bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 144: Astrocyte-Derived Interleukin-15 Accelarates Ischemic Brain Injury
Authors: Li Minshu , Li Zhiguo , Wood Kristofer , Jin Weina , Shi Fu-Dong , Liu Qiang
Published: March 2022

Background and Purpose:
Astrocytes play a pivotal role in post-ischemic brain inflammation, but the relevant astrocyte-derived mediators of ischemic brain injury remain to be defined. This study aims to investigate the impact of astrocyte-derived factors such as IL-15 on ischemic brain injury.

Methods and Results:
We show that IL-15 is a prominent factor relased by astrocytes after brain ischemia in a mouse model of transient focal brain ischemia. To further eluciate the biological functions of astrcoyte-derived IL-15 in ischemic stroke, we generated a glial fibrillary acidic protein (GFAP) promoter-controlled IL-15-expressing transgenic mouse line (GFAP-IL-15
tg
). We demonstrate that astrocyte-specific overproduction of IL-15 leads to larger brain infarcts, worse neurodeficits and enhanced lymphocyte infiltration. In GFAP-IL-15
tg
mice, we found increased accumulation and activation of CD8
+
T and natural killer (NK) cells after cerebral ischemia. Importantly, depletion of either CD8
+
T or NK cells in GFAP-IL-15
tg
mice prior to cerebral ischemia attenuates the accelerated brain infarction and neurodeficits. Of note, CD8
+
T and NK cells are within the proximity of astrocytes in the post-ischemic brain and either knockdown of IL-15 receptor α or blockade of cell-to-cell contact diminishes the activation and effector function of CD8
+
T and NK cells caused by astrocytic overproduction of IL-15, suggesting that astrocytic IL-15 is delivered
in trans
to target cells. Additionally, CD8
+
T and NK cells are seen closely adjacent to IL-15-producing astrocytes in acute ischemic lesions of postmortem human brain tissues, implying that astrocytic IL-15-mediated brain injury may be relevant to human stroke.

Conclusion:
These findings indicate that astrocytic IL-15 contributes to post-ischemic brain damage.
Abstract 147: Aberrant Activation of ASK1 Mediates Proinflammatory and Neurotoxic Microglial Responses After Cerebral Ischemia/Reperfusion
Authors: Shi Yejie , Pu Hongjian , Hu Xiaoming , Stetler Ruth A , Leak Rehana K , Zheng Ping , Gao Yanqin , Chen Jun
Published: March 2022

Introduction:
Neuronal death and proinflammatory microglial reactions both contribute to ischemic/reperfusion (I/R) brain injury. However, the molecular interplay of these two events is poorly understood.

Hypothesis:
Activation of ASK1, a key MAPKKK upstream of JNK and p38 MAPK signaling cascades, mediates neuronal death and microglial neurotoxicity after I/R.

Methods:
We created ASK1 kinase dead knock-in mice (ASK1-ki, K716R) with universal loss of ASK1 kinase activity. Brain injury and neurobehavioral deficits were assessed after 1h MCAO and reperfusion. Cell-permeable small peptides mimicking the docking sites on ASK1 for MKK3/6 (TAT-M3i) or MKK4/7 (TAT-M4i) were delivered into primary neurons and microglia, or into mice intranasally to inhibit ASK1-mediated p38 or JNK signaling, respectively.

Results:
MCAO induced robust ASK1/JNK/p38 activation in WT but not in ASK1-ki mice. ASK1-ki mice had reduced infarct (by 41.8%, p≤0.01, n=8) and improved sensorimotor and cognitive functions up to 28d vs. WT littermates. In primary cultures, OGD-induced neuronal death was attenuated in ASK1-ki neurons or in WT neurons treated with TAT-M4i. Conditioned medium from post-OGD neurons stimulated microglia toward the cytotoxic M1 phenotype, promoting the release of neurotoxic cytokines and NO. These responses were suppressed in ASK1-ki microglia, or WT microglia treated with TAT-M3i or p38α shRNA. Consistently, ASK1-ki mice had markedly reduced microglial M1 (but not M2) markers and proinflammatory cytokines after MCAO vs. WT. Finally, intranasal delivery of TAT-M4i and TAT-M3i (2, 24, and 48h after MCAO), but not either peptide alone, conferred long-term protection and improved sensorimotor/cognitive performance of WT mice up to 35d.

Conclusions:
ASK1 is an essential mediator of prodeath neuron-microglia interactions after I/R. Inhibiting ASK1 signaling is a promising and clinically feasible strategy to achieve sustained protection after stroke.
Abstract 152: Complications and Outcomes From Thrombolysis in Stroke Patients With Significant Pre-stroke Disability: Data From the UK National Stroke Registry
Authors: Paley Lizz , Bray Benjamin , James Martin , Tyrrell Pippa , Hoffman Alex , Cloud Geoffrey , Rudd Anthony ,   On behalf of the SSNAP Collaboration
Published: March 2022

Introduction:
National clinical guidelines in England and Wales recommend that intravenous thrombolysis is provided regardless of pre-stroke disability, but thrombolysis trials have included very few patients with a modified Rankin scale (mRS) score of more than 2. We therefore analysed data from the national stroke register of England and Wales of over 100,000 records to determine the safety and outcomes of thrombolysis in patients with varying levels of pre-stroke disability.

Methods:
Data were extracted from the national stroke register (Sentinel Stroke National Audit Programme (SSNAP)) of adults with acute ischemic stroke treated in all hospitals in England and Wales from April 2013-March 2015.

Results:
Of 128826 adults with acute ischemic stroke admitted to 202 hospitals, 23850 (18.5%) were dependent in some activities of daily living before stroke (mRS of more than 2). Of these, 1926 (8.1%) were treated with intravenous alteplase (iv-tPA).

Of the patients with an mRS greater than 2 who were treated with iv-tPA, 1239 (64.3%) were female, 120 (6.2%) had an onset whilst already an inpatient, and 1395 (72.4%) were fully conscious upon arrival at hospital. The median age was 84 years (IQR 78-89); the median NIHSS score 15 (IQR 9-21).

Of the 1320 patients (68.5%) with a fully completed NIHSS at arrival and at 24h after thrombolysis, the median change in NIHSS was a 3 point improvement (IQR 0-7).

A total of 214 patients (11.1%) had complications from thrombolysis; 104 (5.4%) had symptomatic intracranial hemorrhage, 10 (0.5%) had angioedema, 21 (1.1%) had extracranial bleeds and 82 (4.3%) had some other type of thrombolysis complication.

Inpatient case fatality rate was 29.2%, and 10.2% were newly institutionalised in a care home (14.4% of those discharged alive).

Conclusions:
Patients treated with iv-tPA who were not independent before stroke have similar rates of complications as reported for independent patients in national registries and clinical trials. However stroke for patients with pre-stroke disability carries a high risk of mortality and a high proportion of survivors are discharged to long term care for the first time.
Abstract 161: Prediction of Thrombolysis-induced Parenchymal Hemorrhage in Patients With Acute Ischemic Stroke: Use of MR Perfusion and Diffusion Biomarkers
Authors: Nael Kambiz , Knitter James , Jahan Reza , Alger Jeffry R , Nenov Val , Ajani Zahra , Feng Lei , Meyer Brett C , Olson Scott , Schwamm Lee H , Yoo Albert J , Marshall Randolph S , Meyers Philip M , Yavagal Dileep R , Wintermark Max , Liebeskind David S , Guzy Judy , Saver Jeffrey L , Kidwell Chelsea S
Published: March 2022

Purpose:
Ischemic stroke patients with low cerebral blood volume (CBV), low apparent diffusion coefficient (ADC) and increased microvascular permeability (K2) have increased risk of parenchymal hemorrhage (PH) after recanalization therapies. We have developed a predictive model to examine the risk of PH following revascularization therapies using combined MR perfusion and diffusion biomarkers.

Methods:
Voxel-based values of rCBV, K2, and ADC from the infarction core were obtained using pre-treatment MRI data from patients enrolled in the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) clinical trial. Using histogram analyses the 10
th
and 90
th
percentile values were calculated for the rCBV, ADC, and K2 variables for each patient. The associations between PH and extreme values of CBV (10%rCBV), ADC (10%ADC), and K2 (90%K2) in each patient were assessed in univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was performed to determine the optimal parameter/s and threshold for predicting PH.

Results:
In 83 patients included in this analysis, 20 (24%, 13 PH1, 7 PH2) developed PH. Univariate analysis showed significantly lower 10%rCBV and 10%ADC values and significantly higher 90%K2 values in patients with PH. After controlling for age, baseline NIHSS, infarct volume, and status of recanalization, multivariate logistic regression analysis identified 10%rCBV (p=0.002) and 90%K2 (p=0.03), but not 10%ADC (p=0.07), as independent predictors of PH. For 10%RCBV, ROC analysis showed the greatest AUC (0.87) at a threshold < 0.45 with sensitivity/specificity of 95%70%. For 90%K2, the greatest AUC (0.75) was obtained at a threshold of > 0.27 with sensitivity/specificity of 90%/60%. In a separate model, a combined K2-rCBV classifier remained the single independent predictor of PH (OR=33).

Conclusion:
Our results suggest that combined increased permeability and decreased rCBV derived from MR perfusion can be used for risk stratification in patients with AIS before undergoing revascularization therapies.
Abstract 166: Supervised Learning Based Detection of Stroke and Stroke Mimic
Authors: Abedi Vida , Goyal Nitin , Hosseinichimeh Niyousha , Tsivgoulis Georgios , Hontecillas Raquel , Bassaganya-Riera Josep , Lu Pinyi , Chang Jason , Ghaffarzadegan Navid , Elijovich Lucas , Metter Jeffrey E , Alexandrov Anne W , Liebeskind David S , Alexandrov Andrei , Zand Ramin
Published: March 2022

Background & Purpose:
Up to 30% of treated patients for suspected acute ischemic stroke (AIS) could be stroke mimic (SM). Using a balanced clinical dataset, we have developed a supervised learning method from artificial intelligence to classify AIS/transient ischemic attack (TIA) and SM in an emergency room (ER) setting.

Methods:
We labeled and randomly partitioned consecutive patients who received intravenous thrombolysis for suspected AIS in three tertiary centers during a three year period. The clinical data includes patients’ demographic information, past medical history, blood pressure and glucose level at presentation, NIH Stroke Scale, and presence of facial weakness. The clinical data were used to create a balanced training and testing set. We developed an Artificial Neural Network (ANN) model on patients’ clinical data, using the training set ( Figure 1). The model was used to classify the diagnosis of AIS/TIA versus SM. The ANN model was subsequently assessed using the testing set. In addition, we compared the ANN model with three regression models (ordinary least squares, logistic, and reduced logistic model).

Results:
In total 803 patients (mean age 62±15 years, 52% men, median admission NIHSS-score: 6 points, IQR 3-11) were analyzed. Data from 56 random patients, not included in the training set, were used to test the model. Of 56 predictions, 49 were correct (19 out of 20 correct prediction for SM, and 30 out of 36 correct prediction for AIS/TIA). Additional analysis indicated that the model detects SM with 95% sensitivity (95%, CI: 73-99%) and 83% specificity (95%, CI: 66-93%). We further performed a 10-fold cross validation to better estimate the performance of the model. In addition, the three regression models were comparable to the ANN model at a specific adjusted threshold.

Conclusions:
This study highlights a potential for ANN to discriminate AIS/TIA and SM. This model can be further optimized and integrated in patient management software in an ER setting.
Abstract 168: Feasibility and Safety of Thrombolysis by Telestroke Through Off-site Mobile Teleconsultation With iPad
Authors: Soo Yannie O , Ip Vincent , Leung K.T. , Chan Anne , Au Lisa , Fan Florence , Fan Florence , Ma S.H. , Leung Howan , Granham Colin , Wong Lawrence , Leung Thomas
Published: March 2022

Introduction:
For successful telestroke through the “hub-and-spoke model”, availability of neurologists 24-hour daily in hub hospitals is pivotal for immediate treatment advice. Unfortunately, this luxury is not available in Hong Kong due to shortage of neurologists.

To facilitate 24-hour thrombolysis service in Hong Kong, we provide telestroke support with a different model. During non-working hours, when no on-site neurologist is available, patients are evaluated by off-site neurologists through mobile teleconsultation with iPads. On contrary to hub-and-spoke model, where teleconsultations are conducted within the hospital under stable network with direct access to electronic patient records, we perform teleconsultations with iPads outside the hospital where mobile network is location-dependent and access to electronic record is indirectly through a firewalled hospital network.

Hypothesis & Objectives:
The objective of this study is to evaluate the feasibility and safety of this telestroke model.

Methods:
We recruited 118 consecutive patients evaluated by off-site mobile telestroke for thrombolysis triage in Prince of Wales Hospital during the period from May 2012 to November 2014.

Results:
Technical problems were encountered in 27 patients (22.8%), including failure to access CT brain images in 13 cases, which required use of backup teleradiology system. Nevertheless, since the implementation of telestroke, the number of patients who received thrombolysis has increased by > 3-fold. Seventy-eight patients received thrombolysis through telestroke, and had outcome comparable to 84 patients thrombolysed by on-site neurologists. Favorable outcome at 3 months (mRS 0-1) were 46.2% in telestroke group vs 45.2% in on-site group, p = 0.907. Symptomatic intracerebral hemorrhage and mortality were similar between the two groups.

Conclusion:
Technical problems are common with off-site teleconsultations in the initial implementation of telestroke, that backup teleradiology system is essential. In Hong Kong where mobile network broadly covers most areas in the city, telestroke through off-site mobile teleconsultation with iPad is feasible, safe and significantly facilitates the implementation of 24-hour thrombolysis service.
Abstract 175: A Novel Orally-Active Small-Molecule Antagonist of the Platelet Protease-Activated Receptor-4, BMS-986120, Inhibits Arterial Thrombosis With Limited Impact on Hemostasis in Cynomolgus Monkeys
Authors: Wong Pancras C , Watson Carol , Bostwick Jeffery , Banville Jacques , Wexler Ruth , Priestley Scott , Marinier Anne , Bouvier Michel , Gordon David , Schumacher William , Yang Jing
Published: March 2022

Introduction:
BMS-986120 (BMS) is a novel orally-active antagonist of protease-activated receptor-4 (PAR4), a human platelet thrombin receptor, and is in phase I clinical trial. The antithrombotic potential of BMS was studied in models of electrically-mediated carotid artery thrombosis and bleeding time (BT) in cynomolgus monkeys, which have platelet thrombin receptors similar to human.

Methods:
Individual anesthetized monkeys were given orally of BMS (0.2, 0.5,1 mg/kg) or vehicle (n=8/group) 2 hour before a combination of thrombosis, BT and
ex vivo
biomarker experiments. Aspirin alone (ASA, 4 mg/kg/h IV) or in combination with BMS (0.5, 1 mg/kg) was also studied (n=8/group). Thrombus weight (TW) reduction, BT increase over vehicle in kidney (KBT) and mesenteric artery (MBT), and platelet aggregation (PA) inhibition were determined. Peak PA responses to activation peptides selective for PAR4 (PAR4-AP, 12.5 μM) and PAR1 (PAR1-AP, 18 μM), ADP (20 μM), and collagen (5 μg/ml) were determined by whole blood aggregometry.

Results:
BMS comparably inhibited PA induced by PAR4-AP in human and monkey blood
in vitro
(IC
50
of 9.5±2.7 and 2.1±0.4 nM, respectively). In monkeys, BMS produced parallel rightward shifts in the log PA dose response to PAR4-AP without affecting maximum response, suggesting surmountable antagonism. BMS (1 mg/kg) did not inhibit PA induced by PAR1-AP, ADP and collagen, supporting selectivity. BMS (0.2, 0.5, 1 mg/kg) reduced TW by 35±5, 49±4, and 83±4%, respectively. Maximum KBT and MBT increases were only 2.2-fold and 1.8-fold, respectively. A maximum antiplatelet dose of ASA (4 mg/kg/h, n=8) slightly reduced TW by 12±2% and increased KBT and MBT by 2.2- and 2.7-fold, respectively. Co-administration of ASA and BMS (0.5 or 1 mg/kg) reduced TW by 54±3 and 95±2%, increased KBT by 3.1- and 3.6-fold, and increased MBT by 2.6- and 3.3-fold, respectively (n=8/group). In companion monkey studies, clopidogrel (0.3 mg/kg/day, n=6) alone reduced TW by 49±6%, but increased KBT and MBT by 7.3- and 8.1-fold, respectively.

Conclusion:
In monkeys, BMS alone or combined with ASA prevents occlusive carotid artery thrombosis with limited impact on BT, demonstrating a wider therapeutic window than the standard of care antiplatelet drugs, aspirin and clopidogrel.
Abstract 193: Clinico-radiologic Severity of Subarachnoid Hemorrhage Predicts Coated-platelet Levels and Associated In-hospital Morbidity
Authors: Ray Bappaditya , Pandav Vijay M , Mathews Eleanor A , Thompson David M , Traore Aminata A , Dale George L , Prodan Calin I
Published: March 2022

Introduction:
Coated-platelets (CP), a subpopulation of activated platelets, can be used as a surrogate marker for systemic thrombogenic propensity. Microthrombosis causes delayed cerebral ischemia (DCI) and is a major determinant of morbidity after subarachnoid hemorrhage (SAH). Association studies have reported increased morbidity and mortality after SAH depending on disease severity at admission.

Hypothesis:
We hypothesized that severe clinical and radiological grades of SAH would be associated with increased CP and contribute to DCI.

Methods:
Prospective cohort of 44 patients with non-traumatic, spontaneous SAH was enrolled. Clinical and radiological severity was recorded using Hunt and Hess (H&H), World Federation of Neurosurgeons Scale (WFNS), Simplified Applied Physiology Score (SAPS-II), Acute Physiology and Chronic Health Evaluation (APACHE-II) and modified Fisher scale (mFS). DCI and clinical vasospasm were used to assess in-hospital morbidity. CP levels were measured on predetermined days after SAH for each patient using flow cytometry. Mixed linear models were used to study test hypothesis.

Results:
Cohort average age was 51.4 (IQR 44-58.5) and women representing 70.5% patients. Fifteen (34.1%) developed symptomatic vasospasm, and imaging identified 21 (47.7%) with DCI. During the first 5 days after SAH, scales indicating severe disease were associated with a 5-10% increase in CP. But this was only significant for mFS, 10.4% higher CP in grades 3 and 4 (95%CI: 1.5%, 19.4%; p=0.0251) than in those with grades 1 and 2. Similarly, higher clinical and radiological severity were associated with subsequent downtrending levels of CP after an initial rise but was only statistically significant for SAPS-II (upper tertile 0.8%/day vs middle tertile 1.7% vs lower tertile 1.02%/day, p=0.0297).

Conclusion:
Higher initial CP levels among patients with severe clinico-radiologic findings, along with declining CP trends over 21 days, suggest that neurohumoral triggers may induce systemic thrombogenicity and contribute to DCI and clinical vasospasm after SAH.
Abstract 199: Greater Clinical Impact From Accelerating Endovascular Reperfusion for Acute Ischemic Stroke Than Acute Myocardial Infarction
Authors: Aggarwal Sudhir , Saver Jeffery L
Published: March 2022

Introduction:
Time is brain; time is muscle. Faster endovascular reperfusion is associated with better outcome for both acute ischemic stroke due to large vessel occlusion (AIS-LVO) and ST-elevation myocardial infarction (STEMI). However, their relative pace of benefit gain with accelerated time has not been systematically investigated.

Methods:
We performed a systematic literature search to identify all multi center studies (RCTs and registries) between 2000-2015 reporting relation between onset to reperfusion (OTR) and clinical outcome for AIS-LVO, or onset to balloon (OTB) and clinical outcome for STEMI. Study sample size weighting was used to produce a combined estimate of outcome change associated with every 15 min reduction in total ischemia time.

Results:
Systematic search identified 11 AIS-LVO studies with 611 patients and 8 STEMI studies with 15,827 patients. Across AIS-LVO trials, median OTRs were 132 to 440 minutes; across STEMI trials median OTBs were 75 to 330 minutes. Among all clinical outcomes (Table), the one most responsive to faster treatment was functional independence at 90 days for AIS-LVO: for which every 15 min acceleration in OTR, 37 more of 1000 treated patients achieved functional independence. Degree of mortality reduction with faster treatment was relatively similar for both AIS-LVO and STEMI; for every 15 min acceleration, 2-6 more of 1000 treated patients survived. MI recurrence was insensitive to treatment times. For AIS-LVO, speedier treatment was also associated with reduced intracranial hemorrhage (ICH), with 19 fewer ICHs per 1000 patients with every 15 min acceleration.

Conclusion:
Considering important dichotomous clinical outcomes, accelerating onset to endovascular reperfusion time has 7-fold greater benefit in acute ischemic stroke than in acute myocardial infarction. As the nervous system has greater eloquence, functional diversity, and sensitivity to ischemia, time is more brain than muscle.
Abstract 205: Preceding Valsalva Maneuver Significantly Associated With Pathogenic Patent Foramen Ovale (PFO) in Patients With Cryptogenic Stroke
Authors: Nedeltchev Krassen , Lemmens Robin , Thaler David E , Michel Patrik , Weimar Christian , Kahles Timo , Serena Joaquin L , Thijs Vincent , Krämer Markus , Zedde Maria Luisa , Engelter Stefan , Luft Andreas , Eberli Franz , Müller-Eichelberg Andreas , Collins Lester , Hemelsoet Dimitri , De Pauw Adinda , Armon Carmel , Arnold Marcel , Mono Marie-Luise ,   The International PFO Consortium, NCT00859885
Published: March 2022

Background:
In patients with cryptogenic stroke (CS), a patent foramen ovale (PFO) can be incidental or pathogenic. The Risk of Paradoxical Embolism (RoPE) score has been developed to determine the likelihood that a PFO is pathogenic or incidental using clinical variables. We hypothesize that echocardiographic features and conditions promoting paradoxical embolism differ between patients with pathogenic and incidental PFOs.

Methods:
The International PFO Consortium collects clinical, radiological and echocardiographic data of patients with CS and PFO. In the original RoPE score, a value of 0-6 was classified as a low RoPE score and 7-10 as a high score. Since information on cortical versus deep stroke location (one of the items on the RoPE score) was not available, we used two alternative approaches to stratify for PFO pathogenicity. In a first approach, we used a 9-point score and lowered the cut-off for dichotomization by 1 point (RoPE score 0-5 vs 6-9). In a second approach, patients with a RoPE score of 6 were excluded since they could either be classified as low or high RoPE score depending on stroke location. The associations between RoPE stratum and echocardiographic features (atrial septal aneurysm (ASA), right-to-left shunt (RLS) at rest and large RLS) as well as conditions promoting paradoxical embolism (deep vein thrombosis (DVT), pulmonary embolism (PE) and Valsalva maneuver (VM) were studied.

Results:
We analyzed 1044 CS patients with a PFO. Average age was 55 (SD 16) and 635 patients (61%) were male. Preceding VM was more frequent in patients with a high vs low RoPE score in both analyses: 11% vs 5% (OR: 2.1 95%CI 1.3-4.3) and 10% vs 5% (OR: 2.0 95%CI 1.2-3.6). The distribution of ASA (35% vs 34% and 32% vs 34%, in the first and the second analysis respectively), RLS at rest (28% vs 28% and 29% vs 28%), large RLS (67% vs 66% and 65% vs 66%), PE (2% vs 2% and 1% vs 2%), and DVT (4% vs 4% and 3% vs 4%) did not differ by RoPE stratum.

Conclusion:
In patients with CS, preceding VM was significantly associated with pathogenic PFO, while echocardiographic features or conditions promoting paradoxical embolism were not. The formation of a significant right-to-left pressure gradient at the atrial septum level appears to play a substantial role in the pathogenicity of PFO.
Abstract 208: Non-gated Cardiac Ct Angiograms for Detection of Embolic Sources in Acute Ischemic Stroke
Authors: Yeo Leonard , Ting Eric , Eide Sterling E , Rathakrishnan Rahul , Soon Derek , Chan Bernard , Teoh Hock Luen , Wong Ho-fai , Sharma Vijay
Published: March 2022

Background and Purpose:
We assessed the diagnostic feasibility of using a 2-phase 64-slice non-gated cardiac computed tomographic angiography (CTA) in acute stroke patients, done in the same sitting as the brain CTA and using the same contrast dose, for the detection of a cardiac source of embolism. We expected to identify additional causes of stroke related to other unexpected pathology of heart or ascending aorta, which might be useful in therapeutic decision making and prognostication.

Methods:
We recruited 20 consecutive patients with acute ischemic stroke within the 4.5hours of symptom-onset, activated for intravenous thrombolysis. In addition to our usual CTA protocol that spanned from the arch of aorta to the circle of Willis, we enlarged the field of scanning to include the heart. Radio-contrast load (Omipaque 350) remained unchanged (injected at 3-4ml/sec; total 60-80mls, triggered by bolus tracking). All scans were 0.5cm thick slices and were reviewed by a radiologist and cardiologist and the abnormal findings were conveyed to the treating neurologist. In patients with potential cardiac source of embolism, an urgent trans-thoracic or trans-esophageal echocardiogram was arranged.

Results:
Of 20 patients, there were 3 abnormal findings, 1patient had a ventricular thrombus , 1 had a localized dissection in the ascending aorta and the third patient had a thrombus at the atrial appendage. Both were confirmed by trans-esophageal echocardiography and anticoagulation was started urgently the next day. None of our patients developed contrast nephropathy on follow up.

Conclusions:
expanding the field of scanning to include the heart and ascending aorta ( a non-gated cardiac CTA) to the routinely performed CTA of cervico-cranial arterial tree is a noninvasive and useful modality for detecting high-risk cardiac and aortic sources of embolism in acute stroke patients.
Abstract 210: Association between Paroxysmal Supraventricular Tachycardia and Ischemic Stroke in Patients Without Atrial Fibrillation
Authors: Kamel Hooman , Gladstone David , Turakhia Mintu , Healey Jeff , Elkind Mitchell , Karas Maria , Okin Peter , Iadecola Costantino
Published: March 2022

Introduction:
Paroxysmal supraventricular tachycardia (PSVT) is viewed as a benign heart-rhythm disorder. However, recent studies suggest that atrial dysrhythmias other than atrial fibrillation/flutter (AF) may signify an increased stroke risk.

Hypothesis:
PSVT is associated with subsequent ischemic stroke in patients without documented AF.

Methods:
We obtained inpatient and outpatient claims data from 2010-2011 in a 5% sample of Medicare beneficiaries ≥66 years of age. We included only patients with a pacemaker or defibrillator, since such patients often undergo interrogation of heart rhythm. Patients with AF or stroke before or at the time of device implantation were excluded. Our predictor variable was PSVT. The primary outcome was ischemic stroke and the secondary outcome was embolic stroke. All diagnoses were ascertained from ICD-9-CM codes using previously validated algorithms. We used Kaplan-Meier survival analysis and the log-rank test to compare outcomes in patients with and without PSVT, which was modeled as a time-varying covariate. Patients were censored at the time of incident AF, stroke, death, or on December 31, 2011. Cox proportional hazards analysis was used to assess the relationship between PSVT and stroke while adjusting for demographic characteristics and vascular risk factors.

Results:
Among 42,152 eligible patients with a median 1.8 years of follow-up, 2,245 (5.3%) had PSVT and 1,007 (2.4%) developed a stroke. The incidence of stroke after a PSVT diagnosis (2.17% per year; 95% confidence interval [CI], 1.45-3.24%) was significantly higher than in patients without PSVT (0.95% per year; 95% CI, 0.87-1.03%; P < 0.001). After adjustment for demographic characteristics and vascular risk factors, PSVT was associated with a higher hazard of stroke (hazard ratio [HR], 2.0; 95% CI, 1.3-3.0). This association appeared stronger for embolic stroke (HR, 3.6; 95% CI, 1.1-11.8).

Conclusions:
In Medicare beneficiaries with implantable pacemakers or defibrillators, PSVT was associated with ischemic stroke, especially embolic stroke, in the absence of documented AF. These results build on recent findings that disturbances of atrial rhythm and function other than AF may be a previously unrecognized stroke risk factor.
Abstract 211: Do Women Receive Less Aggressive Care Following Intracerebral Hemorrhage?
Authors: Chaturvedi Seemant , Koch Sebastian , Sekar Padmini , Moomaw Charles , Osborne Jennifer , Boehme Amelia , Demel Stacie , Li Janet J , Woodrich Elisabeth , Bracho Jorge , James Michael , Sheth Kevin , Cai Xuemei , Langefeld Carl , Woo Daniel ,   for the ERICH Investigators
Published: March 2022

Background:
Several studies have shown that women with ischemic stroke receive fewer proven therapies for secondary prevention. A small study found that women receive early DNR orders after intracerebral hemorrhage (ICH) more often than men (
Stroke
2013; 44: 3229) but national data regarding sex differences in ICH are lacking.

Objective:
To compare comorbidities and use of surgical treatments and palliative care between men and women with ICH. We tested the hypothesis that women receive less aggressive care after ICH.

Methods:
ERICH is a multi-center study of ICH risk factors and outcomes. We compared clinical variables, treatments (e.g., hematoma evacuation), and use of DNR orders in men compared with women. Chi square tests(categorical items) and t-tests (continuous items) were performed. Multivariable analyses assessed the likelihood of ICH surgery and/or palliative care after adjustment for variables that were significant (p<.05) in univariate analyses.

Results:
2964 patients (1220 women) were analyzed. Mean age was higher in women (65.0 vs. 59.9, p<.0001). There was no sex difference in hypertension frequency but women had a higher proportion of previous stroke (24.1% vs. 19.3%, p=.002), dementia (6.1% vs. 3.4%, p=.0007), and anticoagulant use (12.8% vs. 10.1%, p=.02). Men had a higher proportion of cocaine use (10.1% vs. 4.7%, p<.0001) and higher initial SBP (187.5 mm vs. 183.5 mm, p=.007). A higher proportion of women reported living alone (23.1% vs. 18.0%, p=.0005) and a higher proportion of women had a lobar ICH (36.9% vs. 27.4%, p<.0001). After adjustment for age, dementia, prior stroke, anticoagulant use, and ICH location, there was no difference in surgical treatment between men and women (OR=0.92, 95%CI=0.67-1.26, p=.59). Although a higher proportion of women were made DNR/comfort care (19.4% vs. 15.3%, p=.003), this finding was no longer significant after adjustment for ICH score, prior stroke, and dementia (OR for male sex=.96, 95%CI=0.77-1.22, p=.76).

Conclusions:
Despite sex differences in several categories, no observable sex differences were found in use of surgical therapies or use of DNR/comfort care in an American population. Future work should focus on whether sex differences exist following ICH in patient-centered outcomes.
Abstract 213: Effect of Idarucizumab on Intracranial Bleeding in Dabigatran-treated Patients: Initial Results From RE-VERSE AD
Authors: Bernstein Richard A , Pollack, Jr. Charles V , Weitz Jeffrey I , Reilly Paul A , Eikelboom John , Huisman Menno V , Kamphuisen Pieter W , Kreuzer Jörg , Levy Jerrold H , Steiner Thorsten
Published: March 2022

Introduction:
Dabigatran is a non-vitamin K antagonist oral anticoagulant (NOAC) licensed for stroke prevention in nonvalvular atrial fibrillation. In the RE-LY trial, both doses of dabigatran (110 mg and 150 mg bid) were associated with a significantly lower annualized rate of intracranial hemorrhage (ICH) than warfarin (0.23%, 0.32% and 0.76%, respectively). Nonetheless, the mortality rate with ICH in the context of any anticoagulation remains high, probably reflecting the effects of hematoma expansion. Whether a specific reversal agent for dabigatran will improve clinical outcomes in dabigatran-treated patients with ICH is unknown. RE-VERSE AD is an ongoing, open-label, phase 3, cohort study evaluating the extent to which idarucizumab, a humanized Fab fragment directed against dabigatran, reverses the latter’s anticoagulant effects in patients with serious bleeding or in those requiring urgent interventions. This study focuses on the results in patients with ICH.

Hypothesis:
Compared with historical controls, idarucizumab improves clinical outcomes in dabigatran-treated patients with ICH.

Methods:
Patients presenting with ICH were given intravenous idarucizumab 5 g as two 2.5 g bolus infusions administered no more than 15 minutes apart. The primary endpoint was the maximum reversal of the anticoagulant effect of dabigatran, based on central laboratory determination of the dilute thrombin time or ecarin clotting time.

Results:
In an interim analysis at 90 patients, 18 with ICH had been enrolled in RE-VERSE AD. Updated results on the effects of idarucizumab on coagulation parameters, imaging studies, and clinical outcomes in this patient subgroup will be presented.

Conclusions:
Currently, there are no specific reversal agents for the NOACs. We present the first data on the clinical outcomes for idarucizumab in dabigatran-treated patients who present with ICH.
Abstract 22: Reducing Readmissions in Stroke Patients With a Structured Nurse Practitioner (NP)/RN Follow-up Program
Authors: Condon Christina N , Lycan Sarah , Riddle Paula , Duncan Pamela , Bushnell Cheryl
Published: March 2022

Background:
Our aim was to determine whether a structured stroke follow-up clinic (SFC) could reduce 30-day and 90-day readmission rates for patients discharged home with ischemic/hemorrhagic stroke or TIA.

Methods:
Prior to discharge, NPs identified patients at high risk for readmission, an RN performed follow-up phone calls, and the clinic visit included a standardized and comprehensive stroke nurse practitioner (NPs) assessment. Phase 1 of the SFC (10/2012) consisted of phone calls within 7 days of discharge, and 2 NPs seeing patients within 2 weeks of discharge, which focused on education, prevention, recovery and evaluation for complications. Phase 2 (9/2014) expanded to an RN calling 90% of patients discharged home within 2 days, and any issues identified were managed by NPs before the SFC visit. Demographics, medical history, and processes of care were entered into a REDcap database. Differences in these factors and readmission across the 2 phases of the SFC were assessed. Multivariate logistic regression models for 30-day and 90-day readmissions were performed with adjustment for NIHSS and hospitalizations prior to the index stroke.

Results:
We analyzed 280 consecutive patients through 4/2015. Mean age 66.1 y ± 14.5, 51% women, median NIHSS 3 (IQR 1-5), 34% prior stroke/TIA, and 20% with prior hospitalizations. From phase I to phase 2, days from discharge to SFC decreased, and 90-day readmissions decreased (table). Patients readmitted within 30 days had lower SFC show rates (60% vs 82.9% not readmitted; p=0.006), as well as 90-days (69% vs 83% not readmitted; p=0.034). Multivariable modeling after adjustment for prior hospitalizations, prior stroke, and NIHSS showed that SFC show rate was associated with a 74% reduction in 30-day readmission (OR 0.26; 95% CI 0.11-0.66) and a 63% reduction in 90-day readmission (OR 0.37; 0.15-0.89).

Conclusions:
Stroke patients’ show rate for this SFC was independently associated with reduced 30-day and 90-day readmission.
Abstract 222: Hyperglycemia Reduces Levels of Soluble Amyloid Precursor Protein-α in Mouse Hippocampus and Cortex - Role of Cerebral Microvessels
Authors: He Tongrong , Santhanam Anantha , Katusic Zvonimir
Published: March 2022

In the present study, we tested hypothesis that hyperglycemia impairs the neuro-protective function of cerebral microvessels. Type 1 diabetes (T1D) was induced by treatment of mice with streptozotocin (blood glucose >300 mg/dL for 2 months). Brain tissues and cerebral microvessels were isolated from diabetic and control mice. We observed significant decrease in the protein levels of soluble amyloid precursor protein-α (sAPPα, a product of α-cleavage of APP and a neurotrophic and neuroprotective molecule) in the total brain tissue of diabetic mice (n=5, P<0.05). Further examination of brain regions revealed that the reduction of protein levels of sAPPα was only detected in hippocampus and cortex but not in cerebellum (n=6, P<0.05). Our studies also revealed that there were no significant differences in the protein expression of APP and its non-amyloidogenic processing enzymes, α-secretases (a disintegrin and metalloprotease 10 [ADAM10], ADAM9, and ADAM17) in total brain tissue between T1D mice and control mice (n=5-6, P>0.05). The protein level of β-processing enzyme BACE1 was also not changed in T1D mouse brain. In contrast, the protein levels of APP and ADAM10 were significantly decreased in cerebral microvasculature of T1D mice, as compared to control mice (n=9-10, P<0.05). Immunofluorescent confocal microscopy also demonstrated that expressions of APP and ADAM10 in cerebral microvasculature (identified by co-staining with CD31) in hippocampus and cortex were reduced in T1D mice. Of note, cerebrovascular protein levels of ADAM9, ADAM17 and BACE1 were not affected by hyperglycemia (n=5-7, P>0.05). These results suggest that hyperglycemia impairs APP expression and α-processing in brain vasculature, thereby leading to the reduction of brain content of sAPPα. The selective loss of neuro-protective molecule sAPPα in hippocampus and cortex may be an important mechanism contributing to the development of cognitive dysfunction in diabetes.
Abstract 23: Feasibility of the Stroke COunseling for Risk REduction (SCORRE) Intervention
Authors: Aycock Dawn M , Pycard Randa A , Thomas-Seaton LaTeshia C , Clark Patricia C
Published: March 2022

Young adult African Americans (AA) are disproportionately affected by stroke and stroke risk factors. Hypertension, diabetes and obesity contribute to early-onset stroke and strategies are needed to help AA adopt healthy lifestyles early.

Purpose:
To assess feasibility of the SCORRE intervention in at risk, young adult AA. SCORRE consists of a video of young AA stroke champions sharing their experiences with stroke and advice for reducing stroke risk; the AHA’s, web-based Life’s Simple 7 (LS7) risk assessment and education tool, and a behavioral risk reduction diary.

Methods:
A randomized controlled, two-group pre-post design with a 6-week follow-up was used. Data were collected using questionnaires, physiological measures, and a diary. We assessed stroke risk factor knowledge, perceived and actual stroke risk, risk reduction behaviors, and intervention satisfaction.

Results:
Of the 52 individuals who responded to flyers, 30 were enrolled and 29 completed the 6-week follow up. On average, participants were 23 ± 4.4 years, female, had some college education, and low-income. Mean LS7 scores were less than ideal, 8.1 ± 1.2 out of 10; participants averaged 2.1 ± 1.1 out of 7 risk factors, mostly inadequate diet, obesity and pre-hypertension. SCORRE participants (
n
=19) had significant improvements in stroke risk factor knowledge following SCORRE (pre=11.5 ± 1.6, post=13.2 ± 1.3 out of 15;
p
=.001) but not at 6 weeks (12.2 ± 2.5;
p
=.31); while control participants (
n
=11) had no significant improvements. SCORRE participants with an accurate perception of their stroke risk almost doubled (47% to 89%) compared to control participants (36% to 46%). The majority (89%) of SCORRE participants had diet or physical activity improvements at 6 weeks compared to 27% of control participants. SCORRE satisfaction scores were high 3.49 ± .35 out of 4; ≥83% were motivated to achieve better health, enjoyed the video, LS7 and diary, and felt the program length was appropriate.

Conclusion:
Results demonstrate SCORRE is feasible; had low attrition, improvements in knowledge, accuracy, and health behaviors were observed, and satisfaction of SCORRE was high. Further testing of SCORRE as a stroke risk reduction intervention is needed in a larger sample with a longer follow-up period.
Abstract 27: Stroke Camp Offers Emotional and Physical Relief for Stroke Caregivers
Authors: Mathews Maureen , Beck Judi , Bogner Anna , Dong Yi , Gibbons Michael , Jahnel Jan , Kramer Lauren , McNeil Clayton , Nair Deepak , Nunley Marylee , Parker Sarah , Schaer Larry , Swanson-Devlin Teresa , Wang David
Published: March 2022

Background:
Depression, loneliness, and social isolation are common among stroke survivors and caregivers (CG). Stroke camps offer a unique and positive experience for stroke survivors and CG. However, no data was found on impact of a stroke camp experience for CG. The Retreat and Refresh Stroke Camp provides two and a half days of education, recreation and support activities bringing survivors and CG together to share experiences. Camp is staffed by volunteer healthcare providers and therapists. A comprehensive questionnaire was used to conduct a survey of caregiver camp participants. Results are used to assess caregiver burden, education, and support activities

Objectives:
Determine the effect of stroke camp on the emotional well being and social conditions of CG.

Study Method:
Study was approved by local IRB. A comprehensive tool was used to survey all camp CG. Tool contains questions regarding demographics; items from PHQ-9, Caregiver Strain Index (CSI); effect of camp. Individuals attending camps from 2009 to 2015 were asked to participate. Survey data was collected utilizing SurveyMonkey, compiled and analyzed with descriptive statistic methodology.

Results:
Each camp hosted 10-12 stroke survivors and their CG. Sixty seven CG completed the survey. Seventy eight percent were female, 22% were from rural area and 80% of survivors were spouse/significant other. Majority (80%) felt stroke impacted work/ life with top three CSI indices including change in personal plans (64%), being confined to home (43%), and financial strain (40%). Most (75%) noted loss of time/freedom, 50% loss of communication capability, 45% loss of companionship. Half of CG felt overwhelmed/stressed/depressed upon returning home from the hospital. Stroke camp experience has made them feel less alone (79%), recharged (77%) and educated (58%).

Conclusion:
Stroke has a major adverse effect on most stroke CG. They must adapt to a new life style to adjust for the care of disabled loved ones. Stroke camp is an effective way of providing peer support, offering emotional relief, and presenting learning opportunities for stroke CG. Its long term impact and cost benefit still needs to be analyzed.
Abstract 28: A Nursing Swallow Screen is Better Than the National Institutes of Health Stroke Scale at Predicting Dysphagia
Authors: Cline Kristen G , Tart Rebecca C
Published: March 2022

Introduction:
The Joint Commission recommends all acute stroke patients undergo swallow screening prior to any oral intake to decrease risk of aspiration pneumonia. In a 2009 study, a nursing swallow screening tool was compared to the National Institutes of Health Stroke Scale (NIHSS) to identify dysphagia in acute stroke patients. They found the NIHSS was a better predictor for identifying dysphagia. This IRB-approved study replicated and expanded the 2009 study in a community hospital with stroke patients using a facility-based nursing Stroke Swallow Screen (SSS).

Hypothesis:
The investigators hypothesized that the results would corroborate the 2009 study for the purpose of streamlining acute stroke assessment in the Emergency Department (ED).

Methods:
SSS results, NIHSS scores and speech-language pathology (SLP) swallowing evaluations of adult ischemic and hemorrhagic stroke patients were collected retrospectively via medical chart review. SSS results and NIHSS scores were compared against the “gold standard” for dysphagia diagnosis, the SLP evaluation. Convenience sampling, based on diagnosis within a 24-month time interval, determined the study sample.

Results:
Dysphagia prevalence among subjects (N=240) was 45%. The SSS demonstrated 95.4% sensitivity compared to 80.6% for the NIHSS.

Conclusion:
The SSS was a better predictor for presence of dysphagia in acute stroke patients than the NIHSS. Our findings stand in contrast to the 2009 report, in which dysphagia sensitivities of their screening tool and the NIHSS were 29% and 79%, respectively. Therefore, streamlining these ED stroke assessments would not be efficacious in our facility.
Abstract 3: Endovascular Thrombectomy Increases Disability-free Survival, Quality of Life and Life Expectancy After Ischemic Stroke With Reduced Costs
Authors: Campbell Bruce , Mitchell Peter , Churilov Leonid , Keshtkaran Mahsa , Meretoja Atte , Donnan Geoffrey , Davis Stephen ,   on behalf of the EXTEND-IA Investigators
Published: March 2022

Background:
Recent trials have demonstrated improved outcomes with endovascular therapy for ischemic stroke due to large vessel occlusion compared with alteplase. We examined the effects on disability, quality of life, survival and acute care cost in the EXTEND-IA trial.

Methods:
Patients receiving alteplase within 4.5h of onset with major vessel occlusion and CT perfusion evidence of salvageable brain were randomized to endovascular thrombectomy after alteplase vs alteplase alone. Expected survival for each individual patient was modeled using age, gender and 3 month modified Rankin Scale (mRS). Utility scores were applied to estimate Disability/Quality-adjusted life years (DALY/QALY) saved. Cost of procedure and inpatient care within the first 3 months was calculated.

Results:
There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15. The median disability-weighted utility score at 3 months based on the observed mRS increased from 0.65 (IQR 0-0.91) in alteplase only to 0.91 (IQR 0.65-1) in the endovascular group (unadjusted p=0.005, adjusted for age and baseline NIHSS p=0.02). Modelled life expectancy was greater in the endovascular versus alteplase-only group (median 12.6 vs 7.4 years, p=0.048 unadjusted; HR 0.59 CI95 0.35-0.99, p=0.046 adjusted for age and baseline NIHSS). Applying utility scores, endovascular thrombectomy reduced lifetime DALY lost, median 5.5 (IQR 3.2-8.7) vs 8.9 (IQR 4.7-13.8), p=0.02 (non-discounted, non-age-weighted, with similar results regardless of age-weighting and discounting) and increased QALY gained, median 7.5 (IQR 2.7-10.2) vs 4.0 (IQR 0.3-6.9), p=0.03, (discounted, with similar results undiscounted). Endovascular patients spent less time in hospital (median 5 versus 8 days, p=0.04) and rehabilitation (median 0 versus 27 days, p=0.03) with reduced cost of inpatient care in the first 3 months (median US$12,188 versus US$26,112, p=0.009), saving US$2,417/patient after US$11,507 transport and thrombectomy procedural costs.

Conclusions:
In ischemic stroke patients with large vessel occlusion and salvageable tissue on CT-perfusion, thrombectomy reduced costs and increased expected long term survival with reduced disability and improved quality of life.