by nearly 60%.

Conclusions:
Humanized sickle mice develop hyper-coagulation and hypersensitivity to HI-induced stroke without large-vessel obstructive vasculopathy at up to 6 months of age. Elevated RI may be an early ultrasonic marker for sickle cell vasculopathy and the risk of SCI in SCA. Future studies are warranted to confirm the therapeutic benefits of thrombolytic stroke therapy in SCA.
Abstract TMP108: Stroke Prediction for Patient Undergoing Carotid Artery Occlusion for Carotid Blowout Syndrome Using Computed Tomography Angiography of the Circle of Willis
Authors: Lee Bo-Ching , Lin Yen-Heng , Lee Chung-Wei
Published: October 2018

Permanent common and/or internal carotid artery occlusion (PCO) is an effective treatment for carotid blowout syndrome (CBS). However, PCO may cause stroke, especially border zone infarction, when the collateral flow to the deprived brain territory is insufficient. In this study, we aimed to test the predictive value of collateral reserve on computed tomography angiography (CTA) for assessing post-PCO stroke risk in patients with CBS. In this retrospective institutional review board–approved study, we included 31 patients receiving unilateral PCO for CBS between May 2009 and December 2016. Two neuroradiologists evaluated all preprocedural CTA to determine the collateral reserve of the circle of Willis. The risk of post-PCO stroke was graded into very high risk, high risk, intermediate risk, low risk, and no risk, and were subjected to receiver operating characteristic curve analysis. Defining the very high risk and high risk groups as positive, the performance of reader’s consensus on CTA for predicting border zone infarction was excellent, with an area under receiver operating characteristics curve of 0.938 (95% confidence interval: 0.85–1.00). The overall sensitivity, specificity, positive predictive value, and negative predictive value was 85.7%, 87.5%, 66.7%, and 95.5%, respectively. The interobserver reliability was excellent (κ = 0.807). No significant difference in the receiver operating characteristics curves were found between the two readers (P = 0.114). In conclusion, CTA can be used to predict border zone infarction after PCO by measuring the collateral reserve of the circle of Willis.
Abstract TMP109: Remote Platelet Function Testing Using Measurement of P-selectin in Patients in the Triple Antiplatelets for Reducing Dependency in Ischaemic Stroke (TARDIS) Trial
Authors: Woodhouse Lisa J , Dovlatova Natalia , May Jane , Heptinstall Stan , Bath Philip M
Published: October 2018

Background:
Platelet activity may be measured remotely as surface P-selectin expression and varies between antiplatelet agents and patient responses to them.

Methods:
In TARDIS, patients with acute non-cardioembolic ischaemic stroke or transient ischaemic attack were randomised to intensive (combined aspirin, clopidogrel and dipyridamole, ACD) or guideline antiplatelets (combined aspirin and dipyridamole, AD; or clopidogrel alone, C). On-treatment platelet function, assessed as surface P-selectin expression, was measured remotely at 7 days post randomisation. The tests detected the effects of aspirin and of clopidogrel (Platelet Solutions Ltd). Data are mean difference (MD) with 95% confidence intervals (CI).

Results:
626 patients (intensive 312, guideline AD 142, C 172) had P-selectin taken at day 7: mean age 68.3 (10.0), 66.3% male. In a comparison of on-treatment P-selectin (Table 1), the aspirin test showed that platelet reactivity was lower with ACD than AD (p=0.005) and C (p<0.001). ACD failed to suppress P-selectin levels below 500 units in 13 (4.4%) patients. Conversely, the clopidogrel test demonstrated that platelet reactivity was higher in patients receiving ACD than C (p=0.020). Treatment with C did not suppress P-selectin levels below 860 units in 22 (12.9%) patients.

Conclusion:
The aspirin test indicated that ACD was more effective in supressing stimulated platelet surface P-selectin than AD. However, the clopidogrel test showed treatment with C to be more effective than ACD, although 12.9% of patients had high residual platelet reactivity.
Abstract TMP114: Oxidized Low Density Lipoprotein Predicts Recurrent Stroke in Patients With Minor Stroke or Transient Ischemic Attack
Authors: Wang Anxin , Meng Xia , Wang Yongjun , Wang Yilong
Published: October 2018

Introduction:
Elevated oxidized low-density lipoprotein (oxLDL) was shown to be related to atherosclerotic cardiovascular diseases, but the role of oxLDL in predicting recurrent stroke in patients with minor stroke or transient ischemic attack remains unclear. We aimed to investigate the association between oxLDL and recurrent stroke.

Methods:
In the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial, baseline oxLDL levels were measured. The primary outcomes were any stroke within 90 days and 1 year. The association of oxLDL with recurrent stroke was analyzed by using Cox proportional hazards model.

Results:
Among the 3019 patients included in this study, the median (IQR) of oxLDL was 13.96 (6.65-28.81) ug/dl. After adjusted for conventional confounding factors, patients in the highest oxLDL quartile had a higher risk of recurrent stroke within 90 days (HR, 1.42; 95% CI, 1.02-1.96) and 1 year (HR, 1.41; 95% CI, 1.05-1.90) compared with the lowest oxLDL quartile. There was no significant interaction between oxLDL levels and randomized antiplatelet therapy.

Conclusions:
Elevated oxLDL levels can independently predict recurrent stroke in patients with minor stroke or transient ischemic attack.
Abstract TMP17: Impaired Perfusion Imaging Predicts Recurrent Cerebrovascular Events in Symptomatic Large Vessel Stenosis
Authors: Sacchetti Daniel C , Cutting Shawna M , McTaggart Ryan A , Chang Andrew D , Hemendinger Morgan , Dakay Katarina , Mac Grory Brian , Siket Matthew S , Burton Tina , Thompson Bradford , Rostanski Sara K , Merkler Alexander , Gialdini Gino , Lerario Michael P , Prabakharan Shyam , Rogg Jeffrey , Kamel Hooman , Willey Joshua Z , Marshall Randolph S , Elkind Mitchell S , Khatri Pooja , Furie Karen L , Jayaraman Mahesh V , Yaghi Shadi
Published: October 2018

Importance:
Large vessel disease (LVD) stroke subtype carries the highest risk of early recurrent stroke, reaching up to 30% in the first few days. Predictors of early recurrence have been previously described, but less is known regarding infarct expansion and other causes of neurological worsening. We aim to determine the association between impaired perfusion and neurological decline in patients with LVD subtype.

Methods:
This is a single center retrospective cohort study of all consecutive patients 18 years or older with LVD admitted with a diagnosis of ischemic stroke within 24 hours from symptom onset (12/1/2016 to 3/31/2017). Patients with 1) evidence of ≥ 50% stenosis of a large intra- or extracranial artery on computerized tomography angiography (CTA); 2) symptoms referable to the territory of the affected artery and NIHSS < 15 and 3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable mismatch volume ≥15 mL, defined as perfusion deficit of Tmax > 6sec volume minus infarct volume similar to neuro-interventional trials. The outcome was recurrent cerebrovascular events (RCVE) at 90 days (adjudicated independently by two vascular neurologists) defined as a decline in neurologic function in the absence of a medical cause, or new infarct or infarct extension in the territory of the affected artery. We estimated the hazard ratio (HR) and 95% confidence interval (CI) for unfavorable perfusion imaging as predictor of RCVE using univariable and multivariable Cox proportional hazards models.

Results:
Sixty-eight patients met our inclusion criteria (mean age 64.7 years; 61.8% male; 58.8% intracranial LVD). When compared to patients without RCVE, patients with RCVE were more likely to have unfavorable mismatch volume [71.4% vs. 14.8%, p<0.001]. This association persisted after adjusting for sex, dual antiplatelet therapy, initial stroke severity, and intracranial location of LVD (adjusted HR 15.6, 95% CI 3.7-66.7, p<0.001).

Conclusion:
Perfusion mismatch is associated with RCVE in patients with ischemic stroke due to LVD. Pursuit of more aggressive treatment and management strategies may be warranted in this population.
Abstract TMP18: Heparin Resistance is an Independent Predictor of Poor outcome in Cerebral Venous Sinus Thrombosis
Authors: Aksan Nazan , Samaniego Edgar , Shaban Amir , Siddiqui Fazeel , Dai Biyue , Ahmed Uzair , Granchi Julia , Zheng-Lin Binbin , Morcuende Jorge , Adams Harold , Leira Enrique , Ortega-Gutierrez Santiago
Published: October 2018

Background and purpose:
Unfractionated Heparin (UFH) infusion represents the most commonly used therapy in the acute management of cerebral venous sinus thrombosis (CVST). effectiveness of heparin in reaching therapeutic anti-coagulation levels has not been well studied in this population. Identifying subgroup of patients who will not respond to Heparin may prove useful in studying alternative treatments such as the new oral anticoagulants and endovascular therapy. We aimed to evaluate the initial response to heparin infusion measured by partial thromboplastin time (PTT) and it implication in discharge outcome.

Methods:
Retrospective review of all consecutive patients at University of Iowa Hospitals and Clinics between 2004-2014 with CVST was conducted. All patients were treated with initial weight based bolus (14units/kg) of UFH followed by infusion. Consecutive PTT values in the first 48hrs of admission were classified as either therapeutic (40-87), supra-therapeutic (>87), or resistant (<40). Then patients were classified as good responders if 80% of PTT values were in the therapeutic range, classified as adequate if 65-79% of PTT values were therapeutic; rest of patients were classified as non-responders. Univariate and multivariate regressions models were performed to assess the association with discharge mRS, the primary outcome.

Results:
115 patients met inclusion criteria (76 women), mean age was 42. Mean PTT was 44.8 (SD=18.6; 95%CI of 41.2-48.5) in the first 48 hours. Patients resistant to Heparin (44%) had significantly worse functional outcomes, mRS [95%CI 2.3-3.6], compared to good [41%, 95%CI 1.2-2.3] and adequate responders to Heparin [15%, 95%CI 0.5-2.3] (p=.003). Mean PTT in the first 48 hours predicted discharge mRS, r=-.28,p<.005 and this effect remained significant when age, sex, altered mental status at admission were controlled, p=.001.

Conclusion:
A significant portion of patients that receive heparin do not reach therapeutic levels within the initial days after hospitalization, and this does not appear to be a consequence of disease burden in our population. Specifying clinical features that predict heparin resistance might help to identify patients that benefit from alternative anticoagulation therapies.
Abstract TMP25: Short Chain Fatty Acids Mediate the Beneficial Effects of Young Microbiome on Recovery in Aged Mice after Ischemic Stroke
Authors: Lee Juneyoung , Ganesh Bhanu P , Spychala Monica , Putluri Nagireddy , Ajami Nadim J , Durgan David J , Bryan Robert , McCullough Louise D , Venna Venugopal R
Published: October 2018

Introduction:
Age is a non-modifiable risk factor for stroke. The elderly have high mortality and delayed recovery after a stroke compared to younger patients, a finding that is recapitulated in murine models. Young animals that received aged biome after stroke had lower short chain fatty acids (SCFAs) in their feces and delayed recovery compared to young mice receiving young biome. SCFAs, generated primarily by gut bacteria are important signaling molecules for gut homeostasis. We hypothesize that fecal transplant from young donor/ SCFA producing bacteria into aged mice will improve recovery compared to mice that received aged biome.

Methods:
Aged C57BL/6 male mice (18-20 months) were subjected to middle cerebral artery occlusion and randomly assigned to one of two groups, either received: 1. aged biome or 2. young biome. In addition, a separate cohort of aged mice were randomized as above, and divided into two groups: 1. received a cocktail of SCFA producers + Inulin as substrate or 2. received vehicle control group. Mice were tested for motor and cognitive recovery for 14 days. Fecal samples were subjected to 16s sequencing and metabolomics. Tissues were collected at sacrifice and used for flow cytometry and IHC.

Results:
Aged mice that received young fecal transplants after stroke expressed higher SCFAs in their fecal samples (p<0.05) and demonstrated significantly improved stroke recovery in comparison to mice that received aged biome (n=9-10/grp; p<0.05). Young biome treated mice demonstrated rapid improvement in hang time (54.6±7.9s vs 32.6±3.3s; p<0.05) and better outcomes in open field (p<0.05). Aged mice with young biome had better cognitive outcomes compared to the aged biome group. Consistently, our ongoing studies show that transplanting selected strains of SCFA producing bacteria is sufficient to enhance recovery, as tested in hang wire test (64.7±20.4% vs vehicle 25.0±12.5%; n=4/grp; p<0.05).

Conclusions:
Metabolites produced by young microbiome improve post-stroke recovery in aged mice, enhance SCFAs, and reduce inflammation. Although SCFA production appears to be a key contributor to recovery, more studies are needed to elucidate the underlying mechanisms in order to develop a therapeutic strategy for the treatment of stroke patients.
Abstract TMP3: Age-Adjusted Infarct Volume Cut-off For Favorable Outcome After Large Vessel Occlusion Stroke Endovascular Therapy
Authors: Bouslama Mehdi , Haussen Diogo C , Grossberg Jonathan A , Barreira Clara M , Dehkharghani Seena , Rangaraju Srikanant , Frankel Michael R , Yoo Albert , Nogueira Raul G
Published: October 2018

Background:
Optimal selection paradigms for large vessel occlusion acute stroke endovascular therapy are yet to be established. Previous studies have shown the benefit of adjusting infarct size to age. We sought to study the impact of age-adjusted final infarct volumes (FIV), a surrogate for pre-reperfusion infarct core, on functional outcomes and determine the ideal thresholds for good outcome discrimination (90-day mRS 0-2).

Methods:
We reviewed our prospectively collected endovascular database at a tertiary care academic institution between 9/2010- 8/2016. All patients that underwent endovascular therapy for large vessel occlusion anterior circulation acute ischemic stroke were stratified into five age groups: (G1) <50 years, (G2) 50-69, (G3) 70-79 (G4) 80-89 and (G5) ≥90. Baseline, procedural, and radiological characteristics, as well as outcome parameters were compared. FIV was measure on follow-up MRI or CT within 5 days of treatment. : 966 patients were studied (G1:136, G2:408, G3:233, G4:160, G5:29). Overall, the mean FIV was 59.9±79.9mL and 46% had good outcome. Patients with poor outcome had larger FIV in each group (Mean/Median[IQR]) (G1:46.8/29.2[8.7-64.6] vs 145.3/91.5[51.9-223.5], G2:26.9/15.8[7.7-37.2] vs 93.6/68.1[22.2-146.8], G3:26.2/17.6[7.6-34.1] vs 96.1/61.9[25.5-130.9], G4:14.7/8.7[3.9-16.4] vs 60.2/29[13.6-85.2], G5:2.9/1.3[0.6-4.3] vs 58.3/36.6[18.2-91.1], p<0.01 for all). The target FIV cut-off (mL) decreased with increased age: G1:52.4(SE 75%, SP 65%); G2:23.2(SE 75%,SP 64%); G3:24.6(SE 76%,SP 64%); G4:13.4(SE 75%,SP 70%); G5:12.8(SE 79%,SP 100%). In multivariate analysis, after adjusting for age, baseline NIHSS, glucose level, reperfusion status, parenchymal hematoma and FIV, achieving a final infarct volume less than the age-adjusted target was an independent predictor of good outcome (OR:1.94 95%CI [1.06-3.53], p=0.03).

Conclusions:
Age-adjusted infarct volume represents a strong outcome discriminator substitute and might help refine patient selection for stroke endovascular therapy
Abstract TMP31: Exosomes Role in Brain Repair and Recovery in Stroke. A Dose Response Study
Authors: Gutiérrez-Fernãndez María , Laso-García Fernando , Gømez-de Frutos Mari Carmen , Otero-Ortega Laura , Alonso Løpez Elisa , Martínez Arroyo Arturo , Diekhorst Luke , Arrúe Gonzalo Mercedes , Fuentes Blanca , Diez Tejedor Exuperio
Published: October 2018

Aim:
To assess the efficacy of 3 doses of exosomes from adipose tissue derived human mesenchymal stem cells to identify the minimal effective dose to enhance brain repair and recovery after subcortical stroke in rats.

Methods:
Male and female Sprague-Dawley rats (250gr) were injected with endothelin-1 to induce subcortical stroke. 24h after stroke, exosomes were administrated by the tail vein. Study groups were: Sham (n=10): without stroke neither treatment; control: stroke+saline (n=8); stroke+low dose (50μg) (n=10); stroke+intermediate dose (100μg) (n=9); stroke+high dose (200μg) (n=10). We evaluated: motor function (Roger’s, Rotarod and Walking beam test) at 24h, 7 and 28d, lesion volume and tract connectivity were studied by magnetic resonance image at 24h and 28d, brain repair markers: GFAP (Glial Fibrillary Acidic Protein), MOG (Myelin Oligodendrocyte Glycoprotein), MBP (Myelin Basic Protein) by immunofluorescence at 28d.

Results:
Animals treated with 50μg, 100μg or 200μg of exosomes showed a significant improvement in functional evaluation compared to control (p<0.05). Between treatments, high dose of exosomes demonstrates better functional recovery than low and intermediate doses at 24h and 7d, but without significant differences at 28d (p<0.05). We did not observe reduction of lesion size in treated compared to control groups, however, all doses showed the same significant increase in tract connectivity compared to control group at 28d (p<0.01).All the doses (low, intermediate and high) decrease GFAP expression and increase MOG and MBP expression compared to control group. Also GFAP expression was significantly downregulated in high dose compared to intermediate and low doses (p<0.05).MOG expression was higher in intermediate and high doses compared to low dose (p<0.05).

Conclusion:
Intravenous administration of different doses of exosomes (50μg, 100μg and 200μg) improves the functional recovery, tract connectivity and expression of brain repair markers. Low dose is as effective as intermediate and high doses. Therefore, 50μg of exosomes is the minimal effective dose to enhance brain repair and recovery in stroke.From a translational point of view, this dose decreases the cost and risk.
Abstract TMP33: TXA302 Promotes Permanent Functional Recovery With Delivery Initiated Up to 4 Weeks After Stroke in Multiple Rodent Models
Authors: Caggiano Anthony O , Iaci Jennifer F , Wagner A. Elizabeth , Franklin Richard
Published: October 2018

Introduction:
TXA302 is a proprietary analogue of angiotensin 1-7 (Ang1-7). Previous studies have shown that intracerebroventricular administration of Ang1-7 as a pre-treatment to experimental occlusive rodent stroke resulted in improved neurological function, decreased infarct volume, enhanced cerebral blood flow and decreased inflammation. Here, systemic administration of TXA302 was evaluated with treatment delayed up to 4 weeks to assess the potential of TXA302 to promote recovery in chronic stroke.

Methods and Results:
Four independent studies were conducted in the rat transient (2 hour) and permanent middle cerebral artery occlusion (MCAO) models. Daily subcutaneous delivery of TXA302 or vehicle was started either 24 hours or 4 weeks after MCAO and continued for 4, 6 or 8 weeks. Treatment was started at 4 weeks to assess the ability of TXA302 to promote recovery independent of neuroprotection and to model the chronic phase of the injury. Two of the studies employed a dose range of TXA302 from 1 to 500 μg/kg and two studies had a washout period of 4 weeks after the completion of dosing to assess the permanence of the recovery effect. Sensorimotor recovery was measured by limb placing, stepping, and body swing tests along with composite neurological scoring. Cerebral blood flow (CBF) was evaluated by doppler ultrasonography. All studies were conducted in a blinded fashion and recovery of treated animals was compared to vehicle by repeated measures ANOVA with corrections for multiple comparisons. TXA302 treatment resulted in significant, robust and permanent dose-responsive improvements in neurological function and CBF compared to vehicle treated animals.

Conclusions:
The ability to delay treatment for 4 weeks suggests the changes are not attributable to neuroprotection. Furthermore, this wide therapeutic window enhances translational potential as clinical trials can be conducted without confounding factors of treating, stabilizing and assessing baseline functional measures in acute stroke patients. Ongoing studies are exploring the potential of TXA302 to enhance endogenous remodeling through angiogenesis and neural plasticity. Non-clinical studies and manufacturing development are underway to enable an IND for stroke recovery.
Abstract TMP37: Social Network Size at Stroke Onset is Associated With 3 and 6-Month Stroke Outcomes
Authors: Dhand Amar , Luke Douglas , Kim Angela , Feske Steven K , Lang Catherine E , Lee Jin-Moo
Published: October 2018

Introduction:
Social mechanisms involved in stroke recovery are important and underutilized. For at least three decades, research has shown that social factors such as living alone negatively influence outcomes after stroke. Prior studies relied on social support measures without study of the network social structure. Our study uses higher-resolution social network analysis to examine structure (e.g., size and connectivity) and composition (e.g., proportion kin) in relation to stroke outcomes at 3 and 6 months.

Hypothesis:
Social network structural traits, size and connectivity, at stroke onset is related to the Patient Recovery Outcome Measurement Information System (PROMIS) physical function score at 3 and 6 months.

Methods:
In a cohort study, 160 patients with a first-time ischemic stroke were enrolled at stroke hospitalization. Social network characteristics were assessed using a bedside survey interview. The PROMIS physical function score was assessed on the phone at 3 and 6 months after stroke. Unadjusted and adjusted analyses were completed using Spearman Correlation and multivariate linear regression.

Results:
144 patients (90%) at 3 months and 120 patients (75%) at 6 months completed the study. The mean age was 62, and NIH stroke scale was 3. Social network size at stroke onset was positively associated with 3- (spearman correlation=0.22, p<0.01) and 6-month (spearman correlation=0.21, p=0.02) PROMIS physical function score. Connectivity measures and the proportion of kin in the network were not associated with the outcome. After control of age, stroke severity, and depression, network size remained strongly associated to physical function at 3 and 6-months, beta=0.74 [0.51,0.97], p<0.01.

Conclusions:
Of social network traits, network size at stroke onset is independently associated with physical function after stroke. Small networks are an important risk factor for poor recovery, likely equivalent to traditional risk factors.
Abstract TMP39: Patterns of Discharge Antidepressant Therapy Use After Acute Ischemic Stroke: Insights From the Prosper Study
Authors: Shah Shreyansh , Xu Haolin , Xian Ying , Maisch Lesley , Hannah Deidre , Lindholm Brianna , Lytle Barbara L , Pencina Michael , Olson DaiWai M , Smith Eric E , Fonarow Gregg C , Schwamm Lee H , Bhatt Deepak L , Hernandez Adrian F , O’Brien Emily C
Published: October 2018

Background:
Antidepressant (AD) therapy has been shown to improve post-stroke depressive symptoms, yet few data are available on characteristics associated with treatment at the time of discharge after ischemic stroke.

Methods:
PROSPER is a PCORI-funded study designed by researchers and stroke survivors to evaluate the effectiveness of therapies post-stroke. We used information from ischemic stroke patients discharged from April 2014 - December 2014 in the American Heart Association’s Get With The Guidelines (GWTG)-Stroke registry who were linked to Centers for Medicare and Medicaid Services (CMS) data to evaluate antidepressant medication use following hospitalization for ischemic stroke.

Results:
Of 29,177 eligible patients from 1,023 hospitals, n=7,593 (26.0%) were prescribed AD at hospital discharge. The majority of discharge AD prescriptions were for an SSRI (70.6%) and in patients with history of depression and on AD prior to admission. Patients discharged on an AD were more likely to be female, of white race, and to have a prior history of cardiovascular diseases (Table). Discharge AD prescription was more common at teaching hospitals, hospitals with larger bed size and higher annual volume of ischemic stroke admissions. Amongst the patients who were not on AD prior to admission (22,437), only 8.1% were discharged on AD. Patients discharged on AD amongst AD naïve population were more likely to be female, of white race, had prior history of depression, had higher initial NIHSS and more likely to be discharged to a facility.

Conclusions:
Among CMS linked patients, antidepressant prescription after ischemic stroke is low and varies by key patient and hospital level characteristics. Future research examining the association between discharge AD use and patient reported outcomes after stroke is needed.